Entry
stringlengths 6
10
| Entry Name
stringlengths 5
11
| Sequence
stringlengths 2
35.2k
| EC number
stringlengths 7
118
⌀ | Cofactor
stringlengths 38
1.77k
⌀ | Gene Ontology (biological process)
stringlengths 18
11.3k
⌀ | Gene Ontology (cellular component)
stringlengths 17
1.75k
⌀ | Gene Ontology (molecular function)
stringlengths 24
2.09k
⌀ | Pfam
stringlengths 8
232
⌀ | Gene3D
stringlengths 10
250
⌀ | Protein families
stringlengths 9
237
⌀ | Post-translational modification
stringlengths 16
8.52k
⌀ | Subcellular location [CC]
stringlengths 29
6.18k
⌀ | Catalytic activity
stringlengths 64
35.7k
⌀ | Kinetics
stringlengths 69
11.7k
⌀ | Pathway
stringlengths 27
908
⌀ | pH dependence
stringlengths 64
955
⌀ | Temperature dependence
stringlengths 70
1.16k
⌀ | Function [CC]
stringlengths 17
15.3k
⌀ | Organism
stringlengths 8
196
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
O89039
|
ACKR3_RAT
|
MDVHLFDYVEPGNYSDINWPCNSSDCIVVDTVQCPAMPNKNVLLYTLSFIYIFIFVIGMIANSVVVWVNIQAKTTGYDTHCYILNLAIADLWVVITIPVWVVSLVQHNQWPMGELTCKITHLIFSINLFGSIFFLACMSVDRYLSITYFTSTSSYKKKMVRRVVCVLVWLLAFFVSLPDTYYLKTVTSASNNETYCRSFYPEHSIKEWLIGMELVSVILGFAVPFTIIAIFYFLLARAMSASGDQEKHSSRKIIFSYVVVFLVCWLPYHFVVLLDIFSILHYIPFTCQLENVLFTALHVTQCLSLVHCCVNPVLYSFINRNYRYELMKAFIFKYSAKTGLTKLIDASRVSETEYSALEQNTK
| null | null |
angiogenesis [GO:0001525]; calcium-mediated signaling [GO:0019722]; cell adhesion [GO:0007155]; cell chemotaxis [GO:0060326]; chemokine-mediated signaling pathway [GO:0070098]; immune response [GO:0006955]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage [GO:1902230]; oculomotor nerve development [GO:0021557]; positive regulation of cytosolic calcium ion concentration [GO:0007204]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of mesenchymal stem cell migration [GO:1905322]; receptor internalization [GO:0031623]; vasculogenesis [GO:0001570]
|
cell surface [GO:0009986]; clathrin-coated pit [GO:0005905]; early endosome [GO:0005769]; endosome [GO:0005768]; external side of plasma membrane [GO:0009897]; plasma membrane [GO:0005886]; recycling endosome [GO:0055037]
|
C-C chemokine binding [GO:0019957]; C-C chemokine receptor activity [GO:0016493]; C-X-C chemokine binding [GO:0019958]; C-X-C chemokine receptor activity [GO:0016494]; coreceptor activity [GO:0015026]; scavenger receptor activity [GO:0005044]
|
PF00001;
|
1.20.1070.10;
|
G-protein coupled receptor 1 family, Atypical chemokine receptor subfamily
|
PTM: The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated. {ECO:0000250|UniProtKB:P25106}.; PTM: Ubiquitinated at the Lys residues in its C-terminal cytoplasmic tail and is essential for correct trafficking from and to the cell membrane. Deubiquitinated by CXCL12-stimulation in a reversible manner. {ECO:0000250|UniProtKB:P25106}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21655198}; Multi-pass membrane protein {ECO:0000269|PubMed:21655198}. Early endosome {ECO:0000305|PubMed:21655198}. Recycling endosome {ECO:0000305|PubMed:21655198}. Note=Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via clathrin-coated pits in a beta-arrestin -dependent manner. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane (By similarity). {ECO:0000250|UniProtKB:P25106}.
| null | null | null | null | null |
FUNCTION: Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. {ECO:0000269|PubMed:20018651}.; FUNCTION: Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1 (By similarity). Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway (PubMed:20018651). Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Regulates axon guidance in the oculomotor system through the regulation of CXCL12 levels (By similarity). {ECO:0000250|UniProtKB:P25106, ECO:0000269|PubMed:20018651}.
|
Rattus norvegicus (Rat)
|
O89040
|
PLCB2_RAT
|
MSLLNPVLLPPKVKAYLSQGERFIKWDDETSIASPVILRVDPKGYYLYWTHQSKEMEFLDVTSIRDTRFGKFAKIPKSQKLREVFNMDFPDNHFLLKTFTVVSGPDMVGLTFHNFVSYKENVGKDWAEDVLALAKHPMTANASRSTFLDKILVKLKMQLSPEGKIPVKNFFQMFPADRKRVEAALSACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFTSYHAKAKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQALIDKYEPSGINVQRGQLSPEGMVWFLCGPENSVLAHDTLRIHQDMTQPLNHYFINSSHNTYLTAGQFSGPSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTDILFKEAVEAIAESAFKTSPYPVILSFENHVDSPRQQAKMAEYCRTMFGETLLTEPLENFPLKPGMPLPSPEDLRGKILIKNKKNQFSGPASPNKKPDGVSEGGFPSSVPVEEDTGWTAEDRTEVEEGEEEEEVEEEEEEESGNLDEEEIKKMQSDEGTAGLEVTAYEEMSSLVNYIQPTKFISFEFSAQKNRSYLVSSFTELKAYELLSKASMQFVDYNKRQMSRVYPKGTRMDSSNYMPQMFWNAGCQMVALNFQTMDLPMQQNMALFEFNGQSGYLLKHEFMRRQDKQFNPFSVDRIDVVVATTLSITVISGQFLSERSVRTYVEVELFGLPGDPKRRYRTKLSPTANSINPVWKEEPFIFEKILVPELASLRIAVMEEGGKFIGHRIIPINALHSGYHHLCLRSESNMPLTMPALFVFLEMKDYVPDTWADLTVALANPIKYFSAHDKKSVKLKEVTGSLPEKLFSGIPVASQSNGAPVSAGNGSTAPGTKAKEEATKEVAEPQTTSLEELRELKGVVKLQRRHEKELRELERRGARRWEELLQRGAAQLAELQDPAASCKLRPGKGSRKKRIVPCEETIVVPREVLEGPDPRVQDLKDRLEQELQQQGEEQYRSVLKRKEQHVTEQIAKMMELAREKQAAELKSFKETSETDTKEMKKKLEAKRLERIQAMTKVTTDKVAQERLKREINNSHIQEVVQAVKQMTETLERHQEKLEEKQTACLEQIQAMEKQFQEKALAEYEAKMKGLEAEVKESMRACFKACFPTEAEEKPERPCEASEESCPQEPLVNKTDTQESRL
|
3.1.4.11
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250|UniProtKB:Q00722}; Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250|UniProtKB:Q00722};
|
detection of chemical stimulus involved in sensory perception of bitter taste [GO:0001580]; G protein-coupled receptor signaling pathway [GO:0007186]; lipid catabolic process [GO:0016042]; phosphatidylinositol metabolic process [GO:0046488]; phosphatidylinositol-mediated signaling [GO:0048015]; phospholipase C-activating G protein-coupled receptor signaling pathway [GO:0007200]; release of sequestered calcium ion into cytosol [GO:0051209]; sensory perception of bitter taste [GO:0050913]
|
cytoplasm [GO:0005737]; G-protein beta/gamma-subunit complex [GO:0031680]; neuronal dense core vesicle [GO:0098992]
|
calcium ion binding [GO:0005509]; G-protein beta/gamma-subunit complex binding [GO:0031683]; phosphatidylinositol phospholipase C activity [GO:0004435]; phospholipase C activity [GO:0004629]; phospholipid binding [GO:0005543]
|
PF00168;PF09279;PF17787;PF00388;PF00387;PF08703;
|
2.30.29.240;2.60.40.150;1.10.238.10;3.20.20.190;1.20.1230.10;
| null | null | null |
CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:58456, ChEBI:CHEBI:203600; EC=3.1.4.11; Evidence={ECO:0000250|UniProtKB:Q00722}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180; Evidence={ECO:0000250|UniProtKB:Q00722}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = 1D-myo-inositol 1-phosphate + a 1,2-diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:43484, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:57880, ChEBI:CHEBI:58433; Evidence={ECO:0000250|UniProtKB:Q00722}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43485; Evidence={ECO:0000250|UniProtKB:Q00722};
| null | null | null | null |
FUNCTION: The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. This protein may be involved in the transduction of bitter taste stimuli. {ECO:0000250|UniProtKB:Q00722, ECO:0000303|PubMed:9860142}.
|
Rattus norvegicus (Rat)
|
O89042
|
DPOLA_RAT
|
MAPVHGDDCKLETSAVSDSGSFVASRARREKKSKKGRQEALERLKKAKAGEKYKYEVEDLTSVYEEVDEEQYSKLVQARQDDDWIVDDDGIGYVEDGREIFDDDLEDDALDTCGEGSDGKAHRKDRKDVKKPSVTKPNNIKAMFIASAGKKTTDKTVDLSKDDLLGDILQDLNTETPQIAPPPVLIPKKKRSTGASPNPFSVHTATAVPSGKIASPVSRKEPPLTPVPLKRAEFAGDLAQPECPEDEQESGVIEFEDGDFDEPMDTEEVDEEEPVTAKIWDQESEPVEGVKHEADPETGTTSFLDSFLPDVSCWDIDQKDENSFLLQEVQVDSNHLPLVKGADDEQVFQFYWLDAYEDPYNQPGVVFLFGKVWVESAKTHVSCCVMVKNIERTLYFLPREMKIDLNTGKETATPITMKDVYEEFDSKISAKYKIMKFKSKIVEKNYAFEIPDVPEKSEYLEVRYSAEVPQLPQNLKGETFSHVFGTNTSSLELFLMNRKIKGPCWLEVKNPQLLNQPISWCKFEAMALKPDLVNVIKDVSPPPLVVMSFSMKTMQNVQNHQHEIIAMAALVHHNFPLDKAPPKPPFQTHFCVVSKPKDCIFPCAFKEVIKKKNMEVEVAATERTLLGFFLAKVHKLDPDILVGHNICGFELEVLLQRINECKVPFWSKIGRLRRSNMPKLGSRSGFGERNATCGRMICDVEISVKELIHCKSYHLSELVQQILKTERIVIPTENIRNMYSEPSHLLYLLEHIWKDARFILQIMCELNVLPLALQITNIAGNIMSRTLMGGRSERNEFLLLHAFYENNYIVPDKQIFRKPQQKPGDEDEEIDGDTNKYKKGRKKAAYAGGLVLDPKVGFYDKFILLLDFNSLYPSIIQEFNICFTTVQRVASETLKATEDEEQEQIPELPDPNLDMGILPREIRKLVERRKQVKQLMKQQDLNPDLVLQYDIRQKALKLTANSMYGCLGFSYSRFYAKPLAALVTYKGREILMHTKEMVQKMNLEVIYGDTDSIMINTNSTNLEEVFKLGNKVKNEVNKLYKLLEIDIDGVFKSLLLLKKKKYAALVVEPTSDGNYITKQELKGLDIVRRDWCDLAKDTGNFVIGQILSDQSRDTIVENIQKRLIEIGENVLNGSVPVSQFEINKALTKDPQDYPDKKSLPHVHVALWINSQGGRKVKAGDTVSYVICQDGSNLPATQRAYAPEQLQKQDNLAIDTQYYLAQQIHPVVARICEPIDGIDAVLIALWLGLDSTQFRVHQYHKDEENDALLGGPAQLTDEEKYKDCEKFKCLCPSCGTENIYDNVFEGSGMDMEPSLNRCSNIDCKASPATFMVQLSNKLIMDIRRCIKKYYDGWLICEEPTCRNRIRRLPLHFSRNGPLCPACMKAVLRPEYSDKSLYTQLCFYRYIFDADCALEKLPEHEKDKLKKQFFTPRVLQDYRKVKNIAEHFLSWSG
|
2.7.7.7
| null |
DNA biosynthetic process [GO:0071897]; DNA repair [GO:0006281]; DNA replication [GO:0006260]; DNA replication initiation [GO:0006270]; DNA replication, synthesis of RNA primer [GO:0006269]; DNA strand elongation involved in DNA replication [GO:0006271]; DNA synthesis involved in DNA repair [GO:0000731]; double-strand break repair via nonhomologous end joining [GO:0006303]; lagging strand elongation [GO:0006273]; leading strand elongation [GO:0006272]; mitotic DNA replication initiation [GO:1902975]; regulation of type I interferon production [GO:0032479]
|
alpha DNA polymerase:primase complex [GO:0005658]; chromatin [GO:0000785]; cytosol [GO:0005829]; nuclear envelope [GO:0005635]; nuclear matrix [GO:0016363]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
chromatin binding [GO:0003682]; DNA binding [GO:0003677]; DNA replication origin binding [GO:0003688]; DNA-directed DNA polymerase activity [GO:0003887]; double-stranded DNA binding [GO:0003690]; nucleotide binding [GO:0000166]; protein kinase binding [GO:0019901]; purine nucleotide binding [GO:0017076]; pyrimidine nucleotide binding [GO:0019103]; single-stranded DNA binding [GO:0003697]; zinc ion binding [GO:0008270]
|
PF12254;PF00136;PF03104;PF08996;
|
2.40.50.730;3.30.70.2820;1.10.3200.20;1.10.132.60;1.10.287.690;3.90.1600.10;3.30.420.10;
|
DNA polymerase type-B family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P09884}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P09884}. Note=In the cytosol, colocalizes with RNA:DNA hybrids with a speckled pattern. {ECO:0000250|UniProtKB:P09884}.
|
CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000269|PubMed:10541966}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22509; Evidence={ECO:0000269|PubMed:10541966};
| null | null | null | null |
FUNCTION: Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis (PubMed:10541966). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, a regulatory subunit POLA2 and two primase subunits PRIM1 and PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses (By similarity) (PubMed:10541966). {ECO:0000250|UniProtKB:P09884, ECO:0000269|PubMed:10541966}.
|
Rattus norvegicus (Rat)
|
O89046
|
COR1B_RAT
|
MSFRKVVRQSKFRHVFGQPVKNDQCYEDIRVSRVTWDSTFCAVNPKFLAVIVEASGGGAFMVLPLNKTGRIDKAYPTVCGHTGPVLDIDWCPHNDEVIASGSEDCTVMVWQIPENGLTSPLTEPVVVLEGHTKRVGIITWHPTARNVLLSAGCDNVVLIWNVGTAEELYRLDSLHPDLIYNVSWNHNGSLFCTACKDKSVRIIDPRRGTLVAEREKAHEGARPMRAIFLADGKVFTAGFSRMSERQLALWDPENFEEPMALQELDSSNGALLPFYDPDTSVVYVCGKGDSSIRYFEITDEPPYIHFLNTFTSKEPQRGMGSMPKRGLEVSKCEIARFYKLHERKCEPIVMTVPRKSDLFQDDLYPDTAGPDAALEAEDWVSGQDADPILISLREAYVPSKQRDLKVSRRNVLSDSKPAGYSRSGVSTATAITDIPSGNLAGSGEAGKLEEVMHGLRALRVLVKEQGERISRLEEHLGRMENGDT
| null | null |
actin cytoskeleton organization [GO:0030036]; actin filament branching [GO:0090135]; actin filament bundle assembly [GO:0051017]; actin filament organization [GO:0007015]; cell migration [GO:0016477]; cellular response to platelet-derived growth factor stimulus [GO:0036120]; endothelial cell chemotaxis [GO:0035767]; negative regulation of Arp2/3 complex-mediated actin nucleation [GO:0034316]; negative regulation of lamellipodium morphogenesis [GO:2000393]; negative regulation of smooth muscle cell chemotaxis [GO:0071672]; positive regulation of lamellipodium morphogenesis [GO:2000394]; protein kinase C signaling [GO:0070528]; protein localization to cell leading edge [GO:1902463]; regulation of Arp2/3 complex-mediated actin nucleation [GO:0034315]; ruffle organization [GO:0031529]; wound healing [GO:0042060]
|
actin filament [GO:0005884]; cell leading edge [GO:0031252]; cell periphery [GO:0071944]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; lamellipodium [GO:0030027]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; stress fiber [GO:0001725]
|
actin filament binding [GO:0051015]; Arp2/3 complex binding [GO:0071933]; cytoskeletal protein binding [GO:0008092]; identical protein binding [GO:0042802]; protein-containing complex binding [GO:0044877]
|
PF08953;PF00400;PF16300;
|
2.130.10.10;
|
WD repeat coronin family
|
PTM: Phosphorylation on Ser-2 regulates the interaction with the Arp2/3 complex and cell motility in fibroblasts. Phosphorylation does not seem to affect subcellular location (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q9BR76}. Cytoplasm, cytoskeleton, stress fiber {ECO:0000250|UniProtKB:Q9BR76}. Note=Localized to the leading edge in fibroblasts, as well as weakly along actin stress fibers. {ECO:0000250|UniProtKB:Q9BR76}.
| null | null | null | null | null |
FUNCTION: Regulates leading edge dynamics and cell motility in fibroblasts. May be involved in cytokinesis and signal transduction (By similarity). {ECO:0000250}.
|
Rattus norvegicus (Rat)
|
O89047
|
KCNH3_RAT
|
MPAMRGLLAPQNTFLDTIATRFDGTHSNFVLGNAQVAGLFPVVYCSDGFCDLTGFSRAEVMQRGCACSFLYGPDTSELVRQQIRKALDEHKEFKAELILYRKSGLPFWCLLDVIPIKNEKGEVALFLVSHKDISETKNRGGPDNWKERGGGRRRYGRAGSKGFNANRRRSRAVLYHLSGHLQKQPKGKHKLNKGVFGEKPNLPEYKVAAIRKSPFILLHCGALRATWDGFILLATLYVAVTVPYSVCVSTAREPSAARGPPSVCDLAVEVLFILDIVLNFRTTFVSKSGQVVFAPKSICLHYVTTWFLLDVIAALPFDLLHAFKVNVYVGAHLLKTVRLLRLLRLLPRLDRYSQYSAVVLTLLMAVFALLAHWVACVWFYIGQQEIENSESELPEIGWLQELARRLETPYYLVSRSPDGGNSSGQSENCSSSGGGSEANGTGLELLGGPSLRSAYITSLYFALSSLTSVGFGNVSANTDTEKIFSICTMLIGALMHAVVFGNVTAIIQRMYARRFLYHSRTRDLRDYIRIHRIPKPLKQRMLEYFQATWAVNNGIDTTELLQSLPDELRADIAMHLHKEVLQLPLFEAASRGCLRALSLALRPAFCTPGEYLIHQGDALQALYFVCSGSMEVLKGGTVLAILGKGDLIGCELPQREQVVKANADVKGLTYCVLQCLQLAGLHESLALYPEFAPRFSRGLRGELSYNLGAGGVSAEVDTSSLSGDNTLMSTLEEKETDGEQGHTISPAPADEPSSPLLSPGCTSSSSAAKLLSPRRTAPRPRLGGRGRPSRAGVLKPEAGPSAHPRTLDGLQLPPMPWNVPPDLSPRVVDGIEDGCGSDQHKFSFRVGQSGPECSSSPSPGTESGLLTVPLVPSEARNTDTLDKLRQAVTELSEQVLQMREGLQSLRQAVQLILVPQGEGQCPRVSGEGPCPATASGLLQPLRVDTGASSYCLQPPAGSVLSGTWPHPRPGHPPPLMAPWPWGPPASQSSPWPRATALWTSTSDSEPPGSGDLCSEPSTPASPPPPEEGARTGTPAPVSQAEATSTGEPPPGSGGRALPWDPHSLEMVLIGCHGPGSVQWTQEEGTGV
| null | null |
potassium ion transmembrane transport [GO:0071805]; regulation of membrane potential [GO:0042391]
|
monoatomic ion channel complex [GO:0034702]; plasma membrane [GO:0005886]
|
voltage-gated potassium channel activity [GO:0005249]
|
PF00027;PF00520;PF13426;
|
1.10.1200.260;1.10.287.70;2.60.120.10;3.30.450.20;
|
Potassium channel family, H (Eag) (TC 1.A.1.20) subfamily, Kv12.2/KCNH3 sub-subfamily
| null |
SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
| null | null | null | null | null |
FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits an outward current with fast inactivation. Channel properties may be modulated by cAMP and subunit assembly.
|
Rattus norvegicus (Rat)
|
O89049
|
TRXR1_RAT
|
MNDSKDAPKSYDFDLIIIGGGSGGLAAAKEAAKFDKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKKLMHQAALLGQALKDSRNYGWKLEDTVKHDWEKMTESVQNHIGSLNWGYRVALREKKVVYENAYGKFIGPHKIMATNNKGKEKVYSAERFLIATGERPRYLGIPGDKEYCISSDDLFSLPYCPGKTLVVGASYVALECAGFLAGIGLDVTVMVRSILLRGFDQDMANKIGEHMEEHGIKFIRQFVPTKIEQIEAGTPGRLKVTAKSTNSEETIEDEFNTVLLAVGRDSCTRTIGLETVGVKINEKTGKIPVTDEEQTNVPYIYAIGDILEGKLELTPVAIQAGRLLAQRLYGGSTVKCDYDNVPTTVFTPLEYGCCGLSEEKAVEKFGEENIEVYHSFFWPLEWTVPSRDNNKCYAKVICNLKDNERVVGFHVLGPNAGEVTQGFAAALKCGLTKQQLDSTIGIHPVCAEIFTTLSVTKRSGGDILQSGCUG
|
1.11.1.2; 1.8.1.9
|
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:10849437, ECO:0000269|PubMed:11481439}; Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:11481439};
|
benzene-containing compound metabolic process [GO:0042537]; cell population proliferation [GO:0008283]; cell redox homeostasis [GO:0045454]; cellular response to copper ion [GO:0071280]; cellular response to hyperoxia [GO:0071455]; cellular response to oxidative stress [GO:0034599]; gastrulation [GO:0007369]; glutathione metabolic process [GO:0006749]; halogen metabolic process [GO:0070276]; hydrogen peroxide catabolic process [GO:0042744]; mesoderm formation [GO:0001707]; NADPH oxidation [GO:0070995]; positive regulation of apoptotic process [GO:0043065]; response to axon injury [GO:0048678]; response to hyperoxia [GO:0055093]; response to oxidative stress [GO:0006979]; response to selenium ion [GO:0010269]; response to xenobiotic stimulus [GO:0009410]; selenocysteine metabolic process [GO:0016259]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; mitochondrion [GO:0005739]; neuronal cell body [GO:0043025]; nucleus [GO:0005634]
|
FAD binding [GO:0071949]; glutathione-disulfide reductase (NADP) activity [GO:0004362]; identical protein binding [GO:0042802]; mercury ion binding [GO:0045340]; NAD(P)H oxidase H2O2-forming activity [GO:0016174]; NADPH peroxidase activity [GO:0050137]; selenate reductase activity [GO:0033797]; thioredoxin-disulfide reductase (NADP) activity [GO:0004791]
|
PF07992;PF02852;
|
3.30.390.30;3.50.50.60;
|
Class-I pyridine nucleotide-disulfide oxidoreductase family
|
PTM: ISGylated. {ECO:0000250|UniProtKB:Q16881}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16881}.
|
CATALYTIC ACTIVITY: Reaction=[thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide + H(+) + NADPH; Xref=Rhea:RHEA:20345, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.8.1.9; Evidence={ECO:0000269|PubMed:10849437}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20347; Evidence={ECO:0000269|PubMed:10849437}; CATALYTIC ACTIVITY: Reaction=H(+) + H2O2 + NADPH = 2 H2O + NADP(+); Xref=Rhea:RHEA:15173, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.11.1.2; Evidence={ECO:0000269|PubMed:10849437}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15174; Evidence={ECO:0000305|PubMed:10849437};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=3.3 uM for thioredoxin {ECO:0000269|PubMed:10849437}; Note=kcat is 2500 min(-1) with thioredoxin as substrate. {ECO:0000269|PubMed:10849437};
| null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.5. {ECO:0000269|PubMed:10849437};
| null |
FUNCTION: Reduces disulfideprotein thioredoxin (Trx) to its dithiol-containing form. Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. Contains a selenocysteine residue at the C-terminal active site that is essential for catalysis (PubMed:10849437). Also has reductase activity on hydrogen peroxide (H2O2) (PubMed:10849437). {ECO:0000269|PubMed:10849437}.
|
Rattus norvegicus (Rat)
|
O89050
|
MKLN1_MOUSE
|
MAAGGAVAVAPECRLLPYALHKWSSFSSTYLPENILVDKPNDQSSRWSSESNYPPQYLILKLERPAIVQNITFGKYEKTHVCNLKKFKVFGGMNEENMTELLSSGLKNDYNKETFTLKHKIDEQMFPCRFIKIVPLLSWGPSFNFSIWYVELSGIDDPDIVQPCLNWYSKYREQEAIRLCLKHFRQHNYTEAFESLQKKTKIALEHPMLTDMHDKLVLKGDFDACEELIEKAVNDGLFNQYISQQEYKPRWSQIIPKSTKGDGEDNRPGMRGGHQMVIDVQTETVYLFGGWDGTQDLADFWAYSVKENQWTCISRDTEKENGPSARSCHKMCIDIQRRQIYTLGRYLDSSVRNSKSLKSDFYRYDIDTNTWMLLSEDTAADGGPKLVFDHQMCMDSEKHMIYTFGGRILTCNGSVDDSRASEPQFSGLFAFNCQCQTWKLLREDSCNAGPEDIQSRIGHCMLFHSKNRCLYVFGGQRSKTYLNDFFSYDVDSDHVDIISDGTKKDSGMVPMTGFTQRATIDPELNEIHVLSGLSKDKEKREENVRNSFWIYDIVRNSWSCVYKNDQATKDNLSKSLQEEEPCPRFAHQLVYDELHKVHYLFGGNPGKSCSPKMRLDDFWSLKLCRPSKDYLLRHCKYLIRKHRFEEKAQMDPLSALKYLQNDLYITVDHSDPEETKEFQLLASALFKSGSDFTALGFSDVDHTYAQRTQLFDTLVNFFPDSMTPPKGNLVDLITL
| null | null |
actin cytoskeleton organization [GO:0030036]; cell-matrix adhesion [GO:0007160]; regulation of cell shape [GO:0008360]; regulation of receptor internalization [GO:0002090]
|
cell cortex [GO:0005938]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; nucleoplasm [GO:0005654]; postsynapse [GO:0098794]; ruffle [GO:0001726]; ubiquitin ligase complex [GO:0000151]
|
identical protein binding [GO:0042802]; protein homodimerization activity [GO:0042803]
|
PF01344;PF13415;PF06588;
|
2.60.120.260;2.120.10.80;
| null | null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9724633}. Cytoplasm, cytosol {ECO:0000269|PubMed:18710924}. Nucleus, nucleoplasm {ECO:0000269|PubMed:18710924}. Cell projection, ruffle {ECO:0000269|PubMed:9724633}. Cytoplasm, cell cortex {ECO:0000269|PubMed:9724633}. Synapse {ECO:0000269|PubMed:21482357}. Postsynapse {ECO:0000269|PubMed:21482357}. Note=Colocalizes with GABRA1 at synapses and in postsynaptic regions (PubMed:21482357). Colocalizes with actin fibers in the cell cortex. {ECO:0000269|PubMed:21482357, ECO:0000269|PubMed:9724633}.
| null | null | null | null | null |
FUNCTION: Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (By similarity). Required for internalization of the GABA receptor GABRA1 from the cell membrane via endosomes and subsequent GABRA1 degradation (PubMed:21482357). Acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component THBS1 (PubMed:18710924, PubMed:9724633). {ECO:0000250|UniProtKB:Q9UL63, ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:21482357, ECO:0000269|PubMed:9724633}.
|
Mus musculus (Mouse)
|
O89051
|
ITM2B_MOUSE
|
MVKVTFNSALAQKEAKKDEPKSSEEALIVPPDAVAVDCKDPGDVVPVGQRRAWCWCMCFGLAFMLAGVILGGAYLYKYFALQPDDVYYCGLKYIKDDVILNEPSADAPAARYQTIEENIKIFEEDAVEFISVPVPEFADSDPANIVHDFNKKLTAYLDLNLDKCYVIPLNTSIVMPPKNLLELLINIKAGTYLPQSYLIHEHMVITDRIENVDNLGFFIYRLCHDKETYKLQRRETIRGIQKREASNCFTIRHFENKFAVETLICS
| null | null |
negative regulation of amyloid precursor protein biosynthetic process [GO:0042985]
|
endosome membrane [GO:0010008]; extracellular exosome [GO:0070062]; extracellular space [GO:0005615]; Golgi apparatus [GO:0005794]; Golgi membrane [GO:0000139]; Golgi-associated vesicle membrane [GO:0030660]; organelle membrane [GO:0031090]; plasma membrane [GO:0005886]
|
amyloid-beta binding [GO:0001540]; ATP binding [GO:0005524]
|
PF04089;
| null |
ITM2 family
|
PTM: The ectodomain C-terminal part of the imBRI2 is processed by furin producing a secreted Bri23 peptide and a mature BRI2, membrane form (mBRI2). The remaining part of the ectodomain of mBRI2 containing the BRICHOS domain is cleaved by ADAM10 and is secreted (BRI2C, soluble form). The membrane-bound N-terminal fragment (BRI2C, membrane form) is further proteolytically processed by SPPL2A and SPPL2B through regulated intramembrane proteolysis producing a secreted C-peptide and a BRI2 intracellular domain (BRI2 ICD) released in the cytosol. Shedding by ADAM10 facilitates intramembrane cleavage but is not absolutely required for BRI2 ICD generation (By similarity). {ECO:0000250}.; PTM: Glycosylation at Asn-170 is important for cell surface localization, but doesn't affect furin- and ADAM10-induced proteolytic processing. {ECO:0000250}.
|
SUBCELLULAR LOCATION: [Integral membrane protein 2B]: Golgi apparatus membrane {ECO:0000250|UniProtKB:Q9Y287}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9Y287}. Note=Immature BRI2 (imBRI2) is cleaved by furin in the Golgi into mBRI2 and a Bri23 peptide. mBRI2 is transported to the plasma membrane and Bri23 peptide is secreted. {ECO:0000250|UniProtKB:Q9Y287}.; SUBCELLULAR LOCATION: [BRI2, membrane form]: Cell membrane {ECO:0000250|UniProtKB:Q9Y287}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9Y287}. Endosome membrane {ECO:0000250|UniProtKB:Q9Y287}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9Y287}. Note=Mature BRI2 (mBRI2) needs to be transported from the endoplasmic reticulum compartment to the cell membrane in order to be able to inhibit APP processing. {ECO:0000250|UniProtKB:Q9Y287}.; SUBCELLULAR LOCATION: [Bri23 peptide]: Secreted {ECO:0000250|UniProtKB:Q9Y287}. Note=Detected in the cerebral spinal fluid (CSF). {ECO:0000250|UniProtKB:Q9Y287}.; SUBCELLULAR LOCATION: [BRI2C, soluble form]: Secreted {ECO:0000250|UniProtKB:Q9Y287}.
| null | null | null | null | null |
FUNCTION: Plays a regulatory role in the processing of the amyloid-beta A4 precursor protein (APP) and acts as an inhibitor of the amyloid-beta peptide aggregation and fibrils deposition. Plays a role in the induction of neurite outgrowth. Functions as a protease inhibitor by blocking access of secretases to APP cleavage sites (By similarity). {ECO:0000250}.; FUNCTION: Mature BRI2 (mBRI2) functions as a modulator of the amyloid-beta A4 precursor protein (APP) processing leading to a strong reduction in the secretion of secretase-processed amyloid-beta protein 40 and amyloid-beta protein 42. {ECO:0000250}.; FUNCTION: Bri23 peptide prevents aggregation of APP amyloid-beta protein 42 into toxic oligomers. {ECO:0000250}.
|
Mus musculus (Mouse)
|
O89053
|
COR1A_MOUSE
|
MSRQVVRSSKFRHVFGQPAKADQCYEDVRVSQTTWDSGFCAVNPKFMALICEASGGGAFLVLPLGKTGRVDKNVPLVCGHTAPVLDIAWCPHNDNVIASGSEDCTVMVWEIPDGGLVLPLREPVITLEGHTKRVGIVAWHPTAQNVLLSAGCDNVILVWDVGTGAAVLTLGPDVHPDTIYSVDWSRDGALICTSCRDKRVRVIEPRKGTVVAEKDRPHEGTRPVHAVFVSEGKILTTGFSRMSERQVALWDTKHLEEPLSLQELDTSSGVLLPFFDPDTNIVYLCGKGDSSIRYFEITSEAPFLHYLSMFSSKESQRGMGYMPKRGLEVNKCEIARFYKLHERKCEPIAMTVPRKSDLFQEDLYPPTAGPDPALTAEEWLGGRDAGPLLISLKDGYVPPKSRELRVNRGLDSARRRATPEPSGTPSSDTVSRLEEDVRNLNAIVQKLQERLDRLEETVQAK
| null | null |
actin filament organization [GO:0007015]; calcium ion transport [GO:0006816]; cell migration [GO:0016477]; cell-substrate adhesion [GO:0031589]; cellular response to interleukin-4 [GO:0071353]; early endosome to recycling endosome transport [GO:0061502]; epithelial cell migration [GO:0010631]; establishment of localization in cell [GO:0051649]; homeostasis of number of cells within a tissue [GO:0048873]; leukocyte chemotaxis [GO:0030595]; natural killer cell degranulation [GO:0043320]; negative regulation of actin nucleation [GO:0051126]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of vesicle fusion [GO:0031339]; nerve growth factor signaling pathway [GO:0038180]; neuron apoptotic process [GO:0051402]; phagolysosome assembly [GO:0001845]; positive chemotaxis [GO:0050918]; positive regulation of T cell activation [GO:0050870]; positive regulation of T cell migration [GO:2000406]; positive regulation of T cell proliferation [GO:0042102]; regulation of actin filament polymerization [GO:0030833]; regulation of actin polymerization or depolymerization [GO:0008064]; regulation of cell shape [GO:0008360]; regulation of release of sequestered calcium ion into cytosol [GO:0051279]; response to cytokine [GO:0034097]; T cell activation [GO:0042110]; T cell homeostasis [GO:0043029]; T cell migration [GO:0072678]; T cell proliferation [GO:0042098]; thymocyte migration [GO:0072679]; uropod organization [GO:0032796]; vesicle fusion [GO:0006906]
|
actin cytoskeleton [GO:0015629]; actin filament [GO:0005884]; axon [GO:0030424]; cell leading edge [GO:0031252]; cell-cell junction [GO:0005911]; cortical actin cytoskeleton [GO:0030864]; early endosome [GO:0005769]; glutamatergic synapse [GO:0098978]; immunological synapse [GO:0001772]; lamellipodium [GO:0030027]; phagocytic cup [GO:0001891]; phagocytic vesicle membrane [GO:0030670]; plasma membrane [GO:0005886]; protein-containing complex [GO:0032991]; stereocilium tip [GO:0032426]; synapse [GO:0045202]
|
actin filament binding [GO:0051015]; actin monomer binding [GO:0003785]; cytoskeletal protein binding [GO:0008092]; identical protein binding [GO:0042802]; myosin heavy chain binding [GO:0032036]; phosphatidylinositol 3-kinase binding [GO:0043548]; protein homodimerization activity [GO:0042803]
|
PF08953;PF08954;PF00400;PF16300;
|
2.130.10.10;
|
WD repeat coronin family
|
PTM: phosphorylation at Ser-412 by PKC strongly down-regulates the association with actin. {ECO:0000250}.; PTM: Polyubiquitinated by RNF128 with 'Lys-48'-linked chains, leading to proteasomal degradation. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:10338208}. Cytoplasm, cell cortex {ECO:0000269|PubMed:10338208}. Cytoplasmic vesicle, phagosome membrane {ECO:0000269|PubMed:10338208}. Note=In non-infected macrophages, associated with the cortical microtubule network. In mycobacteria-infected macrophages, becomes progressively relocalized and retained around the mycobacterial phagosomes. Retention on the phagosomal membrane is strictly dependent on mycobacterial viability and not due to impaired acidification.
| null | null | null | null | null |
FUNCTION: May be a crucial component of the cytoskeleton of highly motile cells, functioning both in the invagination of large pieces of plasma membrane, as well as in forming protrusions of the plasma membrane involved in cell locomotion. In mycobacteria-infected cells, its retention on the phagosomal membrane prevents fusion between phagosomes and lysosomes. {ECO:0000269|PubMed:10338208}.
|
Mus musculus (Mouse)
|
O89084
|
PDE4A_MOUSE
|
MEPPAAPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERSEPERSPHRPIERADAVDTGDRPGLRTTRMSWPSSFHGTGTGGGSSRRLEAENGPTPSPGRSPLDSQASPGLMLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVASEAHGEDLIVTPFAQVLASLRNVRSNFSLLTNVPIPSNKRSPLGGPPSVCKATLSEETCQQLARETLEELDWCLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISNTFLDKQHEVEIPSPTPRQRPFQQPPPAAVQQAQPMSQITGLKKLVHTGSLNINVPRFGVKTDQEDLLAQELENLSKWGLNIFCVSEYAGGRSLSCIMYTIFQERDLLKKFHIPVDTMMTYMLTLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGVSNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEENCDIFQNLSKRQRQSLRKMVIDMVLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLELYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADLVHPDAQDILDTLEDNRDWYHSAIRQSPSPTLEEEPGVLSDPALPDKFQFELTLEEEDEEDSLEVPGLPCTEETLLAPHDTRAQAMEQSKVKGQSPAVVEVAESLKQETASAHGAPEESAEAVGHSFSLETSILPDLRTLSPSEEAQGLLGLPSMAAEVEAPRDHLAAMRACSACSGTSGDNSAVISAPGRWGSGGDPA
|
3.1.4.53
|
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P27815}; Note=Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions. {ECO:0000250|UniProtKB:P27815}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P27815}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250|UniProtKB:Q07343}; Note=Binds 2 divalent metal cations per subunit (By similarity). Site 2 has a preference for magnesium and/or manganese ions (By similarity). {ECO:0000250|UniProtKB:P27815, ECO:0000250|UniProtKB:Q07343};
|
cAMP catabolic process [GO:0006198]; cAMP-mediated signaling [GO:0019933]; cellular response to xenobiotic stimulus [GO:0071466]; modulation of chemical synaptic transmission [GO:0050804]; regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway [GO:0106070]; regulation of protein kinase A signaling [GO:0010738]; sensory perception of smell [GO:0007608]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; membrane [GO:0016020]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; Schaffer collateral - CA1 synapse [GO:0098685]
|
3',5'-cyclic-AMP phosphodiesterase activity [GO:0004115]; 3',5'-cyclic-GMP phosphodiesterase activity [GO:0047555]; cAMP binding [GO:0030552]; metal ion binding [GO:0046872]
|
PF18100;PF00233;
|
1.10.1300.10;
|
Cyclic nucleotide phosphodiesterase family, PDE4 subfamily
|
PTM: Proteolytically cleaved by CASP3. {ECO:0000250|UniProtKB:P27815}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P27815}. Membrane; Peripheral membrane protein {ECO:0000250|UniProtKB:P27815}.
|
CATALYTIC ACTIVITY: [Isoform 2]: Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165, ChEBI:CHEBI:456215; EC=3.1.4.53; Evidence={ECO:0000269|PubMed:11267656}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278; Evidence={ECO:0000305|PubMed:11267656};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=9.2 uM for cAMP {ECO:0000269|PubMed:11267656}; Vmax=37.9 nmol/min/mg enzyme toward cAMP {ECO:0000269|PubMed:11267656};
|
PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1. {ECO:0000305|PubMed:11267656}.
| null | null |
FUNCTION: Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:11267656}.; FUNCTION: [Isoform 2]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:11267656}.
|
Mus musculus (Mouse)
|
O89086
|
RBM3_MOUSE
|
MSSEEGKLFVGGLNFNTDEQALEDHFSSFGPISEVVVVKDRETQRSRGFGFITFTNPEHASDAMRAMNGESLDGRQIRVDHAGKSARGSRGGAFGGRGRSYSRGGGDQGYGSGRYDSRPGGYGYGYGRSRDYSGSQGGYDRYSGGNYRDNYDN
| null | null |
miRNA processing [GO:0035196]; positive regulation of mRNA splicing, via spliceosome [GO:0048026]; positive regulation of translation [GO:0045727]; regulation of translation [GO:0006417]; response to cold [GO:0009409]; translation [GO:0006412]
|
cytoplasm [GO:0005737]; dendrite [GO:0030425]; large ribosomal subunit [GO:0015934]; nucleus [GO:0005634]; spliceosomal complex [GO:0005681]
|
ribosomal large subunit binding [GO:0043023]; RNA binding [GO:0003723]
|
PF00076;
|
3.30.70.330;
| null |
PTM: Arg-103 is dimethylated, probably to asymmetric dimethylarginine. {ECO:0000250}.; PTM: Phosphorylated. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Cell projection, dendrite {ECO:0000250}. Note=Localizes in mRNA granules in dentrites. {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Cold-inducible mRNA binding protein that enhances global protein synthesis at both physiological and mild hypothermic temperatures. Reduces the relative abundance of microRNAs, when overexpressed. Enhances phosphorylation of translation initiation factors and active polysome formation. {ECO:0000269|PubMed:15684048}.
|
Mus musculus (Mouse)
|
O89090
|
SP1_MOUSE
|
MSDQDHSMDEVTAVVKIEKDVGGNNGGSGNGGGAAFSQTRSSSTGSSSSSGGGGGQESQPSPLALLAATCSRIESPNENSNNSQGPSQSGGTGELDLTATQLSQGANGWQIISSSSGATPTSKEQSGNSTNGSNGSESSKNRTVSGGQYVVAATPNLQNQQVLTGLPGVMPNIQYQVIPQFQTVDGQQLQFAATGAQVQQDGSGQIQIIPGANQQIIPNRGSGGNIIAAMPNLLQQAVPLQGLANNVLSGQTQYVTNVPVALNGNITLLPVNSVSAATLTPSSQAGTISSSGSQESSSQPVTSGTAISSASLVSSQASSSSFFTNANSYSTTTTTSNMGIMNFTSSGSSGTSSQGQTPQRVGGLQGSDSLNIQQNQTSGGSLQGSQQKEGEQSQQTQQQQILIQPQLVQGGQALQALQAAPLSGQTFTTQAISQETLQNLQLQAVQNSGPIIIRTPTVGPNGQVSWQTLQLQNLQVQNPQAQTITLAPMQGVSLGQTSSSNTTLTPIASAASIPAGTVTVNAAQLSSMPGLQTINLSALGTSGIQVHQLPGLPLAIANTPGDHGTQLGLHGSGGDGIHDETAGGEGENSSDLQPQAGRRTRREACTCPYCKDSEGRASGDPGKKKQHICHIQGCGKVYGKTSHLRAHLRWHTGERPFMCNWSYCGKRFTRSDELQRHKRTHTGEKKFACPECPKRFMRSDHLSKHIKTHQNKKGGPGVALSVGTLPLDSGAGSEGTATPSALITTNMVAMEAICPEGIARLANSGINVMQVTELQSINISGNGF
| null | null |
cellular response to insulin stimulus [GO:0032869]; definitive hemopoiesis [GO:0060216]; embryonic camera-type eye morphogenesis [GO:0048596]; embryonic placenta development [GO:0001892]; embryonic process involved in female pregnancy [GO:0060136]; embryonic skeletal system development [GO:0048706]; enucleate erythrocyte differentiation [GO:0043353]; in utero embryonic development [GO:0001701]; liver development [GO:0001889]; lung development [GO:0030324]; megakaryocyte differentiation [GO:0030219]; mRNA transcription by RNA polymerase II [GO:0042789]; myeloid progenitor cell differentiation [GO:0002318]; ossification [GO:0001503]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of DNA-templated transcription [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]; response to hydroperoxide [GO:0033194]; rhythmic process [GO:0048511]; trophectodermal cell differentiation [GO:0001829]
|
chromatin [GO:0000785]; cytoplasm [GO:0005737]; nucleus [GO:0005634]; protein-DNA complex [GO:0032993]
|
bHLH transcription factor binding [GO:0043425]; cis-regulatory region sequence-specific DNA binding [GO:0000987]; DNA binding [GO:0003677]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; double-stranded DNA binding [GO:0003690]; histone acetyltransferase binding [GO:0035035]; metal ion binding [GO:0046872]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; RNA polymerase II transcription regulatory region sequence-specific DNA binding [GO:0000977]; RNA polymerase II-specific DNA-binding transcription factor binding [GO:0061629]; sequence-specific DNA binding [GO:0043565]; transcription coregulator binding [GO:0001221]
|
PF00096;
|
3.30.160.60;
|
Sp1 C2H2-type zinc-finger protein family
|
PTM: Phosphorylated on multiple serine and threonine residues. Phosphorylation is coupled to ubiquitination, sumoylation and proteolytic processing. Phosphorylation on Ser-61 enhances proteolytic cleavage. Phosphorylation on Ser-7 enhances ubiquitination and protein degradation. Hyperphosphorylation on Ser-103 in response to DNA damage has no effect on transcriptional activity. MAPK1/MAPK3-mediated phosphorylation on Thr-455 and Thr-738 enhances VEGF transcription but, represses FGF2-triggered PDGFR-alpha transcription. Also implicated in the repression of RECK by ERBB2. Hyperphosphorylated on Thr-280 and Thr-738 during mitosis by MAPK8 shielding SP1 from degradation by the ubiquitin-dependent pathway. Phosphorylated in the zinc-finger domain by calmodulin-activated PKCzeta. Phosphorylation on Ser-642 by PKCzeta is critical for TSA-activated LHR gene expression through release of its repressor, p107. Phosphorylation on Thr-669, Ser-671 and Thr-682 is stimulated by angiotensin II via the AT1 receptor inducing increased binding to the PDGF-D promoter. This phosphorylation is increased in injured artey wall. Ser-61 and Thr-682 can both be dephosphorylated by PP2A during cell-cycle interphase. Dephosphorylation on Ser-61 leads to increased chromatin association during interphase and increases the transcriptional activity. On insulin stimulation, sequentially glycosylated and phosphorylated on several C-terminal serine and threonine residues (By similarity). {ECO:0000250}.; PTM: Acetylated. Acetylation/deacetylation events affect transcriptional activity. Deacetylation leads to an increase in the expression the 12(s)-lipooxygenase gene though recruitment of p300 to the promoter (By similarity). {ECO:0000250}.; PTM: Ubiquitinated. Ubiquitination occurs on the C-terminal proteolytically-cleaved peptide and is triggered by phosphorylation (By similarity). {ECO:0000250}.; PTM: Sumoylated with SUMO1. Sumoylation modulates proteolytic cleavage of the N-terminal repressor domain. Sumoylation levels are attenuated during tumorigenesis. Phosphorylation mediates SP1 desumoylation (By similarity). {ECO:0000250}.; PTM: Proteolytic cleavage in the N-terminal repressor domain is prevented by sumoylation. The C-terminal cleaved product is susceptible to degradation (By similarity). {ECO:0000250}.; PTM: O-glycosylated; Contains 8 N-acetylglucosamine side chains. Levels are controlled by insulin and the SP1 phosphorylation states. Insulin-mediated O-glycosylation locates SP1 to the nucleus, where it is sequentially deglycosylated and phosphorylated. O-glycosylation affects transcriptional activity through disrupting the interaction with a number of transcription factors including ELF1 and NFYA. Inhibited by peroxisomome proliferator receptor gamma (PPARgamma) (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27918959}. Cytoplasm {ECO:0000250}. Note=Nuclear location is governed by glycosylated/phosphorylated states. Insulin promotes nuclear location, while glucagon favors cytoplasmic location (By similarity). {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter Plays an essential role in the regulation of FE65 gene expression (By similarity). Positively regulates the transcription of the core clock component BMAL1 (PubMed:24030830). Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (PubMed:27918959). {ECO:0000250|UniProtKB:P08047, ECO:0000250|UniProtKB:Q01714, ECO:0000269|PubMed:24030830, ECO:0000269|PubMed:27918959}.
|
Mus musculus (Mouse)
|
O89091
|
KLF10_MOUSE
|
MLNFGASLQQASEGKMELISEKPREGMHPWDKAEQSDFEAVEALMSMSCDWKSHFKKYLENRPVTPVSDTSEDDSLLPGTPDLQTVPAFCLTPPYSPSDFEPSQGSNLTASAPSTGHFKSFSDAAKPPGATPFKEEEKNPLAAPPLPKAQATSVIRHTADAQLCNHQSCPVKAASILNYQDNSFRRRTHGNVEATRKNIPCAAVSPNRSKPEPSTVSDGDEKAGAALYDFAVPSSETVICRSQPAPSSPVQKSVLVSSPTVSTGGVPPLPVICQMVPLPANNSLVSTVVPSTPPSQPPAVCSPVLFMGTQVPEGTVVFVVPQPVVQSPRPPVVSPSGTRLSPIAPAPGFSPSAARVTPQIDSSRVRSHICSHPGCGKTYFKSSHLKAHVRTHTGEKPFSCSWKGCERRFARSDELSRHRRTHTGEKKFACPMCDRRFMRSDHLTKHARRHLSAKKLPNWQMEVSKLNDIALPPTPASAQ
| null | null |
bone mineralization [GO:0030282]; cellular response to starvation [GO:0009267]; circadian rhythm [GO:0007623]; negative regulation of DNA-templated transcription [GO:0045892]; positive regulation of osteoclast differentiation [GO:0045672]; regulation of circadian rhythm [GO:0042752]; regulation of DNA-templated transcription [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]; somatic stem cell population maintenance [GO:0035019]
|
nucleus [GO:0005634]
|
core promoter sequence-specific DNA binding [GO:0001046]; DNA binding [GO:0003677]; DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; metal ion binding [GO:0046872]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]
|
PF00096;
|
3.30.160.60;
|
Sp1 C2H2-type zinc-finger protein family
|
PTM: Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q13118}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20070857}.
| null | null | null | null | null |
FUNCTION: Transcriptional repressor which binds to the consensus sequence 5'-GGTGTG-3'. May play a role in the cell cycle regulation (By similarity). Plays a role in the regulation of the circadian clock; binds to the GC box sequence in the promoter of the core clock component ARTNL/BMAL1 and represses its transcriptional activity. Regulates the circadian expression of genes involved in lipogenesis, gluconeogenesis, and glycolysis in the liver. Represses the expression of PCK2, a rate-limiting step enzyme of gluconeogenesis. {ECO:0000250|UniProtKB:Q13118, ECO:0000269|PubMed:20070857, ECO:0000269|PubMed:20385766}.
|
Mus musculus (Mouse)
|
O89093
|
CCL20_MOUSE
|
MACGGKRLLFLALAWVLLAHLCSQAEAASNYDCCLSYIQTPLPSRAIVGFTRQMADEACDINAIIFHTKKRKSVCADPKQNWVKRAVNLLSLRVKKM
| null | null |
calcium-mediated signaling using intracellular calcium source [GO:0035584]; cell chemotaxis [GO:0060326]; cellular response to interleukin-1 [GO:0071347]; cellular response to tumor necrosis factor [GO:0071356]; cellular response to type II interferon [GO:0071346]; chemokine-mediated signaling pathway [GO:0070098]; chemotaxis [GO:0006935]; G protein-coupled receptor signaling pathway [GO:0007186]; inflammatory response [GO:0006954]; lymphocyte chemotaxis [GO:0048247]; monocyte chemotaxis [GO:0002548]; neutrophil chemotaxis [GO:0030593]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of interleukin-1 alpha production [GO:0032730]; positive regulation of nitric-oxide synthase biosynthetic process [GO:0051770]; positive regulation of T cell migration [GO:2000406]; T cell migration [GO:0072678]; thymocyte migration [GO:0072679]
|
extracellular space [GO:0005615]
|
CCR chemokine receptor binding [GO:0048020]; CCR6 chemokine receptor binding [GO:0031731]; chemokine activity [GO:0008009]; cytokine activity [GO:0005125]
|
PF00048;
|
2.40.50.40;
|
Intercrine beta (chemokine CC) family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P78556}.
| null | null | null | null | null |
FUNCTION: Acts as a ligand for C-C chemokine receptor CCR6. Signals through binding and activation of CCR6 and induces a strong chemotactic response and mobilization of intracellular calcium ions (PubMed:20068036, PubMed:9862452). The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and autoimmune diseases (PubMed:21376174). CCL20 acts as a chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes (By similarity). Involved in the recruitment of both the pro-inflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation (PubMed:19050256). Required for optimal migration of thymic natural regulatory T cells (nTregs) and DN1 early thymocyte progenitor cells (PubMed:24638065). Positively regulates sperm motility and chemotaxis via its binding to CCR6 which triggers Ca2+ mobilization in the sperm which is important for its motility (PubMed:25122636). May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells (PubMed:10064080). {ECO:0000250|UniProtKB:P78556, ECO:0000269|PubMed:10064080, ECO:0000269|PubMed:19050256, ECO:0000269|PubMed:20068036, ECO:0000269|PubMed:24638065, ECO:0000269|PubMed:25122636, ECO:0000269|PubMed:9862452, ECO:0000303|PubMed:21376174}.
|
Mus musculus (Mouse)
|
O89094
|
CASPE_MOUSE
|
MESEMSDPQPLQEERYDMSGARLALTLCVTKAREGSEVDMEALERMFRYLKFESTMKRDPTAQQFLEELDEFQQTIDNWEEPVSCAFVVLMAHGEEGLLKGEDEKMVRLEDLFEVLNNKNCKALRGKPKVYIIQACRGEHRDPGEELRGNEELGGDEELGGDEVAVLKNNPQSIPTYTDTLHIYSTVEGYLSYRHDEKGSGFIQTLTDVFIHKKGSILELTEEITRLMANTEVMQEGKPRKVNPEVQSTLRKKLYLQ
|
3.4.22.-
| null |
cell differentiation [GO:0030154]; positive regulation of neuron apoptotic process [GO:0043525]; proteolysis [GO:0006508]
|
cornified envelope [GO:0001533]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; keratin filament [GO:0045095]; mitochondrion [GO:0005739]; nucleoplasm [GO:0005654]
|
cysteine-type endopeptidase activity [GO:0004197]; peptidase activity [GO:0008233]
|
PF00656;
|
3.40.50.1460;
|
Peptidase C14A family
|
PTM: Maturation by proteolytic processing appears to be a two-step process. The precursor is processed by KLK7 to yield the p20/p8 intermediate form which acts the precursor to yield the p17/p10 mature form (By similarity). Initially it was reported that cleavage by granzyme B, caspase-8 and -10 generates the two active subunits, however the physiological relevance has not been established (PubMed:9823333). {ECO:0000250|UniProtKB:P31944, ECO:0000305|PubMed:9823333}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11175259}. Nucleus {ECO:0000269|PubMed:11175259}.
| null | null | null | null | null |
FUNCTION: Non-apoptotic caspase which is involved in epidermal differentiation. Seems to play a role in keratinocyte differentiation and is required for cornification (PubMed:18156206). Regulates maturation of the epidermis by proteolytically processing filaggrin (PubMed:21654840). In vitro is equally active on the synthetic caspase substrates WEHD-ACF and IETD-AFC. Involved in processing of prosaposin in the epidermis (PubMed:24872419). May be involved in retinal pigment epithelium cell barrier function (By similarity). {ECO:0000250|UniProtKB:P31944, ECO:0000269|PubMed:11175259, ECO:0000269|PubMed:17515931, ECO:0000269|PubMed:18156206, ECO:0000269|PubMed:21654840, ECO:0000269|PubMed:24872419}.
|
Mus musculus (Mouse)
|
O89098
|
CYTF_MOUSE
|
MWLAILLALCCLTSDTHGARPPDFCSKDLISSVKPGFPKTIETNNPGVLKAARHSVEKFNNCTNDIFLFKESHVSKALVQVVKGLKYMLEVKIGRTTCRKTMHHQLDNCDFQTNPALKRTLYCYSEVWVIPWLHSFEVPVLLCQ
| null | null |
immune response [GO:0006955]; negative regulation of microglial cell activation [GO:1903979]; negative regulation of peptidase activity [GO:0010466]; positive regulation of myelination [GO:0031643]
|
cytoplasm [GO:0005737]; cytoplasmic vesicle [GO:0031410]; endoplasmic reticulum [GO:0005783]; extracellular space [GO:0005615]; Golgi apparatus [GO:0005794]; late endosome [GO:0005770]; lysosome [GO:0005764]; multivesicular body [GO:0005771]
|
cysteine-type endopeptidase inhibitor activity [GO:0004869]; peptidase inhibitor activity [GO:0030414]; protein homodimerization activity [GO:0042803]
|
PF00031;
|
3.10.450.10;
|
Cystatin family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Inhibits papain and cathepsin L but with affinities lower than other cystatins. May play a role in immune regulation through inhibition of a unique target in the hematopoietic system.
|
Mus musculus (Mouse)
|
O89100
|
GRAP2_MOUSE
|
MEATAKFDFMASGEDELSFRTGDILKILSNQEEWLKAELGSQEGYVPKNFIDIEFPEWFHEGLSRHQAENLLMGKDIGFFIIRASQSSPGDFSISVRHEDDVQHFKVMRDTKGNYFLWTEKFPSLNKLVDYYRTTSISKQKQVFLRDGTQDQGHRGNSLDRRSQGGPHPSGTVGEEIRPSVNRKLSDHLPLGPQQFHPHQQPSPQFTPGPQPPQQQRYLQHFHQDRRGGSLDINDGHCGLGSEVNATLMHRRHTDPVQLQAAGRVRWARALYDFEALEEDELGFRSGEVVEVLDSSNPSWWTGRLHNKLGLFPANYVAPMMR
| null | null |
regulation of MAPK cascade [GO:0043408]; signal transduction [GO:0007165]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; endosome [GO:0005768]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; plasma membrane [GO:0005886]
|
phosphotyrosine residue binding [GO:0001784]
|
PF00017;PF00018;
|
3.30.505.10;2.30.30.40;
|
GRB2/sem-5/DRK family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Endosome {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Interacts with SLP-76 to regulate NF-AT activation. Binds to tyrosine-phosphorylated shc.
|
Mus musculus (Mouse)
|
O89101
|
FGF18_MOUSE
|
MYSAPSACTCLCLHFLLLCFQVQVLAAEENVDFRIHVENQTRARDDVSRKQLRLYQLYSRTSGKHIQVLGRRISARGEDGDKYAQLLVETDTFGSQVRIKGKETEFYLCMNRKGKLVGKPDGTSKECVFIEKVLENNYTALMSAKYSGWYVGFTKKGRPRKGPKTRENQQDVHFMKRYPKGQAELQKPFKYTTVTKRSRRIRPTHPG
| null | null |
angiogenesis [GO:0001525]; animal organ morphogenesis [GO:0009887]; cell differentiation [GO:0030154]; cell population proliferation [GO:0008283]; chondrocyte development [GO:0002063]; chondrocyte differentiation [GO:0002062]; endochondral ossification [GO:0001958]; ERK1 and ERK2 cascade [GO:0070371]; fibroblast growth factor receptor signaling pathway [GO:0008543]; intramembranous ossification [GO:0001957]; lung development [GO:0030324]; nervous system development [GO:0007399]; ossification [GO:0001503]; positive regulation of angiogenesis [GO:0045766]; positive regulation of blood vessel endothelial cell migration [GO:0043536]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of chondrocyte differentiation [GO:0032332]; positive regulation of endothelial cell chemotaxis to fibroblast growth factor [GO:2000546]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of gene expression [GO:0010628]; positive regulation of hepatocyte proliferation [GO:2000347]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of vascular endothelial growth factor receptor signaling pathway [GO:0030949]; regulation of cell migration [GO:0030334]; signal transduction [GO:0007165]; vascular endothelial growth factor receptor signaling pathway [GO:0048010]
|
cytoplasm [GO:0005737]; extracellular space [GO:0005615]; nucleolus [GO:0005730]; nucleus [GO:0005634]
|
fibroblast growth factor receptor binding [GO:0005104]; growth factor activity [GO:0008083]; type 1 fibroblast growth factor receptor binding [GO:0005105]; type 2 fibroblast growth factor receptor binding [GO:0005111]
|
PF00167;
|
2.80.10.50;
|
Heparin-binding growth factors family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Plays an important role in the regulation of cell proliferation, cell differentiation and cell migration. Required for normal ossification and bone development. Stimulates hepatic and intestinal proliferation (By similarity). {ECO:0000250}.
|
Mus musculus (Mouse)
|
O89103
|
C1QR1_MOUSE
|
MAISTGLFLLLGLLGQPWAGAAADSQAVVCEGTACYTAHWGKLSAAEAQHRCNENGGNLATVKSEEEARHVQQALTQLLKTKAPLEAKMGKFWIGLQREKGNCTYHDLPMRGFSWVGGGEDTAYSNWYKASKSSCIFKRCVSLILDLSLTPHPSHLPKWHESPCGTPEAPGNSIEGFLCKFNFKGMCRPLALGGPGRVTYTTPFQATTSSLEAVPFASVANVACGDEAKSETHYFLCNEKTPGIFHWGSSGPLCVSPKFGCSFNNGGCQQDCFEGGDGSFRCGCRPGFRLLDDLVTCASRNPCSSNPCTGGGMCHSVPLSENYTCRCPSGYQLDSSQVHCVDIDECQDSPCAQDCVNTLGSFHCECWVGYQPSGPKEEACEDVDECAAANSPCAQGCINTDGSFYCSCKEGYIVSGEDSTQCEDIDECSDARGNPCDSLCFNTDGSFRCGCPPGWELAPNGVFCSRGTVFSELPARPPQKEDNDDRKESTMPPTEMPSSPSGSKDVSNRAQTTGLFVQSDIPTASVPLEIEIPSEVSDVWFELGTYLPTTSGHSKPTHEDSVSAHSDTDGQNLLLFYILGTVVAISLLLVLALGILIYHKRRAKKEEIKEKKPQNAADSYSWVPERAESQAPENQYSPTPGTDC
| null | null |
cell migration [GO:0016477]; cell-cell adhesion [GO:0098609]
|
cell surface [GO:0009986]; cytoplasmic vesicle [GO:0031410]; external side of plasma membrane [GO:0009897]; extracellular matrix [GO:0031012]; plasma membrane [GO:0005886]
|
calcium ion binding [GO:0005509]; carbohydrate binding [GO:0030246]; complement component C1q complex binding [GO:0001849]; extracellular matrix binding [GO:0050840]; extracellular matrix protein binding [GO:1990430]
|
PF12662;PF07645;PF00059;
|
2.10.25.10;3.10.100.10;
| null |
PTM: N- and O-glycosylated. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
| null | null | null | null | null |
FUNCTION: Receptor (or element of a larger receptor complex) for C1q, mannose-binding lectin (MBL2) and pulmonary surfactant protein A (SPA). May mediate the enhancement of phagocytosis in monocytes and macrophages upon interaction with soluble defense collagens. May play a role in intercellular adhesion. Marker for early multipotent hematopoietic precursor cells. May play a role in cell-cell interactions during hematopoietic and vascular development.
|
Mus musculus (Mouse)
|
O89106
|
FHIT_MOUSE
|
MSFRFGQHLIKPSVVFLKTELSFALVNRKPVVPGHVLVCPLRPVERFRDLHPDEVADLFQVTQRVGTVVEKHFQGTSITFSMQDGPEAGQTVKHVHVHVLPRKAGDFPRNDNIYDELQKHDREEEDSPAFWRSEKEMAAEAEALRVYFQA
|
2.7.7.51; 3.6.1.29; 3.6.2.1; 3.9.1.-
| null |
diadenosine triphosphate catabolic process [GO:0015964]; DNA replication [GO:0006260]; intrinsic apoptotic signaling pathway by p53 class mediator [GO:0072332]; negative regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032435]; purine nucleotide metabolic process [GO:0006163]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; mitochondrion [GO:0005739]; nucleus [GO:0005634]; plasma membrane [GO:0005886]
|
adenosine 5'-monophosphoramidase activity [GO:0043530]; adenylylsulfatase activity [GO:0047627]; adenylylsulfate-ammonia adenylyltransferase activity [GO:0047352]; bis(5'-adenosyl)-triphosphatase activity [GO:0047710]; nickel cation binding [GO:0016151]; nucleotide binding [GO:0000166]; ubiquitin protein ligase binding [GO:0031625]
|
PF01230;
|
3.30.428.10;
| null |
PTM: Phosphorylation at Tyr-114 by SRC is required for induction of apoptosis. {ECO:0000250|UniProtKB:P49789}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9699672}. Nucleus {ECO:0000250|UniProtKB:P49789}. Mitochondrion {ECO:0000250|UniProtKB:P49789}.
|
CATALYTIC ACTIVITY: Reaction=H2O + P(1),P(3)-bis(5'-adenosyl) triphosphate = ADP + AMP + 2 H(+); Xref=Rhea:RHEA:13893, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58529, ChEBI:CHEBI:456215, ChEBI:CHEBI:456216; EC=3.6.1.29; Evidence={ECO:0000250|UniProtKB:P49789}; CATALYTIC ACTIVITY: Reaction=adenosine 5'-phosphosulfate + H2O = AMP + 2 H(+) + sulfate; Xref=Rhea:RHEA:17041, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16189, ChEBI:CHEBI:58243, ChEBI:CHEBI:456215; EC=3.6.2.1; Evidence={ECO:0000250|UniProtKB:P49789}; CATALYTIC ACTIVITY: Reaction=adenosine 5'-phosphosulfate + NH4(+) = adenosine 5'-phosphoramidate + 2 H(+) + sulfate; Xref=Rhea:RHEA:19197, ChEBI:CHEBI:15378, ChEBI:CHEBI:16189, ChEBI:CHEBI:28938, ChEBI:CHEBI:57890, ChEBI:CHEBI:58243; EC=2.7.7.51; Evidence={ECO:0000250|UniProtKB:P49789}; CATALYTIC ACTIVITY: Reaction=adenosine 5'-phosphoramidate + H2O = AMP + NH4(+); Xref=Rhea:RHEA:67916, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:57890, ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:P49789};
| null | null | null | null |
FUNCTION: Possesses dinucleoside triphosphate hydrolase activity (By similarity). Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP (By similarity). Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP (By similarity). Exhibits adenylylsulfatase activity, hydrolyzing adenosine 5'-phosphosulfate to yield AMP and sulfate (By similarity). Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (By similarity). Exhibits adenylylsulfate-ammonia adenylyltransferase, catalyzing the ammonolysis of adenosine 5'-phosphosulfate resulting in the formation of adenosine 5'-phosphoramidate (By similarity). Also catalyzes the ammonolysis of adenosine 5-phosphorofluoridate and diadenosine triphosphate (By similarity). Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5 (By similarity). Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways (By similarity). Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis (By similarity). Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity (By similarity). Functions as a tumor suppressor (PubMed:10758156, PubMed:11517343). {ECO:0000250|UniProtKB:P49789, ECO:0000269|PubMed:10758156, ECO:0000269|PubMed:11517343}.
|
Mus musculus (Mouse)
|
O89107
|
DNSL3_RAT
|
MSLYPASPYLASLLLFILALHGALSLRLCSFNVRSFGESKKENHNAMDIIVKIIKRCDLILLMEIKDSNNNICPMLMEKLNGNSRRSTTYNYVISSRLGRNTYKEQYAFLYKEKLVSVKAKYLYHDYQDGDTDVFSREPFVVWFQAPFTAAKDFVIVPLHTTPETSVKEIDELADVYTDVRRRWKAENFIFMGDFNAGCSYVPKKAWKNIRLRTDPNFVWLIGDQEDTTVKKSTSCAYDRIVLRGQEIVNSVVPRSSGVFDFQKAYELSEEEALDVSDHFPVEFKLQSSRAFTNSRKSVSLKKKKKGSRS
|
3.1.21.-
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:9665719}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:9665719};
|
apoptotic DNA fragmentation [GO:0006309]; DNA catabolic process [GO:0006308]; neutrophil activation involved in immune response [GO:0002283]; programmed cell death involved in cell development [GO:0010623]; regulation of acute inflammatory response [GO:0002673]; regulation of neutrophil mediated cytotoxicity [GO:0070948]
|
endoplasmic reticulum [GO:0005783]; extracellular region [GO:0005576]; nucleus [GO:0005634]
|
deoxyribonuclease I activity [GO:0004530]; DNA binding [GO:0003677]; DNA endonuclease activity [GO:0004520]; endonuclease activity [GO:0004519]
|
PF03372;
|
3.60.10.10;
|
DNase I family
|
PTM: Seems to be synthesized as an inactive precursor protein and converted into an active mature enzyme by removal of the N-terminal precursor peptide during apoptosis.; PTM: Poly-ADP-ribosylated by PARP1. ADP-ribosylation negatively regulates enzymatic activity during apoptosis. {ECO:0000250|UniProtKB:Q13609}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9665719}. Secreted {ECO:0000250|UniProtKB:O55070, ECO:0000250|UniProtKB:Q13609}. Note=May first pass through the ER membrane before being imported in the nucleus. Contradictory reports exist about the subcellular localization under normal physiological conditions. Under conditions of cell death, may diffuse and/or be actively transported to the nucleus (By similarity). {ECO:0000250|UniProtKB:O55070, ECO:0000305}.
| null | null | null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.2. Active from pH 6.0 to 9.0. {ECO:0000269|PubMed:9665719};
| null |
FUNCTION: Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (PubMed:7957253). Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA. Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis. The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells. Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (By similarity). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (By similarity). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (By similarity). {ECO:0000250|UniProtKB:O55070, ECO:0000250|UniProtKB:Q13609, ECO:0000269|PubMed:7957253}.
|
Rattus norvegicus (Rat)
|
O89109
|
KCNN4_MOUSE
|
MGGELVTGLGALRRRKRLLEQEKRVAGWALVLAGTGIGLMVLHAEMLWFLGCKWVLYLLLVKCLITLSTAFLLCLIVVFHAKEVQLFMTDNGLRDWRVALTRRQVAQILLELLVCGVHPVPLRSPHCALAGEATDAQPWPGFLGEGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYRSIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLTDTLWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHNFMMDIHYAKEMKESAARLLQEAWMYYKHTRRKDSRAARRHQRKMLAAIHTFRQVRLKHRKLREQVNSMVDISKMHMILCDLQLGLSSSHRALEKRIDGLAGKLDALTELLGTALQQQQLPEPSQEAT
| null | null |
calcium ion transport [GO:0006816]; cardiac muscle hypertrophy [GO:0003300]; cell volume homeostasis [GO:0006884]; establishment of localization in cell [GO:0051649]; hepatocyte apoptotic process [GO:0097284]; monoatomic anion transport [GO:0006820]; mononuclear cell migration [GO:0071674]; negative regulation of cardiac muscle hypertrophy [GO:0010614]; negative regulation of cell volume [GO:0045794]; negative regulation of hepatic stellate cell proliferation [GO:1904898]; phospholipid translocation [GO:0045332]; positive regulation of G0 to G1 transition [GO:0070318]; positive regulation of microglial cell activation [GO:1903980]; positive regulation of p38MAPK cascade [GO:1900745]; positive regulation of protein secretion [GO:0050714]; positive regulation of smooth muscle cell proliferation [GO:0048661]; positive regulation of T cell receptor signaling pathway [GO:0050862]; potassium ion export across plasma membrane [GO:0097623]; potassium ion transmembrane transport [GO:0071805]; potassium ion transport [GO:0006813]; regulation of angiotensin levels in blood [GO:0002002]; regulation of monocyte chemotactic protein-1 production [GO:0071637]; regulation of renin secretion into blood stream [GO:1900133]; regulation of smooth muscle cell proliferation [GO:0048660]; regulation of tumor necrosis factor production [GO:0032680]; saliva secretion [GO:0046541]; stabilization of membrane potential [GO:0030322]; vascular associated smooth muscle cell migration [GO:1904738]
|
apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; cytosol [GO:0005829]; neuron projection [GO:0043005]; neuronal cell body [GO:0043025]; plasma membrane [GO:0005886]; vesicle [GO:0031982]
|
calcium-activated potassium channel activity [GO:0015269]; calmodulin binding [GO:0005516]; intermediate conductance calcium-activated potassium channel activity [GO:0022894]; inward rectifier potassium channel activity [GO:0005242]; potassium channel activity [GO:0005267]; protein phosphatase binding [GO:0019903]; small conductance calcium-activated potassium channel activity [GO:0016286]
|
PF02888;PF07885;PF03530;
|
1.10.287.70;
|
Potassium channel KCNN family, KCa3.1/KCNN4 subfamily
|
PTM: Phosphorylation at His-356 by NDKB activates the channel, and conversely it's dephosphorylation by PHPT1 inhibits the channel. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O15554}; Multi-pass membrane protein {ECO:0000250|UniProtKB:O15554}.
| null | null | null | null | null |
FUNCTION: Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:9705284). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells (PubMed:20884616). Plays a role in the late stages of EGF-induced macropinocytosis (By similarity). {ECO:0000250|UniProtKB:O15554, ECO:0000269|PubMed:20884616, ECO:0000269|PubMed:9705284}.
|
Mus musculus (Mouse)
|
O89110
|
CASP8_MOUSE
|
MDFQSCLYAIAEELGSEDLAALKFLCLDYIPHKKQETIEDAQKLFLRLREKGMLEEGNLSFLKELLFHISRWDLLVNFLDCNREEMVRELRDPDNAQISPYRVMLFKLSEEVSELELRSFKFLLNNEIPKCKLEDDLSLLEIFVEMEKRTMLAENNLETLKSICDQVNKSLLGKIEDYERSSTERRMSLEGREELPPSVLDEMSLKMAELCDSPREQDSESRTSDKVYQMKNKPRGYCLIINNHDFSKAREDITQLRKMKDRKGTDCDKEALSKTFKELHFEIVSYDDCTANEIHEILEGYQSADHKNKDCFICCILSHGDKGVVYGTDGKEASIYDLTSYFTGSKCPSLSGKPKIFFIQACQGSNFQKGVPDEAGFEQQNHTLEVDSSSHKNYIPDEADFLLGMATVKNCVSYRDPVNGTWYIQSLCQSLRERCPQGDDILSILTGVNYDVSNKDDRRNKGKQMPQPTFTLRKKLFFPP
|
3.4.22.61
| null |
angiogenesis [GO:0001525]; apoptotic process [GO:0006915]; apoptotic signaling pathway [GO:0097190]; cardiac muscle tissue development [GO:0048738]; execution phase of apoptosis [GO:0097194]; extrinsic apoptotic signaling pathway [GO:0097191]; extrinsic apoptotic signaling pathway via death domain receptors [GO:0008625]; heart development [GO:0007507]; hepatocyte apoptotic process [GO:0097284]; macrophage differentiation [GO:0030225]; necroptotic process [GO:0070266]; negative regulation of necroptotic process [GO:0060546]; neural tube formation [GO:0001841]; positive regulation of apoptotic process [GO:0043065]; positive regulation of execution phase of apoptosis [GO:1900119]; positive regulation of extrinsic apoptotic signaling pathway [GO:2001238]; positive regulation of neuron apoptotic process [GO:0043525]; protein processing [GO:0016485]; proteolysis involved in protein catabolic process [GO:0051603]; pyroptosis [GO:0070269]; regulation of apoptotic signaling pathway [GO:2001233]; regulation of cytokine production [GO:0001817]; regulation of innate immune response [GO:0045088]; regulation of thymocyte apoptotic process [GO:0070243]; response to ethanol [GO:0045471]; self proteolysis [GO:0097264]
|
CD95 death-inducing signaling complex [GO:0031265]; cell body [GO:0044297]; cytoplasm [GO:0005737]; death-inducing signaling complex [GO:0031264]; mitochondrion [GO:0005739]; Noc1p-Noc2p complex [GO:0030690]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; protein-containing complex [GO:0032991]; ripoptosome [GO:0097342]
|
cysteine-type endopeptidase activator activity involved in apoptotic process [GO:0008656]; cysteine-type endopeptidase activity [GO:0004197]; cysteine-type endopeptidase activity involved in apoptotic process [GO:0097153]; cysteine-type endopeptidase activity involved in apoptotic signaling pathway [GO:0097199]; death effector domain binding [GO:0035877]; death receptor binding [GO:0005123]; endopeptidase activity [GO:0004175]; peptidase activity [GO:0008233]; protein-containing complex binding [GO:0044877]; tumor necrosis factor receptor binding [GO:0005164]
|
PF01335;PF00656;
|
3.40.50.1460;1.10.533.10;
|
Peptidase C14A family
|
PTM: Generation of the subunits requires association with the death-inducing signaling complex (DISC), whereas additional processing is likely due to the autocatalytic activity of the activated protease (PubMed:31511692). GZMB and CASP10 can be involved in these processing events (By similarity). {ECO:0000250|UniProtKB:Q14790, ECO:0000269|PubMed:31511692}.; PTM: (Microbial infection) Proteolytically cleaved by the cowpox virus CRMA death inhibitory protein. {ECO:0000269|PubMed:9837723}.; PTM: Phosphorylation on Ser-389 during mitosis by CDK1 inhibits activation by proteolysis and prevents apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (By similarity). {ECO:0000250|UniProtKB:Q14790}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12065591}. Nucleus {ECO:0000269|PubMed:12065591}. Note=Translocates into the nucleus during apoptosis. {ECO:0000269|PubMed:12065591}.
|
CATALYTIC ACTIVITY: Reaction=Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala).; EC=3.4.22.61; Evidence={ECO:0000269|PubMed:12065591, ECO:0000269|PubMed:32971525, ECO:0000269|PubMed:9654089, ECO:0000269|PubMed:9837723};
| null | null | null | null |
FUNCTION: Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (PubMed:12065591, PubMed:18455983, PubMed:30361383, PubMed:30381458, PubMed:31511692, PubMed:31748744, PubMed:33397971). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated and TNFRSF1A-induced cell death (PubMed:24813849, PubMed:24813850, PubMed:9654089, PubMed:9837723). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (By similarity). Binding to the adapter molecule FADD recruits it to either receptor FAS/CD95 or TNFRSF1A (PubMed:29440439). The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (By similarity). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (By similarity). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (By similarity). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-325', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31511692). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-C and -D (GSDMC and GSDMD, respectively): gasdermin cleavage promotes release of the N-terminal moiety that binds to membranes and forms pores, triggering pyroptosis (PubMed:30361383, PubMed:30381458). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (PubMed:30361383, PubMed:30381458). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (PubMed:32971525). May participate in the Granzyme B (GZMB) cell death pathways (By similarity). Cleaves PARP1 and PARP2 (PubMed:12065591). {ECO:0000250|UniProtKB:Q14790, ECO:0000269|PubMed:12065591, ECO:0000269|PubMed:18455983, ECO:0000269|PubMed:24813849, ECO:0000269|PubMed:24813850, ECO:0000269|PubMed:29440439, ECO:0000269|PubMed:30361383, ECO:0000269|PubMed:30381458, ECO:0000269|PubMed:31511692, ECO:0000269|PubMed:31748744, ECO:0000269|PubMed:32971525, ECO:0000269|PubMed:33397971, ECO:0000269|PubMed:9654089, ECO:0000269|PubMed:9837723}.
|
Mus musculus (Mouse)
|
O89112
|
LANC1_MOUSE
|
MAQRAFPNPYADYNKSLAENYFDSTGRLTPEFSHRLTNKIRELLQQMERGLKSADPRDGTGYTGWAGIAVLYLHLHNVFGDPAYLQMAHSYVKQSLNCLSRRSITFLCGDAGPLAVAAVLYHKMNSEKQAEECITRLIHLNKIDPHVPNEMLYGRIGYIFALLFVNKNFGEEKIPQSHIQQICENILTSGENLSRKRNLAAKSPLMYEWYQEYYVGAAHGLAGIYYYLMQPSLQVNQGKLHSLVKPSVDFVCRLKFPSGNYPPCLDDTRDLLVHWCHGAPGVIYMLIQAYKVFKEERYLCDAQQCADVIWQYGLLKKGYGLCHGAAGNAYAFLALYNLTQDLKYLYRACKFAEWCLDYGEHGCRTADTPFSLFEGMAGTIYFLADLLVPTKAKFPAFEL
|
2.5.1.18
| null |
carbohydrate metabolic process [GO:0005975]; cellular detoxification [GO:1990748]; peptide modification [GO:0031179]
|
cytoplasm [GO:0005737]; plasma membrane [GO:0005886]
|
glutathione binding [GO:0043295]; glutathione transferase activity [GO:0004364]; low-density lipoprotein particle receptor binding [GO:0050750]; SH3 domain binding [GO:0017124]; zinc ion binding [GO:0008270]
|
PF05147;
|
1.50.10.10;
|
LanC-like protein family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O43813}. Cell membrane {ECO:0000250|UniProtKB:O43813}; Peripheral membrane protein {ECO:0000250|UniProtKB:O43813}.
|
CATALYTIC ACTIVITY: Reaction=glutathione + RX = a halide anion + an S-substituted glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378, ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925, ChEBI:CHEBI:90779; EC=2.5.1.18; Evidence={ECO:0000269|PubMed:25158856}; CATALYTIC ACTIVITY: Reaction=1-chloro-2,4-dinitrobenzene + glutathione = 2,4-dinitrophenyl-S-glutathione + chloride + H(+); Xref=Rhea:RHEA:51220, ChEBI:CHEBI:15378, ChEBI:CHEBI:17996, ChEBI:CHEBI:34718, ChEBI:CHEBI:57925, ChEBI:CHEBI:133977; EC=2.5.1.18; Evidence={ECO:0000269|PubMed:25158856};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.93 mM for 1-chloro-2,4-dinitrobenzene {ECO:0000269|PubMed:25158856}; Vmax=1087 nmol/min/mg enzyme {ECO:0000269|PubMed:25158856};
| null | null | null |
FUNCTION: Functions as a glutathione transferase (PubMed:25158856). Catalyzes conjugation of the glutathione (GSH) to artificial substrates 1-chloro-2,4-dinitrobenzene (CDNB) and p-nitrophenyl acetate (PubMed:25158856). Mitigates neuronal oxidative stress during normal postnatal development and in response to oxidative stresses probably through GSH antioxidant defense mechanism (PubMed:25158856). May play a role in EPS8 signaling. Binds glutathione (By similarity). {ECO:0000250|UniProtKB:O43813, ECO:0000269|PubMed:25158856}.
|
Mus musculus (Mouse)
|
O89116
|
VTI1A_MOUSE
|
MSSDFEGYEQDFAVLTAEITSKIARVPRLPPDEKKQMVANVEKQLEEARELLEQMDLEVREIPPQSRGMYSNRMRSYKQEMGKLETDFKRSRIAYSDEVRNELLGDAGNSSENQRAHLLDNTERLERSSRRLEAGYQIAVETEQIGQEMLENLSHDREKIQRARDRLRDADANLGKSSRILTGMLRRIIQNRILLVILGIIVVIAILTAIAFFVKGH
| null | null |
endoplasmic reticulum to Golgi vesicle-mediated transport [GO:0006888]; Golgi to vacuole transport [GO:0006896]; intra-Golgi vesicle-mediated transport [GO:0006891]; intracellular protein transport [GO:0006886]; macroautophagy [GO:0016236]; retrograde transport, endosome to Golgi [GO:0042147]; synaptic vesicle to endosome fusion [GO:0016189]; vesicle fusion with Golgi apparatus [GO:0048280]
|
clathrin-coated vesicle [GO:0030136]; cytosol [GO:0005829]; endoplasmic reticulum membrane [GO:0005789]; endosome [GO:0005768]; ER to Golgi transport vesicle membrane [GO:0012507]; Golgi apparatus [GO:0005794]; Golgi membrane [GO:0000139]; hippocampal mossy fiber to CA3 synapse [GO:0098686]; late endosome membrane [GO:0031902]; neuron projection terminus [GO:0044306]; neuronal cell body [GO:0043025]; perinuclear region of cytoplasm [GO:0048471]; SNARE complex [GO:0031201]; synaptic vesicle [GO:0008021]
|
SNAP receptor activity [GO:0005484]; SNARE binding [GO:0000149]
|
PF05008;PF12352;
|
1.20.5.110;1.20.58.400;
|
VTI1 family
| null |
SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-pass type IV membrane protein {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: V-SNARE that mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane. These interactions are proposed to mediate aspects of the specificity of vesicle trafficking and to promote fusion of the lipid bilayers. Involved in vesicular transport from the late endosomes to the trans-Golgi network. Along with VAMP7, involved in an non-conventional RAB1-dependent traffic route to the cell surface used by KCNIP1 and KCND2. May be concerned with increased secretion of cytokines associated with cellular senescence. {ECO:0000269|PubMed:19138172}.
|
Mus musculus (Mouse)
|
O89290
|
POL_HV193
|
MGARASVLSGGKLDAWEKIRLRPGGKKKYRLKHLVWASRELERFALDPGLLETSEGCRKIIGQLQPSLQTGSEELKSLYNTIAVLYYVHQKVEVKDTKEALEKLEEEQNKGRQKTQQATAEKGVSQNYPIVQNLQGQMVHQSLSPRTLNAWVKVIEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKDTINEEAAEWDRLHPTQAGPIPPGQIREPRGSDIAGTTSTLQEQIQWMTGNPPVPVGEMYKRWIILGLNKIVRMYSPVGILDIRQGPKEPFRDYVDRFFKTLRAEQATQEVKGWMTDTLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPSHKARVLAEAMSQATNTAIMMQKSNFKGQRRIVKCFNCGKEGHIAKNCRAPRKKGCWKCGREGHQMKDCTERQAKFFRENLAFQQGEARKLHPEQARAVSPASRELQVRGGDNPISEAGAERRGTVPSLSFPQITLWQRPLVTIRVGGQLKEALLDTGADDTVLEDVNLPGKWKPKMIGGIGGFIKVKQYDSILIEICGHRAIGTVLVGPTPVNIIGRNMLTQIGCTLHFPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALTEICMEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDKDFRKYTASTIPSTNNETPGVRYQYNVLPQGWKGSPAIFQYSMTKILDPFRAKNPDIVIYQYMDDLYVGSDLEIGQHRTKIEELREHLLKWGLTTPDKKHQKEPPFLWMGYELHPDKWTVQPIQLPDKDSWTVNDIQKLVGKLNWASQIYPGIKVKQLCKLLRGAKALTDIVPLTTEAELELAENREILKEPVHGAYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYAKMRSAHTNDVKQLTEAVQKISLESIVIWGKTPKFRLPILKETWDTWWTEYWQATWIPEWEFVNTPPLVKLWYQLETEPIVGAETFYVDGASNRETKKGKAGYVTDRGRQKAVSLTETTNQKAELQAIQLALQDSGSEVNIVTDSQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLSWVPAHKGIGGNEQVDKLVSAGIRKVLFLDGIDKAQEEHEKYHNNWRAMASDFNIPAVVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKIILVAVHVASGYLEAEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGTNFTSATVKAACWWAGIQQEFGIPYNPQSQGVVESMNKELKKIIGQIRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERTIDIIATDIQTRELQKQIIKIQNFRVYYRDSRDPVWKGPAKLLWKGEGAVVIQDNSEIKVVPRRKAKIIRDYGKQMAGDDCVAGRQDED
|
2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.13.2; 3.1.26.13; 3.4.23.16
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
|
DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral genome integration into host DNA [GO:0044826]; viral penetration into host nucleus [GO:0075732]
|
host cell [GO:0043657]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; exoribonuclease H activity [GO:0004533]; lipid binding [GO:0008289]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF19317;PF00552;PF02022;PF00075;PF00665;PF00077;PF00078;PF06815;PF06817;PF00098;
|
1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;1.20.5.760;4.10.60.10;
| null |
PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12497}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.; EC=3.4.23.16; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275}; CATALYTIC ACTIVITY: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
| null | null | null | null |
FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation. {ECO:0000250}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. Also mediates cleavage of host YTHDF3. Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250|UniProtKB:P04585}.
|
Human immunodeficiency virus type 1 group M subtype F1 (isolate 93BR020) (HIV-1)
|
O89291
|
GAG_HV193
|
MGARASVLSGGKLDAWEKIRLRPGGKKKYRLKHLVWASRELERFALDPGLLETSEGCRKIIGQLQPSLQTGSEELKSLYNTIAVLYYVHQKVEVKDTKEALEKLEEEQNKGRQKTQQATAEKGVSQNYPIVQNLQGQMVHQSLSPRTLNAWVKVIEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKDTINEEAAEWDRLHPTQAGPIPPGQIREPRGSDIAGTTSTLQEQIQWMTGNPPVPVGEMYKRWIILGLNKIVRMYSPVGILDIRQGPKEPFRDYVDRFFKTLRAEQATQEVKGWMTDTLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPSHKARVLAEAMSQATNTAIMMQKSNFKGQRRIVKCFNCGKEGHIAKNCRAPRKKGCWKCGREGHQMKDCTERQANFLGKIWPSNKGRPGNFIQNRPEPSAPPAESFRFGEETTPSPKQEQKDEGLYPPLASLKSLFGNDP
| null | null |
viral budding via host ESCRT complex [GO:0039702]
|
host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
RNA binding [GO:0003723]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF00607;PF19317;PF08705;PF00098;
|
1.10.1200.30;6.10.250.390;1.10.375.10;1.10.150.90;1.20.5.760;4.10.60.10;
|
Primate lentivirus group gag polyprotein family
|
PTM: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000250|UniProtKB:P12493}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04591}.; PTM: Capsid protein p24 is phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: Nucleocapsid protein p7 is methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag polyprotein]: Host cell membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P12493}. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000250|UniProtKB:P12493}.
| null | null | null | null | null |
FUNCTION: [Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). The capsid promotes immune invasion by cloaking viral DNA from CGAS detection (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid (By similarity). {ECO:0000250|UniProtKB:P04591, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000250|UniProtKB:P12493}.
|
Human immunodeficiency virus type 1 group M subtype F1 (isolate 93BR020) (HIV-1)
|
O89292
|
ENV_HV193
|
MRVRGMQRNWQHLGKWGLLFLGTLIICNAAENLWVTVYYGVPVWKEATTTLFCASDAKSYEKEAHNVWATHACVPTDPNPQEVVLENVTERFNMWENNMVEQMHTDIISLWDQSLKPCVKLTPLCVTLDCRNIATNGTNDTIAINDTLKEDPEAIQNCSFNTTTEIRDKQLKVHALFYKLDIVQINKDDNRTYRLINCDASTITQACPKVSWDPIPIHYCAPAGYAILKCNEKNFTGTGSCKNVSTVQCTHGIKPVVSTQLLLNGSLAEGEIVIRSQNISDNAKTIIVHLNESVQINCTRPNNNTRKRISLGPGRVFYTTGEIIGDIRKAHCNVSGTQWRNTLAKVKAKLGSYFPNATIKFNSSSGGDLEITRHNFNCMGEFFYCNTDELFNDTKFNDTGFNGTITLPCRIKQIVNMWQEVGRAMYANPIAGNITCNSNITGLLLTRDGGLNSTNETFRPGGGNMKDNWRSELYKYKVVEIEPLGVAPTKAKRQVVKRERRAVGLGALFLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAIEAQQHLLQLTVWGIKQLQARVLAVERYLKDQQLLGLWGCSGKLICTTNVPWNSSWSNKSLEEIWGNMTWMEWEKEVSNYSKEIYRLIEDSQNQQEKNEQELLALDKWASLWNWFDITQWLWYIKIFIMIVGGLIGLRIVFTVLSIVNRVRKGYSPLSFQTHIPSPREPDRPEGIEEGGGEQGKDRSVRLVTGFLALAWDDLRNLCLFSYRHLRDFILIAARIVDRGLKRGWEALKYLGNLTQYWGQELKNSAISLLNATAIAVAEWTDRVIEALQRAGRAILNIPRRIRQGLERALL
| null | null |
clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of establishment of T cell polarity [GO:1903905]; positive regulation of plasma membrane raft polarization [GO:1903908]; positive regulation of receptor clustering [GO:1903911]; viral protein processing [GO:0019082]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
structural molecule activity [GO:0005198]
|
PF00516;PF00517;
|
1.10.287.210;2.170.40.20;1.20.5.490;
|
HIV-1 env protein family
|
PTM: Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.; SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.
| null | null | null | null | null |
FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Surface protein gp120]: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
Human immunodeficiency virus type 1 group M subtype F1 (isolate 93BR020) (HIV-1)
|
O89293
|
NEF_HV193
|
MGGKWSKSSIVGWPAIRERMRRTPPTPPAAEGVGAVSQDLERRGAITSSNTRANNPDLAWLEAQEEDEVGFPVRPQVPLRPMTYKGAVDLSHFLKEKGGLEGLIYSKRRQEILDLWVYHTQGYFPDWQNYTPGPGIRYPLTMGWCFKLVPVDPEEVEKANEGENNCLLHPMSQHGMEDEDKEVLKWEFDSRLALRHIARERHPEYYQD
| null | null |
suppression by virus of host autophagy [GO:0039521]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I [GO:0046776]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class II [GO:0039505]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell Golgi membrane [GO:0044178]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; virion component [GO:0044423]
|
GTP binding [GO:0005525]; SH3 domain binding [GO:0017124]
|
PF00469;
|
4.10.890.10;3.30.62.10;
|
Lentivirus primate group Nef protein family
|
PTM: The virion-associated Nef proteins are cleaved by the viral protease to release the soluble C-terminal core protein. Nef is probably cleaved concomitantly with viral structural proteins on maturation of virus particles. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Phosphorylated on serine residues, probably by host PKCdelta and theta. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
SUBCELLULAR LOCATION: Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04078}; Lipid-anchor {ECO:0000255|HAMAP-Rule:MF_04078}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_04078}. Virion {ECO:0000255|HAMAP-Rule:MF_04078}. Secreted {ECO:0000255|HAMAP-Rule:MF_04078}. Host Golgi apparatus membrane {ECO:0000255|HAMAP-Rule:MF_04078}. Note=TGN localization requires PACS1. Associates with the inner plasma membrane through its N-terminal domain. Nef stimulates its own export via the release of exosomes. Incorporated in virions at a rate of about 10 molecules per virion, where it is cleaved. {ECO:0000255|HAMAP-Rule:MF_04078}.
| null | null | null | null | null |
FUNCTION: Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection). Down-regulates host SERINC3 and SERINC5 thereby excluding these proteins from the viral particles. Virion infectivity is drastically higher when SERINC3 or SERINC5 are excluded from the viral envelope, because these host antiviral proteins impair the membrane fusion event necessary for subsequent virion penetration. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life of TP53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of host BAD. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
Human immunodeficiency virus type 1 group M subtype F1 (isolate 93BR020) (HIV-1)
|
O89939
|
GAG_HV1SE
|
MGARASVLTGGKLDAWEKIRLRPGGRKSYKIKHLVWASRELERFALNPDLLETAEGCQQIMRQLQPSLQTGTEEIKSLYNAVATLYCVHQRIEVKDTKEALEEVEKIQKKSQEKIQQAAMDKGNSNQVSQNYPIVQNAQGQMVHQAITPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNLMLNTVGGHQAAMQMLKDTINEEAAEWDRMHPQQAGPFPPGQIREPRGSDIAGTTSSLQEQITWMTGNPPIPVGEIYKRWIILGLNKIVRMYSPVSILDIRQGPKEPFRDYVDRFFKCLRAEQASQDVKGWMTDTLLVQNANPDCKTILRALGQGASLEEMMTACQGVGGPSHKARVLAEAMSQASGAAAAIMMQRSNFKGPRRTIKCFNCGKEGHLARNCRAPRKKGCWKCGKEGHQMKDCTERQANFLGKIWPSNKGRPGNFLQNRTEPTAPPAESLGFGEEIAPSPKQEMKEKELYPSLKSLFGSDP
| null | null |
viral budding via host ESCRT complex [GO:0039702]
|
host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
RNA binding [GO:0003723]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF19317;PF08705;PF00098;
|
1.10.1200.30;6.10.250.390;1.10.375.10;1.10.150.90;1.20.5.760;4.10.60.10;
|
Primate lentivirus group gag polyprotein family
|
PTM: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000250|UniProtKB:P12493}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04591}.; PTM: Capsid protein p24 is phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: Nucleocapsid protein p7 is methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag polyprotein]: Host cell membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P12493}. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000250|UniProtKB:P12493}.
| null | null | null | null | null |
FUNCTION: [Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). The capsid promotes immune invasion by cloaking viral DNA from CGAS detection (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid (By similarity). {ECO:0000250|UniProtKB:P04591, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000250|UniProtKB:P12493}.
|
Human immunodeficiency virus type 1 group M subtype G (isolate SE6165) (HIV-1)
|
O89940
|
POL_HV1SE
|
MGARASVLTGGKLDAWEKIRLRPGGRKSYKIKHLVWASRELERFALNPDLLETAEGCQQIMRQLQPSLQTGTEEIKSLYNAVATLYCVHQRIEVKDTKEALEEVEKIQKKSQEKIQQAAMDKGNSNQVSQNYPIVQNAQGQMVHQAITPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNLMLNTVGGHQAAMQMLKDTINEEAAEWDRMHPQQAGPFPPGQIREPRGSDIAGTTSSLQEQITWMTGNPPIPVGEIYKRWIILGLNKIVRMYSPVSILDIRQGPKEPFRDYVDRFFKCLRAEQASQDVKGWMTDTLLVQNANPDCKTILRALGQGASLEEMMTACQGVGGPSHKARVLAEAMSQASGAAAAIMMQRSNFKGPRRTIKCFNCGKEGHLARNCRAPRKKGCWKCGKEGHQMKDCTERQANFFRENLAFQQGEAREFSSEQDRTNSPTCRKPRVRRGDSPLPEAGDEGKGAISLPQITLWQRPLVTVKIGGQLIEALLDTGADDTVLEEINLPGRWKPKMIGGIGGFIKVRQYDQVPIEISGKKAIGTILVGPTPINIIGRNMLTQIGCTLNFPISPIETVPVKLKPGMDGPRVKQWPLTEEKIKALTEICKEMEEEGKISKIGPENPYNTPIFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGVRYQYNVLPQGWKGSPAIFQSSMTRILEPFRANNPEMVIYQYMDDLYVGSDLEIGQHRAKIEELREHLLKWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQPIQLPDKESWTVNDIQKLVGKLNWASQIYPGIKVTHLCKLLRGAKALTDIVSLTAEAEMELAENREILREPVHGVYYDPSKELIAEVQKQGLDQWTYQIYQEPYKNLKTGKYAKRGSAHTNDVKQLTEVVQKIATESIVIWGKTPKFKLPIRKETWEIWWTDYWQATWIPEWEFVNTPPLVKLWYRLETEPIPGAETYYVDGAANRETKLGKAGYVTDKGKQKIITLTETTNQKAELQAIQLALQDSRSEVNIVTDSQYALGIIQAQPDRSEAELVNQIIEQLIKKEKVYLSWVPAHKGIGGNEQVDKLVSSGIRKVLFLDGIDKAQEEHERYHNNWRAMASDFNLPPIVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGKIIIVAVHVASGYIEAEVIPAETGQETAYFILKLAGRWPVTVIHTDNGSNFTSAAVKAACWWANITQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIIDIIASDIQTKELQKQITKIQNFRVYYRDSRDPVWKGPAKLLWKGEGAVVIQDNNEIKVVPRRKAKIIRDYGKQMAGDDCVAGRQDED
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2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.13.2; 3.1.26.13; 3.4.23.16
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COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
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DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral genome integration into host DNA [GO:0044826]; viral penetration into host nucleus [GO:0075732]
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host cell [GO:0043657]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; exoribonuclease H activity [GO:0004533]; lipid binding [GO:0008289]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF00540;PF19317;PF00552;PF02022;PF00075;PF00665;PF00077;PF00078;PF06815;PF06817;PF00098;
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1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;1.20.5.760;4.10.60.10;
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PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
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SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12497}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
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CATALYTIC ACTIVITY: Reaction=Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.; EC=3.4.23.16; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275}; CATALYTIC ACTIVITY: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
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FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation. {ECO:0000250}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. Also mediates cleavage of host YTHDF3. Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250|UniProtKB:P04585}.
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Human immunodeficiency virus type 1 group M subtype G (isolate SE6165) (HIV-1)
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O89943
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TAT_HV1SE
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MDPVDPNLEPWNHPGSQPKTPCNKCFCKVCCWHCQVCFLNKGLGISYGRKKRKHRRGTPQSSKGHQDPVPKQPLPTTRGNPTGPKESKKEVASKAEADQCD
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DNA-templated transcription [GO:0006351]; modulation by virus of host chromatin organization [GO:0039525]; negative regulation of peptidyl-threonine phosphorylation [GO:0010801]; positive regulation of transcription elongation by RNA polymerase II [GO:0032968]; positive regulation of viral transcription [GO:0050434]; symbiont-mediated suppression of host translation initiation [GO:0039606]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; virus-mediated perturbation of host defense response [GO:0019049]
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extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]
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actinin binding [GO:0042805]; cyclin binding [GO:0030332]; metal ion binding [GO:0046872]; protein domain specific binding [GO:0019904]; protein serine/threonine phosphatase inhibitor activity [GO:0004865]; RNA-binding transcription regulator activity [GO:0001070]; trans-activation response element binding [GO:1990970]
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PF00539;
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4.10.20.10;
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Lentiviruses Tat family
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PTM: Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-Rule:MF_04079}.
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SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04079}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04079}. Secreted {ECO:0000255|HAMAP-Rule:MF_04079}. Note=Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occurs through a Golgi-independent pathway. Tat is released from infected cells to the extracellular space where it remains associated to the cell membrane, or is secreted into the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed by surrounding uninfected cells via binding to several receptors depending on the cell type. {ECO:0000255|HAMAP-Rule:MF_04079}.
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FUNCTION: Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR) and recruits the cyclin T1-CDK9 complex (P-TEFb complex) that will in turn hyperphosphorylate the RNA polymerase II to allow efficient elongation. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B by interacting with host RELA. Through its interaction with host TBP, Tat may also modulate transcription initiation. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-Rule:MF_04079}.; FUNCTION: Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. {ECO:0000255|HAMAP-Rule:MF_04079}.
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Human immunodeficiency virus type 1 group M subtype G (isolate SE6165) (HIV-1)
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O89945
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NEF_HV1SE
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MGGKWSKSSIVGWPEVRERIRNTPTAAEGVGAVSQDLDRHGAITSSNTAANNPDCAWLEAQEEDSEVGFPVRPQVPLRPMTFKGAFDLSFFLKEKGGLDGLIYSKKRQEILDLWVYNTQGYFPDWQNYTPGPGTRFPLTFGWCFKLVPMDPAEVEEANKGENNSLLHPICQHGMEDEDREVLVWRFDSSLARRHIARELHPEYYKDC
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suppression by virus of host autophagy [GO:0039521]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I [GO:0046776]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class II [GO:0039505]; virus-mediated perturbation of host defense response [GO:0019049]
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extracellular region [GO:0005576]; host cell Golgi membrane [GO:0044178]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; virion component [GO:0044423]
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GTP binding [GO:0005525]; SH3 domain binding [GO:0017124]
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PF00469;
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4.10.890.10;3.30.62.10;
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Lentivirus primate group Nef protein family
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PTM: The virion-associated Nef proteins are cleaved by the viral protease to release the soluble C-terminal core protein. Nef is probably cleaved concomitantly with viral structural proteins on maturation of virus particles. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Phosphorylated on serine residues, probably by host PKCdelta and theta. {ECO:0000255|HAMAP-Rule:MF_04078}.
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SUBCELLULAR LOCATION: Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04078}; Lipid-anchor {ECO:0000255|HAMAP-Rule:MF_04078}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_04078}. Virion {ECO:0000255|HAMAP-Rule:MF_04078}. Secreted {ECO:0000255|HAMAP-Rule:MF_04078}. Host Golgi apparatus membrane {ECO:0000255|HAMAP-Rule:MF_04078}. Note=TGN localization requires PACS1. Associates with the inner plasma membrane through its N-terminal domain. Nef stimulates its own export via the release of exosomes. Incorporated in virions at a rate of about 10 molecules per virion, where it is cleaved. {ECO:0000255|HAMAP-Rule:MF_04078}.
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FUNCTION: Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection). Down-regulates host SERINC3 and SERINC5 thereby excluding these proteins from the viral particles. Virion infectivity is drastically higher when SERINC3 or SERINC5 are excluded from the viral envelope, because these host antiviral proteins impair the membrane fusion event necessary for subsequent virion penetration. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life of TP53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of host BAD. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078}.
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Human immunodeficiency virus type 1 group M subtype G (isolate SE6165) (HIV-1)
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O90304
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SPIKE_BRV1
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MFLCFCTAPILCLWINSGGAVVVSNESLVVCEPVSYPYSLQVLRSFSQRVNLRTKRAVTTDAWSFAYQISTSSLNVNGWYVNFTSPLGWSYPNGKLFGIVLGSDAMMRASVSTFTYDVISYVGQRPNLDCQINDLANGGLESRYSTVRVDNCGNYPCHGGGKPGCSIGHPYMANGVRTRVLLTTQSPGIQYEIYSGQDYAVYQITPYTQYTVTMPSGTSGYCQQTPLYVECGSWTPYRVHAYGCDKATQSCNYTISSDWVVAFKSKASAIILRSQLIVALAQKLSRTVGVNKAVYFWFLKQPYHYLSLVNFSPNYALFSPLCKSLRQQSATYSALSYGSPFFVAQECYNNALYLPDCCLYTLFSILFSWDYQVNYPVNNVLQANETFLQLPTTGYLGQTVSQGRMLNLFKDAIVFLDFYDTKFYRTNDGPGGDIFAVVVKQVPVIAYSAFRIEQQTGYLAVKCNGVIQATLAPHSSRVVLLARHMSMWSIAAANSTTIYCPIYTLTSFVRLDISTSWYFHTLAQPSGPIQQVSMPVLSTGAAGVYMHPMIEHWVTLLAQSSVYQPSMFNMGVNKSVTLTTQLQAYAQVYTAWFLSILYTRLPESRRLTLGAQLTPFIQALLSFKQADIDATDVDTVARYNVLILMWGRKYAAVIYNQLPEWSYPLFKGGVGDSMWFRKKFLVTTKIHQTASHFPFIAGYLDFLDYKYIPKYKDVACPLSTMVPSILQVYETPQLFVIIVQCVSTTYSWYPGLRNPHTIYRSYKLGTICVLVPYSSPTDVYSSFGFFFQSALTIPTVQTTDDILPGCVGFVQDSVFTPCHPSGCPVRNSYDNYIICPGSSASNYTLRNYYRTTTPVTNVPIEEVPLQLEIPTVSLTSYELKQSESVLLQDIEGGIVVDHNTGSIWYPGGQAYDVSFYVSVIIRYAPPKLELPSTLANFTSCLDYICFGNQQCRGEAQTFCTSMDYFEQVFNKSLTSLITALQDLHYVLKLVLPETTLELTEDTRRRRRAVDEFSDTISLLSESFERFMSPASQAYMANMMWWDEAFDGISLPQRTGSILSSAPSLSSISSWHSYSSRTPLISNVKTPKTTFNVKLSMPKLPKASTLSTIGSVLSSGLSIASLGLSIFSIIEDRRVIELTQQQIMALEDQITILAGYTTKNFEEIQSSLNTLGQQVQDFSQTSALSLQQLSNGFEQITQQLDKSIYYVMAVQQYATYMSSLVNQLNELSQAVYKTQDMYITCIHSLQSGVLSPNCITPFQICHLYQVAKNLSSGECQPILSEREISRFYSLPLVTDAMVHNDTYWFSWSIPITCSNILGSVYKVQPGYIVNPHHPTSLQYDVPTHVVTSNAGALIFDEHYCDRYNQVYLCTKSAFDLAEASYLTMLYSNQTDNSSLTFHPAPRPDPCVYLSASALYCYYSDECHQCVIAVGNCTNRTVTYENYTYPIMDPQCRGFDQITISSPIAIGADFTALPSRPPLPLHLSYVNVTFNVTLPNELNWTDLVLDYSFKDKVYEISKNITQLHEQILQVSNWASGWFQRLRDFLYGLIPAWITWLTLGFSLFSILISGVNIILFFEMNGKVKKS
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membrane fusion involved in viral entry into host cell [GO:0039663]; symbiont entry into host cell [GO:0046718]; virion attachment to host cell [GO:0019062]
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membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
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PF17072;
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Torovirinae spike protein family
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SUBCELLULAR LOCATION: Virion membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.
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FUNCTION: Mediates the binding of virions to the host cell receptor and is involved in membrane fusion. {ECO:0000250}.
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Breda virus 1 (BRV-1)
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O90368
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POLN_ONNVS
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MDSVYVDIDADSAFLKALQRAYPMFEVEPKQVTPNDHANARAFSHLAIKLIEQEIDPDSTILDIGPAPARRMMSDRKYHCVCPMRSAEDPERLANYARKLASAAGKVTDKNISGKINDLQAVMAVPNMETSTFCLHTDATCKQRGDVAIYQDVYAVHAPTSLYHQAIKGVRVAYWIGFDTTPFMYNAMAGAYPSYSTNWADEQVLKAKNIGLCSTDLSEGRRGKLSIMRGKKLKPCDRVLFSVGSTLYPESRKLLQSWHLPSVFHLKGKLSFTCRCDTIVSCEGYVVKRVTMSPGIYGKTSGYAVTHHADGFLMCKTTDTVDGERVSFSVCTYVPATICDQMTGILATEVTPEDAQKLLVGLNQRIVVNGRTQRNTNTMKNYLLPIVAQAFSKWAKECRKDMEDEKLLGVRERTLTCCCLWAFRKHKTHTVYKRPDTQSIQKVPAEFDSFVIPSLWSSGLSIPLRTRIKWLLSKAPKHEQLPHSGNAEEAAQAEMDAAEEREAELTREAMPPLQATQDDVQVEIDVEQLEDRAGAGIVETPRGAIKVTAQPSDRVVGEYLVLTPQAVLRSQKLSLIHALAEQVKTCTHSGRAGRYAVEAYDGRVLVPSGYAIPQEDFQSLSESATMVFNEREFVNRKLHHIAMHGPALNTDEESYELVRVEKTEHEYVYDVDQKKCCKREEATGLVLVGDLTSPPYHEFAYEGLKIRPACPYKTAVIGVFGVPGSGKSAIIKNLVTRQDLVTSGKKENCQEISNDVMRQRKLEISARTVDSLLLNGCNKPVEVLYVDEAFACHSGTLLALIAMVRPRQKVVLCGDPKQCGFFNMMQMKVNYNHNICTQVYHKSISRRCTLPVTAIVSSLHYESKMRTTNEYNQPIVVDTTGITKPEPGDLVLTCFRGWVKQLQIDYRGNEVMTAAASQGLTRKGVYAVRQKVNENPLYASTSEHVNVLLTRTEGKLIWKTLSGDPWIKILQNPPKGNFKATIKEWEAEHASIMAGICNHQMAFDTFQNKANVCWAKCLVPILDTAGIKLSDRQWSQIVQAFKEDRAYSPEVALNEICTRIYGVDLDSGLFSKPLISVYYADNHWDNRPGGKMFGFNPEVALMLEKKYPFTKGKWNINKQICITTRKVDEFNPETNIIPANRRLPHSLVAEHHTVRGERMEWLVNKINGHHMLLVSGYNLILPTKRVTWVAPLGTRGADYTYNLELGLPATLGRYDLVVINIHTPFRIHHYQQCVDHAMKLQMLGGDSLRLLKPGGSLLIRAYGYADRTSERVISVLGRKFRSSRALKPQCITSNTEMFFLFSRFDNGRRNFTTHVMNNQLNAVYAGLATRAGCAPSYRVKRMDIAKNTEECVVNAANPRGVPGDGVCKAVYRKWPESFRNSATPVGTAKTIMCGQYPVIHAVGPNFSNYSEAEGDRELASVYREVAKEVSRLGVSSVAIPLLSTGVYSGGKDRLLQSLNHLFTAMDSTDADVVIYCRDKEWEKKITEAISLRSQVELLDDHISVDCDIVRVHPDSSLAGRKGYSTVEGALYSYLEGTRFHQTAVDMAEIYTMWPKQTEANEQVCLYALGESIESVRQKCPVDDADASFPPKTVPCLCRYAMTPERVARLRMNHTTSIIVCSSFPLPKYKIEGVQKVKCSKALLFDHNVPSRVSPRTYRPADEIIQTPQIPTEACQDAQFVQSITDEAVPVPSDLEACDATMDWPSIDIVPTRQRSDSFDSEYSSRSNIQLVTADVHAPMYANSLASSGGSVLSLSSEQAQNGIMILPDSEDTDSISRVSTPIAPPRRRLGRTINVTCDEREGKILPMASDRLFTAKPYTVALGVSTADITAYPIQAPLGSTQPPALEQITFGDFAEGEIDNLLTGALTFGDFEPGEVEELTDSEWSTCSDTDEELXLDRAGGYIFSSDTGQGHLQQKSVRQTTLPVNIVEEVHEEKCYPPKLDEIKEQLLLKRLQESASTANRSRYQSRKVENMKATIIHRLKEGCRLYLASDTPRVPSYRITYPAPVYSPSISIKLNNPETAVAVCNEFLARNYPTVASYQVTDEYDAYLDMVDGSESCLDRATFNPSKLRSYPKQHSYHAPTIRSAVPSPFQNTLQNVLAAATKRNCNVTQMRELPTMDSAVFNVECFKKYACNQEYWREFASSPIRVTTENLTMYVTKLKGPKAAALFAKTHNLLPLQEVPMDRFTMDMKRDVKVTPGTKHTEERPKVQVIQAAEPLATAYLCGIHRELVRRLNAVLLPNVHTLFDMSAEDFDAIISTHFKPGDAVLETDIASFDKSQDDSLALTAMMLLEDLGVDQPILDLIEAAFGEISSCHLPTGTRFKFGAMMKSGMFLTLFVNTLLNITIASRVLEERLTTSACAAFIGDDNIIHGVVSDALMAARCATWMNMEVKIIDAVVSEKAPYFCGGFILHDTVTGTSCRVADPLKRLFKLGKPLAAGDEQDEDRRRALADEVTRWQRTGLITELEKAVYSRYEVQGITAVITSMATFASSKENFKKLRGPVVTLYGGPK
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2.1.1.-; 2.7.7.-; 2.7.7.19; 2.7.7.48; 3.1.3.84; 3.4.22.-; 3.6.1.15; 3.6.1.74; 3.6.4.13
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COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P03317}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250|UniProtKB:P03317}; Note=For nsP4 adenylyltransferase activity; Mn(2+) supports catalysis at 60% of the levels observed with Mg(2+). {ECO:0000250|UniProtKB:P03317}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=For nsP4 RNA-directed RNA polymerase activity. {ECO:0000250|UniProtKB:P03317}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P27282}; Note=For nsP1 guanylylation. {ECO:0000250|UniProtKB:P27282}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=For nsP2 RNA triphosphatase activity. {ECO:0000250|UniProtKB:Q8JUX6}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=For nsP2 NTPase activity. {ECO:0000250|UniProtKB:Q8JUX6};
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7-methylguanosine mRNA capping [GO:0006370]; DNA-templated transcription [GO:0006351]; proteolysis [GO:0006508]; symbiont-mediated suppression of host mRNA transcription via inhibition of RNA polymerase II activity [GO:0039523]; viral RNA genome replication [GO:0039694]
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host cell cytoplasmic vesicle membrane [GO:0044162]; host cell filopodium [GO:0044176]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type peptidase activity [GO:0008234]; GTP binding [GO:0005525]; metal ion binding [GO:0046872]; mRNA 5'-phosphatase activity [GO:0140818]; mRNA methyltransferase activity [GO:0008174]; poly(A) RNA polymerase activity [GO:1990817]; polynucleotide 5'-phosphatase activity [GO:0004651]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]
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PF01661;PF20852;PF01707;PF00978;PF20896;PF01443;PF01660;
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3.90.70.110;3.40.220.10;3.40.50.300;3.40.50.150;
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PTM: [Polyprotein P1234]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The processing of the polyprotein is temporally regulated (By similarity). In early stages (1.7 hpi), P1234 is first cleaved in trans through its nsP2 protease activity, releasing P123' and nsP4, which associate to form the early replication complex (By similarity). At the same time, P1234 is also cut at the nsP1/nsP2 site early in infection but with lower efficiency (By similarity). After replication of the viral minus-strand RNAs (4 hpi), the polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very efficiently, preventing accumulation of P123' and P1234 and allowing the formation of the late replication complex (By similarity). NsP3'/nsP4 site is not cleaved anymore and P34 is produced rather than nsP4 (By similarity). {ECO:0000250|UniProtKB:P03317}.; PTM: [Polyprotein P123]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The processing of the polyprotein is temporally regulated (By similarity). In early stages (1.7 hpi), P123 is cleaved at the nsP1/nsP2 site with low efficiency (By similarity). After replication of the viral minus-strand RNAs (4 hpi), the polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very efficiently, preventing accumulation of P123 and allowing the formation of the late replication complex (By similarity). {ECO:0000250|UniProtKB:P03317}.; PTM: [Polyprotein P123']: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The processing of the polyprotein is temporally regulated (By similarity). In early stages (1.7 hpi), P123 is cleaved at the nsP1/nsP2 site with low efficiency (By similarity). After replication of the viral minus-strand RNAs (4 hpi), the polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very efficiently, preventing accumulation of P123' and allowing the formation of the late replication complex (By similarity). {ECO:0000250|UniProtKB:P03317}.; PTM: [mRNA-capping enzyme nsP1]: Palmitoylated by host palmitoyltransferases ZDHHC2 and ZDHHC19. {ECO:0000250|UniProtKB:Q8JUX6}.; PTM: [Non-structural protein 3]: Phosphorylated by host on serines and threonines. {ECO:0000250|UniProtKB:P08411}.; PTM: [Non-structural protein 3']: Phosphorylated by host on serines and threonines. {ECO:0000250|UniProtKB:P08411}.; PTM: [RNA-directed RNA polymerase nsP4]: Ubiquitinated; targets the protein for rapid degradation via the ubiquitin system (By similarity). Nsp4 is present in extremely low quantities due to low frequency of translation through the amber stop-codon and the degradation by the ubiquitin pathway (By similarity). {ECO:0000250|UniProtKB:P03317}.
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SUBCELLULAR LOCATION: [Polyprotein P1234]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=Part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex. {ECO:0000305}.; SUBCELLULAR LOCATION: [Polyprotein P123]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=Part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex. {ECO:0000305}.; SUBCELLULAR LOCATION: [mRNA-capping enzyme nsP1]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P08411}; Lipid-anchor {ECO:0000250|UniProtKB:P08411}. Host cell membrane {ECO:0000250|UniProtKB:P08411}; Lipid-anchor {ECO:0000250|UniProtKB:P08411}; Cytoplasmic side {ECO:0000250|UniProtKB:P08411}. Host cell projection, host filopodium {ECO:0000250|UniProtKB:Q8JUX6}. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then a fraction of nsP1 localizes to the inner surface of the plasma membrane and its filopodial extensions. Only the palmitoylated nsP1 localizes to the host filopodia (By similarity). NsP1 is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex (By similarity). {ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:Q8JUX6}.; SUBCELLULAR LOCATION: [Protease nsP2]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P08411}; Peripheral membrane protein {ECO:0000250|UniProtKB:P08411}. Host nucleus {ECO:0000250|UniProtKB:P27282}. Host cytoplasm {ECO:0000250|UniProtKB:P27282}. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then approximately half of nsP2 is found in the nucleus (By similarity). Shuttles between cytoplasm and nucleus (By similarity). NsP2 is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex (By similarity). {ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:P27282}.; SUBCELLULAR LOCATION: [Non-structural protein 3']: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P03317}; Peripheral membrane protein {ECO:0000305}. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then nsP3 and nsP3' form aggregates in cytoplasm (By similarity). NsP3' is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex (By similarity). {ECO:0000250|UniProtKB:P03317}.; SUBCELLULAR LOCATION: [Non-structural protein 3]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P03317}; Peripheral membrane protein {ECO:0000305}. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then nsP3 and nsP3' form aggregates in cytoplasm (By similarity). NsP3 is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex (By similarity). {ECO:0000250|UniProtKB:P03317}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase nsP4]: Host cytoplasmic vesicle membrane; Peripheral membrane protein {ECO:0000250|UniProtKB:P08411}. Note=NsP4 is part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex. {ECO:0000250|UniProtKB:P08411}.
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CATALYTIC ACTIVITY: Reaction=GTP + S-adenosyl-L-methionine = N(7)-methyl-GTP + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:46948, ChEBI:CHEBI:37565, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:87133; Evidence={ECO:0000250|UniProtKB:P27282}; CATALYTIC ACTIVITY: Reaction=L-histidyl-[protein] + N(7)-methyl-GTP = diphosphate + N(tele)-(N(7)-methylguanosine 5'-phospho)-L-histidyl-[protein]; Xref=Rhea:RHEA:54792, Rhea:RHEA-COMP:9745, Rhea:RHEA-COMP:13995, ChEBI:CHEBI:29979, ChEBI:CHEBI:33019, ChEBI:CHEBI:87133, ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54793; Evidence={ECO:0000250|UniProtKB:P27282}; CATALYTIC ACTIVITY: Reaction=a 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+) + N(tele)-(N(7)-methylguanosine 5'-phospho)-L-histidyl-[protein] = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(purine-ribonucleoside) in mRNA + L-histidyl-[protein]; Xref=Rhea:RHEA:54800, Rhea:RHEA-COMP:9745, Rhea:RHEA-COMP:12925, Rhea:RHEA-COMP:13929, Rhea:RHEA-COMP:13995, ChEBI:CHEBI:15378, ChEBI:CHEBI:29979, ChEBI:CHEBI:133968, ChEBI:CHEBI:138276, ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282}; CATALYTIC ACTIVITY: Reaction=a 5'-end triphospho-ribonucleoside in mRNA + H2O = a 5'-end diphospho-ribonucleoside in mRNA + H(+) + phosphate; Xref=Rhea:RHEA:67004, Rhea:RHEA-COMP:17164, Rhea:RHEA-COMP:17165, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:167616, ChEBI:CHEBI:167618; EC=3.6.1.74; Evidence={ECO:0000250|UniProtKB:P08411}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67005; Evidence={ECO:0000250|UniProtKB:P08411}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: Reaction=4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + H2O = ADP-D-ribose + H(+) + L-aspartyl-[protein]; Xref=Rhea:RHEA:54428, Rhea:RHEA-COMP:9867, Rhea:RHEA-COMP:13832, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29961, ChEBI:CHEBI:57967, ChEBI:CHEBI:138102; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54429; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; CATALYTIC ACTIVITY: Reaction=5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + H2O = ADP-D-ribose + H(+) + L-glutamyl-[protein]; Xref=Rhea:RHEA:58248, Rhea:RHEA-COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:57967, ChEBI:CHEBI:142540; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; CATALYTIC ACTIVITY: Reaction=ATP + RNA(n) = diphosphate + RNA(n)-3'-adenine ribonucleotide; Xref=Rhea:RHEA:11332, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17347, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:140395, ChEBI:CHEBI:173115; EC=2.7.7.19; Evidence={ECO:0000250|UniProtKB:P03317}; CATALYTIC ACTIVITY: Reaction=ADP-alpha-D-ribose 1''-phosphate + H2O = ADP-D-ribose + phosphate; Xref=Rhea:RHEA:25029, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57967, ChEBI:CHEBI:58753; EC=3.1.3.84; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25030; Evidence={ECO:0000250|UniProtKB:Q8JUX6};
| null | null | null | null |
FUNCTION: [Polyprotein P1234]: Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2. {ECO:0000250|UniProtKB:Q8JUX6}.; FUNCTION: [Polyprotein P123']: The early replication complex formed by the polyprotein P123' and nsP4 synthesizes minus-strand RNAs (Probable). Polyprotein P123' is a short-lived polyprotein that accumulates during early stage of infection (Probable). As soon P123' is cleaved into mature proteins, the plus-strand RNAs synthesis begins (Probable). {ECO:0000305}.; FUNCTION: [Polyprotein P123]: The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs (By similarity). As soon P123 is cleaved into mature proteins, the plus-strand RNAs synthesis begins (By similarity). {ECO:0000250|UniProtKB:P03317}.; FUNCTION: [mRNA-capping enzyme nsP1]: Cytoplasmic capping enzyme that catalyzes two virus-specific reactions: methyltransferase and nsP1 guanylyltransferase (By similarity). mRNA-capping is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus (Probable). The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP (Probable). nsP1 capping consists in the following reactions: GTP is first methylated into 7-methyl-GMP and then is covalently linked to nsP1 to form the m7GMp-nsP1 complex from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure (By similarity). NsP1 is also needed for the initiation of the minus-strand RNAs synthesis (By similarity). Probably serves as a membrane anchor for the replication complex composed of nsP1-nsP4 (By similarity). Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell (By similarity). {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:P27282, ECO:0000250|UniProtKB:Q8JUX6, ECO:0000305}.; FUNCTION: [Protease nsP2]: Multifunctional protein whose N-terminus is part of the RNA polymerase complex and displays NTPase, RNA triphosphatase and helicase activities (By similarity). NTPase and RNA triphosphatase are involved in viral RNA capping and helicase keeps a check on the dsRNA replication intermediates (By similarity). The C-terminus harbors a protease that specifically cleaves the polyproteins and releases the mature proteins (By similarity). Required for the shutoff of minus-strand RNAs synthesis (By similarity). Specifically inhibits the host IFN response by promoting the nuclear export of host STAT1 (By similarity). Also inhibits host transcription by inducing the rapid proteasome-dependent degradation of POLR2A, a catalytic subunit of the RNAPII complex (By similarity). The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity). {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:Q8JUX6}.; FUNCTION: [Non-structural protein 3']: Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis (By similarity). Displays mono-ADP-ribosylhydrolase activity (Probable). ADP-ribosylation is a post-translational modification that controls various processes of the host cell and the virus probably needs to revert it for optimal viral replication (Probable). Binds proteins of FXR family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs (Probable). The nsp3'-FXR complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of FXR family members to self-assemble and bind DNA (Probable). {ECO:0000250|UniProtKB:P03317, ECO:0000305}.; FUNCTION: [Non-structural protein 3]: Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis (By similarity). Displays mono-ADP-ribosylhydrolase activity (By similarity). ADP-ribosylation is a post-translational modification that controls various processes of the host cell and the virus probably needs to revert it for optimal viral replication (By similarity). Binds proteins of G3BP family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs (By similarity). The nsp3-G3BP complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of G3BP family members to self-assemble and bind DNA (By similarity). {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:Q8JUX6}.; FUNCTION: [RNA-directed RNA polymerase nsP4]: RNA dependent RNA polymerase (By similarity). Replicates genomic and antigenomic RNA by recognizing replications specific signals. The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs (By similarity). The late replication complex composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus-strand RNAs (By similarity). {ECO:0000250|UniProtKB:P03317}.
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O'nyong-nyong virus (strain SG650) (ONNV)
|
O90369
|
POLS_ONNVS
|
MEFIPAQTYYNRRYQPRPWTQRPTIQVIRPKPRRSRPAGQLAQLISAVSRLALRTVPQKPRRTRKTKKQKQVKQEQQSTRNQKKKAPKQKQTQKKKRPGRRERMCMKIENDCIFEVKHEGKITGYACLVGDKVMKPAHVKGTIDNADLAKLAFKRSSKYDLECAQIPVHMKSDASKFTHEKPEGYYNWHHGAVQYSGGRFTIPTGAGKPGDSGRPIFDNKGRVVAIVLGGANEGTRTALSVVTWNKDIVTKITPEGSVEWSLALPVMCLLANTTFPCSQPPCAPCCYEKKPEETLRMLEDNVMQPGYYQLLDSALACSQHRQRRNARENFNVYKVTRPYLAHCPDCGEGHSCHSPIALERIRSEATDGTLKIQVSLQIGIKTDDSHDWTKLRYMDSHTPVDADRSGLFVRTSAPCTITGTMGHFILARCPKGETLTVGFVDSRRISHTCMHPFHHEPPLIGREKFHSRPQHGKELPCSTYVHTTAATTEEIEVHMPPDTPDYTLMTQQAGNVKITVDGQTVRYKCKCDGSNEGLITTDKVINNCKVDQCHTAVTNHKKWQYNSPLTPRNSEQGDRKGKIHIPFPLVNTTCRVPKARNPTITYGKNRVTLLLYPDHPTLLSYRSMGRIPDYHEEWITSKKEISITVPAEGLEVTWGNNDPYKYWPQLSTNGTAHGHPHEIILYYYELYPTTTIAVLAAASIVVASLVSLSLGMCICARRRCITPYELTPGATIPFLLGVLCCVKTAKAASYYEAATYLWNEQQPLFWLQLLIPLSAAIVACNCLKLLPCCCKTLTFLAVMSIGARTVSAYEHATVIPNTVGVPYKTLVSRPGYSPMVLEMELQSVTLEPTLFLDYITCEYKTITPSPYVKCCGTAECKAKNLPDYNCKVFTGVYPFMWGGAYCFCDAENTQLSEAHVEKSESCKTEFASAYRAHTASVSAKLRVFYQGNNITVSAYANGDHAVTVKDAKFVIGPLSSAWSPFDNKIVVYKGEVYNMDYPPFGAGRPGQFGDIQSRTPDSKDVYANTQLILQRPAAGAIHVPYSQAPSGFKYWLKEKGASLQHTAPFGCQIATNPVRAVNCAVGNIPVSIDIPDAAFTRVTDAPSVTDMSCEVASCTHSSDFGGAAVVKYTASKKGKCAVHSLTNAVTIREPNVDVEGTAQLQIAFSTALASAEFKVQICSTQVHCSATCHPPKDHIVNYPSPHTTLGVQDISTTAMSWVQKITGGVGLVVAIAALILIIVLCVSFSRH
|
3.4.21.90
| null |
fusion of virus membrane with host endosome membrane [GO:0039654]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host toll-like receptor signaling pathway [GO:0039722]; virion attachment to host cell [GO:0019062]
|
host cell cytoplasm [GO:0030430]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; T=4 icosahedral viral capsid [GO:0039619]; virion membrane [GO:0055036]
|
serine-type endopeptidase activity [GO:0004252]; structural molecule activity [GO:0005198]
|
PF01589;PF00943;PF01563;PF00944;
|
1.10.287.2230;2.60.40.350;2.60.40.3200;2.60.40.4310;2.60.40.2400;2.60.98.10;2.40.10.10;
| null |
PTM: Structural polyprotein: Specific enzymatic cleavages in vivo yield mature proteins. Capsid protein is auto-cleaved during polyprotein translation, unmasking a signal peptide at the N-terminus of the precursor of E3/E2. The remaining polyprotein is then targeted to the host endoplasmic reticulum, where host signal peptidase cleaves it into pE2, 6K and E1 proteins. pE2 is further processed to mature E3 and E2 by host furin in trans-Golgi vesicle. {ECO:0000250|UniProtKB:P03315}.; PTM: [Spike glycoprotein E2]: Palmitoylated via thioester bonds. These palmitoylations may induce disruption of the C-terminus transmembrane. This would result in the reorientation of E2 C-terminus from lumenal to cytoplasmic side. {ECO:0000250|UniProtKB:P03315}.; PTM: [Spike glycoprotein E1]: N-glycosylated. {ECO:0000250|UniProtKB:P03315}.; PTM: [Spike glycoprotein E2]: N-glycosylated. {ECO:0000250|UniProtKB:P03315}.; PTM: [Assembly protein E3]: N-glycosylated. {ECO:0000250|UniProtKB:P03315}.; PTM: [6K protein]: Palmitoylated via thioester bonds. {ECO:0000250|UniProtKB:P03315}.
|
SUBCELLULAR LOCATION: [Capsid protein]: Virion {ECO:0000250|UniProtKB:P03316}. Host cytoplasm {ECO:0000250|UniProtKB:P03316}. Host cell membrane {ECO:0000250|UniProtKB:P03316}.; SUBCELLULAR LOCATION: [Spike glycoprotein E2]: Virion membrane {ECO:0000250|UniProtKB:Q8JUX5}; Single-pass type I membrane protein {ECO:0000255}. Host cell membrane {ECO:0000250|UniProtKB:P03316}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q8JUX5}.; SUBCELLULAR LOCATION: [6K protein]: Host cell membrane {ECO:0000250|UniProtKB:P03316}; Multi-pass membrane protein {ECO:0000255}. Virion membrane {ECO:0000250|UniProtKB:P03316}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Spike glycoprotein E1]: Virion membrane {ECO:0000250|UniProtKB:Q8JUX5}; Single-pass type I membrane protein {ECO:0000255}. Host cell membrane {ECO:0000250|UniProtKB:P03316, ECO:0000250|UniProtKB:Q8JUX5}; Single-pass type I membrane protein {ECO:0000255}.
|
CATALYTIC ACTIVITY: Reaction=Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-|-Ser- bond.; EC=3.4.21.90; Evidence={ECO:0000250|UniProtKB:P03316};
| null | null | null | null |
FUNCTION: [Capsid protein]: Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions. In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding. {ECO:0000250|UniProtKB:P03315}.; FUNCTION: [Assembly protein E3]: Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Mediates pH protection of spike glycoprotein E1 during the transport via the secretory pathway. {ECO:0000250|UniProtKB:P03315}.; FUNCTION: [Spike glycoprotein E2]: Plays a role in viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane. {ECO:0000250|UniProtKB:P03315}.; FUNCTION: [6K protein]: Constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins. {ECO:0000250|UniProtKB:P03315}.; FUNCTION: [Spike glycoprotein E1]: Class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group. {ECO:0000250|UniProtKB:P03315}.
|
O'nyong-nyong virus (strain SG650) (ONNV)
|
O90370
|
POLN_ONNVI
|
MDSVYVDIDADSAFLKALQRAYPMFEVEPKQVTPNDHANARAFSHLAIKLIEQEIDPGSTILGIGSAPARRMMSDRKYHCVCPMRSAEDPERLANYARKLASAAGKVTDKNISGKINDLQAVMAVPNMETSTFCLHTDATCKQRGDVAIYQDVYAVHAPTSLYHQAIKGVHVAYWIGFDTTPFMYNAMAGAYPSYSTNWADEQVLKAKNIGLCSTDLSEGRRGKLSIMRGKKFKPCDRVLFSVGSTLYPESRKLLQSWHLPSVFHLKGKLSFTCRCDTIVSCEGYVVKRVTMSPGIYGKTSGYAVTHHADGFLMCKTTDTVDGERVSFSVCTYVPATICDQMTGILATEVTPEDAQKLLVGLNQRIVVNGRTQRNTNTMKNYLLPIVAQAFSKWAKECRKDMEDEKLLGVRERTLTCCCLWAFRKHKTHTVYKRPDTQSIQKVPAEFDSFVIPSLWSSGLSIPLRTRIKWLLSKAPKHEQLPHSGNAEEAAQAETDAVEEREAELTREAMPPLQATQDDVQVEIDVEQLEDRAGAGIVETPRGAIKVTAQPSDLVVGEYLVLTPQAVLRSQKLGLIHALAEQVKTCTHSGRAGRYAVEAYDGRVLVPSGYAIPQEDFQSLSESATMVFNEREFVNRKLHHIAMHGPALNTDEESYELVRVEKTEHEYVYDVDQKKCCKREEATGLVLVGDLTSPPYHEFAYEGLKIRPACPYKTAVIGVFGVPGSGKSAIIKNLVTRQDLVTSGKKENCQEISNDVMRQRKLEISARTVDSLLLNGCNKPVEVLYVDEAFACHSGTLLALIAMVRPRQKVVLCGDPKQCGFFNMMQMKVNYNHNICTQVYHKSISRRCTLPVTAIVSSLHYESKMRTTNEYNQPIVVDTTGTTKPEPGDLVLTCFRGWVKQLQIDYRGNEVMTAAASQGLTRKGVYAVRQKVNENPLYASTSEHVNVLLTRTEGKLIWKTLSGDPWIKILQNPPKGNFKATIKEWEAEHASIMAGICNYQMAFDTFQNKANVCWAKCLVPILDTAGIKLSDRQWSQIVQAFKEDRAYSPEVALNEICTRIYGVDLDSGLFSKPLISVYYADNHWDNRPGGKMFGFNPEVALMLEKKYPFTKGKWNINKQICITTRKVDEFNPETNIIPANRRLPHSLVAEHHSVRGERMEWLVNKINGHHMLLVSGYNLILPTKRVTWVAPLGTRGADYTYNLELGLPATLGRYDLVVINIHTPFRIHHYQQCVDHAMKLQMLGGDSLRLLKPGGSLLIRAYGYADRTSERVISVLGRKFRSSRALKPQCITSNTEMFFLFSRFDNGRRNFTTHVMNNQLNAVYAGLATRAGCAPSYRVKRMDIAKNTEECVVNAANPRGVPGDGVCKAVYRKWPESFRNSATPVGTAKTIMCGQYPVIHAVGPNFSNYSEAEGDRELASAYREVAKEVSRLGVSSVAIPLLSTGVYSGGKDRLLQSLNHLFAAMDSTDADVVIYCRDKEWEKKITEAISLRSQVELLDDHISVDCDIVRVHPDSSLAGRKGYSTVEGALYSYLEGTRFHQTAVDMAEIYTMWPKQTEANEQVCLYALGESIESVRQKCPVDDADASFPPKTVPCLCRYAMTPERVARLRMNHTTSIIVCSSFPLPKYKIEGVQKVKCSKALLFDHNVPSRVSPRTYRPADEIIQTPQISTEACQDAQLVQSINDEAVPVPSDLEACDATMDWPSIGTVPTRQRHDSFDSEYSSRSNIQLVTADVHAPMYANSLASSGGSMLSLSSEPAQNGIMILPDSEDTDSISRVSTPIAPPRRRLGRTINVTCDEREGKILPMASDRFFTAKPYTVALSVSTADITAYPIQAPLGLTQPPTLEQITFGDFAEGEIDNLLTGALTFGDFEPGEVEELTDSEWSTCSDTDEELRLDRAGGYIFSSDTGQGHLQQKSVRQTTLPVNIVEEVHEEKCYPPKLDETKEQLLLKRLQESASTANRSRYQSRKVENMKATIIHRLKEGCRLYLASDTPRVPSYRITYPAPVYSPSINIKLSNPETAVAVCNEFLARNYPTVASYQVTDEYDAYLDMVDGSESCLDRATFNPSKLRSYPKQHSYHAPTIRSAVPSPFQNTLQNVLAAATKRNCNVTQMRELPTMDSAVFNVECFKKYACNQEYWREFASSPIRVTTENLTMYVTKLKGPKAAALFAKTHNLLPLQEVPMDRFTMDMKRDVKVTPGTKHTEERPKVQVIQAAEPLATAYLCGIHRELVRRLNAVLLPNVHTLFDMSAEDFDAIIATHFKPGDAVLETDIASFDKSQDDSLALTAMMLLEDLGVDQPILDLIEAAFGEISSCHLPTGTRFKFGAMMKSGMFLTLFVNTLLNITIASRVLEERLTTSACAAFIGDDNIIHGVVSDALMAARCATWMNMEVKIIDAVVSEKAPYFCGGFILHDTVTGTSCRVADPLKRLFKLGKPLAAGDEQDEDRRRALADEVTRWQRTGLVTELEKAVYSRYEVQGITAVITSMATFASSKENFKKLRGPVVTLYGGPK
|
2.1.1.-; 2.7.7.-; 2.7.7.19; 2.7.7.48; 3.1.3.84; 3.4.22.-; 3.6.1.15; 3.6.1.74; 3.6.4.13
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P03317}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250|UniProtKB:P03317}; Note=For nsP4 adenylyltransferase activity; Mn(2+) supports catalysis at 60% of the levels observed with Mg(2+). {ECO:0000250|UniProtKB:P03317}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=For nsP4 RNA-directed RNA polymerase activity. {ECO:0000250|UniProtKB:P03317}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P27282}; Note=For nsP1 guanylylation. {ECO:0000250|UniProtKB:P27282}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=For nsP2 RNA triphosphatase activity. {ECO:0000250|UniProtKB:Q8JUX6}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=For nsP2 NTPase activity. {ECO:0000250|UniProtKB:Q8JUX6};
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7-methylguanosine mRNA capping [GO:0006370]; DNA-templated transcription [GO:0006351]; proteolysis [GO:0006508]; symbiont-mediated suppression of host mRNA transcription via inhibition of RNA polymerase II activity [GO:0039523]; viral RNA genome replication [GO:0039694]
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host cell cytoplasmic vesicle membrane [GO:0044162]; host cell filopodium [GO:0044176]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type peptidase activity [GO:0008234]; GTP binding [GO:0005525]; metal ion binding [GO:0046872]; mRNA 5'-phosphatase activity [GO:0140818]; mRNA methyltransferase activity [GO:0008174]; poly(A) RNA polymerase activity [GO:1990817]; polynucleotide 5'-phosphatase activity [GO:0004651]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]
|
PF01661;PF20852;PF01707;PF00978;PF20896;PF01443;PF01660;
|
3.90.70.110;3.40.220.10;3.40.50.300;3.40.50.150;
| null |
PTM: [Polyprotein P1234]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The processing of the polyprotein is temporally regulated (By similarity). In early stages (1.7 hpi), P1234 is first cleaved in trans through its nsP2 protease activity, releasing P123 and nsP4, which associate to form the early replication complex (By similarity). At the same time, P1234 is also cut at the nsP1/nsP2 site early in infection but with lower efficiency (By similarity). After replication of the viral minus-strand RNAs (4 hpi), the polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very efficiently, preventing accumulation of P123 and P1234 and allowing the formation of the late replication complex (By similarity). NsP3/nsP4 site is not cleaved anymore and P34 is produced rather than nsP4 (By similarity). {ECO:0000250|UniProtKB:P03317}.; PTM: [Polyprotein P123]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The processing of the polyprotein is temporally regulated (By similarity). In early stages (1.7 hpi), P123 is cleaved at the nsP1/nsP2 site with low efficiency (By similarity). After replication of the viral minus-strand RNAs (4 hpi), the polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very efficiently, preventing accumulation of P123 and allowing the formation of the late replication complex (By similarity). {ECO:0000250|UniProtKB:P03317}.; PTM: [mRNA-capping enzyme nsP1]: Palmitoylated by host palmitoyltransferases ZDHHC2 and ZDHHC19. {ECO:0000250|UniProtKB:Q8JUX6}.; PTM: [Non-structural protein 3]: Phosphorylated by host on serines and threonines. {ECO:0000250|UniProtKB:P08411}.; PTM: [RNA-directed RNA polymerase nsP4]: Ubiquitinated; targets the protein for rapid degradation via the ubiquitin system (By similarity). Nsp4 is present in extremely low quantities due to low frequency of translation through the amber stop-codon and the degradation by the ubiquitin pathway (By similarity). {ECO:0000250|UniProtKB:P03317}.
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SUBCELLULAR LOCATION: [Polyprotein P1234]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=Part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex. {ECO:0000305}.; SUBCELLULAR LOCATION: [Polyprotein P123]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=Part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex. {ECO:0000305}.; SUBCELLULAR LOCATION: [mRNA-capping enzyme nsP1]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P08411}; Lipid-anchor {ECO:0000250|UniProtKB:P08411}. Host cell membrane {ECO:0000250|UniProtKB:P08411}; Lipid-anchor {ECO:0000250|UniProtKB:P08411}; Cytoplasmic side {ECO:0000250|UniProtKB:P08411}. Host cell projection, host filopodium {ECO:0000250|UniProtKB:Q8JUX6}. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then a fraction of nsP1 localizes to the inner surface of the plasma membrane and its filopodial extensions. Only the palmitoylated nsP1 localizes to the host filopodia (By similarity). NsP1 is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex (By similarity). {ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:Q8JUX6}.; SUBCELLULAR LOCATION: [Protease nsP2]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P08411}; Peripheral membrane protein {ECO:0000250|UniProtKB:P08411}. Host nucleus {ECO:0000250|UniProtKB:P27282}. Host cytoplasm {ECO:0000250|UniProtKB:P27282}. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then approximately half of nsP2 is found in the nucleus (By similarity). Shuttles between cytoplasm and nucleus (By similarity). NsP2 is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex (By similarity). {ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:P27282}.; SUBCELLULAR LOCATION: [Non-structural protein 3]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P03317}; Peripheral membrane protein {ECO:0000305}. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then nsP3 forms aggregates in cytoplasm (By similarity). NsP3 is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex (By similarity). {ECO:0000250|UniProtKB:P03317}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase nsP4]: Host cytoplasmic vesicle membrane; Peripheral membrane protein {ECO:0000250|UniProtKB:P08411}. Note=NsP4 is part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex. {ECO:0000250|UniProtKB:P08411}.
|
CATALYTIC ACTIVITY: Reaction=GTP + S-adenosyl-L-methionine = N(7)-methyl-GTP + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:46948, ChEBI:CHEBI:37565, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:87133; Evidence={ECO:0000250|UniProtKB:P27282}; CATALYTIC ACTIVITY: Reaction=L-histidyl-[protein] + N(7)-methyl-GTP = diphosphate + N(tele)-(N(7)-methylguanosine 5'-phospho)-L-histidyl-[protein]; Xref=Rhea:RHEA:54792, Rhea:RHEA-COMP:9745, Rhea:RHEA-COMP:13995, ChEBI:CHEBI:29979, ChEBI:CHEBI:33019, ChEBI:CHEBI:87133, ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54793; Evidence={ECO:0000250|UniProtKB:P27282}; CATALYTIC ACTIVITY: Reaction=a 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+) + N(tele)-(N(7)-methylguanosine 5'-phospho)-L-histidyl-[protein] = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(purine-ribonucleoside) in mRNA + L-histidyl-[protein]; Xref=Rhea:RHEA:54800, Rhea:RHEA-COMP:9745, Rhea:RHEA-COMP:12925, Rhea:RHEA-COMP:13929, Rhea:RHEA-COMP:13995, ChEBI:CHEBI:15378, ChEBI:CHEBI:29979, ChEBI:CHEBI:133968, ChEBI:CHEBI:138276, ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282}; CATALYTIC ACTIVITY: Reaction=a 5'-end triphospho-ribonucleoside in mRNA + H2O = a 5'-end diphospho-ribonucleoside in mRNA + H(+) + phosphate; Xref=Rhea:RHEA:67004, Rhea:RHEA-COMP:17164, Rhea:RHEA-COMP:17165, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:167616, ChEBI:CHEBI:167618; EC=3.6.1.74; Evidence={ECO:0000250|UniProtKB:P08411}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67005; Evidence={ECO:0000250|UniProtKB:P08411}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: Reaction=4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + H2O = ADP-D-ribose + H(+) + L-aspartyl-[protein]; Xref=Rhea:RHEA:54428, Rhea:RHEA-COMP:9867, Rhea:RHEA-COMP:13832, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29961, ChEBI:CHEBI:57967, ChEBI:CHEBI:138102; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54429; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; CATALYTIC ACTIVITY: Reaction=5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + H2O = ADP-D-ribose + H(+) + L-glutamyl-[protein]; Xref=Rhea:RHEA:58248, Rhea:RHEA-COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:57967, ChEBI:CHEBI:142540; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; CATALYTIC ACTIVITY: Reaction=ATP + RNA(n) = diphosphate + RNA(n)-3'-adenine ribonucleotide; Xref=Rhea:RHEA:11332, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17347, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:140395, ChEBI:CHEBI:173115; EC=2.7.7.19; Evidence={ECO:0000250|UniProtKB:P03317}; CATALYTIC ACTIVITY: Reaction=ADP-alpha-D-ribose 1''-phosphate + H2O = ADP-D-ribose + phosphate; Xref=Rhea:RHEA:25029, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57967, ChEBI:CHEBI:58753; EC=3.1.3.84; Evidence={ECO:0000250|UniProtKB:Q8JUX6}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25030; Evidence={ECO:0000250|UniProtKB:Q8JUX6};
| null | null | null | null |
FUNCTION: [Polyprotein P1234]: Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2. {ECO:0000250|UniProtKB:Q8JUX6}.; FUNCTION: [Polyprotein P123]: The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs (By similarity). As soon P123 is cleaved into mature proteins, the plus-strand RNAs synthesis begins (By similarity). {ECO:0000250|UniProtKB:P03317}.; FUNCTION: [mRNA-capping enzyme nsP1]: Cytoplasmic capping enzyme that catalyzes two virus-specific reactions: methyltransferase and nsP1 guanylyltransferase (By similarity). mRNA-capping is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus (Probable). The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP (Probable). nsP1 capping consists in the following reactions: GTP is first methylated into 7-methyl-GMP and then is covalently linked to nsP1 to form the m7GMp-nsP1 complex from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure (By similarity). NsP1 is also needed for the initiation of the minus-strand RNAs synthesis (By similarity). Probably serves as a membrane anchor for the replication complex composed of nsP1-nsP4 (By similarity). Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell (By similarity). {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:P27282, ECO:0000250|UniProtKB:Q8JUX6, ECO:0000305}.; FUNCTION: [Protease nsP2]: Multifunctional protein whose N-terminus is part of the RNA polymerase complex and displays NTPase, RNA triphosphatase and helicase activities (By similarity). NTPase and RNA triphosphatase are involved in viral RNA capping and helicase keeps a check on the dsRNA replication intermediates (By similarity). The C-terminus harbors a protease that specifically cleaves the polyproteins and releases the mature proteins (By similarity). Required for the shutoff of minus-strand RNAs synthesis (By similarity). Specifically inhibits the host IFN response by promoting the nuclear export of host STAT1 (By similarity). Also inhibits host transcription by inducing the rapid proteasome-dependent degradation of POLR2A, a catalytic subunit of the RNAPII complex (By similarity). The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity). {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:Q8JUX6}.; FUNCTION: [Non-structural protein 3]: Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis (By similarity). Displays mono-ADP-ribosylhydrolase activity (By similarity). ADP-ribosylation is a post-translational modification that controls various processes of the host cell and the virus probably needs to revert it for optimal viral replication (By similarity). Binds proteins of G3BP family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs (By similarity). The nsp3-G3BP complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of G3BP family members to self-assemble and bind DNA (By similarity). {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:Q8JUX6}.; FUNCTION: [RNA-directed RNA polymerase nsP4]: RNA dependent RNA polymerase (By similarity). Replicates genomic and antigenomic RNA by recognizing replications specific signals. The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs (By similarity). The late replication complex composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus-strand RNAs (By similarity). {ECO:0000250|UniProtKB:P03317}.
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O'nyong-nyong virus (strain Igbo Ora) (ONNV) (Igbo Ora virus)
|
O90371
|
POLS_ONNVI
|
MEFIPAQTYYNRRYQPRPWTQRPTIQVIRPKPRRRRPAGQLAQLISAVSRLALRTVPQKPRRTRKIKKQKQVKQEQQSTRNQKKKAPKQKQTQKKKRPGRRERMCMKIENDCIFEVKHEGKVTGYACLVGDKVMKPAHVKGTIDNADLAKLAFKRSSKYDLECAQIPVHMKSDASKFTHEKPEGYYNWHHGAVQYSGGRFTIPTGAGKPGDSGRPIFDNKGRVVAIVLGGANEGTRTALSVVTWNKDIVTKITPEGSVEWSLALPVMCLLANTTFPCSQPPCAPCCYEKKPEETLRMLEDNVMQPGYYQLLDSALACSQHRQRRNARENFNVYKVTRPYLAHCPDCGEGHSCHSPIALERIRSEATDGTLKIQVSLQIGIKTADSHDWTKLRYMDSHTPVDADRSGLFVRTSAPCTITGTMGHFILARCPKGETLTVGFVDSRRISHTCMHPFHHEPPLIGREKFHSRPQHGKELPCSTYVHTTAATTEEIEVHMPPDTPDYTLMTQQAGNVKITVDGQTVRYKCKCDGSNEGLITTDKVINNCKVDQCHTAVTNHKKWQYNSPLTPRNSEQGDRKGKIHIPFPLVNTTCRVPKARNPTVTYGKNRVTLLLYPDHPTLLSYRAMGRIPDYHEEWITSKKEISITVPAEGLEVTWGNNDPYKYWPQLSTNGTAHGHPHEIILYYYELYPTTTIAVLAAASIVVASLVGLSLGMCICARRRCITPYELTPGATIPFLLGILCCVKTAKAASYYEAATYLWNEQQPLFWLQLLIPLSAAIVVCNCLKLLPCCCKTLTFLAVMSIGARTVSAYEHATVIPNTVGVPYKTLVSRPGYSPMVLEMELQSVTLEPTLFLDYITCEYKTITPSPYVKCCGTAECKAKNLPDYNCKVFTGVYPFMWGGAYCFCDAENTQLSEAHVEKSESCKTEFASAYRAHTASVSAKLRVFYQGNNITVSAYANGDHAVTVKDAKFVIGPLSSAWSPFDNKIVVYKGEVYNMDYPPFGAGRPGQFGDIQSRTPDSKDVYANTQLILQRPAAGAIHVPYSQAPSGFKYWLKEKGASLQHTAPFGCQIATNPVRAVNCAVGNIPVSIDIPDAAFTRVTDAPSVTDMSCEVASCTHSSDFGGAAVIKYTASKKGKCAVHSLTNAVTIREPNVDVEGTAQLQIAFSTALASAEFKVQICSTQVHCSATCHPPKDHIVNYPSPHTTLGVQDISTTAMSWVQKITGGVGLVVAIAALILIIVLCVSFSRH
|
3.4.21.90
| null |
fusion of virus membrane with host endosome membrane [GO:0039654]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host toll-like receptor signaling pathway [GO:0039722]; virion attachment to host cell [GO:0019062]
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host cell cytoplasm [GO:0030430]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; T=4 icosahedral viral capsid [GO:0039619]; virion membrane [GO:0055036]
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RNA binding [GO:0003723]; serine-type endopeptidase activity [GO:0004252]; structural molecule activity [GO:0005198]
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PF01589;PF00943;PF01563;PF00944;
|
1.10.287.2230;2.60.40.350;2.60.40.3200;2.60.40.4310;2.60.40.2400;2.60.98.10;2.40.10.10;
| null |
PTM: Structural polyprotein: Specific enzymatic cleavages in vivo yield mature proteins. Capsid protein is auto-cleaved during polyprotein translation, unmasking a signal peptide at the N-terminus of the precursor of E3/E2 (By similarity). The remaining polyprotein is then targeted to the host endoplasmic reticulum, where host signal peptidase cleaves it into pE2, 6K and E1 proteins. pE2 is further processed to mature E3 and E2 by host furin in trans-Golgi vesicle (By similarity). {ECO:0000250|UniProtKB:P03315}.; PTM: [Spike glycoprotein E2]: Palmitoylated via thioester bonds. These palmitoylations may induce disruption of the C-terminus transmembrane. This would result in the reorientation of E2 C-terminus from lumenal to cytoplasmic side. {ECO:0000250|UniProtKB:P03315}.; PTM: [Spike glycoprotein E1]: N-glycosylated. {ECO:0000250|UniProtKB:P03315}.; PTM: [Spike glycoprotein E2]: N-glycosylated. {ECO:0000250|UniProtKB:P03315}.; PTM: [Assembly protein E3]: N-glycosylated. {ECO:0000250|UniProtKB:P03315}.; PTM: [6K protein]: Palmitoylated via thioester bonds. {ECO:0000250|UniProtKB:P03315}.
|
SUBCELLULAR LOCATION: [Capsid protein]: Virion {ECO:0000250|UniProtKB:P03316}. Host cytoplasm {ECO:0000250|UniProtKB:Q8JUX5}. Host cell membrane {ECO:0000250|UniProtKB:P03316}. Host nucleus {ECO:0000250|UniProtKB:Q8JUX5}. Note=Shuttles between the cytoplasm and the nucleus. {ECO:0000250|UniProtKB:Q8JUX5}.; SUBCELLULAR LOCATION: [Spike glycoprotein E2]: Virion membrane {ECO:0000250|UniProtKB:Q8JUX5}; Single-pass type I membrane protein {ECO:0000255}. Host cell membrane {ECO:0000250|UniProtKB:P03316}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q8JUX5}.; SUBCELLULAR LOCATION: [6K protein]: Host cell membrane {ECO:0000250|UniProtKB:P03316}; Multi-pass membrane protein {ECO:0000255}. Virion membrane {ECO:0000250|UniProtKB:P03316}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Spike glycoprotein E1]: Virion membrane {ECO:0000250|UniProtKB:Q8JUX5}; Single-pass type I membrane protein {ECO:0000255}. Host cell membrane {ECO:0000250|UniProtKB:P03316, ECO:0000250|UniProtKB:Q8JUX5}; Single-pass type I membrane protein {ECO:0000255}.
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CATALYTIC ACTIVITY: Reaction=Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-|-Ser- bond.; EC=3.4.21.90; Evidence={ECO:0000250|UniProtKB:P03315};
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FUNCTION: [Capsid protein]: Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein surrounded by a lipid membrane through which penetrate 80 spikes composed of trimers of E1-E2 heterodimers (By similarity). The capsid protein binds to the viral RNA genome at a site adjacent to a ribosome binding site for viral genome translation following genome release (By similarity). Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein (By similarity). Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles (By similarity). The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions (By similarity). In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane (By similarity). This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible (By similarity). The uncoating might be triggered by the interaction of capsid proteins with ribosomes (By similarity). Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding (By similarity). Specifically inhibits interleukin-1 receptor-associated kinase 1/IRAK1-dependent signaling during viral entry, representing a means by which the alphaviruses may evade innate immune detection and activation prior to viral gene expression (By similarity). {ECO:0000250|UniProtKB:P03315, ECO:0000250|UniProtKB:P03316, ECO:0000250|UniProtKB:P27284}.; FUNCTION: [Assembly protein E3]: Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Furin-cleaved E3 remains associated with spike glycoprotein E1 and mediates pH protection of the latter during the transport via the secretory pathway. After virion release from the host cell, the assembly protein E3 is gradually released in the extracellular space. {ECO:0000250|UniProtKB:P03315}.; FUNCTION: [Spike glycoprotein E2]: Plays a role in viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane. {ECO:0000250|UniProtKB:P03315}.; FUNCTION: [6K protein]: Constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins. {ECO:0000250|UniProtKB:P03315}.; FUNCTION: [Spike glycoprotein E1]: Class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group. {ECO:0000250|UniProtKB:P03315}.
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O'nyong-nyong virus (strain Igbo Ora) (ONNV) (Igbo Ora virus)
|
O91079
|
GAG_HV1YF
|
MGARASVLTGGKLDQWESIYLRPGGKKKYRMKHLVWASRELERFACNPGLMDTADGCAKLLNQLEPALKTGSEELRSLYNALAVLYCVHSRIQIHNTQEALDKIKEKQEQHKPEPKNPEAGAAAATDSNISRNYPLVQTAQGQMVHQPLTPRTLNAWVKVIEEKAFSPEVIPMFMALSEGATPSDLNTMLNTVGGHQAAMQMLKEVINEEAADWDRTHPVPVGPLPPGQLRDPRGSDIAGTTSTLAEQVAWMTANPPVPVGDIYRRWIVLGLNRIVRMYSPVSILEIKQGPKEPFRDYVDRFYKTLRAEQATQEVKNWMTETLLVQNANPDCKQLLKALGPGATLEEMMTACQGVGGPAHKARVLAEAMSQVQQPTTSVFAQRGNFKGIRKPIKCFNCGKEGHLARNCKAPRRGGCWKCGQEGHQMKDCKNEGRQANFLGKSWSPFKGRPGNFPQTTTRKEPTAPPLESYGFQEEKSTQGKEMQENQERTENSLYPPLTSLRSLFGNDPSSQ
| null | null |
viral budding via host ESCRT complex [GO:0039702]
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host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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RNA binding [GO:0003723]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF00607;PF19317;PF08705;PF00098;
|
1.10.1200.30;6.10.250.390;1.10.375.10;1.10.150.90;1.20.5.760;4.10.60.10;
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Primate lentivirus group gag polyprotein family
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PTM: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000250|UniProtKB:P12493}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04591}.; PTM: Capsid protein p24 is phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: Nucleocapsid protein p7 is methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag polyprotein]: Host cell membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P12493}. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000250|UniProtKB:P12493}.
| null | null | null | null | null |
FUNCTION: [Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). The capsid promotes immune invasion by cloaking viral DNA from CGAS detection (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid (By similarity). {ECO:0000250|UniProtKB:P04591, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000250|UniProtKB:P12493}.
|
Human immunodeficiency virus type 1 group N (isolate YBF30) (HIV-1)
|
O91080
|
POL_HV1YF
|
MGARASVLTGGKLDQWESIYLRPGGKKKYRMKHLVWASRELERFACNPGLMDTADGCAKLLNQLEPALKTGSEELRSLYNALAVLYCVHSRIQIHNTQEALDKIKEKQEQHKPEPKNPEAGAAAATDSNISRNYPLVQTAQGQMVHQPLTPRTLNAWVKVIEEKAFSPEVIPMFMALSEGATPSDLNTMLNTVGGHQAAMQMLKEVINEEAADWDRTHPVPVGPLPPGQLRDPRGSDIAGTTSTLAEQVAWMTANPPVPVGDIYRRWIVLGLNRIVRMYSPVSILEIKQGPKEPFRDYVDRFYKTLRAEQATQEVKNWMTETLLVQNANPDCKQLLKALGPGATLEEMMTACQGVGGPAHKARVLAEAMSQVQQPTTSVFAQRGNFKGIRKPIKCFNCGKEGHLARNCKAPRRGGCWKCGQEGHQMKDCKNEGRQFFREELVSLQRETRKLPPDNNKERAHSPATRELWVSGGEEHTGEGDAGEPGEDRELSVPTFNFPQITLWQRPVITVKIGKEVREALLDTGADDTVIEELQLEGKWKPKMIGGIGGFIKVRQYDNITVDIQGRKAVGTVLVGPTPVNIIGRNLLTQIGCTLNFPISPIETVPVKLKPGMDGPKVKQWPLTTEKIEALREICTEMEKEGKISRIGPENPYNTPIFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKQKKSVTVLDVGDAYFSCPLDKDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSTMTKILEPFREKHPEIIIYQYMDDLYVGSDLELAQHREAVEDLRDHLLKWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQPIKLPEKDVWTVNDIQKLVGKLNWASQIYPGIRVKQLCKLIRGTKALTEVVNFTEEAELELAENREILKEPLHGVYYDPGKELVAEIQKQGQGQWTYQIYQELHKNLKTGKYAKMRSAHTNDIKQLVEVVRKVATESIVIWGKTPKFRLPVQKEVWEAWWTDHWQATWIPEWEFVNTPPLVKLWYQLETEPISGAETFYVDGAANRETKLGKAGFVTDRGRQKVVSIADTTNQKAELQAILMALQESGRDVNIVTDSQYAMGIIHSQPDKSESELVSQIIEELIKKERVYLSWVPAHKGIGGNEQVDKLVSSGIRKILFLDGIEKAQEDHDRYHSNWKAMASDFNLPPIVAKEIVASCDKCQLKGEAMHGQVNCSPGVWQLDCTHLEGKIILVAVHVASGYLEAEVIPAETGQETAYFILKLAGRWPVKVIHTDNGSNFTSATVKAACWWANIKQEFGIPYNPQSQGAVESMNKELKKIIGQIRDQAEHLKTAVQMAVFIHNFKRKGGIGGYTAGERIIDIIATDIQTTNLQTQILKVQNFRVYYRDSRDPIWKGPAKLLWKGEGAVVIQDNGDIKVVPRRKAKIIRDYGKQMAGDGCVASGQDENQEME
|
2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.13.2; 3.1.26.13; 3.4.23.16
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
|
DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral genome integration into host DNA [GO:0044826]; viral penetration into host nucleus [GO:0075732]
|
host cell [GO:0043657]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
|
aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; exoribonuclease H activity [GO:0004533]; lipid binding [GO:0008289]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF19317;PF00552;PF02022;PF00075;PF00665;PF00077;PF00078;PF06815;PF06817;PF00098;
|
1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;1.20.5.760;4.10.60.10;
| null |
PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12497}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.; EC=3.4.23.16; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275}; CATALYTIC ACTIVITY: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
| null | null | null | null |
FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation. {ECO:0000250}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. Also mediates cleavage of host YTHDF3. Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250|UniProtKB:P04585}.
|
Human immunodeficiency virus type 1 group N (isolate YBF30) (HIV-1)
|
O91083
|
TAT_HV1YF
|
MEPVDPRLEPWNHPGSQPKTACNNCYCKRCCYHCLYCFTKKGLGISYGRKKRSQRRRTPQSSKSHQDLIPEQPLSQQQGDQTGQKKQKEALESKTEADPCD
| null | null |
DNA-templated transcription [GO:0006351]; modulation by virus of host chromatin organization [GO:0039525]; negative regulation of peptidyl-threonine phosphorylation [GO:0010801]; positive regulation of transcription elongation by RNA polymerase II [GO:0032968]; positive regulation of viral transcription [GO:0050434]; symbiont-mediated suppression of host translation initiation [GO:0039606]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell cytoplasm [GO:0030430]; host cell nucleolus [GO:0044196]
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actinin binding [GO:0042805]; cyclin binding [GO:0030332]; metal ion binding [GO:0046872]; protein domain specific binding [GO:0019904]; protein serine/threonine phosphatase inhibitor activity [GO:0004865]; RNA-binding transcription regulator activity [GO:0001070]; trans-activation response element binding [GO:1990970]
|
PF00539;
|
4.10.20.10;
|
Lentiviruses Tat family
|
PTM: Asymmetrical arginine methylation by host PRMT6 seems to diminish the transactivation capacity of Tat and affects the interaction with host CCNT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Acetylation by EP300, CREBBP, GCN5L2/GCN5 and PCAF regulates the transactivation activity of Tat. EP300-mediated acetylation of Lys-50 promotes dissociation of Tat from the TAR RNA through the competitive binding to PCAF's bromodomain. In addition, the non-acetylated Tat's N-terminus can also interact with PCAF. PCAF-mediated acetylation of Lys-28 enhances Tat's binding to CCNT1. Lys-50 is deacetylated by SIRT1. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Polyubiquitination by host MDM2 does not target Tat to degradation, but activates its transactivation function and fosters interaction with CCNT1 and TAR RNA. {ECO:0000255|HAMAP-Rule:MF_04079}.; PTM: Phosphorylated by EIF2AK2 on serine and threonine residues adjacent to the basic region important for TAR RNA binding and function. Phosphorylation of Tat by EIF2AK2 is dependent on the prior activation of EIF2AK2 by dsRNA. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP-Rule:MF_04079}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04079}. Secreted {ECO:0000255|HAMAP-Rule:MF_04079}. Note=Probably localizes to both nuclear and nucleolar compartments. Nuclear localization is mediated through the interaction of the nuclear localization signal with importin KPNB1. Secretion occurs through a Golgi-independent pathway. Tat is released from infected cells to the extracellular space where it remains associated to the cell membrane, or is secreted into the cerebrospinal fluid and sera. Extracellular Tat can be endocytosed by surrounding uninfected cells via binding to several receptors depending on the cell type. {ECO:0000255|HAMAP-Rule:MF_04079}.
| null | null | null | null | null |
FUNCTION: Transcriptional activator that increases RNA Pol II processivity, thereby increasing the level of full-length viral transcripts. Recognizes a hairpin structure at the 5'-LTR of the nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR) and recruits the cyclin T1-CDK9 complex (P-TEFb complex) that will in turn hyperphosphorylate the RNA polymerase II to allow efficient elongation. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B by interacting with host RELA. Through its interaction with host TBP, Tat may also modulate transcription initiation. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. {ECO:0000255|HAMAP-Rule:MF_04079}.; FUNCTION: Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines or cytokine receptors. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. {ECO:0000255|HAMAP-Rule:MF_04079}.
|
Human immunodeficiency virus type 1 group N (isolate YBF30) (HIV-1)
|
O91086
|
ENV_HV1YF
|
MGMKSGWLLFYLLVSLIKVIGSEQHWVTVYYGVPVWREAETTLFCASDAKAHSTEAHNIWATQACVPTDPNPQEVLLPNVTEKFNMWENKMADQMQEDIISLWEQSLKPCVKLTPLCVTMLCNDSYGEERNNTNMTTREPDIGYKQMKNCSFNATTELTDKKKQVYSLFYVEDVVPINAYNKTYRLINCNTTAVTQACPKTSFEPIPIHYCAPPGFAIMKCNEGNFSGNGSCTNVSTVQCTHGIKPVISTQLILNGSLNTDGIVIRNDSHSNLLVQWNETVPINCTRPGNNTGGQVQIGPAMTFYNIEKIVGDIRQAYCNVSKELWEPMWNRTREEIKKILGKNNITFRARERNEGDLEVTHLMFNCRGEFFYCNTSKLFNEELLNETGEPITLPCRIRQIVNLWTRVGKGIYAPPIRGVLNCTSNITGLVLEYSGGPDTKETIVYPSGGNMVNLWRQELYKYKVVSIEPIGVAPGKAKRRTVSREKRAAFGLGALFLGFLGAAGSTMGAASITLTVQARTLLSGIVQQQNILLRAIEAQQHLLQLSIWGIKQLQAKVLAIERYLRDQQILSLWGCSGKTICYTTVPWNETWSNNTSYDTIWNNLTWQQWDEKVRNYSGVIFGLIEQAQEQQNTNEKSLLELDQWDSLWSWFGITKWLWYIKIAIMIVAGIVGIRIISIVITIIARVRQGYSPLSLQTLIPTARGPDRPEETEGGVGEQDRGRSVRLVSGFSALVWEDLRNLLIFLYHRLTDSLLILRRTLELLGQSLSRGLQLLNELRTHLWGILAYWGKELRDSAISLLNTTAIVVAEGTDRIIELAQRIGRGILHIPRRIRQGLERALI
| null | null |
clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; fusion of virus membrane with host plasma membrane [GO:0019064]; positive regulation of establishment of T cell polarity [GO:1903905]; positive regulation of plasma membrane raft polarization [GO:1903908]; positive regulation of receptor clustering [GO:1903911]; viral protein processing [GO:0019082]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
|
host cell endosome membrane [GO:0044175]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
|
structural molecule activity [GO:0005198]
|
PF00516;PF00517;
|
1.10.287.210;2.170.40.20;1.20.5.490;
|
HIV-1 env protein family
|
PTM: Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.; PTM: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.; SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag. {ECO:0000255|HAMAP-Rule:MF_04083}.
| null | null | null | null | null |
FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Surface protein gp120]: Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.; FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
|
Human immunodeficiency virus type 1 group N (isolate YBF30) (HIV-1)
|
O91087
|
NEF_HV1YF
|
MGKIWSKSSLVGWPEIRERMRRQTQEPAVEPAVGAGAASQDLANRGAITIRNTRDNNESIAWLEAQEEEEEVGFPVRPQVPLRPITYKQAFDLSFFLKDKGGLEGLVWSRKRQDILDLWMYHTQGILPDWHNYTPGPGIRYPVTFGWCFKLVPLSAEEVEEANEGDNNALLHPICQHGADDDHKEVLVWRFDSSLARRHVARELHPEFYKNC
| null | null |
suppression by virus of host autophagy [GO:0039521]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I [GO:0046776]; symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class II [GO:0039505]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell Golgi membrane [GO:0044178]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; virion component [GO:0044423]
|
GTP binding [GO:0005525]; SH3 domain binding [GO:0017124]
|
PF00469;
|
4.10.890.10;3.30.62.10;
|
Lentivirus primate group Nef protein family
|
PTM: The virion-associated Nef proteins are cleaved by the viral protease to release the soluble C-terminal core protein. Nef is probably cleaved concomitantly with viral structural proteins on maturation of virus particles. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04078}.; PTM: Phosphorylated on serine residues, probably by host PKCdelta and theta. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
SUBCELLULAR LOCATION: Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04078}; Lipid-anchor {ECO:0000255|HAMAP-Rule:MF_04078}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_04078}. Virion {ECO:0000255|HAMAP-Rule:MF_04078}. Secreted {ECO:0000255|HAMAP-Rule:MF_04078}. Host Golgi apparatus membrane {ECO:0000255|HAMAP-Rule:MF_04078}. Note=TGN localization requires PACS1. Associates with the inner plasma membrane through its N-terminal domain. Nef stimulates its own export via the release of exosomes. Incorporated in virions at a rate of about 10 molecules per virion, where it is cleaved. {ECO:0000255|HAMAP-Rule:MF_04078}.
| null | null | null | null | null |
FUNCTION: Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection). Down-regulates host SERINC3 and SERINC5 thereby excluding these proteins from the viral particles. Virion infectivity is drastically higher when SERINC3 or SERINC5 are excluded from the viral envelope, because these host antiviral proteins impair the membrane fusion event necessary for subsequent virion penetration. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life of TP53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of host BAD. {ECO:0000255|HAMAP-Rule:MF_04078}.; FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors. {ECO:0000255|HAMAP-Rule:MF_04078}.
|
Human immunodeficiency virus type 1 group N (isolate YBF30) (HIV-1)
|
O91464
|
POLG_AIVA8
|
MAATRVSRSVLAAVAHSAAHRTYHTVLDCYDRLYLNTNPHLSYPLPKNSSFPCPFCQYDEQNEVLSPESLRGEGAEPCWKCSQDKPRRKYNTTPPEDWLYDSDVQSWFYPETYYSDLQQKFFDKLALLSLPGAYQAKTPEERALAGALTQLLNFPSTPPLTLPTTNLQRQGNSVTNIYGNGNNVTTDVGANGWAPTVSTGLGDGPVSASADSLPGRSGGASSEKTHTVSGSSNKVGSRFSKWWEPAAARASESATDSAIEGIDAAGKAASKAITRKLDRPAAPSSTANPQPSLIALNPSATQSGNASILTGSTAPSLLAYPTATPVPLPNPDEPSQPGPSGDRTWLLDTVTWSQEFTRGWNIAGSNGMQWTGLESLIFPVSTDTNWTSTSSPTAYPLPFSFVRAYPDSSWAAMYNTHSMWNCGWRVQVTVNGSQFHAGALILYMVPEATTHAIQTARDNAGFVFPYVILNLYESNTATIEVPYISPTPNTSSGLHAPWTFYLQVLSPLNPPPSLPTSLSCSIYVTPVDSSFHGLRYLAPQHWKTRAVPGAGTFGSAVAGQELPLCGVRAYYPPNAYIPAQVRDWLEFAHRPGLMATVPWTMADEPAERLGIFPVSPSAIAGTGAPISYVISLFSQWRGELAAHLLFTGSAQHYGRLVVCYTPAAPQPPSTMQEAMRGTYTVWDVNAASTLEFTIPFISNSYWKTVDVNNPDALLSTTGYVSIWVQNPLVGPHTAPASALVQAFISAGESFNVRLMQNPALTSQTLTEDLDAPQDTGNIENGAADNSPQPRTTFDYTGNPLPPDTKLENFFSFYRLLPMGGSGAPSLSFPADEGTIIPLNPINWLKGADVSGIAAMLSCFTYIAADLRITLRFSNPNDNPATMLVAFAPPGATIPLKPTRQMLSNFYMAEVPVSAATSTMVSFSIPYTSPLSAIPTSYFGWEDWSGTNFGQLSSGSWGNLMLIPSLSVDSAIPFDFQLSCWVAFGNFKAWVPRPPPPLPPLPTPAANAERTVAVIKQGAASATPDVDPDDRVYIVRAQRPTYVHWAIRKVAPDGSAKQISLSRSGIQALVALEPPEGEPYLEILPSHWTLAELQLGNKWEYSATNNCTHFVSSITGESLPNTGFSLALGIGALTAIAASAAVAVKALPGIRRQGLLTLSADTETNQTLNKITESVNQAAQVVSQFDLSGPANSVSLAASDIREAAHKVASSLNGFTDVIADIKDSLFTRVSDAVESGVATFLTWLVKLFGYLLVLFGSPTPMSISGLLVIICADLAPHAREFFTASGNVLSSLYYWIASKLGLSVTPQECERATLEPQGLKDFNDGALAMRNVEWIGETAWKWAHRLLDWIRGKAKTDPQAKLADVHDEIMLHYSDSILALGSEKLPIDHITKSISRCRELVSIAQEAKSGPHSSFLNQAIKNYTLAISQHRKCQTGPRPEPVVVYLYGPPGTGKSLLASLLAQTLSQRLAGTPDDVYSPSSASCEYFDGYTGQTVHFIDDIGQDPEGRDWANFPNLVSSAPFIVPMASLEEKGTHYTSKVIVVTSNFHEPNERAARSMGALRRRVHLRINVTSNGVPFDPTNALNPIPGTQSKYFTAQTPLTLFQSNTVRLDRDSIWTPTFTNMDELVDAIVTRLDRSTGVSNSLASLIRRQGNRVIDAEPREIPLEYADDLLEAMAHHRPVPCSLGLSQAIANNTPIQQISETFWKYRKPIFTCTTFLAVLGFLCSVIPLARSLWKSKQDTPQEPQAAYSAISHQKPKPKSQKPVPTRHIQRQGISPAVPGISNNVVHVESGNGLNKNVMSGFYIFSRFLLVPTHLREPHHTTLTVGADTYDWATLQTQEFGEITIVHTPTSRQYKDMRRFIGAHPHPTGLLVSQFKAAPLYVRISDNRILDLDFPGVVVCKQAYGYRAATFEGLCGSPLVTDDPSGVKILGLHVAGVAGTSGFSAPIHPILGQITQFATTQQSLIVPTAEVRPGVNVNRMSRLHPSPAYGAFPVKKQPAPLKRNDKRLQEGVDLDTQLFLKHGKGDVTEPWPGLEAAADLYFSTFPTSLPVLTQEQAIHGTPNMEGLDMGQAAGYPWNTLGRSRRSLFDEVEPGVFVPKPELQAEINQTLEDPDYVYSTFLKDELRPTAKVEQGLTRIVEAAPIHAIVAGRMLLGGLIDYMQGRPGEHGSAVGCNPDVHWTSFFYAFSEFSQVYDLDYKCFDATLPSAVFTLVADHLTRITGDPRVGRYIHSIRHSHHIYGNRMYDMIGGNPSGCVATSILNTIINNICVLSALIQHPDFSPSRFHILAYGDDVIYATEPPIHPSFLREFYQKHTPLVVTPANKGQDFPPTSTIYEVTFLKRWFVPDDVRPIYIHPVMDPDTYEQSVMWLRDGDFQDVVTSLCHLAFHSGPKTYAAWCMKVREQCLKSGFAPNFLPYSYLQLRWLNLLAA
|
2.7.7.48; 3.4.22.28; 3.6.4.13
| null |
DNA-templated transcription [GO:0006351]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; suppression by virus of host mRNA export from nucleus [GO:0039522]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]
|
host cell cytoplasmic vesicle membrane [GO:0044162]; host cell Golgi membrane [GO:0044178]; membrane [GO:0016020]; T=pseudo3 icosahedral viral capsid [GO:0039618]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; structural molecule activity [GO:0005198]
|
PF00548;PF00680;PF00073;PF00910;
|
1.20.960.20;2.60.120.20;3.30.70.270;3.40.50.300;2.40.10.10;
| null |
PTM: [Genome polyprotein]: Specific enzymatic cleavages by the viral protease in vivo yield a variety of precursors and mature proteins (PubMed:22226945). The leader protein-VP0 junction is cleaved by 3C proteinase (PubMed:14512530). The VP1/2A junction is cleaved by the protein 3CD in association with protein 2A (PubMed:22226945). {ECO:0000269|PubMed:14512530, ECO:0000269|PubMed:22226945}.; PTM: [VPg]: Uridylylated by the polymerase and is covalently linked to the 5'-end of genomic RNA. This uridylylated form acts as a nucleotide-peptide primer for the polymerase. {ECO:0000250|UniProtKB:P12296}.
|
SUBCELLULAR LOCATION: [Capsid protein VP0]: Virion {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}. Host cytoplasm {ECO:0000250|UniProtKB:P12296}.; SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}. Host cytoplasm {ECO:0000250|UniProtKB:P12296}.; SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}. Host cytoplasm {ECO:0000250|UniProtKB:P12296}.; SUBCELLULAR LOCATION: [Protein 2B]: Host cytoplasmic vesicle membrane {ECO:0000269|PubMed:22124328, ECO:0000269|PubMed:24672044}; Peripheral membrane protein {ECO:0000250|UniProtKB:P03304}; Cytoplasmic side {ECO:0000250|UniProtKB:P03304}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are probably autophagosome-like vesicles. {ECO:0000250|UniProtKB:P03304}.; SUBCELLULAR LOCATION: [Protein 2C]: Host cytoplasmic vesicle membrane {ECO:0000269|PubMed:22124328, ECO:0000269|PubMed:24672044}; Peripheral membrane protein {ECO:0000250|UniProtKB:P03304}; Cytoplasmic side {ECO:0000250|UniProtKB:P03304}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are probably autophagosome-like vesicles. {ECO:0000250|UniProtKB:P03304}.; SUBCELLULAR LOCATION: [Protein 3A]: Host cytoplasmic vesicle membrane {ECO:0000269|PubMed:22124328, ECO:0000269|PubMed:24672044}; Single-pass membrane protein {ECO:0000255}. Host Golgi apparatus membrane {ECO:0000269|PubMed:30755512}; Single-pass membrane protein {ECO:0000255}. Note=Probably localizes to intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. {ECO:0000250|UniProtKB:P03304}.; SUBCELLULAR LOCATION: [VPg]: Virion {ECO:0000250|UniProtKB:P03304}.; SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm {ECO:0000250|UniProtKB:P03304}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P03304}; Peripheral membrane protein {ECO:0000250|UniProtKB:P03304}; Cytoplasmic side {ECO:0000250|UniProtKB:P03304}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are probably autophagosome-like vesicles. {ECO:0000250|UniProtKB:P03304}.
|
CATALYTIC ACTIVITY: Reaction=Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.; EC=3.4.22.28; Evidence={ECO:0000255|PROSITE-ProRule:PRU01222}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P03300};
| null | null | null | null |
FUNCTION: [Leader protein]: Inhibits the integrated stress response (ISR) in the infected cell by preventing the sequestration of eIF2B by phosphorylated EIF2S1/eIF-2alpha (PubMed:32690955). Stress granule formation in response to EIF2S1/eIF-2alpha phosphorylation is thus inhibited, which allows protein synthesis and viral replication (PubMed:32690955). Does not have any proteolytic activity (PubMed:14512530). Required for viral RNA replication and viral RNA encapsidation (PubMed:14512530). {ECO:0000269|PubMed:14512530, ECO:0000269|PubMed:32690955}.; FUNCTION: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP3 (PubMed:27595320, PubMed:27681122). Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3 (PubMed:27595320, PubMed:27681122). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:27595320). {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}.; FUNCTION: [Capsid protein VP0]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP1 and VP3 (PubMed:27595320, PubMed:27681122). Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3 (PubMed:27595320, PubMed:27681122). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:27595320). {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}.; FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP1 (PubMed:27595320, PubMed:27681122). Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3 (PubMed:27595320, PubMed:27681122). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:27595320). {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}.; FUNCTION: [Protein 2A]: Required for viral RNA replication (PubMed:18653460). Does not have any proteolytic activity (PubMed:18653460). {ECO:0000269|PubMed:18653460}.; FUNCTION: [Protein 2B]: Affects membrane integrity and causes an increase in membrane permeability. {ECO:0000250}.; FUNCTION: [Protein 2C]: Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 3A]: Serves as membrane anchor via its hydrophobic domain. Plays an essential role in viral RNA replication by recruiting PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place (PubMed:22124328, PubMed:22258260, PubMed:24672044, PubMed:27989622, PubMed:30755512). Stimulates the enzymatic activity of PI4KB, this activation is sensitized by ACBD3 (PubMed:24672044, PubMed:27989622). {ECO:0000269|PubMed:22124328, ECO:0000269|PubMed:22258260, ECO:0000269|PubMed:24672044, ECO:0000269|PubMed:27989622, ECO:0000269|PubMed:30755512}.; FUNCTION: [VPg]: Forms a primer, VPg-pU, which is utilized by the polymerase for the initiation of RNA chains. {ECO:0000250|UniProtKB:P03304}.; FUNCTION: [Protease 3C]: Cysteine protease that generates mature viral proteins from the precursor polyprotein (By similarity). In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate cooperatively bind to the protease (By similarity). {ECO:0000250|UniProtKB:P03304, ECO:0000250|UniProtKB:P12296}.; FUNCTION: [RNA-directed RNA polymerase]: Replicates the genomic and antigenomic RNAs by recognizing replications specific signals (By similarity). Performs VPg uridylylation (By similarity). {ECO:0000250|UniProtKB:P12296}.
|
Aichi virus (strain Human/A846/88/1989) (AiV) (Aichi virus (strain A846/88))
|
O91532
|
HBEAG_HBVA7
|
MQLFHLCLIISCTCPTVQASKLCLGWLWGMDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQAILCWVELMTLATWVGNNLQDPASRDLVVNYVNTNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRDRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC
| null | null |
microtubule-dependent intracellular transport of viral material towards nucleus [GO:0075521]; symbiont entry into host cell [GO:0046718]; viral penetration into host nucleus [GO:0075732]; virus-mediated perturbation of host defense response [GO:0019049]
|
extracellular region [GO:0005576]; host cell [GO:0043657]; host cell cytoplasm [GO:0030430]; host cell nucleus [GO:0042025]; T=4 icosahedral viral capsid [GO:0039619]
|
DNA binding [GO:0003677]; RNA binding [GO:0003723]; structural molecule activity [GO:0005198]
|
PF08290;PF00906;
|
1.10.4090.10;
|
Orthohepadnavirus precore antigen family
|
PTM: Phosphorylated. {ECO:0000255|HAMAP-Rule:MF_04076}.; PTM: Cleaved by host furin. {ECO:0000255|HAMAP-Rule:MF_04076}.
|
SUBCELLULAR LOCATION: Secreted {ECO:0000255|HAMAP-Rule:MF_04076}. Host nucleus {ECO:0000255|HAMAP-Rule:MF_04076}.
| null | null | null | null | null |
FUNCTION: May regulate immune response to the intracellular capsid in acting as a T-cell tolerogen, by having an immunoregulatory effect which prevents destruction of infected cells by cytotoxic T-cells. This immune regulation may predispose to chronicity during perinatal infections and prevent severe liver injury during adult infections. {ECO:0000255|HAMAP-Rule:MF_04076}.
|
Hepatitis B virus genotype A2 (isolate Japan/11D11HCCW/1998) (HBV-A)
|
O91534
|
HBSAG_HBVA7
|
MGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGFTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQTLQDPRVRGLYLPAGGSSSGTVNPAPNIASHISSISARTGDPVTNMENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGSPVCLGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLIPGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIPSSWAFAKFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMMWYWGPSLYSIVRPFIPLLPIFFCLWVYI
| null | null |
caveolin-mediated endocytosis of virus by host cell [GO:0075513]; fusion of virus membrane with host endosome membrane [GO:0039654]; virion attachment to host cell [GO:0019062]
|
membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
| null |
PF00695;
| null |
Orthohepadnavirus major surface antigen family
|
PTM: Isoform M is N-terminally acetylated by host at a ratio of 90%, and N-glycosylated by host at the pre-S2 region. {ECO:0000250|UniProtKB:P03138, ECO:0000255|HAMAP-Rule:MF_04075}.; PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04075}.
|
SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04075}.
| null | null | null | null | null |
FUNCTION: The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches the virus to cell receptors and thereby initiating infection. This interaction determines the species specificity and liver tropism. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis. The large envelope protein also assures fusion between virion membrane and endosomal membrane. In its internal conformation the protein plays a role in virion morphogenesis and mediates the contact with the nucleocapsid like a matrix protein. {ECO:0000255|HAMAP-Rule:MF_04075}.; FUNCTION: The middle envelope protein plays an important role in the budding of the virion. It is involved in the induction of budding in a nucleocapsid independent way. In this process the majority of envelope proteins bud to form subviral lipoprotein particles of 22 nm of diameter that do not contain a nucleocapsid. {ECO:0000255|HAMAP-Rule:MF_04075}.
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Hepatitis B virus genotype A2 (isolate Japan/11D11HCCW/1998) (HBV-A)
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O91734
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POLG_EC01F
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MGAQVSTQKTGAHETSLSATGNSIIHYTNINYYKDAASNSANRQDFTQDPGKFTEPMKDVMIKTLPALNSPTVEECGYSDRVRSITLGNSTITTQECANVVVGYGEWPEYLSDNEATAEDQPTQPDVATCRFYTLDSVQWENGSPGWWWKFPDALRDMGLFGQNMYYHYLGRAGYTIHVQCNASKFHQGCILVVCVPEAEMGSAQTSGVVNYEHISKGEIASRFTTTTTAEDHGVQAAVWNAGMGVGVGNLTIFPHQWINLRTNNSATIVMPYVNSVPMDNMYRHHNFTLMIIPFVPLDFSAGASTYVPITVTVAPMCAEYNGLRLAGHQGLPTMNTPGSNQFLTSDDFQSPSAMPQFDVTPEMHIPGEVRNLMEIAEVDSVMPINNDSAAKVSSMEAYRVELSTNTNAGTQVFGFQLNPGAESVMNRTLMGEILNYYAHWSGSIKITFVFCGSAMTTGKFLLSYAPPGAGAPKTRKDAMLGTHVVWDVGLQSSCVLCIPWISQTHYRFVEKDPYTNAGFVTCWYQTSVVSPASNQPKCYMMCMVSACNDFSVRMLRDTKFIEQTSFYQGDVQNAVEGAMVRVADTVQTSATNSERVPNLTAVETGHTSQAVPGDTMQTRHVINNHVRSESTIENFLARSACVFYLEYKTGTKEDSNSFNNWVITTRRVAQLRRKLEMFTYLRFDMEITVVITSSQDQSTSQNQNAPVLTHQIMYVPPGGPIPVSVDDYSWQTSTNPSIFWTEGNAPARMSIPFISIGNAYSNFYDGWSHFSQAGVYGFTTLNNMGQLFFRHVNKPNPAAITSVARIYFKPKHVRAWVPRPPRLCPYINSTNVNFEPKPVTEVRTNIITTGAFGQQSGAVYVGNYRVVNRHLATHIDWQNCVWEDYNRDLLVSTTTAHGCDTIARCQCTTGVYFCLSRNKHYPVSFEGPGLVEVQESEYYPKRYQSHVLLAAGFSEPGDCGGILRCEHGVIGIVTMGGEGVVGFADVRDLLWLEDDAMEQGVKDYVEQLGNAFGSGFTNQICEQVNLLKESLVGQDSILEKSLKALVKIISALVIVVRNHDDLITVTATLALIGCTSSPWRWLKQKVSQYYGIPMAERQNNGWLKKFTEMTNACKGMEWIAIKIQKFIEWLKVKILPEVKEKHEFLNRLKQLPLLESQIATIEQSAPSQGDQEQLFSNVQYFAHYCRKYAPLYAAEAKRVFSLEKKMSNYIQFKSKCRIEPVCLLLHGSPGAGKSVATNLIGRSLAEKLNSSVYSLPPDPDHFDGYKQQAVVIMDDLCQNPDGKDVSLFCQMVSSVDFVPPMAALEEKGILFTSPFVLASTNAGSINAPTVSDSRALARRFHFDMNIEVISMYSQNGKINMPMSVKTCDEDCCPVNFKKCCPLVCGKAIQFIDRKTQVRYSLDMLVTEMFREYNHRHSVGATLEALFQGPPVYREIKISVAPETPPPPAIADLLKSVDSEAVREYCKEKGWLVPEISSTLQIEKHVSRAFICLQALTTFVSVAGIIYIIYKLFAGFQGAYTGMPNQKPKVPTLRQAKVQGPAFEFAVAMMKRNASTVKTEYGEFTMLGIYDRWAVLPRHAKPGPTILMNDQEVGVLDAKELVDKDGTNLELTLLKLNRNEKFRDIRGFLAREEAEVNEAVLAINTSKFPNMYIPVGQVTDYGFLNLGGTPTKRMLMYNFPTRAGQCGGVLMSTGKVLGIHVGGNGHQGFSAALLRHYFNEEQGEIEFIESSKDAGFPVINTPSKTKLEPSVFHQVFEGNKEPAVLRNGDPRLKVNFEEAIFSKYIGNVNTHVDEYMQEAVDHYAGQLATLDISTEPMKLEDAVYGTEGLEALDLTTSAGYPYVALGIKKRDILSKKTKDLTKLKECMDKYGLNLPMVTYVKDELRSAEKVAKGKSRLIEASSLNDSVAMRQTFGNLYKTFHLNPGIVTGSAVGCDPDVFWSKIPVMLDGHLIAFDYSGYDASLSPVWFACLKLLLEKLGYTNKETNYIDYLCNSHHLYRDKHYFVRGGMPSGCSGTSIFNSMINNIIIRTLMLKVYKGIDLDQFRMIAYGDDVIASYPWPIDASLLAEAGKDYGLIMTPADKGECFNEVTWTNVTFLKRYFRADEQYPFLVHPVMPMKDIHESIRWTKDPKNTQDHVRSLCLLAWHNGEHEYEEFIRKIRSVPVGRCLTLPAFSTLRRKWLDSF
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2.7.7.48; 3.4.22.28; 3.4.22.29; 3.6.1.15
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COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P03300}; Note=Binds 2 magnesium ions that constitute a dinuclear catalytic metal center (By similarity). The magnesium ions are not prebound but only present for catalysis (By similarity). Requires the presence of 3CDpro or 3CPro (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03313};
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caveolin-mediated endocytosis of virus by host cell [GO:0075513]; DNA replication [GO:0006260]; DNA-templated transcription [GO:0006351]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; suppression by virus of host mRNA export from nucleus [GO:0039522]; symbiont genome entry into host cell via pore formation in plasma membrane [GO:0044694]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity [GO:0039540]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
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host cell cytoplasmic vesicle membrane [GO:0044162]; host cell nucleus [GO:0042025]; membrane [GO:0016020]; T=pseudo3 icosahedral viral capsid [GO:0039618]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; metal ion binding [GO:0046872]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; structural molecule activity [GO:0005198]
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PF08727;PF00548;PF02226;PF00947;PF01552;PF00680;PF00073;PF00910;
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1.20.960.20;2.60.120.20;3.30.70.270;4.10.80.10;6.10.20.20;4.10.880.10;2.40.10.10;
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Picornaviruses polyprotein family
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PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo by the viral proteases yield processing intermediates and the mature proteins. {ECO:0000250|UniProtKB:P03300}.; PTM: [Capsid protein VP0]: Myristoylation is required for the formation of pentamers during virus assembly. Further assembly of 12 pentamers and a molecule of genomic RNA generates the provirion. {ECO:0000250|UniProtKB:P03300}.; PTM: [Capsid protein VP0]: During virion maturation, immature virions are rendered infectious following cleavage of VP0 into VP4 and VP2. This maturation seems to be an autocatalytic event triggered by the presence of RNA in the capsid and it is followed by a conformational change infectious virion. {ECO:0000250|UniProtKB:P03300}.; PTM: [Capsid protein VP4]: Myristoylation is required during RNA encapsidation and formation of the mature virus particle. {ECO:0000250|UniProtKB:P03300}.; PTM: [Viral protein genome-linked]: VPg is uridylylated by the polymerase into VPg-pUpU. This acts as a nucleotide-peptide primer for the genomic RNA replication. {ECO:0000250|UniProtKB:P03300}.
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SUBCELLULAR LOCATION: [Capsid protein VP0]: Virion. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP4]: Virion.; SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Protein 2B]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Protein 2C]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Protein 3A]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Protein 3AB]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Viral protein genome-linked]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000250|UniProtKB:Q66478}.; SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm.; SUBCELLULAR LOCATION: [Protein 3CD]: Host nucleus {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000250|UniProtKB:P03300}. Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.
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CATALYTIC ACTIVITY: [Protein 2C]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P03300}; CATALYTIC ACTIVITY: [Protease 2A]: Reaction=Selective cleavage of Tyr-|-Gly bond in the picornavirus polyprotein.; EC=3.4.22.29; Evidence={ECO:0000250|UniProtKB:P03300}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: [Protease 3C]: Reaction=Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.; EC=3.4.22.28; Evidence={ECO:0000255|PROSITE-ProRule:PRU01222};
| null | null | null | null |
FUNCTION: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Capsid protein VP1 mainly forms the vertices of the capsid (By similarity). Capsid protein VP1 interacts with host ITGA2/ITGB1 to provide virion attachment to target host cells (By similarity). This attachment induces virion internalization predominantly through caveolin-mediated endocytosis (PubMed:11799180, PubMed:15356270). Tyrosine kinases are probably involved in the entry process (By similarity). After binding to its receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized (By similarity). Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000269|PubMed:11799180, ECO:0000269|PubMed:15356270}.; FUNCTION: [Capsid protein VP2]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Capsid protein VP4]: Lies on the inner surface of the capsid shell (By similarity). After binding to the host receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Capsid protein VP0]: Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation (By similarity). Allows the capsid to remain inactive before the maturation step (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protease 2A]: Cysteine protease that cleaves viral polyprotein and specific host proteins (By similarity). It is responsible for the autocatalytic cleavage between the P1 and P2 regions, which is the first cleavage occurring in the polyprotein (By similarity). Cleaves also the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA translation (By similarity). Inhibits the host nucleus-cytoplasm protein and RNA trafficking by cleaving host members of the nuclear pores (By similarity). Counteracts stress granule formation probably by antagonizing its assembly or promoting its dissassembly (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03301}.; FUNCTION: [Protein 2B]: Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 2C]: Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 3AB]: Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 3A]: Localizes the viral replication complex to the surface of membranous vesicles (By similarity). It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction (By similarity). This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface (By similarity). Plays an essential role in viral RNA replication by recruiting ACBD3 and PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03313}.; FUNCTION: [Viral protein genome-linked]: Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU (By similarity). The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome (By similarity). Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By similarity). During the late stage of the replication cycle, host TDP2 is excluded from sites of viral RNA synthesis and encapsidation, allowing for the generation of progeny virions (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 3CD]: Involved in the viral replication complex and viral polypeptide maturation. It exhibits protease activity with a specificity and catalytic efficiency that is different from protease 3C. Protein 3CD lacks polymerase activity. Protein 3CD binds to the 5'UTR of the viral genome. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [RNA-directed RNA polymerase]: Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protease 3C]: Major viral protease that mediates proteolytic processing of the polyprotein (By similarity). Cleaves host EIF5B, contributing to host translation shutoff (By similarity). Cleaves also host PABPC1, contributing to host translation shutoff (By similarity). Cleaves host NLRP1, triggers host N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03303}.
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Echovirus 1 (strain Human/Egypt/Farouk/1951) (E-1)
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O91936
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POLG_HCVSA
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MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPTGRSWGQPGYPWPLYANEGLGWAGWLLSPRGSRPNWGPNDPRRKSRNLGKVIDTLTCGFADLMGYIPLVGGPVGGVARALAHGVRVLEDGVNYATGNLPGCSFSIFILALLSCLTVPTSAVPYRNASGVYHVTNDCPNSSIVYEAEDLILHAPGCVPCVRQGNVSRCWVQITPTLSAPSLGAVTAPLRRAVDYLAGGAALCSALYVGDACGAVFLVGQMFTYSPRRHNVVQDCNCSIYSGHITGHRMAWDMMMNWSPTTALVMAQLLRIPQVVIDIIAGAHWGVLFAAAYYASAANWAKVVLVLFLFAGVDANTRTVGGSAAQGARGLASLFTPGPQQNLQLINTNGSWHINRTALNCNDSLQTGFVAGLLYYHKFNSTGCPQRMASCRPLAAFDQGWGTISYAAVSGPSDDKPYCWHYPPRPCGIVPARGVCGPVYCFTPSPVVVGTTDRKGNPTYSWGENETDIFLLNNTRPPTGNWFGCTWMNSTGFVKTCGAPPCNLGPTGNNSLKCPTDCFRKHPDATYTKCGSGPWLTPRCLVHYPYRLWHYPCTLNYTIFKVRMYIGGLEHRLEVACNWTRGERCDLEDRDRAELSPLLHTTTQWAILPCSFTPTPALSTGLIHLHQNIVDTQYLYGLSSSIVSWAVKWEYIVLAFLLLADARICTCLWIMLLVCQAEAALENVIVLNAAAAAGTHGFFWGLLVICFAWHFKGRLVPGATYLCLGIWPLLLLLFLLPQRALALDSSDGGTVGCLVLTILTIFTLTPGYKKMVVLVIWWLQYFIARVEAFIHVWVPPLQVRGGRDAIIMLTCLFHPALGFEVTKILLGILGPLYLLQYSLIKLPYFIRARALLRACLLAKHLACGRYVQAALLHLGRLTGTYIYDHLAPMKDWAASGLRDLAVATEPIIFSPMETKVITWGADTAACGDILAGLPVSARRGHEIFLGPADDIREAGWRLLAPITAYAQQTRGVLGAIIVSLTGRDKNEAEGEVQVLSTATQTFLGTCINGVMWTVFHGAGAKTLAGPKGPVVQMYTNVDKDLVGWPTPPGTRSLTPCTCGSADLYLVTRHADVVPARRRGDTRASLLSPRPISYLKGSSGGPVMCPSGHVVGVFRAAVCTRGVAKALDFIPVENLETTMRSPVFTDNSTPPAVPHEFQVGHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSRAYGVDPNIRTGVRTVTTGAAITYSTYGKFLADGGCSGGAYDVIICDECHSQDATTILGIGTVLDQAETAGARLVVLATATPPGSVTTPHPNIEEVALPSEGEIPFYGRAIPLALIKGGRHLIFCHSKKKCDELAKQLTSQGVNAVAYYRGLDVAVIPATGDVVVCSTDALMTGFTGDFDSVIDCNTTVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRHGIYRYVSSGERPSGIFDSVVLCECYDAGCAWYDLTPAETTVRLRAYLNTPGLPVCQDHLEFWEGVFTGLTNIDAHMLSQTKQGGENFPYLVAYQATVCVRAKAPPPSWDTMWKCMLRLKPTLTGPTPLLYRLGAVQNEITLTHPITKYIMACMSADLEVITSTWVLVGGVVAALAAYCLTVGSVAIVGRIILSGRPAIIPDREVLYQQFDEMEECSASLPYMDEARAIAEQFKEKVLGLIGTAGQKAETLKPAATSMWNRAEQFWAKHMWNFVSGIQYLAGLSTLPGNPAVATLMSFTAAVTSPLTTQQTLLFNILGGWVASQIAPPTAATAFVVSGMAGAAVGSIGLGRVLIDILAGYGAGVAGALVAFKIMCGEKPTAEDLVNLLPSILCPGALVVGVICAAVLRRHIGPGEGAVQWMNRLIAFASRGNHVSPTHYVPETDASAKVTQLLSSLTVTSLLKRLHTWIGEDYSTPCDGTWLRAIWDWVCTALTDFKAWLQAKLLPQLPGVPFLSCQRGYRGVWRGDGVNSTKCPCGATISGHVKNGTMRIVGPKLCSNTWHGTFPINATTTGPSVPAPAPNYKFALWRVGAADYAEVRRVGDYHYITGVTQDNLKCPCQVPSPEFFTELDGVRIHRYAPPCNPLLREEVCFSVGLHSFVVGSQLPCEPEPDVTVLTSMLSDPAHITAETAKRRLDRGSPPSLASSSASQLSAPSLKATCTTQGHHPDADLIEANLLWRQCMGGNITRVEAENKVVILDSFEPLKADDDDREISVSADCFRRGPAFPPALPIWARPGYDPPLLETWKQPDYDPPQVSGCPLPPAGLPPVPPPRRKRKPVVLSDSNVSQVLADLAHARFKADTQSIEGQDSAVGTSSQPDSGPEEKRDDDSDAASYSSMPPLEGEPGDPDLSSGSWSTVSDEDSVVCCSMSYSWTGALITPCSAEEEKLPINPLSNTLLRHHNLVYSTSSRSAGQRQKKVTFDRLQVLDDHYREVVDEMKRLASKVKARLLPLEEACGLTPPHSARSKYGYGAKEVRSLDKKALNHIKGVWQDLLDDSDTPLPTTIMAKNEVFAVEPSKGGKKPARLIVYPDLGVRVCEKRALYDIAQKLPTALMGPSYGFQYSPAQRVEFLLKTWRSKKTPMAFSYDTRCFDSTVTEHDIMTEESIYQSCDLQPEARAAIRSLTQRLYCGGPMYNSKGQQCGYRRCRASGVFTTSMGNTMTCYIKALASCRAAKLRDCTLLVCGDDLVAICESQGTHEDEASLRAFTEAMTRYSAPPGDPPVPAYDLELVTSCSSNVSVAHDASGNRVYYLTRDPQVPLARAAWETAKHSPVNSWLGNIIMYAPTLWARIVLMTHFFSVLQSQEQLEKALAFEMYGSVYSVTPLDLPAIIQRLHGLSAFTLHSYSPSEINRVSSCLRKLGVPPLRAWRHRARAVRAKLIAQGGKAAICGIYLFNWAVKTKRKLTPLADADRLDLSSWFTVGAGGGDIYHSMSRARPRCILLCLLLLTVGVGIFLLPAR
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2.7.7.48; 3.4.21.98; 3.4.22.-; 3.6.1.15; 3.6.4.13
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COFACTOR: [Protease NS2]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3). {ECO:0000250|UniProtKB:P26663}; COFACTOR: [Serine protease/helicase NS3]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9WMX2}; Note=Binds 1 zinc ion, which has a structural role (By similarity). The magnesium ion is essential for the helicase activity (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q9WMX2}; COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal center. {ECO:0000250|UniProtKB:P26663};
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clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint [GO:0039645]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity [GO:0039545]; symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity [GO:0039563]; symbiont-mediated suppression of host TRAF-mediated signal transduction [GO:0039527]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; transformation of host cell by virus [GO:0019087]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
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host cell endoplasmic reticulum membrane [GO:0044167]; host cell lipid droplet [GO:0044186]; host cell mitochondrial membrane [GO:0044191]; host cell nucleus [GO:0042025]; host cell perinuclear region of cytoplasm [GO:0044220]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; ribonucleoprotein complex [GO:1990904]; viral envelope [GO:0019031]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type endopeptidase activity [GO:0004252]; SH3 domain binding [GO:0017124]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF07652;PF01543;PF01542;PF01539;PF01560;PF01538;PF01006;PF01001;PF01506;PF08300;PF08301;PF12941;PF02907;PF00998;
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2.40.10.120;3.30.70.270;6.10.250.1610;6.10.250.1750;6.10.250.2920;2.20.25.210;3.30.160.890;2.30.30.710;1.20.1280.150;2.20.25.220;3.40.50.300;1.10.820.10;2.40.10.10;
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Hepacivirus polyprotein family
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PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (By similarity). Cleavage by the signal peptidase releases the 21 kDa mature core protein (By similarity). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (By similarity). Some degraded forms of the core protein appear as well during the course of infection (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; PTM: [Mature core protein]: Phosphorylated by host PKC and PKA. {ECO:0000250|UniProtKB:Q01403}.; PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q03463}.; PTM: [Envelope glycoprotein E1]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Envelope glycoprotein E2]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Protease NS2]: Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 4B]: Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal form termed p56 (By similarity). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664}.; PTM: [Non-structural protein 5A]: Tyrosine phosphorylation is essential for the interaction with host SRC. {ECO:0000250|UniProtKB:Q99IB8}.; PTM: [RNA-directed RNA polymerase]: The N-terminus is phosphorylated by host PRK2/PKN2. {ECO:0000250|UniProtKB:P26662}.
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SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane protein {ECO:0000255}. Host mitochondrion membrane {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein {ECO:0000255}. Note=The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.; SUBCELLULAR LOCATION: [Mature core protein]: Virion {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm {ECO:0000250|UniProtKB:Q99IB8}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P27958}. Host cell membrane {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.; SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=NS3 is associated to the ER membrane through its binding to NS4A. {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Host membrane insertion occurs after processing by the NS3 protease.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-terminus into the ER lumen occurs post-translationally. {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Peripheral membrane protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}. Note=Host membrane insertion occurs after processing by the NS3 protease. {ECO:0000250|UniProtKB:P27958}.
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CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.; EC=3.4.21.98; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
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FUNCTION: [Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Protease NS2]: Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (By similarity). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4A]: Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS4B self-interaction contributes to its function in membranous web formation (By similarity). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. Initiates RNA transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host pattern recognition receptors can be bypassed, thereby evading activation of antiviral pathways. {ECO:0000250|UniProtKB:P27958}.
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Hepatitis C virus genotype 5a (isolate SA13) (HCV)
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O91940
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L_BRSVA
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MDTLIHENSTNVYLTDSYLKGVISFSECNALGSYLLDGPYLKNDYTNIISRQKPLIEHINLKKLSIIQSFVTKYNKGELGLEEPTYFQSLLMTYKSLSTSELITTTTLFKKIIRRAIEISDVKVYAILNKLGLKEKGKVDRCDDTNTTLSNIVRDNILSVISDNTPSTKKPNNSSCKPDQPIKTTILCKLLSSMSHPPTWLIHWFNLYTKLNDILTQYRTNEARNHGYILIDTRTLGEFQFILNQYGCIVYHKKLKKITITTYNQFLTWKDISLSRLNVCMITWISNCLNTLNKSLGLRCEFNNVTLSQLFLHGDCILKLFHNEGYYIIKEVEGFIMSLILNLTEEDQFRKRFFNSMLNNITDAAARAQQDLLSRARHTILDKTISDNILNGKWLILLGKFLKLIKLAGANNLNNLSELYFLFRIFGHPMVDERQAMDAVRLNCNETKFYLLSSLSMLSGAFIYRIIKGFVNTYNRWPTLRNAIVLPLRWINYYKLNTYPSLLELTEADLIILSGLRFYREFHLPKKVDLEVIINDKAISPPKNLIWTSFPKNYMPSHIQIYIEHERLKFTESDRSRRVLEYYLRNNRFSESDLYNCIVNQEYLNNPNHVISLTGKERELSVGRMFAMQPGMFRQVQIMAEKLIAENILQFFPESLTRYGDLELQKILELKAGISNKANRCNDNYNNYISKCSIITDLSKFNQAFRYETSCICSDVLDELHGVQSLFSWLHLTIPFATVICTYRHAPPYIRNHITDLNKVDEQSGLYRYHMGGIEGWCQKLWTIEAITLLDLISIKGKFSITALINGDNQSIDISKPIKLNEGQTHAQADYLLALKSLKLLYKEYASIGHKLKGTETYISRDMQFMSKTIQHNGVYYPASIKKVLRVGPWINTILDDFKVSMESIGSLTQELEYRGESLLCSLIFRNVWLYNQIALQLKNHALCHNKLYLDILKVLAHLKMFFNLDNIDTALTLYMNLPMLFGGGDPNLLYRSFYRRTPDFLTEAIAHSVFVLSYYTGHDLQDKLQDLPDDKLNKFLTCIITFDKNPNAEFVTLMRDPQALGSERQAKVTSEINRLAVTEVLSNAPNKIFAKSAQHYTTTEVDLNDVMQKIEPTYPHGLRVVYESLPFYKAEKIVNLISGTKSITNILEKTSAIDYTDIERAIDMMRKNITLLIRILPLDYNKAKLGLLSLNNLSITDISKYVRERSWSLSNIVGITSPSILYTMDIKYTTSTITSGIIIEKYNSNFLTRGERGPTKPWVGSSTQEKKTMPVYNRQVLTKKQKDQIDLLAKLDWVYASIDNKDEFMEVLCLGTLGLSYEKAKKLFPQYLSVNYLHRLTVSSRPCEFPASIPAYRTTNYHFDTSPINRILTEKYGDEDIDIVFQNCISFGLSLMSVVEQFTNVCPNRIILIPKLNEIHLMKPPIFTGDVDICKLNQVIQKQHMFLPDKISLSQYVELFLSNKTLKNSPHISSNLVLVHKMSDYFLHKYVLSTNLAGHWIMIIQLMKDSKGIFEKDWGEGYITDHMFLDLNVFFDAYKTYLLCFHKGYGKAKLECDMNTSDLFCTLELIDISYWKSMSKVFLEQKVVKHIINQDSSLHRVRGCHSFKLWFLKRLNTSKFIVCPWVVNIDYHPTHMKAILTYMELTTMGLVHVDKLYTDQKHKLNDGFYTSNLFYINYNFSDNTHLLTKQIRVANSELIDNYNTLYHPSPESLESILKRSNQSNNVIELKDYPIDKFQSPKGRGVSDITCISSNQKIKQGYNNQDLYNLFPAVIIDKIVDHSGNIANINQMYTITPNQLTLISNGTSLYCMLPWHHINRFNFVFSSTGCKISTKLILKDLKIKDPHCIAFIGEGAGNLLLRTVVELHPDIKYIYRSLKDCNDHSLPIEFLRLYNGHISIDYGENLTIPATDATNAIHWSYLHIRYAEPINLFVCDAELPDLTNWSRIVSEWYKHVRCCKYCSTIDRSKLIVKYHAQDITDFKLNNISIVKTYVCLGSKLKGSEVYLVLTVGPSNIFPSFNVVQNAKLILSRTQNFPMPKKIDKDSVDANIKSLIPFLCYPITKKGIKAALSKLKDVVDGNILSYSIAGRNEVYSNKLINYKLLNILKWLDHILNFRSLEFSYNHLYMIESTYPFLSELLNSLTTNELKKLIKVTGSVLYSLQHEL
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2.1.1.375; 2.7.7.48; 2.7.7.88; 3.6.1.-
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COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P28887}; Note=For RNA-directed RNA polymerase activity. Mn(2+) can stimulate de novo initiation but it is inefficient at supporting elongation of de novo initiated RNA. {ECO:0000250|UniProtKB:P28887};
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host cell cytoplasm [GO:0030430]; virion component [GO:0044423]
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ATP binding [GO:0005524]; GTPase activity [GO:0003924]; metal ion binding [GO:0046872]; mRNA 5'-cap (guanine-N7-)-methyltransferase activity [GO:0004482]; RNA-dependent RNA polymerase activity [GO:0003968]
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PF14314;PF14318;PF00946;
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Paramyxovirus L protein family
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SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P28887}. Host cytoplasm {ECO:0000250|UniProtKB:P28887}. Note=Localizes in cytoplasmic inclusion bodies. {ECO:0000250|UniProtKB:P28887}.
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CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000250|UniProtKB:P28887}; CATALYTIC ACTIVITY: Reaction=a 5'-end triphospho-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + GDP + H(+) = a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + diphosphate; Xref=Rhea:RHEA:65436, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16799, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:58189, ChEBI:CHEBI:156484, ChEBI:CHEBI:156503; EC=2.7.7.88; Evidence={ECO:0000250|UniProtKB:P28887}; CATALYTIC ACTIVITY: Reaction=a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + 2 S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-adenosine in mRNA + H(+) + 2 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:65376, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16798, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156483, ChEBI:CHEBI:156484; EC=2.1.1.375; Evidence={ECO:0000250|UniProtKB:P03523}; CATALYTIC ACTIVITY: Reaction=a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-methionine = a 5'-end (5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-adenosine in mRNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:65380, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16801, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156482, ChEBI:CHEBI:156484; Evidence={ECO:0000250|UniProtKB:P03523}; CATALYTIC ACTIVITY: Reaction=a 5'-end (5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:65440, Rhea:RHEA-COMP:16798, Rhea:RHEA-COMP:16801, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156482, ChEBI:CHEBI:156483; Evidence={ECO:0000250|UniProtKB:P03523};
| null | null | null | null |
FUNCTION: Responsible for RNA synthesis (replicase and transcriptase), cap addition, and cap methylation. Performs also the polyadenylation of subgenomic mRNAs by a stuttering mechanism at a slipery stop site present at the end of viral genes. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The viral polymerase binds to the genomic RNA at two different sites in the 3' leader promoter thereby initiating either genome replication or mRNA transcription. In the transcription mode, the polymerase performs the sequential transcription of all mRNAs using a termination-reinitiation mechanism responding to gene start and gene end signals. Some polymerase disengage from the template at each gene junction, resulting in a decreasing abundance of transcripts from the 3' to the 5' end of the genome. The first gene is the most transcribed, and the last the least transcribed. Needs as cofactors the phosphoprotein for processivity and the M2-1 anti-termination protein. Polyribonucleotidyl transferase (PRNTase) adds the cap structure when the nascent RNA chain length has reached few nucleotides (By similarity). Ribose 2'-O methylation of viral mRNA cap precedes and facilitates subsequent guanine-N-7 methylation (By similarity). In the replication mode, the polymerase replicates the whole viral genome without recognizing the gene end transcriptional signals. The ability of the polymerase to override the gene end signals as it is producing the antigenome is probably due to replicative RNA becoming encapsidated with nucleoprotein as it is synthesized (By similarity). {ECO:0000250|UniProtKB:P03523, ECO:0000250|UniProtKB:P28887}.
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Bovine respiratory syncytial virus (strain A51908) (BRS)
|
O92446
|
VP91_NPVBM
|
MMSGVMLLVFAIFLIIAFTLIYLAIYFKFDETTYTKRLQVMIEYIKRTNADEPTPNVIGYVSDITQNTYTVTWFNTVDLSTYQESVHDDRNEIFDFLNQKLQPVDRIVHDRVRANDENPNEFILSGDKDDVTMKCPAYFNFDYAQLKCVPVPPCDNKPAGRYPMDERLLDTLVLNQHLDKDYSSNEHLYHPTFYLRCFANGAHAVEECPDNYTFDAKTRQCKVNELCENRPDGYILSYFPSNLLVNQFMQCVSGRHVVRECPANKIFDRNLMSCVEAHPCTFNGAGHTYITADISDAQYFKCLNNNESQLMTCINRIRNSDNQYECSGDSRCIDLPNGTGQQVFKHADDDISYNSGQLVCDNFEIISNIECDQSNVFENKLFMDKFRLNMQFPTEVFDGTACVPATADNVNFLRSTFAIENIPNHYDIDMQTSMLGKIEMIKQLVSKDLSLNNDAIFAQWLLYARDKNAIGLNPLTGEPIDCFGNNLYDVFDARRANVCKDLGKSVLKTLNFGDGEFLNVLSDTLTGKDEDYRQFCAISYENGQKIVENEHFQRRILTNILQSDVCANIYTTLYQKYTTLNPKYTTTPLQYNRILVKRPKNIEIYGANTRLKNATIPKNATTISPVFNPFENQPNNRQNDSISPLFNPFQTTDAVWYSEPDGDEAVAPPPTAPPPPSEPEPEPEPELPSPLILDNKDLFYSCHYSVPFFKLTSCHAENDVIINALNELRNNVKVDADCESAKDLSHVLNAYAYVGNGIGCRSAYDGDAIVVKKEAVPSHVYANLNTQSNDGVKYNRWLHVKNDQYMACPEELYDNDEFKCNVESDKLYYLDNLQEDSIV
| null | null | null |
extracellular region [GO:0005576]; virion component [GO:0044423]
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chitin binding [GO:0008061]; metal ion binding [GO:0046872]
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PF08475;PF01607;
| null | null | null |
SUBCELLULAR LOCATION: Virion {ECO:0000250}. Note=In virions, associates with the capsid and maybe also with the envelope surrounding the capsid. {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Probable capsid-associated protein. {ECO:0000250}.
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Bombyx mori nuclear polyhedrosis virus (BmNPV)
|
O92529
|
POLG_HCVT5
|
MSTLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARPSQGRTWGQPGYPWPLYGNEGCGWAGWLMSPRGSRPSWGPNDPRRRSRNLGKVIDTLTCGLADLMGYIPVVGGPLGGVAAALAHGVRAIEDGINYATGNLPGCSFSIFILALLSCLTTPASALTYGNSSGLYHLTNDCPRSSIVLEAEAMILHLAGCVPCVRAGNISRCWHPVSPTLAVPNASVPASGFRKHVDLLAGAAVVCSSMYIGDLCGAVFLAGQLATFSPRIHDITQDCNCSVYTGHVTGHRMAWDMMMNWSPTTTLVLSSILRVPEIVLEVFAGGHWGVLIAIAYFGMSGNWLKVIAVLFLFAGVEATTTVGRAAGRSAYLFTSIFSSGPNQKIQLINTNGSWHINRTALNCIDSLQTGFLSALFYRSNFNSTGCSERLGACKPLEHFQQGWGPITHKSNITGPSEDRPYCWHYAPRECSVVPASSVCGPVYCFTPSPVVVGTTDRLGNPTYNWGENETDVFMLESLRPPQGGWFGCTWMNSTGFTKTCGAPPCQLIPGDYNSSSNQLLCPTDCFRKHPEATYQKCGSGPWLTPRCLVDYPYRLWHYPCTVNYTIHKVRMFIGGVEHRFDAACNWTRGDRCDLYDRDRIEMSPLLFSTTQLAILPCSFTTMPALSTGLIHLHQNIVDVQYLYGVSSSIVSWAVKWEYVVLMFLVLADARICTCLWLMLLVGKVEAALERLVVLNAASAAGTAGWCWTLIFLCCVWHVKGRLVPACTYTALGMWPILLVILALPQRAYAWDNSQAASLGVVALLVLTIFTLSPMYKQLLTHAIWWNQYMLARAEAMIHDWVPDLRVRGGRDAIILLTCLLHPHLGFEVTKILLAILAPLYILQHSLLKVPYFVRAHILLRACMFFRKVAAGKYVQACLLRLGAWTGTYIYDHLAPLSEWASDGLRDLAVAVEPVIFSPMEKKIITWGADTAACGDILRGLPVSARLGDLVLLGPADDMRHGGWKLLAPITAYAQQTRGLVGTIVTSLTGRDKNEAEGEVQVVSTATQSFLATTINGVLWTVYHGAGSKNLAGPKGPVCQMYTNVDQDLVGWPAPLGARSLAPCTCGSSDLYLVTRGADVIPARRRGDTRAALLSPRPISTLKGSSGGPLMCPSGHVVGLFRAAVCTRGVAKALDFIPVENMDTTMRSPVFTDNSSPPAVPQTYQVGYLHAPTGSGKSTRVPAAYATQGYKVLVLNPSVAATLSFGAYMSKAHGIDPNIRTGVRTITTGGPVTYSTYGKFLADGGCSGGAYDIIICDECHSTDPTTVLGIGTVLDQAETAGVRLTVLATATPPGSVTVPHPNITETALPTTGEIPFYGKCIPLEFIKGGRHLIFCHSKKKCDELSKQLTSLGLNAVAFYRGVDVAVIPTSGDVVVCATDALMTGYTGDFDSVIDCNVAVTQVVDFSLDPTFSIETTTVPQDAVSRSQRRGRTGRGKPGVYRFVSQGERPSGMFDSVVLCEAYDTGCAWYELTPAETTVRLRAYLNTPGLPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQGGENFAYLVAYQATVCARAKAPPPSWDVMWKCLTRLKPTLTGPTPLLYRLGAVQNEIVTTHPITKYIMTCMSADLEVITSTWVIVGGVLAALAAYCLTVGCVVICGRIVTSGKPAVVPDREVLYQQFDEMEECSKHIPYLVEGQQIAEQFKQKVLGLLQAGTKHAEELKPAIHSTWPRVEEFWRKHMWNFVSGIQYLAGLSTLPGSPAVASLMSFTASLTSPLRTSQTLLLNILGGWIASQVAPPSASTAFVVSGLAGATVASIGLGRVIVDILAGYGAGVAGALVAFKIMSGECPSTEDMVNLLPALLSPGALVVGVVCAAILRRHVGPSEGANQWMNRLIAFASRGNHVSPTHYVPETDASNKVTQILSSLTITSLLRRLHQWIHEDTSTPCASSWLRDVWDWVCTVLSDFKTWLKAKITPRIPGIPFISCQAGYRGVWAGDGVCHTTCSCGAQIAGHVKNGSMKITGPRMCSNTWHGTFPINATTTSPSVPVPAPNYKRALWRVSAEEYVEVERHGDRHYVVGVTADGLKCPCQVPGPEFFTEVDGVRIHRYAPPCKPLLRDEVSFSVGLLEFVVGSQLPCEPEPDVTVVTSMLTDPSHITAETASRRLKRGSPPSLASSSASQLSAPSLKATCTANGDHPDAELIEANLLWRQEMGSNITRVESETKVVILDSFDPLVAEYDDREISVSAECHRPPRPKFPPALPIWARPDYNPPLLQKWQMPGYEPPVVSGCALPPAKPTPIPPPRRKRLIQLDESAVSQALQQLADKVFVEDTSTSEPSSGLGGSIAGPSSPDPTTADDTCSDAGSFSSMPPLEGEPGDPDLSTGSWSTVSEEDDVVCCSMSYTWTGALITPCAAEEEKLPINPLSNSLIRHHNMVYSTTSRSAGLRQKKVTFDRLQVVDQHYQDVLKEIKLRASTVHARLLSTEEACSLTPPHSARSRYGYGARDVRSHTSKAVKHIDSVWEDLLEDNATPIPTTIMAKNEVFCVDPSKGGRKPARLIVYPDLSVRVCEKMALYDVTQKLPKTVMGSAYGFQYSPSQRVEYLLKMWRSKKTPMGFSYDTRCFDSTVTERDIRTEEDIYQSCQLDPTARKAISSLTERLYCGGPMFNSKGESCGYRRCRASGVLTTSLGNTLTCYLKAQAACRAANIKNFDMLVCGDDLVVICESAGVQEDVVALRAFTDAMIRYSAPPGDAPQPTYDLELITSCSSNVSVAHDGTGQRYYYLTRDCTTPLARAAWETARHTPVNSWLGNIIMYAPTIWVRMVLMTHFFSILQCQEQLEAALNFDMYGVTYSVTPLDLPAIIQRLHGMAAFSLHGYSPTELNRVGASLRKLGAPPLRAWRHRARAVRAKLIAQGGKAAICGKYLFNWAVKTKLKLTPLAAASQLDLSGWFVAGYDGGDIYHSVSRARPRLLLLGLLLLTVGVGIFLLPAR
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2.7.7.48; 3.4.21.98; 3.4.22.-; 3.6.1.15; 3.6.4.13
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COFACTOR: [Protease NS2]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3). {ECO:0000250|UniProtKB:P26663}; COFACTOR: [Serine protease/helicase NS3]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9WMX2}; Note=Binds 1 zinc ion, which has a structural role (By similarity). The magnesium ion is essential for the helicase activity (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q9WMX2}; COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal center. {ECO:0000250|UniProtKB:P26663};
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clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint [GO:0039645]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity [GO:0039545]; symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity [GO:0039563]; symbiont-mediated suppression of host TRAF-mediated signal transduction [GO:0039527]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; transformation of host cell by virus [GO:0019087]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
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host cell endoplasmic reticulum membrane [GO:0044167]; host cell lipid droplet [GO:0044186]; host cell mitochondrial membrane [GO:0044191]; host cell nucleus [GO:0042025]; host cell perinuclear region of cytoplasm [GO:0044220]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; ribonucleoprotein complex [GO:1990904]; viral envelope [GO:0019031]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type endopeptidase activity [GO:0004252]; SH3 domain binding [GO:0017124]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF07652;PF01543;PF01542;PF01539;PF01560;PF01538;PF01006;PF01001;PF01506;PF08300;PF08301;PF12941;PF02907;PF00998;
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2.40.10.120;3.30.70.270;6.10.250.1610;6.10.250.1750;6.10.250.2920;2.20.25.210;3.30.160.890;2.30.30.710;1.20.1280.150;2.20.25.220;3.40.50.300;1.10.820.10;2.40.10.10;
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Hepacivirus polyprotein family
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PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (By similarity). Cleavage by the signal peptidase releases the 21 kDa mature core protein (By similarity). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (By similarity). Some degraded forms of the core protein appear as well during the course of infection (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; PTM: [Mature core protein]: Phosphorylated by host PKC and PKA. {ECO:0000250|UniProtKB:Q01403}.; PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q03463}.; PTM: [Envelope glycoprotein E1]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Envelope glycoprotein E2]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Protease NS2]: Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 4B]: Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal form termed p56 (By similarity). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664}.; PTM: [Non-structural protein 5A]: Tyrosine phosphorylation is essential for the interaction with host SRC. {ECO:0000250|UniProtKB:Q99IB8}.; PTM: [Non-structural protein 5A]: Ubiquitinated (By similarity). Ubiquitination, most probably at Lys-2356, mediated by host IFI27 and SKP2 leads to proteasomal degradation, restricting viral infection (By similarity). Ubiquitination by host TRIM22 leads to interruption of viral replication (By similarity). {ECO:0000250|UniProtKB:P27958}.; PTM: [RNA-directed RNA polymerase]: The N-terminus is phosphorylated by host PRK2/PKN2. {ECO:0000250|UniProtKB:P26662}.
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SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane protein {ECO:0000255}. Host mitochondrion membrane {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein {ECO:0000255}. Note=The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.; SUBCELLULAR LOCATION: [Mature core protein]: Virion {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm {ECO:0000250|UniProtKB:Q99IB8}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P27958}. Host cell membrane {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.; SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=NS3 is associated to the ER membrane through its binding to NS4A. {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Host membrane insertion occurs after processing by the NS3 protease.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-terminus into the ER lumen occurs post-translationally. {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Peripheral membrane protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}. Note=Host membrane insertion occurs after processing by the NS3 protease. {ECO:0000250|UniProtKB:P27958}.
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CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.; EC=3.4.21.98; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
| null | null | null | null |
FUNCTION: [Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Protease NS2]: Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (By similarity). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4A]: Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS4B self-interaction contributes to its function in membranous web formation (By similarity). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. Initiates RNA transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host pattern recognition receptors can be bypassed, thereby evading activation of antiviral pathways. {ECO:0000250|UniProtKB:P27958}.
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Hepatitis C virus genotype 6b (isolate Th580) (HCV)
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O92530
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POLG_HCVVN
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MSTLPKPQKRNQRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRQTGRTWAQPGYPWPLYGNEGCGWMGWLLSPRGSRPHWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPVVGAPLGGVAAALAHGVRAVEDGINYATGNLPGCSFSIFLLALLSCLTTPASAVHYANKSGIYHLTNDCPNSSIVYEAEDFIMHLPGCVPCIKSGNGSSCWLPATLTIAVPNASIPVRGFRRHVDLMVGAAAFCSAMYVGDLCGGIFLVGQLFSFNPRRHWVVQDCNCSIYVGHITGHRMAWDMMMNWSPTATLVLSYVMRIPQVIMDIFTGGHWGILAGILYYSMVANWAKVLCILFLFAGVDATTRTTGAQAARATLGFTGLFQTGAKQNIHLINTNGSWHINRTALNCNDSLNTGFMAALFYLHKFNSTGCPERLSACKSITQFAQGWGPVTYANVSGSSEDRPYCWHYAPRPCGVVSARSVCGPVYCFTPSPVVVGTTDRRGVPTYTWGENESDVFLLESLRPPAGAWYGCTWMNSTGYTKTCGAPPCHIGPPDQFCPTDCFRKHPEATYRKCGSGPWLTPRCLVDYPYRLWHYPCTVNYTIHKVRLFINGLEHRFDAACNWTRGERCELEDRDRIEMSPLLFSTTELAILPCSFTTMPALSTGLVHLHQNIVDIQYLYGLAPALVSWAVRWEYVVLAFLLLADARICACLWMVLLISQVEAALENLIVLNAASAASSQGWIYCLVFICCAWYIKGRVVPGATYAILHLWPLLLLVLALPQRAYAQDREQGASIGVVVIAAITIFTLTPAYKTMLVHFLWWNQYFIARSEALIQQWVPSLRVRGGRDAVILLTCLLHPSLGFDITKMLLALLGPLYLLQVSLLRVPYYVRAHALLRVCILVRRVAGGKYIQAALLKLGAWTGTYIYDHLAPLSTWASDGLRDLAVAVEPVTFSPMEKKIITWGADTAACGDILAGLPVSARLGHLLFLGPADDMKSMGWRLLAPITAYCQQTRGLLGTIVTSLTGRDRNVVEGEIQVLSTATQSFLGTAINGVMWTVYHGAGSKTLAGPKGPVCQMYTNVDQDMVGWPAPPGTRSLTPCTCGASDLYLVTRNADVIPARRRGDTRAGLLSPRPLSTLKGSSGGPLMCPSDHVVGLFRAAVCTRGVAKALDFVPVENMETTMRSPVFTDNSTPPAVPQTYQVGYLHAPTGSGKSTKVPAAYASQGYKVLVLNPSVAATLGFGSYMSTAHGIDPNIRTGVRTITTGGPITYSTYGKFLADGGCSGGAYDIIICDECHSTDPTTVLGIGTVLDQAETAGVRLTVLATATPPGSVTVPHPNITETALPSTGEVPFYGKAIPLECIKGGRHLIFCHSKKKCDELAKQLRTLGLNAVAFYRGVDVSVIPTAGDVVVCATDALMTGYTGDFDSVIDCNVAVTQIVDFSLDPTFSIETTTVPQDAVARSQRRGRTGRGKPGVYRYVSQGERPSGMFDTVVLCEAYDVGCAWYELTPSETTVRLRAYLNTPGLPVCQDHLEFWEGVFTGMTHIDAHFLSQTKQGGENFAYLVAYQATVCARAKAPPPSWDTMWKCLIRLKPMLTGPTPLLYRLGAVQNEIITTHPITKYIMTCMAADLEVITSTWVLAGGIVAALAAYCLTVGSVVICGRIVTSGKPVPLPDREVLYRQFDEMEECSRHIPYLAEGQQIAEQFKQKILGLLQNTAKQAEDLKPAVQSAWPKLEQFWQKHLWNFVSGVQYLAGLSTLPGNPAVASLMSFSAALTSPLSTSTTLLLNILGGWVASQLAPPTASTAFVVSGLAGAAVGSIGLGKVIIDILAGYGAGVSGALVAFKIMSGEAPAVEDMVNLLPALLSPGALVVGVVCAAVLRRHVGPSEGATQWMNRLIAFASRGNHVSPTHYVPETDASRAVTTILSSLTITSLLRRLHEWISGDWSAPCSCSWLKDVWDWVCTVLSDFKTWLRAKLVPTLPGIPFISCQRGFRGVWRGDGVNYTTCSCGANITGHVKNGSMKIVGPKMCSNVWNNRFPINAITTGPSVPVPEPNYHKALWRVSAEDYVEVVRVNDHHYIVGATADNLKCPCQVPAPEFFTEVDGVRLHRFAPPCRPLMRDDITFSVGLSTYVVGSQLPCEPEPDVVILTSMLTDPDHITAETAARRLARGSPPSLASSSASQLSAPSLKATCTTAGKHPDAELIEANLLWRQEVGGNITRVESENKIIVLDSFDPLIAETDDREISVGAECFNPPRPKFPPALPVWARPDYNPPLLQPWKAPDYEPPLVHGCALPPKGLPPVPPPRKKRVVQLDEGSAKRALAELAQTSFPPSTATLSEDSGRETSTLSSDMTPPREEADRASDDGSYSSMPPLEGEPGDPDLSSGSWSTVSEDHDSVVCCSMSYSWTGALITPCAAEEEKLPISPLSNALIRHHNLVYSTTSRSASLRQKKVTFDRVQVVDQHYYDVLKEIKTKASGVSAKLLSVEEACALTPPHSARSKFGYGAKEVRGLASKAVNHINSVWEDLLEDNSTPIPTTIMAKNEVFCVDAQKGGRKPARLIVYPDLGVRVCEKRALYDVTQKLPIAVMGAAYGFQYSPKQRVDYLLKMWRSKKTPMGFSYDTRCFDSTVTERDIRTEEDIYQCCQLDPVAKKAITSLTERLYCGGPMYNSRGQSCGYRRCRASGVLTTSLGNTLTCYLKAQAACRAAKLKDFDMLVCGDDLVVISESMGVAEDASALRAFTEAMTRYSAPPGDDPQPEYDLELITSCSSNVSVAHDGAGQRYYYLTRDPLTPLSRAAWETARHTPVNSWLGNIIMYAPTIWVRMVLMTHFFAILQSQEILHKALDFDMYGVTYSVTPLDLPYIIQRLHGMAAFSLHGYSPGELNRVASCLRKLGAPPLRAWRHRARAVRAKLIAQGGKHAICGKYLFNWAVRTKLKLTPLRGAANLDLSGWFVSGGSGGDIFHSVSRARPRNLLLCLLLLTVGVGIFLLPAR
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2.7.7.48; 3.4.21.98; 3.4.22.-; 3.6.1.15; 3.6.4.13
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COFACTOR: [Protease NS2]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3). {ECO:0000250|UniProtKB:P26663}; COFACTOR: [Serine protease/helicase NS3]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9WMX2}; Note=Binds 1 zinc ion, which has a structural role (By similarity). The magnesium ion is essential for the helicase activity (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q9WMX2}; COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal center. {ECO:0000250|UniProtKB:P26663};
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clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint [GO:0039645]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity [GO:0039545]; symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity [GO:0039563]; symbiont-mediated suppression of host TRAF-mediated signal transduction [GO:0039527]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; transformation of host cell by virus [GO:0019087]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
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host cell endoplasmic reticulum membrane [GO:0044167]; host cell lipid droplet [GO:0044186]; host cell mitochondrial membrane [GO:0044191]; host cell nucleus [GO:0042025]; host cell perinuclear region of cytoplasm [GO:0044220]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; ribonucleoprotein complex [GO:1990904]; viral envelope [GO:0019031]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type endopeptidase activity [GO:0004252]; SH3 domain binding [GO:0017124]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF07652;PF01543;PF01542;PF01539;PF01560;PF01538;PF01006;PF01001;PF01506;PF08300;PF08301;PF12941;PF02907;PF00998;
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2.40.10.120;3.30.70.270;6.10.250.1610;6.10.250.1750;6.10.250.2920;2.20.25.210;3.30.160.890;2.30.30.710;1.20.1280.150;2.20.25.220;3.40.50.300;1.10.820.10;2.40.10.10;
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Hepacivirus polyprotein family
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PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (By similarity). Cleavage by the signal peptidase releases the 21 kDa mature core protein (By similarity). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (By similarity). Some degraded forms of the core protein appear as well during the course of infection (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; PTM: [Mature core protein]: Phosphorylated by host PKC and PKA. {ECO:0000250|UniProtKB:Q01403}.; PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q03463}.; PTM: [Envelope glycoprotein E1]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Envelope glycoprotein E2]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Protease NS2]: Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 4B]: Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal form termed p56 (By similarity). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664}.; PTM: [Non-structural protein 5A]: Tyrosine phosphorylation is essential for the interaction with host SRC. {ECO:0000250|UniProtKB:Q99IB8}.; PTM: [RNA-directed RNA polymerase]: The N-terminus is phosphorylated by host PRK2/PKN2. {ECO:0000250|UniProtKB:P26662}.
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SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane protein {ECO:0000255}. Host mitochondrion membrane {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein {ECO:0000255}. Note=The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.; SUBCELLULAR LOCATION: [Mature core protein]: Virion {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm {ECO:0000250|UniProtKB:Q99IB8}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P27958}. Host cell membrane {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.; SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=NS3 is associated to the ER membrane through its binding to NS4A. {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Host membrane insertion occurs after processing by the NS3 protease.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-terminus into the ER lumen occurs post-translationally. {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Peripheral membrane protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}. Note=Host membrane insertion occurs after processing by the NS3 protease. {ECO:0000250|UniProtKB:P27958}.
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CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.; EC=3.4.21.98; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
| null | null | null | null |
FUNCTION: [Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Protease NS2]: Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (By similarity). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4A]: Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS4B self-interaction contributes to its function in membranous web formation (By similarity). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. Initiates RNA transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host pattern recognition receptors can be bypassed, thereby evading activation of antiviral pathways. {ECO:0000250|UniProtKB:P27958}.
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Hepatitis C virus genotype 6d (isolate VN235) (HCV)
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O92531
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POLG_HCVVO
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MSTLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQSQGRHWAQPGYPWPLYGNEGCGWAGWLLSPRGSRPNWGPNDPRRRSRNLGKVIDTLTCGFADLMGYIPVVGAPLGGVAAALAHGVRAIEDGINYATGNLPGCSFSIFLLALLSCLTTPASAVHYRNISGIYHLTNDCPNSSIIYEADNIIMHTPGCVPCVKTGNKSQCWVPVAPTLAVANASVPIRGFRSHVDLLVGSAAACSALYIGDLCGGVFLVGQLFTFRPRQHTTVQECNCSIYTGHITGHRMAWDMMMNWSPTVTFITSSLLRVPQLLLEIALEGHWGVIGALLYYSMVANWAKVFAVLLLFAGVDATTHIGSSASATTNRLTSFFSPGSKQNVQLIKTNGSWHINRTALNCNDSLHTGFIAGLLYAHRFNSSGCPERLSSCRPLHAFEQGWGPLTYANISGPSNDKPYCWHYPPRPCDIVPARSVCGPVYCFTPSPVVVGTTDRKGLPTYTWGANESDVFLLRSTRPPRGSWFGCTWMNSTGFVKTCGAPPCNTRPVGSGNDTLVCPTDCFRKHPEATYARCGSGPWLTPRCLVNYPYRLWHYPCTVNYTIHKVRMFVGGIEHRFEAACNWTRGERCELDDRDRVEMSPLLFSTTQLSILPCSFTTMPALSTGLIHLHQNIVDVQYLYGVSSAVVSWAVKWEYIVLAFLVLAVARVCACLWLMFLVGQAEAALENLIVLNATSAAGSQGWVWGVVFICAAWYIRGRAAPITTYAILQLWPLLLLVLALPRRAYAYNGEEAASLGMLAIVIITIFTLTPAYKTLLISTLWWIQYYIARAEAMLYVWVPSLQVRGGRDAVILLTCLLHPQLGFEVTKAILALLGPLYILQYSLLKTPYFVRAHILLRVCMFLRGVAGGKYVQAALLRLGAWTGTYIYDHLTPLSDWACDGLRDLAVAVEPVVFSPMEKKVITWGADTVACGDIISGLPVSARRGNLIFLGPADDIRDGGWRLLAPITAYAQQTRGLVGTIVTSLTGRDKNEVEGEIQVVSTATQSFLATTVNGVLWTVYHGAGSKTLAGPKGPICQMYTNVDQDLVGWPAPPGARSLTPCTCGSSDLYLVTRNADVIPARRRGDTRAALLSPRPISTLKGSSGGPMLCPSGHVAGIFRAAVCTRGVAKSLDFVPVENMQSTARSPSFSDNTTPPAVPQTYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGSYMSTAHGIDPNIRTGVRTITTGGAITYSTYGKFLADGGCSGGAYDIIICDECHSTDPTTVLGIGTVLDQAETAGVRLTVLATATPPGSVTVPHPNITEVALSSTGEVPFYGKAIPLEYIKGGRHLIFCHSKKKCDELAKQLTSLGLNAVAFYRGVDVSVIPTSGDVVVCATDALMTGYTGDFDSVIDCNVSVTQVVDFSLDPTFTIETTTMPQDAVSRSQRRGRTGRGKHGVYRYVSQGERPSGIFDTVVLCEAYDTGCAWYELTPSETTVRLRAYLNTPGLPVCQDHLEFWEGVFTGLTHIDAHLLSQTKQGGENFAYLVAYQATVCARAKAPPPSWDTMWKCLIRLKPMLTGPTPLLYRLGAVQNEITTTHPITKYIMTCMSADLEVITSTWVLVGGVLAALAAYCLSVGCVVVCGRISTTGKPVLIPDREVLYQQFDEMEECSRHIPYLVEGQHLAEQFKQKVLGLIQTTTRQAEEIEPVVHSAWPKLEQFWQKHLWNFVSGIQYLAGLSTLPGNPAVASLMSFSASLTSPLSTSTTLLLNILGGWVASQLANPTASTAFVVSGLAGATVGSIGLGRVLVDIIAGYGAGVSGALVAFKIMSGETPSAEDMVNLLPALLSPGALVVGVVCAAILRRHAGPAEGATQWMNRLIAFASRGNHVSPTHYVPETDTSRQVMAILSSLTVTSLLRKLHEWINSDWSTPCSGSWLRDIWDWVCTVLSDFKVWLKSKLVPALPGVPFLSCQRGFRGVWRGDGICRTTCPCGADIVGHVKNGSMRISGSRWCSNIWHGTFPINATTTGPSVPIPEPNYKRALWRVSAEEYVEVARVGDSHFVVGATNQDLKCPCQVPAPEFFTEVDGVRLHRFAPACKPLLRDEISFLVGLNSYAIGSQLPCEPEPDVTVVTSMLVDPSHLTAEAAARRLARGSPPSCASSLASQLSAPSLKATCTTHCAHPDADLIEANLLWRQEVGGNITRVESENKVIVLDSFDPLVPEYDDREPSVPAECHRPNRPKFPPALPIWARPDYNPPLLETWKKPDYAPPLVHGCALPSPVQPPVPPPRRKSVVHLDDSTVATALAELAEKSFPTQPASTPDSDSGHPTTSKSSDQADEGEDTPSEAGSYSSMPPLEGEPGDPDLSSGSWSTVSEEGDSVVCCSMSYSWTGALVTPCAAEEEKLPINPLSNSLIRHHNLVYSTTTRSAAMRQKKVTFDRLQILDQHYNNVVKEVKLRASGVTAKLLSVEEACSLTPPHSARSKFGYGAKDVRSHTSKAINHINSVWEDLLEDNQTPIPTTIMAKNEVFCADVSKGGRKPARLIVYPDLGVRVCEKRALYDVTRKLPTAIMGDAYGFQYSPKQRVDQLLKMWRSKKTPMGFSYDTRCFDSTVTEHDIKTERDVYLSCKLDPVARKAIESLTERLYIGGPMYNSRGQLCGTRRCRASGVLTTSLGNTMTCFIKAEAACRAAGLTNYDMLVCGDDLVVIAESAGVQEDASNLRAFTEAMTRYSAPPGDEPHPAYDLELITSCSSNVSVAHDHTGQRYYYLTRDPTTPLSRAAWETARHTPVNSWLGNIIMYAPAIWVRMVLMTHFFQILQAQEQLDKVLDFDMYGVTYSVSPLQLPAIIQRLHGMAAFSLHGYSPTELNRVGACLRKLGAPPLRAWRHRARAVRAKLIAQGGGAAICGKYLFNWAVKTKLKLTPIPDAARLDLSGWFISGFSGGDIYHSVSRARPRIFLLCLLLLSVGVGIFLLPAR
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2.7.7.48; 3.4.21.98; 3.4.22.-; 3.6.1.15; 3.6.4.13
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COFACTOR: [Protease NS2]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3). {ECO:0000250|UniProtKB:P26663}; COFACTOR: [Serine protease/helicase NS3]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9WMX2}; Note=Binds 1 zinc ion, which has a structural role (By similarity). The magnesium ion is essential for the helicase activity (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q9WMX2}; COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal center. {ECO:0000250|UniProtKB:P26663};
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clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint [GO:0039645]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity [GO:0039545]; symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity [GO:0039563]; symbiont-mediated suppression of host TRAF-mediated signal transduction [GO:0039527]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; transformation of host cell by virus [GO:0019087]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
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host cell endoplasmic reticulum membrane [GO:0044167]; host cell lipid droplet [GO:0044186]; host cell mitochondrial membrane [GO:0044191]; host cell nucleus [GO:0042025]; host cell perinuclear region of cytoplasm [GO:0044220]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; ribonucleoprotein complex [GO:1990904]; viral envelope [GO:0019031]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type endopeptidase activity [GO:0004252]; SH3 domain binding [GO:0017124]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF07652;PF01543;PF01542;PF01539;PF01560;PF01538;PF01006;PF01001;PF01506;PF08300;PF08301;PF12941;PF02907;PF00998;
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2.40.10.120;3.30.70.270;6.10.250.1610;6.10.250.1750;6.10.250.2920;2.20.25.210;3.30.160.890;2.30.30.710;1.20.1280.150;2.20.25.220;3.40.50.300;1.10.820.10;2.40.10.10;
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Hepacivirus polyprotein family
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PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (By similarity). Cleavage by the signal peptidase releases the 21 kDa mature core protein (By similarity). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (By similarity). Some degraded forms of the core protein appear as well during the course of infection (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; PTM: [Mature core protein]: Phosphorylated by host PKC and PKA. {ECO:0000250|UniProtKB:Q01403}.; PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q03463}.; PTM: [Envelope glycoprotein E1]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Envelope glycoprotein E2]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Protease NS2]: Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 4B]: Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal form termed p56 (By similarity). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664}.; PTM: [Non-structural protein 5A]: Tyrosine phosphorylation is essential for the interaction with host SRC. {ECO:0000250|UniProtKB:Q99IB8}.; PTM: [Non-structural protein 5A]: Ubiquitinated (By similarity). Ubiquitination, most probably at Lys-2353, mediated by host IFI27 and SKP2 leads to proteasomal degradation, restricting viral infection (By similarity). Ubiquitination by host TRIM22 leads to interruption of viral replication (By similarity). {ECO:0000250|UniProtKB:P27958}.; PTM: [RNA-directed RNA polymerase]: The N-terminus is phosphorylated by host PRK2/PKN2. {ECO:0000250|UniProtKB:P26662}.
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SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane protein {ECO:0000255}. Host mitochondrion membrane {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein {ECO:0000255}. Note=The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.; SUBCELLULAR LOCATION: [Mature core protein]: Virion {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm {ECO:0000250|UniProtKB:Q99IB8}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P27958}. Host cell membrane {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.; SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=NS3 is associated to the ER membrane through its binding to NS4A. {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Host membrane insertion occurs after processing by the NS3 protease.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-terminus into the ER lumen occurs post-translationally. {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Peripheral membrane protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}. Note=Host membrane insertion occurs after processing by the NS3 protease. {ECO:0000250|UniProtKB:P27958}.
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CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.; EC=3.4.21.98; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
| null | null | null | null |
FUNCTION: [Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Protease NS2]: Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (By similarity). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4A]: Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS4B self-interaction contributes to its function in membranous web formation (By similarity). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. Initiates RNA transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host pattern recognition receptors can be bypassed, thereby evading activation of antiviral pathways. {ECO:0000250|UniProtKB:P27958}.
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Hepatitis C virus genotype 6k (isolate VN405) (HCV)
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O92532
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POLG_HCVVP
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MSTLPKPQRKTKRNTNRRPMDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARQPIGRSWGQPGYPWPLYGNEGCGWAGWLLSPRGSRPNWGPNDPRRRSRNLGKVIDTLTCGLADLMGYIPVLGGPLGGVAAALAHGVRAIEDGVNYATGNLPGCSFSIFLLALLSCLTTPASAIQVRNASGIYHLTNDCSNNSIVFEAETIILHLPGCVPCIKVGNGSRCWLSVSPTLAVPNSSVPIHGFRRHVDLLVGAAAFCSAMYIGDLCGSVFLVGQLFTFRPKHHQVTQDCNCSIYAGHITGHRMAWDMMLNWSPTVSYVVSSALRVPQLLLEVITGAHWGVLGALLYFSMVANWAKVIAVLFLFAGADATTYTGSAVSSTTGAFVSLFSPGPTQNLQLVNSNGSWHINRTALNCNDSLQTGFIAGLFARYKFNSTGCPERMSKCRPLHSFEQGWGPISYVNISGSSEDKPYCWHYAPRPCGIVPARNVCGPVYCFTPSPVVVGTTDQRGIPTYTWGENVSDVFLLHSARPPLGAWFGCTWMNSSGFVKTCGAPPCRIKPTINETDLVCPTDCFRKHPDASFVKCGSGPWLTPRCMVDYPYRLWHYPCTVNFTIHKVRVFVGGVEHRFNAACNWTRGDRCELDDRDRFEMSPLLFSTTQLAILPCSFTTMPALSTGLIHLHQNIVDIQYLYGVSTAVVSWAMKWEYVVLAFLVLADARVCACLWLMFLVGQAEAALENVIVLNAASAASCQGLLWGLIFICCAWHVRGRAVPVTTYALLQLWPLLLLILALPRRAYAFDSEQAASAGLLVLGLITIFTLTPAYKQLLISMLWWIQYFIALTEAQLHQWVPSLLVRGGRDAVILLACLFHPQLGFEVTKILLALLGPLYLLQYSLLKTPYFVRAHILLRACMFFRGMARGRYAQAILLRIGAWTGTYIYDHLAPLSDWACDGLRDLAVAVEPVVFSPMEKKVITWGADTAACGDIIAGLPVAARRGNLLFLGPADDVKGKGWRLLAPITAYAQQTRGIVGTIVTSLTGRDKNEVEGEIQVVSTATQSFLATAVNGVLWTVYYGAGSKTLAGPKGPVCQMYTNVDQDLVGWPAPAGARSLTPCSCGSSDLYLVTRNADVIPARRRGDNRAALLSPRPISTLKGSSGGPMLCPSGHVAGIFRAAVCTRGVAKSLDFAPVESMQSSQRSPSFSDNTSPPAVPQTYQVGYLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGSYMSTSHGIDPNIRTGVRTITTGGAITYSTYGKFLADGGCSGGAYDVIICDECHSTDPTTVSGIGTVLDQAETSGVRLTVLATATPPGSVTVPHPNITESALPTTGEIPFYGKAVPLEYIKGGRHLIFCHPKKKCDELAKQLVSLGLNAVAFYRGVDVSVIPTSGDVVVCATDALMTGYTGDFDSVIDCNVTVTQVVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGKHGVYRYVSQGERPSGMFDSVILCEAYDTGCAWYELTPAETTVRLRAYLNTPGLPVCQDHLEFWEGVFTGLTHIDAHFLSQTKQAEENFAYLVAYQATVCARAKAPPPSWDTMWKCLIRLKPMLTGPTPLLYRLGPVQNEVVTTHPITKYIMTCMSADLEVITSTWVLVGGVVAALAAYCLSVGCVVICGRISTSGKPVLIPDREVLYQQFDEMEECSRHIPYLAEGHLIAEQFKQKVLGLIQSTSKQAEELKPAVHAAWPKLEQFWQKQLWNFVSGIQYLAGLSTLPGNPAIASLMSFSASLTSPLSTHQTLLLNILGGWVASQLANPTASTAFVVSGLAGAAVGSIGLGRVIVDVLAGYGAGVSGALVAFKIMCGETPSAEDMVNLLPALLSPGALVVGVVCAAILRRHAGPSEGATQWMNRLIAFASRGNHVSPTHYVPETDTSRQIMTILSSLTVTSLLRKLHEWINTDWSTPCSSSWLRDIWDWVCEVLSDFKTWLKAKLVPALPGVPFLSCQRGFRGTWRGDGICHTTCPCGSEITGHVKNGTMKISGPRWCSNVSHRTFPINATTTGPSVPIPEPNYTRALWRVSAEEYVEVKRVGDSHFVVGATTDNLKCPCQVPAPEFFTEVDGVRLHRYAPRCKPLLRDEVSFSVGLSSYAVGSQLPCEPEPDVTVVTSMLIDPSHVTAEAAARRLARGSPPSLASSSASQLSAPSLKATCTMHGAHPDAELIEANLLWRQEMGGNITRVESENKVVILDSFDPLVPEFEEREMSVPAECHRPRRPKFPPALPIWATPGYNPPVLETWKSPTYEPPVVHGCALPPSGPPPIPPPRRKKVVQLDSSNVSAALAQLAAKTFETPSSPTTGYGSDQPDHSTESSEHDRDDGVASEAESYSSMPPLEGEPGDPDLSSGSWSTVSEEGDSVVCCSYSYSWTGALVTPCAAEEEKLPINPLSNSLIRHHNLVYSTSSRSAATRQKKVTFDRVQLLDQHYYDTVKEIKLRASHVKAQLLSTEEACDLTPPHSARSKFGYGAKDVRSHASKAINHINSVWADLLEDTQTPIPTTIMAKNEVFCVDASKGGRKSARLIVYPDLGVRVCEKRALFDVTRKLPTAIMGDAYGFQYSPQQRVDRLLKMWRSKKTPMGFSYDTRCFDSTVTERDIRTEQDIYLSCQLDPEARKVIESLTERLYVGGPMYNSKGQLCGQRRCRASGVLPTSMGNTVTCFLKATAACRAAGFTDYDMLVCGDDLVVVTESAGVNEDIANLRAFTEAMTRYSATPGDEPSPTYDLELITSCSSNVSVAHDGDGRRYYYLTRDPVTPLARAAWETARHTPVNSWLGNIIMYAPTIWVRMVLMTHFFQILQAQETLDRALDFDIYGVTYSITPLDLPVIIQRLHGMAAFSLHGYSPDELNRVASCLRKLGAPPLRAWRHRARAVRAKLIAQGGKAAVCGKYLFNWAIKTKLRLTPLRGASALDLSGWFTSGYGGGDVYHSASRARPRFLLLCLLLLSVGVGIFLLPAR
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2.7.7.48; 3.4.21.98; 3.4.22.-; 3.6.1.15; 3.6.4.13
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COFACTOR: [Protease NS2]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3). {ECO:0000250|UniProtKB:P26663}; COFACTOR: [Serine protease/helicase NS3]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P26663}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9WMX2}; Note=Binds 1 zinc ion, which has a structural role (By similarity). The magnesium ion is essential for the helicase activity (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:Q9WMX2}; COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal center. {ECO:0000250|UniProtKB:P26663};
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clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint [GO:0039645]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity [GO:0039545]; symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity [GO:0039563]; symbiont-mediated suppression of host TRAF-mediated signal transduction [GO:0039527]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; transformation of host cell by virus [GO:0019087]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
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host cell endoplasmic reticulum membrane [GO:0044167]; host cell lipid droplet [GO:0044186]; host cell mitochondrial membrane [GO:0044191]; host cell nucleus [GO:0042025]; host cell perinuclear region of cytoplasm [GO:0044220]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; ribonucleoprotein complex [GO:1990904]; viral envelope [GO:0019031]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type endopeptidase activity [GO:0004252]; SH3 domain binding [GO:0017124]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF07652;PF01543;PF01542;PF01539;PF01560;PF01538;PF01006;PF01001;PF01506;PF08300;PF08301;PF12941;PF02907;PF00998;
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2.40.10.120;3.30.70.270;6.10.250.1610;6.10.250.1750;6.10.250.2920;2.20.25.210;3.30.160.890;2.30.30.710;1.20.1280.150;2.20.25.220;3.40.50.300;1.10.820.10;2.40.10.10;
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Hepacivirus polyprotein family
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PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (By similarity). Cleavage by the signal peptidase releases the 21 kDa mature core protein (By similarity). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (By similarity). Some degraded forms of the core protein appear as well during the course of infection (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; PTM: [Mature core protein]: Phosphorylated by host PKC and PKA. {ECO:0000250|UniProtKB:Q01403}.; PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q03463}.; PTM: [Envelope glycoprotein E1]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Envelope glycoprotein E2]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Protease NS2]: Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 4B]: Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal form termed p56 (By similarity). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664}.; PTM: [Non-structural protein 5A]: Tyrosine phosphorylation is essential for the interaction with host SRC. {ECO:0000250|UniProtKB:Q99IB8}.; PTM: [Non-structural protein 5A]: Ubiquitinated (By similarity). Ubiquitination, most probably at Lys-2352, mediated by host IFI27 and SKP2 leads to proteasomal degradation, restricting viral infection (By similarity). Ubiquitination by host TRIM22 leads to interruption of viral replication (By similarity). {ECO:0000250|UniProtKB:P27958}.; PTM: [RNA-directed RNA polymerase]: The N-terminus is phosphorylated by host PRK2/PKN2. {ECO:0000250|UniProtKB:P26662}.
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SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane protein {ECO:0000255}. Host mitochondrion membrane {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein {ECO:0000255}. Note=The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.; SUBCELLULAR LOCATION: [Mature core protein]: Virion {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm {ECO:0000250|UniProtKB:Q99IB8}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P27958}. Host cell membrane {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.; SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=NS3 is associated to the ER membrane through its binding to NS4A. {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Host membrane insertion occurs after processing by the NS3 protease.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-terminus into the ER lumen occurs post-translationally. {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Peripheral membrane protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}. Note=Host membrane insertion occurs after processing by the NS3 protease. {ECO:0000250|UniProtKB:P27958}.
|
CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.; EC=3.4.21.98; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
| null | null | null | null |
FUNCTION: [Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and ApoE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent facilitated transmission to permissive cells such as hepatocytes and lymphocyte subpopulations (By similarity). The interaction between E2 and host amino acid transporter complex formed by SLC3A2 and SLC7A5/LAT1 may facilitate viral entry into host cell (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (By similarity). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (By similarity). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Protease NS2]: Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (By similarity). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (By similarity). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity). {ECO:0000250|UniProtKB:P26663, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4A]: Peptide cofactor which forms a non-covalent complex with the N-terminal of NS3 serine protease (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS4B self-interaction contributes to its function in membranous web formation (By similarity). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. Initiates RNA transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host pattern recognition receptors can be bypassed, thereby evading activation of antiviral pathways. {ECO:0000250|UniProtKB:P27958}.
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Hepatitis C virus genotype 6h (isolate VN004) (HCV)
|
O92815
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POL_WDSV
|
MGNSSSTPPPSALKNSDLFKTMLRTQYSGSVKTRRINQDIKKQYPLWPDQGTCATKHWEQAVLIPLDSVSEETAKVLNFLRVKIQARKGETARQMTAHTIKKLIVGTIDKNKQQTEILQKTDESDEEMDTTNTMLFIARNKRERIAQQQQADLAAQQQVLLLQREQQREQREKDIKKRDEKKKKLLPDTTQKVEQTDIGEASSSDASAQKPISTDNNPDLKVDGVLTRSQHTTVPSNITIKKDGTSVQYQHPIRNYPTGEGNLTAQVRNPFRPLELQQLRKDCPALPEGIPQLAEWLTQTMAIYNCDEADVEQLARVIFPTPVRQIAGVINGHAAANTAAKIQNYVTACRQHYPAVCDWGTIQAFTYKPPQTAHEYVKHAEIIFKNNSGLEWQHATVPFINMVVQGLPPKVTRSLMSGNPDWSTKTIPQIIPLMQHYLNLQSRQDAKIKQTPLVLQLAMPAQTMNGNKGYVGSYPTNEPYYSFQQQQRPAPRAPPGNVPSNTCFFCKQPGHWKADCPNKTRNLRNMGNMGRGGRMGGPPYRSQPYPAFIQPPQNHQNQYNGRMDRSQLQASAQEWLPGTYPAXDPIDCPYEKSGTKTTQDVITTKNAEIMVTVNHTKIPMLVDTGACLTAIGGAATVVPDLKLTNTEIIAVGISAEPVPHVLAKPTKIQIENTNIDISPWYNPDQTFHILGRDTLSKMRAIVSFEKNGEMTVLLPPTYHKQLSCQTKNTLNIDEYLLQFPDQLWASLPTDIGRMLVPPITIKIKDNASLPSIRQYPLPKDKTEGLRPLISSLENQGILIKCHSPCNTPIFPIKKAGRDEYRMIHDLRAINNIVAPLTAVVASPTTVLSNLAPSLHWFTVIDLSNAFFSVPIHKDSQYLFAFTFEGHQYTWTVLPQGFIHSPTLFSQALYQSLHKIKFKISSEICIYMDDVLIASKDRDTNLKDTAVMLQHLASEGHKVSKKKLQLCQQEVVYLGQLLTPEGRKILPDRKVTVSQFQQPTTIRQIRAFLGLVGYCRHWIPEFSIHSKFLEKQLKKDTAEPFQLDDQQVEAFNKLKHAITTAPVLVVPDPAKPFQLYTSHSEHASIAVLTQKHAGRTRPIAFLSSKFDAIESGLPPCLKACASIHRSLTQADSFILGAPLIIYTTHAICTLLQRDRSQLVTASRFSKWEADLLRPELTFVACSAVSPAHLYMQSCENNIPPHDCVLLTHTISRPRPDLSDLPIPDPDMTLFSDGSYTTGRGGAAVVMHRPVTDDFIIIHQQPGGASAQTAELLALAAACHLATDKTVNIYTDSRYAYGVVHDFGHLWMHRGFVTSAGTPIKNHKEIEYLLKQIMKPKQVSVIKIEAHTKGVSMEVRGNAAADEAAKNAVFLVQRVLKKGDALASTDLVMEYSETDEKFTAGAELHDGVFMRGDLIVPPLEMLHAILLAIHGVSHTHKGGIMSYFSKFWTHPKASQTIDLILGHCQICLKHNPKYKSRLQGHRPLPSRPFAHLQIDFVQMCVKKPMYALVIIDVFSKWPEIIPCNKEDAKTVCDILMKDIIPRWGLPDQIDSDQGTHFTAKISQELTHSIGVAWKLHCPGHPRSSGIVERTNRTLKSKIIKAQEQLQLSKWTEVLPYVLLEMRATPKKHGLSPHEIVMGRPMKTTYLSDMSPLWATDTLVTYMNKLTRQLSAYHQQVVDQWPSTSLPPGPEPGSWCMLRNPKKSSNWEGPFLILLSTPTAVKVEGRPTWIHLDHCKLLRSSLSSSLGGPVNQLLS
|
2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.26.4; 3.4.23.-
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COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
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DNA integration [GO:0015074]; DNA recombination [GO:0006310]; proteolysis [GO:0006508]
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host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]
|
aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; RNA binding [GO:0003723]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural constituent of virion [GO:0039660]; zinc ion binding [GO:0008270]
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PF18697;PF00075;PF17919;PF00665;PF00077;PF00078;PF00098;
|
2.30.30.850;3.10.20.370;3.30.70.270;2.40.70.10;3.10.10.10;3.30.420.10;4.10.60.10;
| null |
PTM: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation (By similarity). {ECO:0000250}.
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SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}.; SUBCELLULAR LOCATION: [Matrix protein p10]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein p25]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p14]: Virion {ECO:0000305}.
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CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4; Evidence={ECO:0000255|PROSITE-ProRule:PRU00408};
| null | null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.0 for protease p14.;
| null |
FUNCTION: [Matrix protein p10]: Targets Gag and gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the pre-integration complex (By similarity). {ECO:0000250}.; FUNCTION: Capsid protein p25 forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex. {ECO:0000250}.; FUNCTION: [Nucleocapsid protein p14]: Involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization (By similarity). {ECO:0000250}.; FUNCTION: [Protease p15]: Mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell (By similarity). {ECO:0000250}.; FUNCTION: [Reverse transcriptase/ribonuclease H p90]: Is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5' end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5' end of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primers. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends (By similarity). {ECO:0000250}.; FUNCTION: [Integrase p46]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step that requires cell division, the PIC enters cell nucleus. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The last step is viral DNA integration into host chromosome. {ECO:0000269|PubMed:24124581}.; FUNCTION: [Gag-Pol polyprotein]: Plays a role in budding and is processed by the viral protease during virion maturation outside the cell. {ECO:0000250}.
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Walleye dermal sarcoma virus (WDSV)
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O92920
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HBEAG_HBVD7
|
MQLFHLCLIISCSCPTVQASKLCLGWLWDMDIDPYKEFGATVQLLSFLPHDFFPSVRDLLDTASALFRDALESPEHCSPHHTALRQAILCWGELMTLATWVGANLQDPASRELVVTYVNINMGLKFRQLLWFHISCLTFGRETVIEYLVSFGVWIRTPQAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC
| null | null |
microtubule-dependent intracellular transport of viral material towards nucleus [GO:0075521]; symbiont entry into host cell [GO:0046718]; viral penetration into host nucleus [GO:0075732]; virus-mediated perturbation of host defense response [GO:0019049]
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extracellular region [GO:0005576]; host cell [GO:0043657]; host cell cytoplasm [GO:0030430]; host cell nucleus [GO:0042025]; T=4 icosahedral viral capsid [GO:0039619]
|
DNA binding [GO:0003677]; RNA binding [GO:0003723]; structural molecule activity [GO:0005198]
|
PF08290;PF00906;
|
1.10.4090.10;
|
Orthohepadnavirus precore antigen family
|
PTM: Phosphorylated. {ECO:0000255|HAMAP-Rule:MF_04076}.; PTM: Cleaved by host furin. {ECO:0000255|HAMAP-Rule:MF_04076}.
|
SUBCELLULAR LOCATION: Secreted {ECO:0000255|HAMAP-Rule:MF_04076}. Host nucleus {ECO:0000255|HAMAP-Rule:MF_04076}.
| null | null | null | null | null |
FUNCTION: May regulate immune response to the intracellular capsid in acting as a T-cell tolerogen, by having an immunoregulatory effect which prevents destruction of infected cells by cytotoxic T-cells. This immune regulation may predispose to chronicity during perinatal infections and prevent severe liver injury during adult infections. {ECO:0000255|HAMAP-Rule:MF_04076}.
|
Hepatitis B virus genotype D (isolate Germany/1-91/1991) (HBV-D)
|
O92921
|
HBSAG_HBVD7
|
MGQNLSTSNPLGFFPDHQLDPAFRANTANPDWDFNPNKDTWPDANKVGAGAFGLGFTPPHGGLLGWSPQAQGIIQTLPANPPPASTNRQTGRQPTPLSPPLRNTHPQAMQWNSTTFHQTLQDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRIGDPALNMENITSGLLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGTTVCLGQNSQSPTSNHSPTSCPPTCPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLIPGSSTTSVGPCRTCTTTVQGTSMYPSCCCTKPSDGNCTCIPIPSSWAFGKFLWEWASARFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYRILSPFLPLLPIFFCLWVYI
| null | null |
caveolin-mediated endocytosis of virus by host cell [GO:0075513]; fusion of virus membrane with host endosome membrane [GO:0039654]; virion attachment to host cell [GO:0019062]
|
membrane [GO:0016020]; viral envelope [GO:0019031]; virion membrane [GO:0055036]
| null |
PF00695;
| null |
Orthohepadnavirus major surface antigen family
|
PTM: Isoform M is N-terminally acetylated by host at a ratio of 90%, and N-glycosylated by host at the pre-S2 region. {ECO:0000250|UniProtKB:P03138, ECO:0000255|HAMAP-Rule:MF_04075}.; PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04075}.
|
SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04075}.
| null | null | null | null | null |
FUNCTION: The large envelope protein exists in two topological conformations, one which is termed 'external' or Le-HBsAg and the other 'internal' or Li-HBsAg. In its external conformation the protein attaches the virus to cell receptors and thereby initiating infection. This interaction determines the species specificity and liver tropism. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis. The large envelope protein also assures fusion between virion membrane and endosomal membrane. In its internal conformation the protein plays a role in virion morphogenesis and mediates the contact with the nucleocapsid like a matrix protein. {ECO:0000255|HAMAP-Rule:MF_04075}.; FUNCTION: The middle envelope protein plays an important role in the budding of the virion. It is involved in the induction of budding in a nucleocapsid independent way. In this process the majority of envelope proteins bud to form subviral lipoprotein particles of 22 nm of diameter that do not contain a nucleocapsid. {ECO:0000255|HAMAP-Rule:MF_04075}.
|
Hepatitis B virus genotype D (isolate Germany/1-91/1991) (HBV-D)
|
O92954
|
GAG_RSVSB
|
MEAVIKVISSACKTYCGKTSPSKKEIGAMLSLLQKEGLLMSPSDLYSPGSWDPITAALSQRAMVLGKSGELKTWGLVLGALKAAREEQVTSEQAKFWLGLGGGRVSPPGPECIEKPATERRIDKGEEVGETTVQRDAKMAPEETATPKTVGTSCYHCGTAIGCNCATASAPPPPYVGSGLYPSLAGVGEQQGQGGDTPRGAEQPRAEPGHAGLAPGPALTDWARIREELASTGPPVVAMPVVIKTEGPAWTPLEPKLITRLADTVRTKGLRSPITMAEVEALMSSPLLPHDVTNLMRVILGPAPYALWMDAWGVQLQTVIAAATRDPRHPANGQGRGERTNLDRLKGLADGMVGNPQGQAALLRPGELVAITASALQAFREVARLAEPAGPWADITQGPSESFVDFANRLIKAVEGSDLPPSARAPVIIDCFRQKSQPDIQQLIRAAPSTLTTPGEIIKYVLDRQKIAPLTDQGIAAAMSSAIQPLVMAVVNRERDGQTGSGGRARRLCYTCGSPGHYQAQCPKKRKSGNSRERCQLCDGMGHNAKQCRRRDSNQGQRPGRGLSSGPWPVSEQPAVSLAMTMEHKDRPLVRVILTNTGSHPVKQRSVYITALLDSGADITIISEEDWPTDWPVVDTANPQIHGIGGGIPMRKSRDMIELGVINRDGSLERPLLLFPAVAMVRGSILGRDCLQGLGLRLTNL
|
3.4.23.-
| null |
proteolysis [GO:0006508]; viral procapsid maturation [GO:0046797]
|
host cell nucleolus [GO:0044196]; host cell nucleoplasm [GO:0044095]; viral capsid [GO:0019028]
|
aspartic-type endopeptidase activity [GO:0004190]; nucleic acid binding [GO:0003676]; structural constituent of virion [GO:0039660]; zinc ion binding [GO:0008270]
|
PF00607;PF02813;PF00077;PF00098;
|
1.10.1200.30;2.40.70.10;1.10.375.10;1.10.150.90;4.10.60.10;
| null |
PTM: [Gag polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins. The cleavage at the C-terminus of the Capsid protein p27 is slowly trimmed by the viral protease, sometimes being cut internally thereby generating the short version of the capsid protein and a capsid protein C-terminally extended by 3 amino acids in a ratio of 2:1. {ECO:0000250|UniProtKB:P03322}.
|
SUBCELLULAR LOCATION: [Matrix protein p19]: Virion {ECO:0000250|UniProtKB:P03322}.; SUBCELLULAR LOCATION: [Capsid protein p27, alternate cleaved 1]: Virion {ECO:0000250|UniProtKB:P03322}.; SUBCELLULAR LOCATION: [Capsid protein p27, alternate cleaved 2]: Virion {ECO:0000250|UniProtKB:P03322}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p12]: Virion {ECO:0000250|UniProtKB:P03322}.; SUBCELLULAR LOCATION: [Gag polyprotein]: Host nucleus, host nucleolus {ECO:0000250|UniProtKB:P03322}. Host nucleus, host nucleoplasm {ECO:0000250|UniProtKB:P03322}. Note=Shuttles between nucleoplasm and nucleolus. {ECO:0000250|UniProtKB:P03322}.
| null | null | null | null | null |
FUNCTION: [Gag polyprotein]: The p10 domain folds back and interacts with the capsid protein domain during Gag polyprotein assembly in the immature particle (before the maturation cleavage that splits the 2 domains). {ECO:0000250|UniProtKB:P03322}.; FUNCTION: [Capsid protein p27, alternate cleaved 1]: Self-associates to form the irregular polyhedron core composed of hexamers and pentamers, that encapsulates the genomic RNA-nucleocapsid complex. Assembles as a tube in vitro (By similarity). Binds to inositol hexakisphosphate (IP6), which allows the assembly of the polyhedral capsid (By similarity). {ECO:0000250|UniProtKB:P03322}.; FUNCTION: [Capsid protein p27, alternate cleaved 2]: Self-associates to form the irregular polyhedron core composed of hexamers and pentamers, that encapsulates the genomic RNA-nucleocapsid complex. Assembles as a tube in vitro (By similarity). Binds to inositol hexakisphosphate (IP6), which allows the assembly of the polyhedral capsid (By similarity). {ECO:0000250|UniProtKB:P03322}.; FUNCTION: [Nucleocapsid protein p12]: Binds strongly to viral nucleic acids and promotes their packaging (By similarity). Plays a role in the maturation-stabilization of the viral dimeric RNA via highly structured zinc-binding motifs (By similarity). {ECO:0000250|UniProtKB:P03322, ECO:0000250|UniProtKB:P0C776}.; FUNCTION: [Spacer peptide]: Plays a role in the oligomerization of the Gag polyprotein and in the stabilization of the immature particle. Essential layering element during tube assembly. {ECO:0000250|UniProtKB:P03322}.; FUNCTION: [Protease p15]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. {ECO:0000255|PROSITE-ProRule:PRU00275}.
|
Rous sarcoma virus subgroup B (strain Schmidt-Ruppin) (RSV-SR-B)
|
O92955
|
ENV_RSVSB
|
MEAVIKAVLTGYPGETSKKDSKKKPPATSKKDPEKTPLLPTRVNYILIIGVLVLCEVTGVRADVHLLEQPGNLWITWASRTGQTDFCLSTQSATSPFQTCLIGIPSPISEGDFKGYVSDNCTTLEPHRLVSRGIPGGPENSTTLTYQKVSCLLLKLNVSLLDEPSELQLLGSQSLPNITNITRIPSVAGGCIGFTPYDSPAGVYGWDRREVTHILLTDPGNNPFFDKASNSSKPFTVVTADRHNLFMGSEYCGAYGYRFWEMYNCSQMRQNWSICQDVWGRGPPENWCTSTGGTWVNQSKEFNETEPFSFTVNCTGSNLGNVSGCCGEPITILPPEAWVDSTQGSFTKPKALPPAIFLICGDRAWQGIPSRPVGGPCYLGKLTMLAPNHTDILKILANSSRTGIRRKRSVSHLDDTCSDEVQLWGPTARIFASILAPGVAAAQALKEIERLACWSVKQANLTTSLLGDLLDDVTSIRHAVLQNRAAIDFLLLAHGHGCEDVAGMCCFNLSDHSESIQKKFQLMKEHVNKIGVDSDPIGSWLRGLFGGIGEWAVHLLKGLLLGLVVILLLVVCLPCLLQIVCGNIRKMINNSISYHTEYKKLQKAYGQPESRIV
| null | null |
fusion of virus membrane with host plasma membrane [GO:0019064]; symbiont entry into host cell [GO:0046718]; virion attachment to host cell [GO:0019062]
|
host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; virion membrane [GO:0055036]
| null |
PF03708;PF00429;
|
1.10.287.210;
|
Alpharetroviruses envelope glycoprotein family
|
PTM: [Envelope glycoprotein gp95]: Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is N-glycosylated and processed likely by host cell furin or by a furin-like protease in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R (By similarity). {ECO:0000250}.; PTM: [Transmembrane protein]: The transmembrane protein is palmitoylated. Palmitoylation is necessary for glycoprotein function and infectivity. {ECO:0000250|UniProtKB:P03396}.
|
SUBCELLULAR LOCATION: [Transmembrane protein]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000303|PubMed:31151254}. Host cell membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000303|PubMed:31151254}.; SUBCELLULAR LOCATION: [Surface protein]: Virion membrane {ECO:0000305}; Peripheral membrane protein. Host cell membrane {ECO:0000305}; Peripheral membrane protein. Note=The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. Both proteins are thought to be concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag (By similarity). {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: [Surface protein]: The surface protein (SU) attaches the virus to the host cell entry receptor TVB-S3/CAR1 (PubMed:8945512). This interaction triggers the refolding of the transmembrane protein (TM) thereby unmasking its fusion peptide and the formation of a reactive thiolate on Cys-100 to activate its fusogenic potential. Fusion occurs at the host cell plasma membrane (By similarity). {ECO:0000250|UniProtKB:P0DTM4, ECO:0000269|PubMed:8945512}.; FUNCTION: [Transmembrane protein]: The transmembrane protein (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. {ECO:0000250|UniProtKB:P0DTM4}.
|
Rous sarcoma virus subgroup B (strain Schmidt-Ruppin) (RSV-SR-B)
|
O92956
|
POL_RSVSB
|
MEAVIKVISSACKTYCGKTSPSKKEIGAMLSLLQKEGLLMSPSDLYSPGSWDPITAALSQRAMVLGKSGELKTWGLVLGALKAAREEQVTSEQAKFWLGLGGGRVSPPGPECIEKPATERRIDKGEEVGETTVQRDAKMAPEETATPKTVGTSCYHCGTAIGCNCATASAPPPPYVGSGLYPSLAGVGEQQGQGGDTPRGAEQPRAEPGHAGLAPGPALTDWARIREELASTGPPVVAMPVVIKTEGPAWTPLEPKLITRLADTVRTKGLRSPITMAEVEALMSSPLLPHDVTNLMRVILGPAPYALWMDAWGVQLQTVIAAATRDPRHPANGQGRGERTNLDRLKGLADGMVGNPQGQAALLRPGELVAITASALQAFREVARLAEPAGPWADITQGPSESFVDFANRLIKAVEGSDLPPSARAPVIIDCFRQKSQPDIQQLIRAAPSTLTTPGEIIKYVLDRQKIAPLTDQGIAAAMSSAIQPLVMAVVNRERDGQTGSGGRARRLCYTCGSPGHYQAQCPKKRKSGNSRERCQLCDGMGHNAKQCRRRDSNQGQRPGRGLSSGPWPVSEQPAVSLAMTMEHKDRPLVRVILTNTGSHPVKQRSVYITALLDSGADITIISEEDWPTDWPVVDTANPQIHGIGGGIPMRKSRDMIELGVINRDGSLERPLLLFPAVAMVRGSILGRDCLQGLGLRLTNLVGRATVLTVALHLAIPLKWKPDHTPVWIDQWPLPEGKLVALTQLVEKELQLGHIEPSLSCWNTPVFVIRKASGSYRLLHDLRAVNAKLVPFGAVQQGAPVLSALPRGWPLMVLDLKDCFFSIPLAEQDREAFAFTLPSVNNQAPARRFQWKVLPQGMTCSPTICQLVVGQVLEPLRLKHPSLRMLHYMDDLLLAASSHDGLEAAGEEVINTLERAGFTISPDKIQREPGVQYLGYKLGSTYVAPVGLVAEPRIATLWDVQKLVGSLQWLRPALGIPPRLMGPFYEQLRGSDPNEAREWNLDMKMAWREIVQLSTTAALERWDPALPLEGAVVRCEQGAIGVLGQGLSTHPRPCLWLFSTQPTKAFTAWLEVLTLLITKLRASAVRTFGKEVDILLLPACFREDLPLPEGILLALRGFAGKIRSSDTPSIFDIARPLHVSLKVRVTDHPVPGPTVFTDASSSTHKGVVVWREGPRWEIKEIADLGASVQQLEARAVAMALLLWPTTPTNVVTDSAFVAKMLLKMGQEGVPSTAAAFILEDALSQRSAMAAVLHVRSHSEVPGFFTEGNDVADSQATFQAYPLREAKDLHTTLHIGPRALSKACNISMQQAREVVQTCPHCNSAPALEAGVNPRGLGPLQIWQTDFTLEPRMAPRSWLAVTVDTASSAIVVTQHGRVTSVAAQHHWATAIAVLGRPKAIKTDNGSCFTSKSTREWLARWGIAHTTGIPGNSQGQAMVERANRLLKDKIRVLAEGDGFMKRIPASKQGELLAKAMYALNHFERGENTKTPVQKHWRPTVLTEGPPVKIRIETGEWEKGWNVLVWGRGYAAVKNRDTDKVIWVPSRKVKPDITQKDEVTKKDEASPLFAGSSDWIPWGDEQEGLQEEAASNKQEGPGEDTLAANES
|
2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.26.4; 3.4.23.-
|
COFACTOR: [Reverse transcriptase alpha-subunit]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=The RT polymerase active site binds 2 magnesium ions. {ECO:0000255|PROSITE-ProRule:PRU00405}; COFACTOR: [Reverse transcriptase alpha-subunit]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: [Integrase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:8805516, ECO:0000269|PubMed:9218451}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:8805516, ECO:0000269|PubMed:9218451}; Note=Binds 8 Mg(2+) ions per integrase homotetramer (Probable). Zn(2+) can also be a cofactor for the nicking activity, but not for the polynucleotidyltransferase activity (PubMed:9218451). {ECO:0000269|PubMed:9218451, ECO:0000305|PubMed:9218451};
|
DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; viral genome integration into host DNA [GO:0044826]
|
virion component [GO:0044423]
|
aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; zinc ion binding [GO:0008270]
|
PF00607;PF00552;PF02022;PF02813;PF00665;PF00077;PF00078;PF06817;PF00098;
|
1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;4.10.60.10;
| null |
PTM: [Isoform Gag-Pol polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins. {ECO:0000250|UniProtKB:P03354}.; PTM: Capsid protein p27: The cleavage at the C-terminus is slowly trimmed by the viral protease, sometimes being cut internally thereby generating the short version of the capsid protein and a capsid protein C-terminally extended by 3 amino acids in a ratio of 2:1. {ECO:0000250|UniProtKB:P03322}.
|
SUBCELLULAR LOCATION: [Matrix protein p19]: Virion {ECO:0000250|UniProtKB:P03354}.; SUBCELLULAR LOCATION: [Capsid protein p27, alternate cleaved 1]: Virion {ECO:0000250|UniProtKB:P03354}.; SUBCELLULAR LOCATION: [Capsid protein p27, alternate cleaved 2]: Virion {ECO:0000250|UniProtKB:P03354}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p12]: Virion {ECO:0000250|UniProtKB:P03354}.
|
CATALYTIC ACTIVITY: [Reverse transcriptase alpha-subunit]: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: [Reverse transcriptase alpha-subunit]: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: [Reverse transcriptase alpha-subunit]: Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4; Evidence={ECO:0000255|PROSITE-ProRule:PRU00408};
| null | null | null | null |
FUNCTION: Capsid protein p27: Self-associates to form the irregular polyhedron core composed of hexamers and pentamers, that encapsulates the genomic RNA-nucleocapsid complex. Assembles as a tube in vitro. Binds to inositol hexakisphosphate (IP6), which allows the assembly of the polyhedral capsid. {ECO:0000250|UniProtKB:P03322}.; FUNCTION: [Spacer peptide]: Plays a role in the oligomerization of the Gag polyprotein and in the stabilization of the immature particle. Essential layering element during tube assembly. Allows the cooperative binging of Gag to the host plasma membrane. {ECO:0000250|UniProtKB:P03322}.; FUNCTION: [Nucleocapsid protein p12]: Binds strongly to viral nucleic acids and promotes their packaging (By similarity). Plays a role in the maturation-stabilization of the viral dimeric RNA via highly structured zinc-binding motifs (By similarity). {ECO:0000250|UniProtKB:P03322, ECO:0000250|UniProtKB:P0C776}.; FUNCTION: [Protease p15]: The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. {ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions (PubMed:9218451). This recombination event is an essential step in the viral replication cycle. Has a strong preference for using the 3'-OH at the viral DNA end as a nucleophile. {ECO:0000250|UniProtKB:P03354, ECO:0000269|PubMed:9218451}.
|
Rous sarcoma virus subgroup B (strain Schmidt-Ruppin) (RSV-SR-B)
|
O92972
|
POLG_HCVJ4
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MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKASERSQPRGRRQPIPKARRPEGRAWAQPGYPWPLYGNEGLGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTIPASAYEVRNVSGIYHVTNDCSNSSIVYEAADVIMHTPGCVPCVREGNSSRCWVALTPTLAARNASVPTTTIRRHVDLLVGTAAFCSAMYVGDLCGSIFLVSQLFTFSPRRHETVQDCNCSIYPGHVSGHRMAWDMMMNWSPTTALVVSQLLRIPQAVVDMVAGAHWGVLAGLAYYSMVGNWAKVLIVALLFAGVDGETHTTGRVAGHTTSGFTSLFSSGASQKIQLVNTNGSWHINRTALNCNDSLQTGFFAALFYAHKFNSSGCPERMASCRPIDWFAQGWGPITYTKPNSSDQRPYCWHYAPRPCGVVPASQVCGPVYCFTPSPVVVGTTDRSGVPTYSWGENETDVMLLNNTRPPQGNWFGCTWMNSTGFTKTCGGPPCNIGGVGNRTLICPTDCFRKHPEATYTKCGSGPWLTPRCLVDYPYRLWHYPCTLNFSIFKVRMYVGGVEHRLNAACNWTRGERCNLEDRDRSELSPLLLSTTEWQILPCAFTTLPALSTGLIHLHQNIVDVQYLYGVGSAFVSFAIKWEYILLLFLLLADARVCACLWMMLLIAQAEAALENLVVLNAASVAGAHGILSFLVFFCAAWYIKGRLAPGAAYAFYGVWPLLLLLLALPPRAYALDREMAASCGGAVLVGLVFLTLSPYYKVFLTRLIWWLQYFITRAEAHMQVWVPPLNVRGGRDAIILLTCAVHPELIFDITKLLLAILGPLMVLQAGITRVPYFVRAQGLIRACMLVRKVAGGHYVQMAFMKLGALTGTYVYNHLTPLRDWAHAGLRDLAVAVEPVVFSAMETKVITWGADTAACGDIILGLPVSARRGKEIFLGPADSLEGQGWRLLAPITAYSQQTRGVLGCIITSLTGRDKNQVEGEVQVVSTATQSFLATCINGVCWTVYHGAGSKTLAGPKGPITQMYTNVDLDLVGWQAPPGARSMTPCSCGSSDLYLVTRHADVIPVRRRGDSRGSLLSPRPVSYLKGSSGGPLLCPSGHVVGVFRAAVCTRGVAKAVDFIPVESMETTMRSPVFTDNSSPPAVPQTFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGAYMSKAHGIDPNIRTGVRTITTGGSITYSTYGKFLADGGCSGGAYDIIICDECHSTDSTTILGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEIGLSNNGEIPFYGKAIPIEAIKGGRHLIFCHSKKKCDELAAKLTGLGLNAVAYYRGLDVSVIPPIGDVVVVATDALMTGFTGDFDSVIDCNTCVTQTVDFSLDPTFTIETTTVPQDAVSRSQRRGRTGRGRSGIYRFVTPGERPSGMFDSSVLCECYDAGCAWYELTPAETSVRLRAYLNTPGLPVCQDHLEFWESVFTGLTHIDAHFLSQTKQAGDNFPYLVAYQATVCARAQAPPPSWDQMWKCLIRLKPTLHGPTPLLYRLGAVQNEVILTHPITKYIMACMSADLEVVTSTWVLVGGVLAALAAYCLTTGSVVIVGRIILSGKPAVVPDREVLYQEFDEMEECASQLPYIEQGMQLAEQFKQKALGLLQTATKQAEAAAPVVESKWRALETFWAKHMWNFISGIQYLAGLSTLPGNPAIASLMAFTASITSPLTTQNTLLFNILGGWVAAQLAPPSAASAFVGAGIAGAAVGSIGLGKVLVDILAGYGAGVAGALVAFKVMSGEVPSTEDLVNLLPAILSPGALVVGVVCAAILRRHVGPGEGAVQWMNRLIAFASRGNHVSPTHYVPESDAAARVTQILSSLTITQLLKRLHQWINEDCSTPCSGSWLRDVWDWICTVLTDFKTWLQSKLLPRLPGVPFLSCQRGYKGVWRGDGIMQTTCPCGAQIAGHVKNGSMRIVGPRTCSNTWHGTFPINAYTTGPCTPSPAPNYSRALWRVAAEEYVEVTRVGDFHYVTGMTTDNVKCPCQVPAPEFFTEVDGVRLHRYAPACKPLLREDVTFQVGLNQYLVGSQLPCEPEPDVTVLTSMLTDPSHITAETAKRRLARGSPPSLASSSASQLSAPSLKATCTTHHDSPDADLIEANLLWRQEMGGNITRVESENKVVILDSFEPLHAEGDEREISVAAEILRKSRKFPSALPIWARPDYNPPLLESWKDPDYVPPVVHGCPLPPTKAPPIPPPRRKRTVVLTESNVSSALAELATKTFGSSGSSAVDSGTATALPDLASDDGDKGSDVESYSSMPPLEGEPGDPDLSDGSWSTVSEEASEDVVCCSMSYTWTGALITPCAAEESKLPINPLSNSLLRHHNMVYATTSRSASLRQKKVTFDRLQVLDDHYRDVLKEMKAKASTVKAKLLSIEEACKLTPPHSAKSKFGYGAKDVRNLSSRAVNHIRSVWEDLLEDTETPIDTTIMAKSEVFCVQPEKGGRKPARLIVFPDLGVRVCEKMALYDVVSTLPQAVMGSSYGFQYSPKQRVEFLVNTWKSKKCPMGFSYDTRCFDSTVTESDIRVEESIYQCCDLAPEARQAIRSLTERLYIGGPLTNSKGQNCGYRRCRASGVLTTSCGNTLTCYLKATAACRAAKLQDCTMLVNGDDLVVICESAGTQEDAAALRAFTEAMTRYSAPPGDPPQPEYDLELITSCSSNVSVAHDASGKRVYYLTRDPTTPLARAAWETARHTPINSWLGNIIMYAPTLWARMILMTHFFSILLAQEQLEKALDCQIYGACYSIEPLDLPQIIERLHGLSAFTLHSYSPGEINRVASCLRKLGVPPLRTWRHRARSVRAKLLSQGGRAATCGRYLFNWAVRTKLKLTPIPAASQLDLSGWFVAGYSGGDIYHSLSRARPRWFPLCLLLLSVGVGIYLLPNR
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2.7.7.48; 3.4.21.98; 3.4.22.-; 3.6.1.15; 3.6.4.13
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COFACTOR: [Protease NS2]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:17239391}; Note=Activity of protease NS2 is dependent on zinc ions and completely inhibited by EDTA. This is probably due to the fact that NS2 protease activity needs NS3 N-terminus that binds a zinc atom (active region NS2-3). {ECO:0000269|PubMed:17239391}; COFACTOR: [Serine protease/helicase NS3]: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:17239391}; Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9WMX2}; Note=Binds 1 zinc ion, which has a structural role (PubMed:17239391). The magnesium ion is essential for the helicase activity (By similarity). {ECO:0000250|UniProtKB:Q9WMX2, ECO:0000269|PubMed:17239391}; COFACTOR: [RNA-directed RNA polymerase]: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P26663}; Note=Binds 2 magnesium ion that constitute a dinuclear catalytic metal center. {ECO:0000250|UniProtKB:P26663};
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clathrin-dependent endocytosis of virus by host cell [GO:0075512]; fusion of virus membrane with host endosome membrane [GO:0039654]; induction by virus of host autophagy [GO:0039520]; protein complex oligomerization [GO:0051259]; proteolysis [GO:0006508]; symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint [GO:0039645]; symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity [GO:0039545]; symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity [GO:0039563]; symbiont-mediated suppression of host TRAF-mediated signal transduction [GO:0039527]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; transformation of host cell by virus [GO:0019087]; viral RNA genome replication [GO:0039694]; virion attachment to host cell [GO:0019062]; virus-mediated perturbation of host defense response [GO:0019049]
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host cell endoplasmic reticulum membrane [GO:0044167]; host cell lipid droplet [GO:0044186]; host cell mitochondrial membrane [GO:0044191]; host cell nucleus [GO:0042025]; host cell perinuclear region of cytoplasm [GO:0044220]; host cell plasma membrane [GO:0020002]; membrane [GO:0016020]; ribonucleoprotein complex [GO:1990904]; viral envelope [GO:0019031]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type endopeptidase activity [GO:0004197]; molecular adaptor activity [GO:0060090]; monoatomic ion channel activity [GO:0005216]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type endopeptidase activity [GO:0004252]; SH3 domain binding [GO:0017124]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF07652;PF01543;PF01542;PF01539;PF01560;PF01538;PF01006;PF01001;PF01506;PF08300;PF08301;PF12941;PF02907;PF00998;
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2.40.10.120;3.30.70.270;6.10.250.1610;6.10.250.1750;6.10.250.2920;2.20.25.210;3.30.160.890;2.30.30.710;1.20.1280.150;2.20.25.220;3.40.50.300;1.10.820.10;2.40.10.10;
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Hepacivirus polyprotein family
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PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The structural proteins, core, E1, E2 and p7 are produced by proteolytic processing by host signal peptidases (By similarity). The core protein precursor is synthesized as a 23 kDa, which is retained in the ER membrane through the hydrophobic signal peptide (By similarity). Cleavage by the signal peptidase releases the 21 kDa mature core protein (By similarity). The cleavage of the core protein precursor occurs between aminoacids 176 and 188 but the exact cleavage site is not known (By similarity). Some degraded forms of the core protein appear as well during the course of infection (By similarity). The other proteins (p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) are cleaved by the viral proteases (By similarity). Autoprocessing between NS2 and NS3 is mediated by the NS2 cysteine protease catalytic domain and regulated by the NS3 N-terminal domain (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; PTM: [Mature core protein]: Phosphorylated by host PKC and PKA. {ECO:0000250|UniProtKB:Q01403}.; PTM: [Mature core protein]: Ubiquitinated; mediated by UBE3A and leading to core protein subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q03463}.; PTM: [Envelope glycoprotein E1]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Envelope glycoprotein E2]: Highly N-glycosylated. {ECO:0000250|UniProtKB:P27958}.; PTM: [Protease NS2]: Palmitoylation is required for NS2/3 autoprocessing and E2 recruitment to membranes. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 4B]: Palmitoylated. This modification may play a role in its polymerization or in protein-protein interactions. {ECO:0000250|UniProtKB:P27958}.; PTM: [Non-structural protein 5A]: Phosphorylated on serines in a basal form termed p56 (By similarity). p58 is a hyperphosphorylated form of p56 (By similarity). p56 and p58 coexist in the cell in roughly equivalent amounts (By similarity). Hyperphosphorylation is dependent on the presence of NS4A (By similarity). Host CSNK1A1/CKI-alpha or RPS6KB1 kinases may be responsible for NS5A phosphorylation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664}.; PTM: [Non-structural protein 5A]: Tyrosine phosphorylation is essential for the interaction with host SRC. {ECO:0000250|UniProtKB:Q99IB8}.; PTM: [RNA-directed RNA polymerase]: The N-terminus is phosphorylated by host PRK2/PKN2. {ECO:0000250|UniProtKB:P26662}.
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SUBCELLULAR LOCATION: [Core protein precursor]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P26664}; Single-pass membrane protein {ECO:0000255}. Host mitochondrion membrane {ECO:0000250|UniProtKB:P26664}; Single-pass type I membrane protein {ECO:0000255}. Note=The C-terminal transmembrane domain of the core protein precursor contains an ER signal leading the nascent polyprotein to the ER membrane.; SUBCELLULAR LOCATION: [Mature core protein]: Virion {ECO:0000250|UniProtKB:Q99IB8}. Host cytoplasm {ECO:0000250|UniProtKB:Q99IB8}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q99IB8}. Note=Only a minor proportion of core protein is present in the nucleus (By similarity). Probably present on the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E1]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Virion membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Host endoplasmic reticulum membrane; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=The C-terminal transmembrane domain acts as a signal sequence and forms a hairpin structure before cleavage by host signal peptidase (By similarity). After cleavage, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). A reorientation of the second hydrophobic stretch occurs after cleavage producing a single reoriented transmembrane domain (By similarity). These events explain the final topology of the protein (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Viroporin p7]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P27958}. Host cell membrane {ECO:0000250|UniProtKB:P27958}. Note=The C-terminus of p7 membrane domain acts as a signal sequence (By similarity). After cleavage by host signal peptidase, the membrane sequence is retained at the C-terminus of the protein, serving as ER membrane anchor (By similarity). ER retention of p7 is leaky and a small fraction reaches the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Protease NS2]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Probably present on the surface of lipid droplets. {ECO:0000250|UniProtKB:Q99IB8}.; SUBCELLULAR LOCATION: [Serine protease/helicase NS3]: Host endoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=NS3 is associated to the ER membrane through its binding to NS4A. {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Host membrane insertion occurs after processing by the NS3 protease.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P27958}. Note=A reorientation of the N-terminus into the ER lumen occurs post-translationally. {ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P27958}; Peripheral membrane protein {ECO:0000250|UniProtKB:P27958}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P27958}. Host mitochondrion {ECO:0000250|UniProtKB:P26662}. Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host nucleus {ECO:0000250|UniProtKB:P26662}. Host lipid droplet {ECO:0000250|UniProtKB:Q9WMX2}. Note=Host membrane insertion occurs after processing by the NS3 protease (By similarity). Localizes at the surface of lipid droplets (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P27958}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:P27958}. Host endoplasmic reticulum membrane; Single-pass type IV membrane protein {ECO:0000250|UniProtKB:P27958}. Note=Host membrane insertion occurs after processing by the NS3 protease. {ECO:0000250|UniProtKB:P27958}.
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CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.; EC=3.4.21.98; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [Serine protease/helicase NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P27958}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
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FUNCTION: [Mature core protein]: Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (By similarity). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (By similarity). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:P29846, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305}.; FUNCTION: [Envelope glycoprotein E1]: Forms a heterodimer with envelope glycoprotein E2, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Envelope glycoprotein E2]: Forms a heterodimer with envelope glycoprotein E1, which mediates virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane (By similarity). Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (By similarity). The interaction between envelope glycoprotein E2 and host apolipoprotein E/APOE allows the proper assembly, maturation and infectivity of the viral particles (By similarity). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (By similarity). E1/E2 heterodimer binds host apolipoproteins such as APOB and APOE thereby forming a lipo-viro-particle (LVP) (By similarity). APOE associated to the LVP allows the initial virus attachment to cell surface receptors such as the heparan sulfate proteoglycans (HSPGs), syndecan-1 (SDC1), syndecan-1 (SDC2), the low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SCARB1) (By similarity). The cholesterol transfer activity of SCARB1 allows E2 exposure and binding of E2 to SCARB1 and the tetraspanin CD81 (By similarity). E1/E2 heterodimer binding on CD81 activates the epithelial growth factor receptor (EGFR) signaling pathway (By similarity). Diffusion of the complex E1-E2-EGFR-SCARB1-CD81 to the cell lateral membrane allows further interaction with Claudin 1 (CLDN1) and occludin (OCLN) to finally trigger HCV entry (By similarity). Inhibits host EIF2AK2/PKR activation, preventing the establishment of an antiviral state (By similarity). Viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses (By similarity). These interactions allow the capture of circulating HCV particles by these cells and subsequent transmission to permissive cells (By similarity). Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity). {ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Viroporin p7]: Ion channel protein that acts as a viroporin and plays an essential role in the assembly, envelopment and secretion of viral particles (Probable). Regulates the host cell secretory pathway, which induces the intracellular retention of viral glycoproteins and favors assembly of viral particles (By similarity). Creates a pore in acidic organelles and releases Ca(2+) and H(+) in the cytoplasm of infected cells, leading to a productive viral infection (Probable). High levels of cytoplasmic Ca(2+) may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication (Probable). This ionic imbalance induces the assembly of the inflammasome complex, which triggers the maturation of pro-IL-1beta into IL-1beta through the action of caspase-1 (By similarity). Targets also host mitochondria and induces mitochondrial depolarization (By similarity). In addition of its role as a viroporin, acts as a lipid raft adhesion factor (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000305, ECO:0000305|PubMed:12560074}.; FUNCTION: [Protease NS2]: Cysteine protease required for the proteolytic auto-cleavage between the non-structural proteins NS2 and NS3 (PubMed:17239391). The N-terminus of NS3 is required for the function of NS2 protease (active region NS2-3) (PubMed:17239391). Promotes the initiation of viral particle assembly by mediating the interaction between structural and non-structural proteins (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000269|PubMed:17239391}.; FUNCTION: [Serine protease/helicase NS3]: Displays three enzymatic activities: serine protease with a chymotrypsin-like fold, NTPase and RNA helicase (By similarity). NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B (By similarity). The NS3/NS4A complex prevents phosphorylation of host IRF3, thus preventing the establishment of dsRNA induced antiviral state (By similarity). The NS3/NS4A complex induces host amino acid transporter component SLC3A2, thus contributing to HCV propagation (By similarity). NS3 RNA helicase binds to RNA and unwinds both dsDNA and dsRNA in the 3' to 5' direction, and likely resolves RNA complicated stable secondary structures in the template strand (By similarity). Binds a single ATP and catalyzes the unzipping of a single base pair of dsRNA (By similarity). Inhibits host antiviral proteins TBK1 and IRF3 thereby preventing the establishment of an antiviral state (By similarity). Cleaves host MAVS/CARDIF thereby preventing the establishment of an antiviral state (By similarity). Cleaves host TICAM1/TRIF, thereby disrupting TLR3 signaling and preventing the establishment of an antiviral state (By similarity). {ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS4B self-interaction contributes to its function in membranous web formation (By similarity). Promotes host TRIF protein degradation in a CASP8-dependent manner thereby inhibiting host TLR3-mediated interferon signaling (By similarity). Disrupts the interaction between STING and TBK1 contributing to the inhibition of interferon signaling (By similarity). {ECO:0000250|UniProtKB:P27958}.; FUNCTION: [Non-structural protein 5A]: Phosphorylated protein that is indispensable for viral replication and assembly (By similarity). Both hypo- and hyperphosphorylated states are required for the viral life cycle (By similarity). The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). Involved in RNA-binding and especially in binding to the viral genome (By similarity). Zinc is essential for RNA-binding (By similarity). Participates in the viral particle production as a result of its interaction with the mature viral core protein (By similarity). Its interaction with host VAPB may target the viral replication complex to vesicles (By similarity). Down-regulates viral IRES translation initiation (By similarity). Mediates interferon resistance, presumably by interacting with and inhibiting host EIF2AK2/PKR (By similarity). Prevents BIN1-induced apoptosis (By similarity). Acts as a transcriptional activator of some host genes important for viral replication when localized in the nucleus (By similarity). Via the interaction with host PACSIN2, modulates lipid droplet formation in order to promote virion assembly (By similarity). Modulates TNFRSF21/DR6 signaling pathway for viral propagation (By similarity). {ECO:0000250|UniProtKB:P26662, ECO:0000250|UniProtKB:P26664, ECO:0000250|UniProtKB:P27958, ECO:0000250|UniProtKB:Q99IB8, ECO:0000250|UniProtKB:Q9WMX2}.; FUNCTION: [RNA-directed RNA polymerase]: RNA-dependent RNA polymerase that performs primer-template recognition and RNA synthesis during viral replication. Initiates RNA transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host pattern recognition receptors can be bypassed, thereby evading activation of antiviral pathways. {ECO:0000250|UniProtKB:P27958}.
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Hepatitis C virus genotype 1b (strain HC-J4) (HCV)
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O93182
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GAG_HV190
|
MGARASVLSGGKLDAWEKIRLRPGGKKKYRLKHLVWASRELERFALNPGLLETPEGCLQIIEQIQPAIKTGTEELKSLFNLVAVLYCVHRKIDVKDTKEALDKIEEIQNKSQQKTQQAAADKEKDNKVSQNYPIVQNAQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNAMLNTVGGHQAAMQMLKDTINEEAAEWDRVHPVHAGPIPPGQMREPRGSDIAGTTSTLQEQIAWMTGNPAIPVGDIYKRWIILGLNKIVRMYSPVSILDIKQGPKEPFRDYVDRFFKTLRAEQATQDVKNWMTETLLVQNANPDCKTILRALGQGASIEEMMTACQGVGGPSHKARVLAEAMSQVTNTNTAIMMQKGNFKGQRKFVKCFNCGKEGHIARNCRAPRKKGCWKCGREGHQMKDCTERQANFLGKIWPSSKGRPGNFLQSRPEPTAPPAESFGFGEEMTPSPKQEQLKDKEPPLASLRSLFGSDPLLQ
| null | null |
viral budding via host ESCRT complex [GO:0039702]
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host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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RNA binding [GO:0003723]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
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PF00540;PF00607;PF19317;PF08705;PF00098;
|
1.10.1200.30;6.10.250.390;1.10.375.10;1.10.150.90;1.20.5.760;4.10.60.10;
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Primate lentivirus group gag polyprotein family
|
PTM: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000250|UniProtKB:P12493}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04591}.; PTM: Capsid protein p24 is phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: Nucleocapsid protein p7 is methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
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SUBCELLULAR LOCATION: [Gag polyprotein]: Host cell membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host endosome, host multivesicular body {ECO:0000250|UniProtKB:P12493}. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane {ECO:0000250|UniProtKB:P12493}; Lipid-anchor {ECO:0000250|UniProtKB:P12493}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000250|UniProtKB:P12493}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000250|UniProtKB:P12493}.
| null | null | null | null | null |
FUNCTION: [Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (By similarity). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). The capsid promotes immune invasion by cloaking viral DNA from CGAS detection (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating (By similarity). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid (By similarity). {ECO:0000250|UniProtKB:P04591, ECO:0000250|UniProtKB:P12493}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04591}.; FUNCTION: [p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000250|UniProtKB:P12493}.
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Human immunodeficiency virus type 1 group M subtype H (isolate 90CF056) (HIV-1)
|
O93209
|
POL_FFV
|
MDLLKPLTVERKGVKIKGYWDSQADITCVPKDLLQGEEPVRQQNVTTIHGTQEGDVYYVNLKIDGRRINTEVIGTTLDYAIITPGDVPWILKKPLELTIKLDLEEQQGTLLNNSILSKKGKEELKQLFEKYSALWQSWENQVGHRRIRPHKIATGTVKPTPQKQYHINPKAKPDIQIVINDLLKQGVLIQKESTMNTPVYPVPKPNGRWRMVLDYRAVNKVTPLIAVQNQHSYGILGSLFKGRYKTTIDLSNGFWAHPIVPEDYWITAFTWQGKQYCWTVLPQGFLNSPGLFTGDVVDLLQGIPNVEVYVDDVYISHDSEKEHLEYLDILFNRLKEAGYIISLKKSNIANSIVDFLGFQITNEGRGLTDTFKEKLENITAPTTLKQLQSILGLLNFARNFIPDFTELIAPLYALIPKSTKNYVPWQIEHSTTLETLITKLNGAEYLQGRKGDKTLIMKVNASYTTGYIRYYNEGEKKPISYVSIVFSKTELKFTELEKLLTTVHKGLLKALDLSMGQNIHVYSPIVSMQNIQKTPQTAKKALASRWLSWLSYLEDPRIRFFYDPQMPALKDLPAVDTGKDNKKHPSNFQHIFYTDGSAITSPTKEGHLNAGMGIVYFINKDGNLQKQQEWSISLGNHTAQFAEIAAFEFALKKCLPLGGNILVVTDSNYVAKAYNEELDVWASNGFVNNRKKPLKHISKWKSVADLKRLRPDVVVTHEPGHQKLDSSPHAYGNNLADQLATQASFKVHMTKNPKLDIEQIKAIQACQNNERLPVGYPKQYTYELQNNKCMVLRKDGWREIPPSRERYKLIKEAHNISHAGREAVLLKIQENYWWPKMKKDISSFLSTCNVCKMVNPLNLKPISPQAIVHPTKPFDKFYMDYIGPLPPSEGYVHVLVVVDAATGFTWLYPTKAQTSKATIKVLNHLTGLAIPKVLHSDQGSAFTSEEFAQWAKERNIQLEFSTPYHPQSSGKVERKNSEIKKLLTKLLVGRPLKWYNLISSVQLALNNTHVVSTKYTPHQLMFGIDCNLPFANKDTLDWTREEELALLQEIRESLQHPVQPPTCSGWSPYVGQLVQERVYRPSQLRPKWRKPTKVLEILNPRTVIIVDHLGQRKSVSIDNLKPTAHQHNGTRTCDDPEGMDGMECSQTTTETSVDSS
|
2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.26.4; 3.4.23.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
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DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; viral genome integration into host DNA [GO:0044826]; viral penetration into host nucleus [GO:0075732]
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host cell [GO:0043657]; host cell cytoplasm [GO:0030430]; host cell nucleus [GO:0042025]; virion component [GO:0044423]
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aspartic-type endopeptidase activity [GO:0004190]; DNA-directed DNA polymerase activity [GO:0003887]; metal ion binding [GO:0046872]; RNA binding [GO:0003723]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]
|
PF17921;PF00075;PF17919;PF00665;PF00078;PF18103;PF03539;
|
1.10.340.70;2.30.30.140;3.30.70.270;6.10.20.110;2.40.70.10;3.10.10.10;3.30.420.10;
| null |
PTM: Specific enzymatic cleavages in vivo by viral protease yield mature proteins. The protease is not cleaved off from Pol. Since cleavage efficiency is not optimal for all sites, long and active p65Pro-RT, p87Pro-RT-RNaseH and even some Pr125Pol are detected in infected cells (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.; SUBCELLULAR LOCATION: [Protease/Reverse transcriptase/ribonuclease H]: Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4; Evidence={ECO:0000255|PROSITE-ProRule:PRU00408}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
| null | null | null | null |
FUNCTION: The aspartyl protease activity mediates proteolytic cleavages of Gag and Pol polyproteins. The reverse transcriptase (RT) activity converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell (early reverse transcription) or after proviral DNA transcription (late reverse transcription). RT consists of a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA-Lys1,2 binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primer. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends (By similarity). {ECO:0000250}.; FUNCTION: Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising at least the viral genome, matrix protein, and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from the 3' end of the viral DNA right (U5) end, leaving the left (U3) intact. In the second step, the PIC enters cell nucleus. This process is mediated through the integrase and allows the virus to infect both dividing (nuclear membrane disassembled) and G1/S-arrested cells (active translocation), but with no viral gene expression in the latter. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. It is however not clear how integration then proceeds to resolve the asymmetrical cleavage of viral DNA (By similarity). {ECO:0000250}.
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Feline foamy virus (FFV) (Feline syncytial virus)
|
O93215
|
POL_HV190
|
MGARASVLSGGKLDAWEKIRLRPGGKKKYRLKHLVWASRELERFALNPGLLETPEGCLQIIEQIQPAIKTGTEELKSLFNLVAVLYCVHRKIDVKDTKEALDKIEEIQNKSQQKTQQAAADKEKDNKVSQNYPIVQNAQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNAMLNTVGGHQAAMQMLKDTINEEAAEWDRVHPVHAGPIPPGQMREPRGSDIAGTTSTLQEQIAWMTGNPAIPVGDIYKRWIILGLNKIVRMYSPVSILDIKQGPKEPFRDYVDRFFKTLRAEQATQDVKNWMTETLLVQNANPDCKTILRALGQGASIEEMMTACQGVGGPSHKARVLAEAMSQVTNTNTAIMMQKGNFKGQRKFVKCFNCGKEGHIARNCRAPRKKGCWKCGREGHQMKDCTERQAKFFRENLAFQQREARKFSPEQARTNSPTSRELRVRRGDDPLSEAGAAEGQGTSLSFPQITLWQRPLVTVKIEGQLREALLDTGADDTVLEEINLPGKWKPKMIGGIGGFIKVRQYEQVAIEICGKKAIGTVLVGPTPVNIIGRNILTQIGCTLNFPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALTEICTEMEKEGKISRIGPENPYSTPIFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVSVLDVGDAYFSVPLDKEFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILAPFREQNPEMVIYQYMDDLYVGSDLEIGQHRAKIEELRAHLLKWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQTVKLPEKDSWTVNDIQKLVGKLNWASQIYPNIKVKQLCKLLRGAKALTDIIPLTKEAELELAENREILREPIHGVYYDPSKDLIAEIRKQGQGQWTYQIYQEPFKNLKTGKYAKMRTAHTNDIKQLTEAVQKISTESIVIWGKIPKFRLPIQKETWETWWTEYWQATWIPEWEFVNTPHLVKLWYQLETEPIAGAETYYIDGAANRETKLGKAGYVTDRGKQKVVSLTETTNQKTELQAIYLALQDSGLEVNIVTDSQYALGIIQAQPDKSESELVNQIIEELIKKEKVYLSWVPAHKGIGGNEQVDKLVSSGVRKVLFLDGIDKAQEEHERYHNNWRAVASDFNLPPIVAKEIVASCDKCQLKGEAMHGQVDCSPGIWQLDCTHLEGQVILVAVHVASGYIEAEVIPAETGKETAYFLLKLASRWPVKVIHTDNGSNFTSAAVKAACWWADIQQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIIDIIATDIQTKELQKQISNIQKFRVYYRDSRDPIWKGPAKLLWKGEGAVVIQDNSEIKVVPRREAKIIRDYGKQMAGDDCVASRQDED
|
2.7.7.-; 2.7.7.49; 2.7.7.7; 3.1.-.-; 3.1.13.2; 3.1.26.13; 3.4.23.16
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for reverse transcriptase polymerase activity. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding. {ECO:0000250}; COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions. {ECO:0000250};
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DNA integration [GO:0015074]; DNA recombination [GO:0006310]; establishment of integrated proviral latency [GO:0075713]; proteolysis [GO:0006508]; symbiont entry into host cell [GO:0046718]; symbiont-mediated suppression of host gene expression [GO:0039657]; viral genome integration into host DNA [GO:0044826]; viral penetration into host nucleus [GO:0075732]
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host cell [GO:0043657]; host cell nucleus [GO:0042025]; host cell plasma membrane [GO:0020002]; host multivesicular body [GO:0072494]; membrane [GO:0016020]; viral nucleocapsid [GO:0019013]; virion membrane [GO:0055036]
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aspartic-type endopeptidase activity [GO:0004190]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; exoribonuclease H activity [GO:0004533]; lipid binding [GO:0008289]; RNA stem-loop binding [GO:0035613]; RNA-directed DNA polymerase activity [GO:0003964]; RNA-DNA hybrid ribonuclease activity [GO:0004523]; structural molecule activity [GO:0005198]; zinc ion binding [GO:0008270]
|
PF00540;PF19317;PF00552;PF02022;PF00075;PF00665;PF00077;PF00078;PF06815;PF06817;PF00098;
|
1.10.10.200;1.10.1200.30;3.30.70.270;2.40.70.10;3.10.10.10;1.10.375.10;1.10.150.90;2.30.30.10;3.30.420.10;1.20.5.760;4.10.60.10;
| null |
PTM: [Gag-Pol polyprotein]: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry. {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00405}.; PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.; PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000250|UniProtKB:P12493}.; PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.
|
SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-anchor. Host endosome, host multivesicular body. Note=These locations are linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000250|UniProtKB:P12497}.; SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.; SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Reverse transcriptase/ribonuclease H]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Integrase]: Virion {ECO:0000305}. Host nucleus {ECO:0000305}. Host cytoplasm {ECO:0000305}. Note=Nuclear at initial phase, cytoplasmic at assembly. {ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.; EC=3.4.23.16; Evidence={ECO:0000255|PROSITE-ProRule:PRU00275}; CATALYTIC ACTIVITY: Reaction=Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.; EC=3.1.26.13; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.; EC=3.1.13.2; Evidence={ECO:0000250}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-ProRule:PRU00405};
| null | null | null | null |
FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation. {ECO:0000250}.; FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA. {ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Capsid protein p24]: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.; FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. Also mediates cleavage of host YTHDF3. Mediates cleavage of host CARD8, thereby activating the CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585, ECO:0000255|PROSITE-ProRule:PRU00275}.; FUNCTION: [Reverse transcriptase/ribonuclease H]: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends. {ECO:0000250|UniProtKB:P04585}.; FUNCTION: [Integrase]: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration. {ECO:0000250|UniProtKB:P04585}.
|
Human immunodeficiency virus type 1 group M subtype H (isolate 90CF056) (HIV-1)
|
O93235
|
CIRBA_XENLA
|
MSDEGKLFIGGLNFETNEDCLEQAFTKYGRISEVVVVKDRETKRSRGFGFVTFENVDDAKDAMMAMNGKSVDGRQIRVDQAGKSSGERRGGYRGGSSGGRGFFRGGRGRGGGDRGYGSSRFDNRSGGYGGSSGSRDYYGSGRSQGSYGDRSGGSYRDSYDSYATHE
| null | null |
cell migration [GO:0016477]; embryo development ending in birth or egg hatching [GO:0009792]; gastrulation [GO:0007369]; kidney field specification [GO:0072004]; mRNA stabilization [GO:0048255]; negative regulation of nuclear-transcribed mRNA poly(A) tail shortening [GO:0060212]; neurogenesis [GO:0022008]; positive regulation of mRNA splicing, via spliceosome [GO:0048026]; positive regulation of translation [GO:0045727]; pronephros development [GO:0048793]; response to cold [GO:0009409]; response to UV [GO:0009411]; stress granule assembly [GO:0034063]
|
cytoplasm [GO:0005737]; cytoplasmic stress granule [GO:0010494]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; spliceosomal complex [GO:0005681]
|
enzyme binding [GO:0019899]; mRNA 3'-UTR binding [GO:0003730]; mRNA binding [GO:0003729]; ribosome binding [GO:0043022]; small ribosomal subunit rRNA binding [GO:0070181]; translation repressor activity [GO:0030371]
|
PF00076;
|
3.30.70.330;
| null |
PTM: Methylated on arginine residues within RGG motifs. Methylation by prmt1 promotes cytoplasmic accumulation (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: Nucleus, nucleoplasm {ECO:0000250}. Cytoplasm {ECO:0000250}. Note=Shuttles between the nucleus and cytoplasm. Predominantly cytoplasmic in oocytes. Translocates from the nucleus to the cytoplasm upon arginine methylation (By similarity). {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Cold-inducible mRNA binding protein. Acts cooperatively with elavl1/elrA to stabilize AU-rich sequence (ARE)-containing mRNAs by binding to them and inhibiting their deadenylation (By similarity). Essential for embryonic gastrulation and neural development, acting to maintain the expression of a set of adhesion molecules and cell movement during embryogenesis. Plays a role in the specification and migration of pronephros cells during embryonic kidney development. {ECO:0000250, ECO:0000269|PubMed:11018519, ECO:0000269|PubMed:16600183, ECO:0000269|PubMed:18687117}.
|
Xenopus laevis (African clawed frog)
|
O93248
|
OPA1_ONCMA
|
MLRVGRAVACVACNNLASKNMGVRFRMPLQKLHPLSRAIHHRYNASANAQRPPHCSAARHFTSMSRLPMRPPKPSPGGHGGWRYQQHRSFWMLRLASRLLKLRYIVLGSAVGGGYTAKKTYEEWKDMLPDMSAYNWVIPDFVWELSDQIDLDKLTKILPELEEIAKLLPELPDFDKIGENFTFLKSILFTAEAPGDTPVKAATEAPVTATPEASDKQFKKSSDKEKVDQLQEELLRTQMKYQRMLERLEKENKDLRKVVLQKDEKGIHQRKIKKSLIDMYSEVLDILSDFDSNYNTQDHLPRVVVVGDQSAGKTSVLEMIAQARIFPRGSGEMMTRSPVKVTLSEGPHHVAMFKDSSREFDLGKEEDLAALRHEIELRMRKSVKEGQTVSPETISLSVKGPGIQRMVLVDLPGVISTVTAGMAADTKETIFSISKNYMQNPNAIILCIQDGSVDAEADRHRPGQSNGPAGERTIFVLTKVDLAEKNLASPNRIQQIVEGKLFPMKALGYFAVVTGKGSAGESIDSIKDYEEDFFQNSRLLRDGMLKAHQVTTKNLSLAVSDCFWKMVRESVEQQADAFKASRFNLETEWKNNYPRLRELDRNELFEKAKNEILDEVISLSQVTPKHWEAILQKKLWERVSTHVIENIYLPAAQTMNSGTFNTTVDIKLKQWTDKQLPHKALEVAWETLQEEFARFMAEYKGKDQDDIFDKLKEAVKDESIKRHKWNERAMDSLRVIQHNALEDRSITDKPQWDAAIQFMEETLQARLKDTDSVINDMVGPDWKQRWMSWKNRSPEQHTRNETRNELERLLKLHEDHTAYLANDEVTTVRKNLEGRGVEVDPALIKDTWHQLYRRHFLQKALQHCNLCRRGFYYYQRHFVDSELECNDVVLFWRIQRMLLITANTLRQQLTNTEVRRLEKNVKEVLEDFGEDNERKVHLITGRRVQLAEDLKKVREIQEKLEAFIEALHKEK
|
3.6.5.5
| null |
apoptotic process [GO:0006915]; GTP metabolic process [GO:0046039]; inner mitochondrial membrane organization [GO:0007007]; membrane tubulation [GO:0097749]; mitochondrial fusion [GO:0008053]; negative regulation of apoptotic process [GO:0043066]; visual perception [GO:0007601]
|
dendrite [GO:0030425]; microtubule [GO:0005874]; mitochondrial crista [GO:0030061]; mitochondrial intermembrane space [GO:0005758]; mitochondrial outer membrane [GO:0005741]
|
cardiolipin binding [GO:1901612]; GTP binding [GO:0005525]; GTPase activity [GO:0003924]; microtubule binding [GO:0008017]; phosphatidic acid binding [GO:0070300]
|
PF00350;PF19434;
|
3.40.50.300;
|
TRAFAC class dynamin-like GTPase superfamily, Dynamin/Fzo/YdjA family
|
PTM: Cleaved by OMA1 or YME1L downstream of the transmembrane region in response to different signals to generate soluble forms. Cleaved by OMA1 at position S1 following stress conditions, generating the short soluble form (Dynamin-like GTPase OPA1, short form; S-OPA1). {ECO:0000250|UniProtKB:O60313}.
|
SUBCELLULAR LOCATION: [Dynamin-like GTPase OPA1, long form]: Mitochondrion inner membrane {ECO:0000250|UniProtKB:O60313}; Single-pass membrane protein {ECO:0000255}. Note=Detected at contact sites between endoplasmic reticulum and mitochondrion membranes. {ECO:0000250|UniProtKB:O60313}.; SUBCELLULAR LOCATION: [Dynamin-like GTPase OPA1, short form]: Mitochondrion intermembrane space {ECO:0000250|UniProtKB:O60313}.
|
CATALYTIC ACTIVITY: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.5; Evidence={ECO:0000250|UniProtKB:O60313};
| null | null | null | null |
FUNCTION: Dynamin-related GTPase that is essential for normal mitochondrial morphology by mediating fusion of the mitochondrial inner membranes, regulating cristae morphology and maintaining respiratory chain function. Exists in two forms: the transmembrane, long form (Dynamin-like GTPase OPA1, long form; L-OPA1), which is tethered to the inner mitochondrial membrane, and the short soluble form (Dynamin-like GTPase OPA1, short form; S-OPA1), which results from proteolytic cleavage and localizes in the intermembrane space. Both forms (L-OPA1 and S-OPA1) cooperate to catalyze the fusion of the mitochondrial inner membrane. The equilibrium between L-OPA1 and S-OPA1 is essential: excess levels of S-OPA1, produced by cleavage by OMA1 following loss of mitochondrial membrane potential, lead to an impaired equilibrium between L-OPA1 and S-OPA1, inhibiting mitochondrial fusion (By similarity). The balance between L-OPA1 and S-OPA1 also influences cristae shape and morphology (By similarity). Its role in mitochondrial morphology is required for mitochondrial genome maintenance (By similarity). {ECO:0000250|UniProtKB:O60313, ECO:0000250|UniProtKB:P58281}.; FUNCTION: [Dynamin-like GTPase OPA1, long form]: Constitutes the transmembrane long form (L-OPA1) that plays a central role in mitochondrial inner membrane fusion and cristae morphology. L-OPA1 and the soluble short form (S-OPA1) form higher-order helical assemblies that coordinate the fusion of mitochondrial inner membranes. Inner membrane-anchored L-OPA1 molecules initiate membrane remodeling by recruiting soluble S-OPA1 to rapidly polymerize into a flexible cylindrical scaffold encaging the mitochondrial inner membrane. Once at the membrane surface, the formation of S-OPA1 helices induce bilayer curvature. OPA1 dimerization through the paddle region, which inserts into cardiolipin-containing membrane, promotes GTP hydrolysis and the helical assembly of a flexible OPA1 lattice on the membrane, which drives membrane curvature and mitochondrial fusion. Plays a role in the maintenance and remodeling of mitochondrial cristae, some invaginations of the mitochondrial inner membrane that provide an increase in the surface area (By similarity). Probably acts by forming helical filaments at the inside of inner membrane tubes with the shape and dimensions of crista junctions (By similarity). {ECO:0000250|UniProtKB:G0SGC7, ECO:0000250|UniProtKB:O60313}.; FUNCTION: [Dynamin-like GTPase OPA1, short form]: Constitutes the soluble short form (S-OPA1) generated by cleavage by OMA1, which plays a central role in mitochondrial inner membrane fusion and cristae morphology. The transmembrane long form (L-OPA1) and the S-OPA1 form higher-order helical assemblies that coordinate the fusion of mitochondrial inner membranes. Inner membrane-anchored L-OPA1 molecules initiate membrane remodeling by recruiting soluble S-OPA1 to rapidly polymerize into a flexible cylindrical scaffold encaging the mitochondrial inner membrane. Once at the membrane surface, the formation of S-OPA1 helices induce bilayer curvature. OPA1 dimerization through the paddle region, which inserts into cardiolipin-containing membrane, promotes GTP hydrolysis and the helical assembly of a flexible OPA1 lattice on the membrane, which drives membrane curvature and mitochondrial fusion. Excess levels of S-OPA1 produced by cleavage by OMA1 following stress conditions that induce loss of mitochondrial membrane potential, lead to an impaired equilibrium between L-OPA1 and S-OPA1, thereby inhibiting mitochondrial fusion. Plays a role in the maintenance and remodeling of mitochondrial cristae, some invaginations of the mitochondrial inner membrane that provide an increase in the surface area (By similarity). Probably acts by forming helical filaments at the inside of inner membrane tubes with the shape and dimensions of crista junctions (By similarity). {ECO:0000250|UniProtKB:G0SGC7, ECO:0000250|UniProtKB:O60313}.
|
Oncorhynchus masou (Cherry salmon) (Masu salmon)
|
O93257
|
XRCC6_CHICK
|
MEMWVLGEVGMAVLSAAAMADWVSYYRGDGPDEEEDGEQQEEEGPEAVADYRFSGRDSLIFLVDASKAMFEPYENEEAATPFDMTMQCIRNVYTSKIISSDKDLLSVVFYGMENNKNSADFKHIYVLQELDNPGAKRILELDQYRGDEGRVLFRETFGHNADYSLGEALWACSNLFSDVRVRLSHKRIMLFTNEDNPHANDSAKAKLARTRAGDLRDTGIILDLMHLKKPGGFDISLFYRDIINVAEDEDLGIQPDESGKLEHLMKKVRAKETRKRALSRLNLYLNKDLSFSVGVYNLIQKAYKPYPVKLYRETNEPVKTKTRVFNGKTGSLLLPSDTKRAQTYGNRQIAMEKEETEEVKRFDSPGLFLIGFKPLSMLKQHHHIRPSQFMYPEESLVTGSTTLFNALLMKCLEKEVMALCRYIARRNTPPRIVALIPQEEEVDEQKVQIAPPGFHIIFLPYADDKRNVDFTEKVPANREQVDKMKGIIQKLRFKYRTDSFENPVLQQHFRNLEALALDMLEPEQAEDLTMPKTEEMSRRLGNLVEEFKQLVYPPDYSPEGKAAKRKQAGDAQAEKRPKIEISEDSLRSYVQNGTLGKLTVSALKDTCRHYGLRSGGKKQELIDALTEYFSGR
|
3.6.4.-; 4.2.99.-
| null |
cellular response to gamma radiation [GO:0071480]; DNA recombination [GO:0006310]; double-strand break repair via nonhomologous end joining [GO:0006303]; negative regulation of DNA-templated transcription [GO:0045892]; telomere maintenance [GO:0000723]
|
chromosome [GO:0005694]; Ku70:Ku80 complex [GO:0043564]; nonhomologous end joining complex [GO:0070419]; nucleoplasm [GO:0005654]; ribonucleoprotein complex [GO:1990904]
|
5'-deoxyribose-5-phosphate lyase activity [GO:0051575]; ATP binding [GO:0005524]; damaged DNA binding [GO:0003684]; DNA helicase activity [GO:0003678]; double-stranded DNA binding [GO:0003690]; hydrolase activity [GO:0016787]; RNA binding [GO:0003723]; telomeric DNA binding [GO:0042162]
|
PF02735;PF03730;PF03731;PF02037;
|
1.10.1600.10;2.40.290.10;4.10.970.10;1.10.720.30;3.40.50.410;
|
Ku70 family
|
PTM: Phosphorylated on serine residues. {ECO:0000250|UniProtKB:P12956}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P12956}. Chromosome {ECO:0000250|UniProtKB:P12956}.
| null | null | null | null | null |
FUNCTION: Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA. Required for double-strand break repair and V(D)J recombination. Also has a role in chromosome translocation. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection. Binding to DNA may be mediated by XRCC6. The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (By similarity). {ECO:0000250|UniProtKB:P12956}.
|
Gallus gallus (Chicken)
|
O93274
|
FZD8_XENLA
|
MESLSLSLLLLVSWLQGSQCAAAKELSCQEITVPLCKDIGYNYTYMPNQFNHDTQDEAGMEVHQFWPLVVIHCSPDLKFFLCSMYTPICLEDYKKPLPPCRSVCERARAGCAPLMRQYGFAWPDRMRCDRLPEQGNPDTLCMDYYNRTEQTTAAPSHPEPPKPPARSVPKGRTRVEPPRSRSRATGCESGCQCRAPMVQVSNERHPLYNRVRTGQIPNCAMPCHNPFFSPEERTFTEFWIGLWSVLCFASTFATVSTFLIDMERFKYPERPIIFLSACYLLVSTGYLIRLIAGHEKVACSRGELDLEHIIHYETTGPALCTLVFLLIYFFGMASSIWWVILSLTWFLAAGMKWGNEAIAGYSQYFHLAAWLVPSIKSIAVLALSSVDGDPVAGICFVGNQNLDNLRGFVLAPLVIYLFIGSMFLLAGFVSLFRIRSVIKQGGTKTDKLEKLMIRIGIFSVLYTVPATIVVACFFYEQHNRQGWEVAHNCNSCQPEMAQPHRPDYAVFMLKYFMCLVVGITSGVWIWSGKTLESWRAFCTRCCWGSKATGGSMYSDVSTGLTWRSGTGSSVSCPKQMPLSQV
| null | null |
canonical Wnt signaling pathway [GO:0060070]; non-canonical Wnt signaling pathway [GO:0035567]; positive regulation of DNA-binding transcription factor activity [GO:0051091]
|
plasma membrane [GO:0005886]
|
G protein-coupled receptor activity [GO:0004930]; Wnt receptor activity [GO:0042813]; Wnt-protein binding [GO:0017147]
|
PF01534;PF01392;
|
1.10.2000.10;1.20.1070.10;
|
G-protein coupled receptor Fz/Smo family
| null |
SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:10097073}; Multi-pass membrane protein {ECO:0000269|PubMed:10097073}. Cell membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Activation by Wnt8, Wnt5A or Wnt3A induces expression of beta-catenin target genes. Displays an axis-inducing activity. {ECO:0000269|PubMed:10097073}.
|
Xenopus laevis (African clawed frog)
|
O93279
|
A4_TAKRU
|
MGETTAFVLLLVATLTRSSEIPADDTVGLLTEPQVAMFCGKLNMHINVQNGKWESDPSGTKSCLNTKEGILQYCQEVYPELQITNVVEANQPVSIQNWCKKGRKQCRSHTHIVVPYRCLVGEFVSDALLVPDKCKFLHQERMNQCESHLHWHTVAKESCGDRSMNLHDYGMLLPCGIDRFRGVKFVCCPAETEQETDSSEVEGEESDVWWGGADPEYSENSPPTPSRATYVAGDAFERDENGDGDEDEEDDEDVDPTDEQESDERTANVAMTTTTTTTTESVEEVVRAVCWAQAESGPCRAMLERWYFNPKKRRCVPFLFGGCGGNRNNFESEEYCLAVCSSSLPTVAPSPPDAVDQYFEAPGDDNEHADFRKAKESLEAKHRERMSQVMREWEEAERQAKNLPRADKKAVIQHFQEKVEALEQEAAGERQQLVETHMARVEALLNSRRRLTLENYLGALQANPPRARQVLSLLKKYVRAEQKDRQHTLKHYEHVRTVDPKKAAQIRPQVLTHLRVIDERMNQSLALLYKVPSVASEIQNQIYPAAGSDCKDPVEHCVCPQVDGLVSYGNDALMPDQAYSSAPMDMGVDGLGSIDQSFNQANTENHVEPVDARPIPDRGLPTRPVSSLKLEEMPEVRTETDKRQSAGYEVYHQKLVFFADDVGSNKGAIIGLMVGGVVIATVIVITLVMLRKKQYTSIHHGVIEVDAAVTPEERHLARMQQNGYENPTYKFFEQMQN
| null | null |
axonogenesis [GO:0007409]; central nervous system development [GO:0007417]
|
cell surface [GO:0009986]; early endosome [GO:0005769]; Golgi apparatus [GO:0005794]; Golgi-associated vesicle [GO:0005798]; membrane raft [GO:0045121]; plasma membrane [GO:0005886]; recycling endosome [GO:0055037]
|
heparin binding [GO:0008201]; serine-type endopeptidase inhibitor activity [GO:0004867]; signaling receptor activator activity [GO:0030546]; signaling receptor binding [GO:0005102]; transition metal ion binding [GO:0046914]
|
PF10515;PF12924;PF12925;PF02177;PF03494;PF00014;
|
6.10.250.1670;1.20.120.770;3.30.1490.140;3.90.570.10;4.10.410.10;2.30.29.30;
|
APP family
| null |
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
| null | null | null | null | null |
FUNCTION: Functional neuronal receptor which couples to intracellular signaling pathway through the GTP-binding protein G(O). {ECO:0000250}.
|
Takifugu rubripes (Japanese pufferfish) (Fugu rubripes)
|
O93308
|
SMC1A_XENLA
|
MGFLKLIEIENFKSYKGRQIIGPFHRFTAIIGPNGSGKSNLMDAISFVLGEKTSNLRVKTLRDLIHGAPVGKPAANRAFVSMVYSEDSGEEKVFSRVIVGGSSEYKINNKVVQLSEYSDSLEKLGILIKARNFLVFQGAVESIAMKNPKERTALFEEISRSGELAQEYDKRKKEMVKAEEDTQFNYHRKKNIAAERKEAKQEKEEAERYQRLKDEVARAQIQLQLFKLYHNESEIEKLNKELSVKNKGIEKDKKHMDKVEEELKDKKKELGKMMREQQAIEKEIKEKDAELNQKLPQYIKAKENPSHKIKKFRAAKKSLQNAQKQYKKRKADMDELEKEMLSVEKARQEFEERMEEESQSQGRDLTLEENQVKKYHRLKEEASKRAATLAQELEKFNRDQKADQDRLDLEERKKVETEAKIKQKLRELEENQKRIEKLEEYIATSKQSLEEQKNLEETLTEEVEMAKRRIDEINSELNQVMEQLGDARIDRQESSRQQRKAEIMESIKRLYPGSVYGRLIDLCQPTQKKYQIAVTKVLGKNMDAIIVDSEKTGRDCIQYIKEQRGEPETFLPLDYLEVKPTDERLRELKGAKLVIDVIRYEPPHIKKALQYACGNALVCDNVEDARRIAFGGHQRHKTVALDGTLFQKSGVISGGASDLKAKARRWDEKAVDKLKEKKERLTEELKEQMKAKRKEAELRQVQSQAHGLQMRLKYSQSDLEQTKTRHLAMNMQEKSKLESELANFSPRINDIKRIIQSRDREMKDLKEKMNQVEDEVFEEFCREIGVRNIREFEEEKVKRQNEIAKKRLEFENQKTRLGIQLDYEKNQLKEDQGKVQTWEQSVKKDDNEIEKLKKEEQRHMKIIDETMAQLQDLKNQHLAKKSEVNDKNHLMEDIRKKLGSANKEVTHLQKEVTAIETKLEQKRSDRHNLLQACKMSDIKLPLSKGTMDDISQEEGSSQGEESASSSQRSSTVYAKEALIEIDYSDLSEDLKDAVADDDIKQEMSALHQKINEQQSILQRISAPNMKAMEKLESVRDKFQETSDEFEAARKRAKKAKQAFEQTKKERFDRFNACFESVATNIDEIYKALSRNSSAQAFLGPENPEEPYLDGINYNCVAPGKRFRPMDNLSGGEKTVAALALLFAIHSYKPSPFFVLDEIDAALDNTNIGKVANYIKEQSMSNFQAIVISLKEEFYTKAESLIGVYPEQGDCVISKVLTFDLTKYPDANPNPND
| null | null |
cell division [GO:0051301]; DNA repair [GO:0006281]; meiotic cell cycle [GO:0051321]; response to DNA damage checkpoint signaling [GO:0072423]; response to radiation [GO:0009314]; sister chromatid cohesion [GO:0007062]
|
kinetochore [GO:0000776]; meiotic cohesin complex [GO:0030893]; nucleus [GO:0005634]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; chromatin binding [GO:0003682]; DNA binding [GO:0003677]
|
PF06470;PF02463;
|
1.20.1060.20;3.30.70.1620;3.40.50.300;
|
SMC family, SMC1 subfamily
| null |
SUBCELLULAR LOCATION: Nucleus. Chromosome. Chromosome, centromere. Note=Associates with chromatin. Before prophase it is scattered along chromosome arms. During prophase, most of cohesin complexes dissociate from chromatin probably because of phosphorylation by PLK, except at centromeres, where cohesin complexes remain. At anaphase, the RAD21 subunit of the cohesin complex is cleaved, leading to the dissociation of the complex from chromosomes, allowing chromosome separation.
| null | null | null | null | null |
FUNCTION: Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate.
|
Xenopus laevis (African clawed frog)
|
O93309
|
SMC3_XENLA
|
MYIKQVIIQGFRSYRDQTIVDPFSSKHNVIVGRNGSGKSNFFYAIQFVLSDEFSHLRPEQRLALLHEGTGPRVISAFVEIIFDNSDNRLPIDKEEVSLRRVIGAKKDQYFLDKKMVTKNDVMNLLESAGFSRSNPYYIVKQGKINQMATAPDSQRLKLLREVAGTRVYDERKEESISLMKETEGKRDKINELLKYIEERLHTLEEEKEELAQYQKWDKMRRALEYTIYNQELNETRAKLDELSSKRETSGEKSRQLRDAQQDARDKMEEIERQVRELKSKISAMKEEKEQLSSERQEQIKQRTKLELKTKDLQDELAGNSEQRKRLLKERQKLLEKIEEKQKELAETEPKFSSVKQKEESGIARLAQATQERTDLYAKQGRGSQFTSKEERDKWIKKELKSLDQAINDKKRQIAAINKDLEETEVNKEKNLEQYTKLDQDLNEVKTRVEELDKKYYEVKNKKDELQSERNYLWREENAEQQSLAAKREDLEKKQQLLRAATGKAILNGIDSINKVLEHFRRKGINQHVINGYHGIVMNNFDCEPAFYTCVEVTAGNRLFYHIVESDEVSTKILMEFNKMNLPGEVTFLPLNKLDVRDTAYPETNDAIPMISKLRYNLRFDKAFKHVFGKTLICRSMEVSTQLARAFTMDCITLEGDQVSHRGALTGGYYDTRKSRLELQKDVRKVEDELHALEAKLNENLRRNIERINNEIDQLMNQMQQIETQQRKFKASRDSILSEMKMLKEKRQQSEKTFMPKQRSLQSLEASLHAMESTRESLKAELGTDLLSQLSLEDQKRVDALNDEIRQLQQENRQLLNERIKLEGTITRVETYLNENLRKRLDQVEQELNELRETEGGTVLTATTSELEAINKRVKDTLARSEGLDITIDKTEVESKDLVKSMDRWKNMEKDHMDAINHDTKELEKMTNRQGMLLKKKEECMKKIRELGSLPQEAFEKYQTLSLKQLFRKLEQCNTELKKYSHVNKKALDQFVNFSEQKEKLIKRQEELDRGHKSIMELMNVLELRKYEAIQLTFKQVSKNFSEVFQKLVPGGKATLVMKKGDVEGSQSQDEGEGSTQSSVPSVDQFTGVGIRVSFTGKQAEMREMQQLSGGQKSLVALALIFAIQKCDPAPFYLFDEIDQALDAQHRKAVSDMIMELASHAQFITTTFRPELLESADKFYGVKFRNKVSHIDVITAEQAKDFVEDDTTHG
| null | null |
cell division [GO:0051301]; DNA repair [GO:0006281]; meiotic cell cycle [GO:0051321]; mitotic sister chromatid cohesion [GO:0007064]; regulation of DNA replication [GO:0006275]
|
chromatin [GO:0000785]; chromosome, centromeric region [GO:0000775]; meiotic cohesin complex [GO:0030893]; nucleus [GO:0005634]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cohesin loader activity [GO:0061775]; double-stranded DNA binding [GO:0003690]
|
PF06470;PF02463;
|
1.10.287.1490;1.20.1060.20;3.30.70.1620;3.40.50.300;
|
SMC family, SMC3 subfamily
|
PTM: Acetylation at Lys-113 and Lys-114 by ESCO1 is important for genome stability and S phase sister chromatid cohesion. {ECO:0000250}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9649503}. Chromosome {ECO:0000269|PubMed:9649503}. Chromosome, centromere {ECO:0000269|PubMed:9649503}. Note=Associates with chromatin. Before prophase it is scattered along chromosome arms. During prophase, most of cohesin complexes dissociate from chromatin probably because of phosphorylation by PLK, except at centromeres, where cohesin complexes remain. At anaphase, the RAD21 subunit of the cohesin complex is cleaved, leading to the dissociation of the complex from chromosomes, allowing chromosome separation.
| null | null | null | null | null |
FUNCTION: Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement. {ECO:0000269|PubMed:9649503}.
|
Xenopus laevis (African clawed frog)
|
O93310
|
RAD21_XENLA
|
MFYAHFVLSKRGPLAKIWLAAHWDKKLTKAHVFECNLESSVESIICPKVKMALRTSGHLLLGVVRIYHRKAKYLLADCNEAFIKIKMAFRPGVVDLPEENREAAYNAITLPEEFHDFDQPLPDLDDIDVAQQFSLNQSRVEEITMREEVSNINILQDNDFGDFGMDDREMMREGSAFEDDMLTTNASNLKLEPEQSTSQLNEKSNHLEYDDQYKDDNFGEGNEGGILDDKLLSNDAGGIFDDPPAMPEEGVAMPEQPVHDDLDDDDNVSMGAPDSPDSVDPVEPLPTMTDQTTLVPNEEEAFALEPIDITVKETKAKRKRKLIVDSVKELDSKTIRAQLSDYSDIVTTLDLAPPTKKLMMWKETGGVEKLFSLPAQPLWNTRLLKLFTRCLTPLVLDDLRKRRKGGEADNLDEFLKEFENPEVPREELRPQDVIDQPILEEASHLQESLMEGSRTHLDDTIMPPPPPKQGVKRDSLQMEPEPMPMMQEAEPQIEMPPPPLPPPLELPPEEPQSISDLIPELNLLPEKEKEKDEEEEEEEEDTTGTEQDQEERRWNKRTQQMLHGLQRVLAKTGAESISLLDLCRNTNRKQAAAKFYSFLVLKKQQAIELTQREPYSDIVATPGPRFHTV
| null | null |
apoptotic process [GO:0006915]; cell division [GO:0051301]; chromosome segregation [GO:0007059]; protein localization to chromatin [GO:0071168]; replication-born double-strand break repair via sister chromatid exchange [GO:1990414]; sister chromatid cohesion [GO:0007062]
|
chromosome, centromeric region [GO:0000775]; cohesin complex [GO:0008278]; cytosol [GO:0005829]; nuclear matrix [GO:0016363]; spindle pole [GO:0000922]
|
chromatin binding [GO:0003682]
|
PF04824;PF04825;
|
1.10.10.580;
|
Rad21 family
|
PTM: Cleaved by separase/ESPL1 at the onset of anaphase; this cleavage is required for sister chromatid separation and cytokinesis (By similarity). Cleaved by caspases at the beginning of apoptosis (By similarity). {ECO:0000250|UniProtKB:O60216}.; PTM: Phosphorylated; becomes hyperphosphorylated in M phase of cell cycle. The large dissociation of cohesin from chromosome arms during prophase may be partly due to phosphorylation by PLK1/PLX1. {ECO:0000269|PubMed:11931760}.
|
SUBCELLULAR LOCATION: [Double-strand-break repair protein rad21 homolog]: Nucleus {ECO:0000250|UniProtKB:O60216}. Nucleus matrix {ECO:0000250|UniProtKB:O60216}. Chromosome {ECO:0000269|PubMed:11931760}. Chromosome, centromere {ECO:0000250|UniProtKB:O60216}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000250|UniProtKB:O60216}. Note=Associates with chromatin. Before prophase, scattered along chromosome arms. During prophase and prometaphase, most cohesins dissociate from the arms of condensing chromosome, possibly through Polo-like kinase PLK1/PLX1-catalyzed phosphorylation (PubMed:11931760). A small amount of cohesin remains in centromeric regions and is removed from chromosomes only at the onset of anaphase. At anaphase, cleavage by separase/ESPL1 leads to the dissociation of cohesin from chromosomes and chromosome separation (By similarity). {ECO:0000250|UniProtKB:O60216, ECO:0000269|PubMed:11931760}.; SUBCELLULAR LOCATION: [64-kDa C-terminal product]: Cytoplasm, cytosol {ECO:0000250|UniProtKB:O60216}. Nucleus {ECO:0000250|UniProtKB:O60216}.
| null | null | null | null | null |
FUNCTION: [Double-strand-break repair protein rad21 homolog]: As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions. The cohesin complex may also play a role in spindle pole assembly during mitosis (By similarity). In interphase, cohesins may function in the control of gene expression by binding to numerous sites within the genome (By similarity). May play a role in embryonic gut development, possibly through the regulation of enteric neuron development (By similarity). {ECO:0000250|UniProtKB:O60216, ECO:0000250|UniProtKB:Q61550, ECO:0000250|UniProtKB:Q6TEL1}.; FUNCTION: [64-kDa C-terminal product]: May promote apoptosis. {ECO:0000250|UniProtKB:O60216}.
|
Xenopus laevis (African clawed frog)
|
O93327
|
H2AY_CHICK
|
MSSRGGKKKSTKTSRSAKAGVIFPVGRMLRYIKKGHPKYRIGVGAPVYMAAVLEYLTAEILELAGNAARDNKKGRVTPRHILLAVANDEELNQLLKGVTIASGGVLPNIHPELLAKKRGSKGKLEAIITPPPAKKAKSPSQKKTVSKKTGGKKGARKSKKKQGEVSKSASADSTTEGTPADGFTVLSTKSLFLGQKLQVVQADIATIDSDAVVHPTNSDFYTGGEVGSTLEKKGGKEFVEAVIELRKKNGPLDIAGAVVSAGHGLPAKFVIHCNSPGWGSDKCEELLEKTVKNCLALADEKKLKSIAFPSIGSGRNGFPKQTAAQLILKAISSYFVSTMSSSIKTVYFVLFDSESIGIYVQEMAKLDAN
| null | null |
heterochromatin organization [GO:0070828]; negative regulation of gene expression, epigenetic [GO:0045814]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of transcription of nucleolar large rRNA by RNA polymerase I [GO:1901837]; nucleosome assembly [GO:0006334]; regulation of NAD metabolic process [GO:1902688]
|
nucleosome [GO:0000786]; nucleus [GO:0005634]
|
ADP-D-ribose binding [GO:0072570]; ADP-D-ribose modification-dependent protein binding [GO:0160002]; nucleosomal DNA binding [GO:0031492]; protein heterodimerization activity [GO:0046982]; structural constituent of chromatin [GO:0030527]
|
PF00125;PF16211;PF01661;
|
1.10.20.10;3.40.220.10;
|
Histone H2A family
|
PTM: ADP-ribosylated. {ECO:0000305, ECO:0000305|PubMed:15718235}.; PTM: Monoubiquitinated at either Lys-116 or Lys-117. May also be polyubiquitinated. Ubiquitination is mediated by the CUL3/SPOP E3 complex and does not promote proteasomal degradation. Instead, it is required for enrichment in inactive X chromosome chromatin. {ECO:0000250|UniProtKB:O75367}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O75367}. Chromosome {ECO:0000250|UniProtKB:O75367}.
| null | null | null | null | null |
FUNCTION: Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. {ECO:0000269|PubMed:15718235}.; FUNCTION: [Isoform 1]: Isoform that specifically binds poly-ADP-ribose and O-acetyl-ADP-ribose and plays a key role in NAD(+) metabolism. Able to bind to the ends of poly-ADP-ribose chains created by PARP1 and cap them. This prevents PARP1 from further addition of ADP-ribose and thus limits the consumption of nuclear NAD(+), allowing the cell to maintain proper NAD(+) levels in both the nucleus and the mitochondria to promote proper mitochondrial respiration. {ECO:0000250|UniProtKB:Q9QZQ8}.; FUNCTION: [Isoform 2]: In contrast to isoform 1, does not bind poly-ADP-ribose. {ECO:0000250|UniProtKB:Q9QZQ8}.
|
Gallus gallus (Chicken)
|
O93344
|
AL1A2_CHICK
|
MTSSKIEMPGEVKADPAALMASLHLLPSPTLNLEIKHTKIFINNEWQNSESGRVFPVYNPATGEQICEIQEADKVDTDKAVRAARLAFSLGSVWRRMDASERGQLLDKLADLVERDRAVLATMESLNSGKPFLQAFYVDLQGVIKTLRYYAGWADKIHGMTIPVDGDYFTFTRHEPIGVCGQIIPWNFPLLMFAWKIAPALCCGNTVVIKPAEQTPLSALYMGALIKEAGFPPGVVNILPGFGPIVGAAIASHVGIDKIAFTGSTEVGKLIQEAAGRSNLKRVTLELGGKSPNIIFADADLDYAVEQAHQGVFFNQGQCCTAGSRIYVEESIYEEFVRRSVERAKRRVVGSPFDPTTEQGPQIDKKQYNKILELIQSGITEGAKLECGGKGLGRKGFFIEPTVFSNVTDDMRIAKEEIFGPVQEILRFKTVDEVIERANNSDFGLVAAVFTNDINKALTVSSAMQAGTVWINCYNALNAQSPFGGFKMSGNGREMGESGLREYSEVKTVTIKIPQKNS
|
1.2.1.36
| null |
heart looping [GO:0001947]; heart morphogenesis [GO:0003007]; positive regulation of gene expression [GO:0010628]; protein homotetramerization [GO:0051289]; response to retinoic acid [GO:0032526]; retinoic acid biosynthetic process [GO:0002138]; retinoic acid metabolic process [GO:0042573]; retinol metabolic process [GO:0042572]; spinal cord motor neuron differentiation [GO:0021522]
|
cytoplasm [GO:0005737]
|
aldehyde dehydrogenase (NAD+) activity [GO:0004029]; NAD-retinol dehydrogenase activity [GO:0004745]; retinal dehydrogenase activity [GO:0001758]
|
PF00171;
| null |
Aldehyde dehydrogenase family
| null |
SUBCELLULAR LOCATION: Cytoplasm.
|
CATALYTIC ACTIVITY: Reaction=H2O + NAD(+) + retinal = 2 H(+) + NADH + retinoate; Xref=Rhea:RHEA:16177, ChEBI:CHEBI:15035, ChEBI:CHEBI:15036, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.36; Evidence={ECO:0000250|UniProtKB:Q62148}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16178; Evidence={ECO:0000250|UniProtKB:Q62148}; CATALYTIC ACTIVITY: Reaction=all-trans-retinal + H2O + NAD(+) = all-trans-retinoate + 2 H(+) + NADH; Xref=Rhea:RHEA:42080, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17898, ChEBI:CHEBI:35291, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.36; Evidence={ECO:0000250|UniProtKB:Q62148}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42081; Evidence={ECO:0000250|UniProtKB:Q62148}; CATALYTIC ACTIVITY: Reaction=all-trans-13,14-dihydroretinal + H2O + NAD(+) = all-trans-13,14-dihydroretinoate + 2 H(+) + NADH; Xref=Rhea:RHEA:75119, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:194182, ChEBI:CHEBI:194183; Evidence={ECO:0000250|UniProtKB:Q62148}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75120; Evidence={ECO:0000250|UniProtKB:Q62148};
| null |
PATHWAY: Cofactor metabolism; retinol metabolism. {ECO:0000250|UniProtKB:Q63639}.
| null | null |
FUNCTION: Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively. Retinoate signaling is critical for the transcriptional control of many genes, for instance it is crucial for initiation of meiosis in both male and female (By similarity). Recognizes retinal as substrate, both in its free form and when bound to cellular retinol-binding protein (By similarity). Lacks activity with benzaldehyde, acetaldehyde and octanal (By similarity). Displays complete lack of activity with citral (By similarity). {ECO:0000250|UniProtKB:Q62148, ECO:0000250|UniProtKB:Q63639}.
|
Gallus gallus (Chicken)
|
O93348
|
HBB1_PAGBO
|
MVEWTDKERSIISDIFSHLDYEDIGPKALSRCLIVYPWTQRHFSGFGNLYNAESIIGNANVAAHGIKVLHGLDRGLKNMDNIEATYADLSTLHSEKLHVDPDNFKLLADCITIVLAAKMGQAFTAEIQGAFQKFLAVVVSALGKQYH
| null | null |
hydrogen peroxide catabolic process [GO:0042744]
|
blood microparticle [GO:0072562]; haptoglobin-hemoglobin complex [GO:0031838]; hemoglobin complex [GO:0005833]
|
haptoglobin binding [GO:0031720]; heme binding [GO:0020037]; hemoglobin alpha binding [GO:0031721]; metal ion binding [GO:0046872]; organic acid binding [GO:0043177]; oxygen binding [GO:0019825]; oxygen carrier activity [GO:0005344]; peroxidase activity [GO:0004601]
|
PF00042;
|
1.10.490.10;
|
Globin family
| null | null | null | null | null | null | null |
FUNCTION: Involved in oxygen transport from gills to the various peripheral tissues.
|
Pagothenia borchgrevinki (Bald rockcod) (Trematomus borchgrevinki)
|
O93349
|
HBB2_TRENE
|
MVEWTDKERTIISDIFSHMDYDDIGPKALSRCLIVYPWTQRHFSGFGNLYNAEAIIGNANVAAHGIKVLHGLDRGMKNMDNIADAYTDLSTLHSEKLHVDPDNFKLLSDCITIVLAAKMGHAFTAETQGAFQKFLAAVVSALGKQYH
| null | null |
hydrogen peroxide catabolic process [GO:0042744]
|
blood microparticle [GO:0072562]; haptoglobin-hemoglobin complex [GO:0031838]; hemoglobin complex [GO:0005833]
|
haptoglobin binding [GO:0031720]; heme binding [GO:0020037]; hemoglobin alpha binding [GO:0031721]; metal ion binding [GO:0046872]; organic acid binding [GO:0043177]; oxygen binding [GO:0019825]; oxygen carrier activity [GO:0005344]; peroxidase activity [GO:0004601]
|
PF00042;
|
1.10.490.10;
|
Globin family
| null | null | null | null | null | null | null |
FUNCTION: Involved in oxygen transport from gills to the various peripheral tissues.
|
Trematomus newnesi (Dusky notothen)
|
O93351
|
HBB_TREHA
|
MVEWTDKERSIISDIFSHMDYDDIGPKALSRCLVVYPWTQRYFSGFGNLYNAEGIMSNANVAAHGIKVLHGLDRGVKNMDNIAATYADLSTLHSEKLHVDPDNFKLLSDCITIVLAAKMGHAFTAETQGAFQKFLAVVVSALGKQYH
| null | null |
hydrogen peroxide catabolic process [GO:0042744]
|
blood microparticle [GO:0072562]; haptoglobin-hemoglobin complex [GO:0031838]; hemoglobin complex [GO:0005833]
|
haptoglobin binding [GO:0031720]; heme binding [GO:0020037]; hemoglobin alpha binding [GO:0031721]; metal ion binding [GO:0046872]; organic acid binding [GO:0043177]; oxygen binding [GO:0019825]; oxygen carrier activity [GO:0005344]; peroxidase activity [GO:0004601]
|
PF00042;
|
1.10.490.10;
|
Globin family
| null | null | null | null | null | null | null |
FUNCTION: Involved in oxygen transport from gills to the various peripheral tissues.
|
Trematomus hansoni (Striped rockcod) (Notothenia hansoni)
|
O93364
|
OXLA_CROAD
|
MNVFFMFSLLFLAALGSCAHDRNPLEECFRETDYEEFLEIAKNGLTATSNPKRVVIVGAGMAGLSAAYVLAGAGHQVTVLEASERVGGRVRTYRKKDWYANLGPMRLPTKHRIVREYIKKFDLKLNEFSQENENAWYFIKNIRKRVREVKNNPGLLEYPVKPSEEGKSAAQLYVESLRKVVEELRSTNCKYILDKYDTYSTKEYLLKEGNLSPGAVDMIGDLLNEDSGYYVSFIESLKHDDIFGYEKRFDEIVGGMDQLPTSMYEAIKEKVQVHFNARVIEIQQNDREATVTYQTSANEMSSVTADYVIVCTTSRAARRIKFEPPLPPKKAHALRSVHYRSGTKIFLTCTKKFWEDDGIHGGKSTTDLPSRFIYYPNHNFTSGVGVIIAYGIGDDANFFQALDFKDCADIVINDLSLIHELPKEDIQTFCHPSMIQRWSLDKYAMGGITTFTPYQFQHFSEALTAPFKRIYFAGEYTAQFHGWIDSTIKSGLTAARDVNRASENPSGIHLSNDNEF
|
1.4.3.2
|
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:6067195};
|
amino acid catabolic process [GO:0009063]; apoptotic process [GO:0006915]; defense response to bacterium [GO:0042742]; killing of cells of another organism [GO:0031640]
|
extracellular region [GO:0005576]
|
L-phenylalaine oxidase activity [GO:0106329]; toxin activity [GO:0090729]
|
PF01593;
|
3.90.660.10;3.50.50.60;1.10.405.10;
|
Flavin monoamine oxidase family, FIG1 subfamily
|
PTM: N-glycosylated. {ECO:0000250|UniProtKB:P81382}.
|
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9703950}.
|
CATALYTIC ACTIVITY: Reaction=an L-alpha-amino acid + H2O + O2 = a 2-oxocarboxylate + H2O2 + NH4(+); Xref=Rhea:RHEA:13781, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:35179, ChEBI:CHEBI:59869; EC=1.4.3.2; Evidence={ECO:0000269|PubMed:6067195}; CATALYTIC ACTIVITY: Reaction=H2O + L-leucine + O2 = 4-methyl-2-oxopentanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:60996, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17865, ChEBI:CHEBI:28938, ChEBI:CHEBI:57427; Evidence={ECO:0000269|PubMed:6067195}; CATALYTIC ACTIVITY: Reaction=H2O + L-phenylalanine + O2 = 3-phenylpyruvate + H2O2 + NH4(+); Xref=Rhea:RHEA:61240, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:18005, ChEBI:CHEBI:28938, ChEBI:CHEBI:58095; Evidence={ECO:0000269|PubMed:6067195}; CATALYTIC ACTIVITY: Reaction=H2O + L-methionine + O2 = 4-methylsulfanyl-2-oxobutanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:61236, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:16723, ChEBI:CHEBI:28938, ChEBI:CHEBI:57844; Evidence={ECO:0000269|PubMed:6067195}; CATALYTIC ACTIVITY: Reaction=H2O + L-arginine + O2 = 5-guanidino-2-oxopentanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:51404, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:32682, ChEBI:CHEBI:58489; Evidence={ECO:0000269|PubMed:6067195};
| null | null | null | null |
FUNCTION: Catalyzes an oxidative deamination of predominantly hydrophobic and aromatic L-amino acids, thus producing hydrogen peroxide that may contribute to the diverse toxic effects of this enzyme (PubMed:6067195). Is active on L-Arg, L-Phe, L-Met, and L-Leu and is weakly active on L-Val (PubMed:6067195). Exhibits diverse biological activities, such as hemorrhage, hemolysis, edema, apoptosis of vascular endothelial cells or tumor cell lines, antibacterial and antiparasitic activities, as well as regulation of platelet aggregation. Its effect on platelets is controversial, since it either induces aggregation or inhibits agonist-induced aggregation. These different effects are probably due to different experimental conditions (By similarity). {ECO:0000250|UniProtKB:P0CC17, ECO:0000269|PubMed:6067195}.
|
Crotalus adamanteus (Eastern diamondback rattlesnake)
|
O93383
|
NRG1_XENLA
|
MAEKKKVKEGKGRKGKGKKDRKGKKAEGSDQGAAASPKLKEIKTQSVQEGKKLVLKCQAVSEQPSLKFRWFKGEKEIGAKNKPDSKPEHIKIRGKKKSSELQISKASSADNGEYKCMVSNQLGNDTVTVNVTIVPKPTYNHLLLMKIYLKVTSVEKSVEPSTLNLLESQKEVIFATTKRGDTTAGPGHLIKCSDKEKTYCVNGGECYVLNGITSSNQFMCKCKPGFTGARCTETDPLRVVRSEKHLGIEFMEAEELYQKRVLTITGICIDLLVVGDMCVVDAYCKTKKQRKKLNDRLRQSLRERNKNITNKDNRPHNPKNPPPRKNVQLVNQYVSKNVISSEHVIERETETSFSTSHYTSTTHHSTTVTQTPSHSWSNGLSESMISEKSYSVIVTSSVENSRHTSPTGPRGRLNGIGGPRDCSYLRHARDTPDSYRDSPHSERYVSAMTTPARMSPVEFKTPISPKSPCLETSPPESSLAVSVPSVAVSPFIEEERPLLLVSPPRLREKRYDRKTPQKTPHKQHNSYHHNPGHDSSSLPPNPLRIVEDEEYETTQEYEPSLEPAKKLVNSRRQKRTKPNGHISNRLELDSDSSSESSTSESETEDERIGEETPFLSIQNPLAASLESASLYRHADSRTNPTSRFSTQEELQARLSSIANQALCDQKKRKMTCKTLFI
| null | null |
animal organ development [GO:0048513]; cell differentiation [GO:0030154]; intracellular signal transduction [GO:0035556]; nervous system development [GO:0007399]
|
extracellular space [GO:0005615]; plasma membrane [GO:0005886]
|
chemorepellent activity [GO:0045499]; growth factor activity [GO:0008083]; protein tyrosine kinase activator activity [GO:0030296]
|
PF07679;PF02158;
|
2.60.40.10;2.10.25.10;
|
Neuregulin family
|
PTM: Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.; PTM: Extensive glycosylation precedes the proteolytic cleavage. {ECO:0000250}.
|
SUBCELLULAR LOCATION: [Pro-neuregulin-1, membrane-bound isoform]: Cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Note=Does not seem to be active. {ECO:0000250}.; SUBCELLULAR LOCATION: [Neuregulin-1]: Secreted {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Direct ligand for the ERBB tyrosine kinase receptors. Induces expression of acetylcholine receptor in synaptic nuclei.
|
Xenopus laevis (African clawed frog)
|
O93385
|
PITX2_CHICK
|
MSCMKDPLSLERLGAGNNKLCSSSPSSSSSSSSCHHQQPALAMATALAPGQARSSLEAAKHRLEVHTISDTSSPEAAEKEKSQQGKSEDAGPEDPSKKKRQRRQRTHFTSQQLQELEATFQRNRYPDMSTREEIAVWTNLTEARVRVWFKNRRAKWRKRERNQQAELCKNGFGPQFNGLMQPYDDMYPGYSYNNWAAKGLTSASLSTKSFPFFNSMNVNPLSSQSMFSPPNSISSMSMSSSMVPSAVTGVPGSGLNSLNNLNNLSNPSLNSAVPTPACPYAPPTPPYVYRDTCNSSLASLRLKAKQHSSFGYASVQNPASNLSACQYPVDRPV
| null | null |
anatomical structure morphogenesis [GO:0009653]; determination of left/right symmetry [GO:0007368]; embryonic limb morphogenesis [GO:0030326]; embryonic organ morphogenesis [GO:0048562]; heart looping [GO:0001947]; heart morphogenesis [GO:0003007]; positive regulation of dermatome development [GO:0061184]; positive regulation of myoblast differentiation [GO:0045663]; positive regulation of myoblast proliferation [GO:2000288]; positive regulation of myotome development [GO:2000287]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of transcription by RNA polymerase II [GO:0006357]; response to retinoic acid [GO:0032526]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]
|
DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]
|
PF00046;PF03826;
|
1.10.10.60;
|
Paired homeobox family, Bicoid subfamily
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Cytoplasm {ECO:0000250|UniProtKB:P97474}.
| null | null | null | null | null |
FUNCTION: May play a role in myoblast differentiation. May be involved in the establishment of left-right asymmetry in the developing embryo (By similarity). May play a role in vasculogenesis during avian embryogenesis. {ECO:0000250|UniProtKB:P97474}.
|
Gallus gallus (Chicken)
|
O93409
|
MLRSA_DANRE
|
MAPKKAKRRAAGGEGSSNVFSMFEQSQIQEYKEAFTIIDQNRDGIISKDDLRDVLASMGQLNVKNEELEAMIKEASGPINFTVFLTMFGEKLKGADPEDVIVSAFKVLDPEGTGSIKKEFLEELLTTQCDRFTAEEMKNLWAAFPPDVAGNVDYKNICYVITHGEEKEE
| null | null |
actin-myosin filament sliding [GO:0033275]; muscle contraction [GO:0006936]; muscle tissue morphogenesis [GO:0060415]; skeletal muscle tissue development [GO:0007519]
|
cytoplasm [GO:0005737]; myosin complex [GO:0016459]
|
calcium ion binding [GO:0005509]
|
PF13405;
|
1.10.238.10;
| null | null | null | null | null | null | null | null |
FUNCTION: Myosin regulatory subunit that plays a role to maintain muscle integrity during early development (PubMed:32707087). Plays a role in muscle contraction (PubMed:32707087). {ECO:0000269|PubMed:32707087}.
|
Danio rerio (Zebrafish) (Brachydanio rerio)
|
O93430
|
GLRA1_DANRE
|
MFALGIYLWETIVFFSLAASQQAAARKAASPMPPSEFLDKLMGKVSGYDARIRPNFKGPPVNVTCNIFINSFGSIAETTMDYRVNIFLRQQWNDPRLAYSEYPDDSLDLDPSMLDSIWKPDLFFANEKGANFHEVTTDNKLLRISKNGNVLYSIRITLVLACPMDLKNFPMDVQTCIMQLESFGYTMNDLIFEWDEKGAVQVADGLTLPQFILKEEKDLRYCTKHYNTGKFTCIEARFHLERQMGYYLIQMYIPSLLIVILSWVSFWINMDAAPARVGLGITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCLLFVFSALLEYAAVNFIARQHKELLRFQRRRRHLKEDEAGDGRFSFAAYGMGPACLQAKDGMAIKGNNNNAPTSTNPPEKTVEEMRKLFISRAKRIDTVSRVAFPLVFLIFNIFYWITYKIIRSEDIHKQ
| null | null |
cellular response to amino acid stimulus [GO:0071230]; cellular response to ethanol [GO:0071361]; cellular response to zinc ion [GO:0071294]; central nervous system development [GO:0007417]; chloride transmembrane transport [GO:1902476]; monoatomic ion transport [GO:0006811]; neuropeptide signaling pathway [GO:0007218]; regulation of neuron differentiation [GO:0045664]; response to amino acid [GO:0043200]; synaptic transmission, glycinergic [GO:0060012]
|
chloride channel complex [GO:0034707]; dendrite [GO:0030425]; membrane [GO:0016020]; neuron projection [GO:0043005]; perikaryon [GO:0043204]; plasma membrane [GO:0005886]; postsynaptic membrane [GO:0045211]; synapse [GO:0045202]; transmembrane transporter complex [GO:1902495]
|
extracellularly glycine-gated chloride channel activity [GO:0016934]; extracellularly glycine-gated ion channel activity [GO:0016933]; glycine binding [GO:0016594]; ligand-gated monoatomic ion channel activity [GO:0015276]; neurotransmitter receptor activity [GO:0030594]; transmembrane signaling receptor activity [GO:0004888]; transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential [GO:1904315]; zinc ion binding [GO:0008270]
|
PF02931;PF02932;
|
2.70.170.10;1.20.58.390;
|
Ligand-gated ion channel (TC 1.A.9) family, Glycine receptor (TC 1.A.9.3) subfamily, GLRA1 sub-subfamily
| null |
SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q64018}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q64018}. Synapse {ECO:0000250|UniProtKB:Q64018}. Perikaryon {ECO:0000250|UniProtKB:Q64018}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q64018}. Cell membrane {ECO:0000269|PubMed:10188956, ECO:0000269|PubMed:26344198}; Multi-pass membrane protein {ECO:0000269|PubMed:26344198}.
|
CATALYTIC ACTIVITY: Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823, ChEBI:CHEBI:17996; Evidence={ECO:0000269|PubMed:10188956, ECO:0000269|PubMed:26344198};
| null | null | null | null |
FUNCTION: Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:10188956, PubMed:26344198). Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents. Channel activity is potentiated by ethanol (By similarity). {ECO:0000250|UniProtKB:P23415, ECO:0000269|PubMed:10188956, ECO:0000269|PubMed:26344198}.
|
Danio rerio (Zebrafish) (Brachydanio rerio)
|
O93507
|
TAL1_DANRE
|
MMEKLKSEQFPLSPSAEGCASPPRGDGDARGKQEGTTAETGEHRLPEELNGVAKETAHHATELKKEVAVIELSRRGGSADIKGRELKAELSHKVQTTELCRPPIPLPLPPRDPLSDTRMVQLSPPAFPLPARAMLYSNMTTPLATINSGFAGDAEQYGMYPSNRVKRRPAPYEVEINDGSQPKIVRRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLNDQDDMVGGEAPARANRDSRDATLVRDDLLQEMLSPNSSCGSLLDGDASPESFTEDQDSSVESRPSARGLHHSSLPLDGNAQR
| null | null |
angiogenesis [GO:0001525]; artery morphogenesis [GO:0048844]; blood vessel development [GO:0001568]; definitive hemopoiesis [GO:0060216]; embryonic heart tube development [GO:0035050]; embryonic hemopoiesis [GO:0035162]; endocardium formation [GO:0060214]; endocardium morphogenesis [GO:0003160]; erythrocyte differentiation [GO:0030218]; heart development [GO:0007507]; heart morphogenesis [GO:0003007]; hemangioblast cell differentiation [GO:0060217]; hematopoietic stem cell differentiation [GO:0060218]; hemopoiesis [GO:0030097]; lateral mesoderm development [GO:0048368]; myeloid cell differentiation [GO:0030099]; nucleate erythrocyte development [GO:0048823]; positive regulation of endothelial cell differentiation [GO:0045603]; primitive hemopoiesis [GO:0060215]; regulation of transcription by RNA polymerase II [GO:0006357]; stem cell population maintenance [GO:0019827]; thyroid gland development [GO:0030878]; vasculogenesis [GO:0001570]
|
nucleus [GO:0005634]
|
DNA binding [GO:0003677]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; protein dimerization activity [GO:0046983]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]
|
PF00010;
|
4.10.280.10;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P22091, ECO:0000255|PROSITE-ProRule:PRU00981}.
| null | null | null | null | null |
FUNCTION: Transcription factor that plays a pivotal role in hemopoietic and endothelial development, acting synergistically with lmo2 and downstream of clo. Specifies mesodermal precursors to a hemangioblast cell fate. Hemangioblasts are bipotential precursors of blood and endothelium, and in the absence of hemopoietic induction cues such as gata1, tal1/scl-lmo2-induced hemangioblasts differentiate into endothelial cells. Isoform alpha and isoform beta are redundant for the initiation of primitive hemopoiesis but have distinct roles in the regulation of primitive erythroid differentiation and definitive hemopoietic stem cell specification, most likely due to differences in expression levels. Specification of definitive hemopoietic stem cells requires isoform beta. DNA binding is required for erythroid maturation, but not for its other hemopoietic functions. Endothelial roles include development of the dorsal aorta, the site of definitive hemopoiesis in the embryo. Required for angiogenesis but not angioblast specification. Has an additional role in endocardium formation during heart development. May play a role in central nervous system development. {ECO:0000269|PubMed:11003831, ECO:0000269|PubMed:14602685, ECO:0000269|PubMed:15617691, ECO:0000269|PubMed:15644413, ECO:0000269|PubMed:16210319, ECO:0000269|PubMed:17090656, ECO:0000269|PubMed:17472439, ECO:0000269|PubMed:17722983, ECO:0000269|PubMed:9499398, ECO:0000269|PubMed:9670018}.
|
Danio rerio (Zebrafish) (Brachydanio rerio)
|
O93523
|
VM3BP_BOTJA
|
MIEVLLVTICLAAFPYQGSSIILESGNVNDYEVVYPRKVTALPKGAVQPKYEDAMQYEFKVNGEPVVLHLEKNKGLFSKDYSETHYSPDGREITTYPAVEDHCYYHGRIENDADSTASISACNGLKGHFKLQRETYFIEPLKLSNSEAHAVFKYENVEKEDEAPKMCGVTQNWKSYEPIKKASQLVVTAEQQKYNPFRYVELFIVVDQGMVTKNNGDLDKIKARMYELANIVNEILRYLYMHAALVGLEIWSNGDKITVKPDVDYTLNSFAEWRKTDLLTRKKHDNAQLLTAIDFNGPTIGYAYIGSMCHPKRSVAIVEDYSPINLVVAVIMAHEMGHNLGIHHDTDFCSCGDYPCIMGPTISNEPSKFFSNCSYIQCWDFIMKENPQCILNEPLGTDIVSPPVCGNELLEVGEECDCGTPENCQNECCDAATCKLKSGSQCGHGDCCEQCKFSKSGTECRASMSECDPAEHCTGQSSECPADVFHKNGQPCLDNYGYCYNGNCPIMYHQCYALFGADVYEAEDSCFKDNQKGNYYGYCRKENGKKIPCAPEDVKCGRLYCKDNSPGQNNPCKMFYSNDDEHKGMVLPGTKCADGKVCSNGHCVDVATAY
|
3.4.24.49
|
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:18831982}; Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:18831982};
|
proteolysis [GO:0006508]
|
extracellular region [GO:0005576]; plasma membrane [GO:0005886]
|
metal ion binding [GO:0046872]; metalloendopeptidase activity [GO:0004222]; toxin activity [GO:0090729]
|
PF08516;PF00200;PF01562;PF01421;
|
3.40.390.10;4.10.70.10;
|
Venom metalloproteinase (M12B) family, P-III subfamily, P-IIIb sub-subfamily
| null |
SUBCELLULAR LOCATION: Secreted.
|
CATALYTIC ACTIVITY: Reaction=Cleavage of 5-His-|-Leu-6, 10-His-|-Leu-11, 14-Ala-|-Leu-15, 16-Tyr-|-Leu-17 and 24-Phe-|-Phe-25 in insulin B chain.; EC=3.4.24.49; Evidence={ECO:0000269|PubMed:6819660};
| null | null | null | null |
FUNCTION: [Zinc metalloproteinase-disintegrin-like bothropasin]: Has caseinolytic activity. Causes hemorrhage on rabbit skin and causes myonecrosis in mouse tibialis anterior muscle.; FUNCTION: [Disintegrin-like bothropasin]: Inhibits platelet aggregation.
|
Bothrops jararaca (Jararaca) (Bothrops jajaraca)
|
O93529
|
FOXB1_XENLA
|
MPRPGRNTYSDQKPPYSYISLTAMAIQGSQEKMLPLSEIYKFIMDRFPYYRENTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPRCGDMFENGSFLRRRKRFKVMKSDHLAPSKASDAAQYLQQQAKLRLSALAASGTHLPPMSTYNLGVSPTSSFKHPFAIENIIAREYKMPGGLAFSTMQPMPAAYPLHNQLTTVGGSIGTGWPHMYSSSMLDSTTPISMANSDYSVSAYGVPIKPICHGAQTLLPAIPVPIKPTAALPALPTHIPAILSNSSPSMSPTSPQTATSQSSPATPSDTLTNPSTALLSVAVH
| null | null |
axon target recognition [GO:0007412]; cell migration in diencephalon [GO:0061381]; ectoderm development [GO:0007398]; floor plate development [GO:0033504]; hypothalamus cell migration [GO:0021855]; inferior colliculus development [GO:0061379]; mammillary body development [GO:0021767]; mammillothalamic axonal tract development [GO:0061374]; midbrain development [GO:0030901]; negative regulation of neuron apoptotic process [GO:0043524]; neurogenesis [GO:0022008]; regulation of DNA-templated transcription [GO:0006355]; somitogenesis [GO:0001756]; telencephalon cell migration [GO:0022029]; visual learning [GO:0008542]
|
nucleus [GO:0005634]
|
DNA binding [GO:0003677]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]
|
PF00250;
|
1.10.10.10;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000255, ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Probable transcription factor. May be involved in the early anteroposterior patterning of the neuroectoderm. {ECO:0000269|PubMed:11404077, ECO:0000269|PubMed:15656969}.
|
Xenopus laevis (African clawed frog)
|
O93530
|
WRN_XENLA
|
MTSLQRKLPEWMSVKQQEDRIDDAKKSFCKKNILEDNLPFMKFNGSIVYSYESNDCSLLSEDIRSSLLEEDVLGFDIEWPPVYTKGKTGKVALIQVCVSEKKCYLFHISPMAGFPKGLKRLLEDESVRKVGVGIEGDQWKLMSDYELKLKGFIELSEMANQKLRCKEKWTFNGLIKHLFKEQLYKRKSYRCSNWDIFLLTEDQKLYAATDAYAGLLIYKKLEGMDAHESDSFRVGREGVADCKGVKRQLTDLSKGLMDLVNQVPNSFGCYTEAVRAVDILEDLSEKLEELRNIMKEASKAEGNGLHFQNSEDCSKKDKSILHVACKESLAEHKMDCKNADSQNNKDIDSCQNENRDEDFFMTLGISEEELYMMEREDDKKQTNPDYKLNKDSCDTNEEKDMSYVIESDEDFDSEIIKSLEDLDNSTEEALGTGVPQAGLIPAKSVDTVADEEEDEGIEEEDDDDDWDPSMPEPSAQHISCLKTYFGHSSFKPVQWKVVHSVLRERRDNLVVMATGYGKSLCYQFAPVYTSGIGIVICPLISLMEDQVLQLEMSNISSCFLGSAQSKNVLQDVKDGKMRVIYMTPEFCSRGISLLQDLDNRYGITLIAIDEAHCISEWGHDFRSAYRSLGSLKRMLPNVPIVALTATASPSIREDITKSLNLHNPQVTCTSFDRPNLYLDVARKTTNISIDLRQFLIKKQQGSGWEFEGATIVYCPTRKTSEQVTAELIKLGIACGTYHAGMGIKQRREVHHRFMRDEIHCVVATVAFGMGINKPDIRKVIHYGAPKEMESYYQEIGRAGRDGLPSCCHALWAQADMNFNRHMLGEIPNKGFREYKLKMLTKMEKYLNSSTCRRKIILSHFEDKQLRKASSGIMGTEKCCDNCKTRLICNISINDTEDNLQDFGPQAYKFISAVDVLGQKFGTGVPVLFLRGSTSQRVPDRFRNHSLFSSGKDQTEAFWKVLARQLITEGYLQESSGQTKFSTICGLTSKGSNWLIKANNEQCPSLLLPSNNELCLQRTRVSNFSSAQAHSSMVPHASSNTRSSMPKAGPEKMELKDKFSYQEAERLSKAAGVSKSSFKLQTPCKLSRPPEPEVSPRERELQTTLYGRLVVARQKIASERDILPAVLATNKVLVDMAKLRPTTSENMKKLDGVSEAKSAMLAPLLEVVKEFCIANSLKVDVFSGSVSQSESTFFTPREQERISLPESQRMSYSLFQEQNLSLKKIADVRCLSMAVVGMHLWQALKAGYSFDVQRAGLTPEMKKLITYAIKKPPINSDLSSFKAIREYVPANIDGYPIRMVISLLEKEGSSGAQGQPEFPTQKTLIQTEENPKNVSVQNTKHKVTMGKSMWIEKKPTQPATAELEVTKGKALAPIMLASWNEASLDADTEELFSESQSSTTRPRRRLPEWFGSTKGNAATRCIQESKNLGEEKGSFFD
|
3.1.-.-; 5.6.2.4
|
COFACTOR: Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Evidence={ECO:0000250|UniProtKB:Q14191}; Note=Binds 2 divalent metal cations in the exonuclease domain; in human Mg(2+) and Mn(2+) give high activity, in mouse Mn(2+) and Zn(2+) give high activity. {ECO:0000250|UniProtKB:O09053, ECO:0000250|UniProtKB:Q14191}; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:Q14191}; Note=Binds a Zn(2+) ion in the helicase domain. {ECO:0000250|UniProtKB:Q14191};
|
DNA metabolic process [GO:0006259]; DNA unwinding involved in DNA replication [GO:0006268]; double-strand break repair via homologous recombination [GO:0000724]; G-quadruplex DNA unwinding [GO:0044806]; telomere maintenance [GO:0000723]
|
chromosome [GO:0005694]; cytoplasm [GO:0005737]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]
|
3'-5' DNA helicase activity [GO:0043138]; 3'-5' exonuclease activity [GO:0008408]; ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; DNA binding [GO:0003677]; four-way junction helicase activity [GO:0009378]; isomerase activity [GO:0016853]; magnesium ion binding [GO:0000287]; manganese ion binding [GO:0030145]
|
PF00270;PF01612;PF00271;PF00570;PF14493;PF16124;PF09382;
|
1.10.150.80;3.40.50.300;3.30.420.10;1.10.10.10;
|
Helicase family, RecQ subfamily
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9697700}. Note=Associates with probable replication foci (PubMed:9697700). {ECO:0000269|PubMed:9697700}.
|
CATALYTIC ACTIVITY: Reaction=Couples ATP hydrolysis with the unwinding of duplex DNA by translocating in the 3'-5' direction.; EC=5.6.2.4; Evidence={ECO:0000250|UniProtKB:Q14191, ECO:0000305|PubMed:9697700}; CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:9697700};
| null | null | null | null |
FUNCTION: Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (PubMed:9697700). {ECO:0000250|UniProtKB:Q14191, ECO:0000269|PubMed:7569932, ECO:0000269|PubMed:9697700}.
|
Xenopus laevis (African clawed frog)
|
O93574
|
RELN_CHICK
|
TNGLNTTTASVLQFSLGSGSCRFSYSDPSITVSYSKNSSADWTQLEKISAPSNVSTIIHILYLPEDAKGENVHFQWKQDYLHAGEVYEACWALDNILIINAAHRKVVLEDNLDPVDTGNWLFFPGATVKHSCQSDGNSIYFHGTEGSEFNFATTRDVDLSTEDAQEQWAEEFESQPKGWDILGAVIGTECGTLESGSSMVFLRDGERKICTPYMDTTGYGNLRFYFSMGGNCDSGESHENDVILYAKIEGRREHIALDTLTYAAYKVPSLVSVVISPDLQTPATKFCLKQKSHQGHNRNVWAVDYFHVLPVLPSTVTHMIQFSINLGCGTYQPGNSVSLEFSTNHGRSWSLLHTECLPEICAGPHLPHSTVYASENYSGWNRITTPVPNAALTSDTRIRWRQTGPIHGNMWAIDNIYIGPSCLKFCSGRGQCTRNGCKCDPGFSGPACETASQTFPMFISESFASSRLSSYHNFYSIRGAEVSFGCGVLASGKALVFNKDGRRQLITAFLDSSQSRFLQFTLRLGSKSVLSTCKAPDQPGEGVLLHYSYDNGITWKLLEHYSYLNYHEPRIISVELPEDARQIGIQFRWWQPYHSSQGEDVWAIDEIVMTSVLFNSISLDFTNLVEVTQSLGFYLGNVQPYCGHDWTLCFTGDSKLTSSMRYVETQSMQIGASYMIQFNLVMGCGQKFTPHMDNQVKLEYSTNHGLTWHLVQEECLPSMPSCQEFTSASIYHSNEFTQWRRITVLLPQKTWSSATRFRWSQCYYTAPDEWALDNIYIGQQCPNMCSGHGWCDHGVCRCDSGFRGTECQPENPLPSTVMSDFENPDVLKTEWQEIIGGEIVKPEEGCGVISSGSSLYFNKAGKRQLVSWDLDTTWVDFVQFYIQIGGESSSCNRPDSREEGVLLQYSNNGGINWQLLAEMYFSDFSKPRFVYLELPAAAKTPCTRFRWWQPVFSGEGYDQWAIDDIIILSEKQKHIIPVVNPTLPQNFYEKPAFDYPMNQLSVWLILANEGMTKNESFCSATPSAMLFGKSDGDRFAVTRDLTLKPGYVLQFKLNIGCTNQYSSSAPVLLQYSHDAGLFWSLVKEGCYPASPGTKGCEGSSRELSEPTVYHTGDFEDWTRITIVIPRSLAASKTRFRWIQESSSHKSVPPFGLDGVYISEPCPNYCNGHGDCVSGVCFCDLGYTASHGTCVSNVPNHSEMFDRFERKLSPLWYKITGGQVGTGCGVLSDGKSLYFNGPGKREARTVPLDTTNIRLVQFYVQIGSKATGNSCNRPRSRNEGLIVQYTNDNGITWHLLRELDFMSYLEPQVVSIDLPREAKTSATAFRWWQPQHGKHSAQWALDDVLIGMNDSSQTGFQDKFDGTVDLQASWYRIQGGQVDIDCLSMDTALMFSENIEKPRYAETWDFHVSASTFLQFELSMGCSKPYSNSHSIHLQYSLNNGRDWHLVTEECVPPTIGCQHYTESSIYTSERFQNWKRITAYLPPITNSPRTRFRWIQYNYASGVDSWAIDNVVLATGCPWMCSGHGICDAGHCVCDRGFGGPYCVHVNPLPSVLKDDFNGNLHPDLWPEVYGAERGNLNGDTIKSGTALIFKGEGLRMLVSRDLDCTNTVYIQFSFKFIAKGTPERSHSILLQYSVNGGITWHLIDEFYFTQTTDVLFINVPLPYTAQSNATRFRLWQPYNSGKKEEIWIIDDFIIDGNNLKNPIILLDTFDFGPKEDNWFFYPGGNIGLYCPYSSKGAPEEDSAMVFVSNEVGEHSITTRDLSVNENTIIQFEINIGCTTDSSSADPVKLEFSRDLGATWHLLLPLCYSSSSHLSSLCSTEHHPSSTYYTGTTQGWRREVIHFGKLHLCGLTRFRWYQGFYPAGSQPVTWAIDNVYIGPQCEEMCNGHGSCINGTKCICDPGYSGPTCKISTKNSDSLKDDFEGQLESDRFLLVSGGKPSRKCGIMSGGNNLFFNEEGLRMLMTRDLDLSQARFVQFFMRLGCGKGVPDPRSQLSXLQYSLNGGLTWSLLQEFLFSNSSNVGRYIALEIPMKARSSSTRLRWWQPSENGHFYSPWVIDQILIGGNISGSTVLEDDFTTLDSRKWLLHPGGTKMPVCGSTGDALVFIEKASTRYVVTTDIVVNEDSFLQIDFAASCSVTGSCYAIELEYSVDLGITWHPILRDCLPTNVECNRYHLQRILISDTFNKWTRITLPLPPYTRSQATRFRWHQPAPFDKQQTWAIDNVYIGDGCIDMCSGHGKCTQDNCVCDEHWGGLYCDEPETPLPTQLKDNFNRSPSNQNWLTVNGGKLSTVCGAVASGMALHFSGGCSRMLVTVDLNLTNAEFIQFYFMYGCLITPNNRNQGVLLEYSVNGGITWSPLMEIFYDQFSKPGFVNILLPYDAKTIGTRFRWWQPKHDGLDQNDWAIDNVLISGSTDQRTVMLDTFSSAPLPQHERSPADAGPTGRIAFDMFMEDKTTVNEHWLFHDDCSIERFCDSPDGVMICGSHDGREVYAVTHDLTPTEGWIMQFKVSVGCKTSEKLAQNQVHVQYSTDFGVSWSYLVPQCLPADPKCSGSVSQPSVFFPTKGWKRVTYSLPENLVGNPVRFRFYQKYSDVQWAIDNFYLGPGCLENCRGHGDCLKEQCICDPGYSGPNCYLTQTLKTFLKERFDNEEIKPDLWMSLEGGNTCTECGILAEDTTLYFGGQTVRQAVTQDLDLRGAKFLQYWGRIGSENNMTTCHRPTCRKEGVLLDYSIDGGITWTLLHEMDYQKYISVRHDYILLPEHALTNTTRLRWWQPFTISNGIVVSGPDRAQWALDNILIGGAEINPSQLVDTFDDEGTSHEENWSSYPNAVRTAGFCGNPSFHLYWPNKKKDKTHNILSSRELIIQPGYMMQFKIVVGCEASSCGDLHSVMLEYTKDARTDSWQLVQTHCLPSSSNSIGCSPFQFHEATIYNSVNSSMWRRITIQLPDHVSSSATQFRWIQKGEELEKQSWAIDHVYIGEACPKLCSGRGYCSTGAICICDEGYQGDDCSVFSHDLPSYIKDNFESERVTEINWETIQGGVIGNGCGQLAPYAHGDSLYFNGCQVRQAVTKPLDLTRASKIMFVLQIGSISQTDSCNTNLIDPNTVDKAVLLQYSVNNGITWQVIAQHQPKDFIQAQRVSYNVPLEARMKGVLLRWWQPRHNGTGHDQWALDHVEVVLISTRKQNYMMNFSRQHGLRHFYNRRRRSLRRYP
|
3.4.21.-
| null |
axon guidance [GO:0007411]; brain development [GO:0007420]; cell adhesion [GO:0007155]; cell morphogenesis [GO:0000902]; central nervous system development [GO:0007417]; cerebral cortex tangential migration [GO:0021800]; glial cell differentiation [GO:0010001]; neuron migration [GO:0001764]; peptidyl-tyrosine phosphorylation [GO:0018108]; positive regulation of protein kinase activity [GO:0045860]; positive regulation of small GTPase mediated signal transduction [GO:0051057]; proteolysis [GO:0006508]; response to pain [GO:0048265]; spinal cord patterning [GO:0021511]; ventral spinal cord development [GO:0021517]
|
collagen-containing extracellular matrix [GO:0062023]; cytoplasm [GO:0005737]; dendrite [GO:0030425]; extracellular space [GO:0005615]; neuron projection [GO:0043005]
|
lipoprotein particle receptor binding [GO:0070325]; metal ion binding [GO:0046872]; serine-type peptidase activity [GO:0008236]
|
PF07974;PF18720;PF21471;
|
2.60.120.260;
|
Reelin family
| null |
SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Extracellular matrix serine protease that plays a role in layering of neurons in the cerebral cortex and cerebellum. Regulates microtubule function in neurons and neuronal migration. Affects migration of sympathetic preganglionic neurons in the spinal cord, where it seems to act as a barrier to neuronal migration. Enzymatic activity is important for the modulation of cell adhesion. Binding to the extracellular domains of lipoprotein receptors VLDLR and LRP8/APOER2 induces tyrosine phosphorylation of DAB1 and modulation of TAU phosphorylation (By similarity). {ECO:0000250}.
|
Gallus gallus (Chicken)
|
O93627
|
RBL_THEKO
|
MVEKFDTIYDYYVDKGYEPSKKRDIIAVFRVTPAEGYTIEQAAGAVAAESSTGTWTTLYPWYEQERWADLSAKAYDFHDMGDGSWIVRIAYPFHAFEEANLPGLLASIAGNIFGMKRVKGLRLEDLYFPEKLIREFDGPAFGIEGVRKMLEIKDRPIYGVVPKPKVGYSPEEFEKLAYDLLSNGADYMKDDENLTSPWYNRFEERAEIMAKIIDKVENETGEKKTWFANITADLLEMEQRLEVLADLGLKHAMVDVVITGWGALRYIRDLAADYGLAIHGHRAMHAAFTRNPYHGISMFVLAKLYRLIGIDQLHVGTAGAGKLEGGKWDVIQNARILRESHYKPDENDVFHLEQKFYSIKAAFPTSSGGLHPGNIQPVIEALGTDIVLQLGGGTLGHPDGPAAGARAVRQAIDAIMQGIPLDEYAKTHKELARALEKWGHVTPV
|
4.1.1.39
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_01133, ECO:0000269|PubMed:11435112, ECO:0000269|PubMed:20926376}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01133, ECO:0000269|PubMed:11435112, ECO:0000269|PubMed:20926376};
|
AMP catabolic process [GO:0006196]; carbon fixation [GO:0015977]
| null |
magnesium ion binding [GO:0000287]; oxidoreductase activity [GO:0016491]; ribulose-bisphosphate carboxylase activity [GO:0016984]
|
PF00016;PF02788;
|
3.20.20.110;3.30.70.150;
|
RuBisCO large chain family, Type III subfamily
| null | null |
CATALYTIC ACTIVITY: Reaction=2 (2R)-3-phosphoglycerate + 2 H(+) = CO2 + D-ribulose 1,5-bisphosphate + H2O; Xref=Rhea:RHEA:23124, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57870, ChEBI:CHEBI:58272; EC=4.1.1.39; Evidence={ECO:0000255|HAMAP-Rule:MF_01133, ECO:0000269|PubMed:9988755}; CATALYTIC ACTIVITY: Reaction=D-ribulose 1,5-bisphosphate + O2 = (2R)-3-phosphoglycerate + 2-phosphoglycolate + 2 H(+); Xref=Rhea:RHEA:36631, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57870, ChEBI:CHEBI:58033, ChEBI:CHEBI:58272; Evidence={ECO:0000255|HAMAP-Rule:MF_01133, ECO:0000269|PubMed:9988755};
| null | null | null |
BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 90 degrees Celsius (PubMed:9988755). Highly thermostable, has a half-life of 220 minutes at 90 degrees Celsius (PubMed:9988755). {ECO:0000269|PubMed:20926376, ECO:0000269|PubMed:9988755};
|
FUNCTION: Catalyzes the addition of molecular CO(2) and H(2)O to ribulose 1,5-bisphosphate (RuBP), generating two molecules of 3-phosphoglycerate (3-PGA) (PubMed:10512715, PubMed:9988755). Functions in an archaeal AMP degradation pathway, together with AMP phosphorylase and R15P isomerase (PubMed:17303759). {ECO:0000255|HAMAP-Rule:MF_01133, ECO:0000269|PubMed:10512715, ECO:0000269|PubMed:12070156, ECO:0000269|PubMed:17303759, ECO:0000269|PubMed:20926376, ECO:0000269|PubMed:9988755}.
|
Thermococcus kodakarensis (strain ATCC BAA-918 / JCM 12380 / KOD1) (Pyrococcus kodakaraensis (strain KOD1))
|
O93715
|
GLCDH_SACSO
|
MKAIIVKPPNAGVQVKDVDEKKLDSYGKIKIRTIYNGICGTDREIVNGKLTLSTLPKGKDFLVLGHEAIGVVEESYHGFSQGDLVMPVNRRGCGICRNCLVGRPDFCETGEFGEAGIHKMDGFMREWWYDDPKYLVKIPKSIEDIGILAQPLADIEKSIEEILEVQKRVPVWTCDDGTLNCRKVLVVGTGPIGVLFTLLFRTYGLEVWMANRREPTEVEQTVIEETKTNYYNSSNGYDKLKDSVGKFDVIIDATGADVNILGNVIPLLGRNGVLGLFGFSTSGSVPLDYKTLQEIVHTNKTIIGLVNGQKPHFQQAVVHLASWKTLYPKAAKMLITKTVSINDEKELLKVLREKEHGEIKIRILWE
|
1.1.1.120; 1.1.1.359; 1.1.1.47; 1.1.1.48
|
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:16556607}; Note=Binds 2 Zn(2+) ions per subunit. One of the zinc atoms is essential for catalytic activity while the other has a structural function. {ECO:0000269|PubMed:16556607};
|
galactose catabolic process via D-galactonate [GO:0033498]; non-phosphorylated glucose catabolic process [GO:0019595]; protein tetramerization [GO:0051262]
| null |
aldose 1-dehydrogenase activity [GO:0047640]; galactose 1-dehydrogenase (NADP+) activity [GO:0047910]; galactose 1-dehydrogenase activity [GO:0019151]; galactose binding [GO:0005534]; glucose 1-dehydrogenase (NAD+) activity [GO:0047934]; glucose 1-dehydrogenase (NADP+) activity [GO:0047935]; glucose 1-dehydrogenase [NAD(P)] activity [GO:0047936]; glucose binding [GO:0005536]; NAD+ binding [GO:0070403]; NADP+ binding [GO:0070401]; xylose binding [GO:0033222]; zinc ion binding [GO:0008270]
|
PF08240;PF16912;
|
3.90.180.10;3.40.50.720;
|
Zinc-containing alcohol dehydrogenase family, Glucose 1-dehydrogenase subfamily
| null | null |
CATALYTIC ACTIVITY: Reaction=D-glucose + NAD(+) = D-glucono-1,5-lactone + H(+) + NADH; Xref=Rhea:RHEA:14293, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378, ChEBI:CHEBI:16217, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.47; Evidence={ECO:0000269|PubMed:12824170, ECO:0000269|PubMed:3827812}; CATALYTIC ACTIVITY: Reaction=D-glucose + NAD(+) = D-glucono-1,5-lactone + H(+) + NADH; Xref=Rhea:RHEA:14293, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378, ChEBI:CHEBI:16217, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.359; Evidence={ECO:0000269|PubMed:12824170, ECO:0000269|PubMed:3827812}; CATALYTIC ACTIVITY: Reaction=D-glucose + NADP(+) = D-glucono-1,5-lactone + H(+) + NADPH; Xref=Rhea:RHEA:14405, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378, ChEBI:CHEBI:16217, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.47; Evidence={ECO:0000269|PubMed:12824170, ECO:0000269|PubMed:3827812}; CATALYTIC ACTIVITY: Reaction=D-glucose + NADP(+) = D-glucono-1,5-lactone + H(+) + NADPH; Xref=Rhea:RHEA:14405, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378, ChEBI:CHEBI:16217, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.359; Evidence={ECO:0000269|PubMed:12824170, ECO:0000269|PubMed:3827812}; CATALYTIC ACTIVITY: Reaction=D-galactose + NAD(+) = D-galactono-1,4-lactone + H(+) + NADH; Xref=Rhea:RHEA:21296, ChEBI:CHEBI:4139, ChEBI:CHEBI:15378, ChEBI:CHEBI:15895, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.48; Evidence={ECO:0000269|PubMed:12824170}; CATALYTIC ACTIVITY: Reaction=D-galactose + NADP(+) = D-galactono-1,5-lactone + H(+) + NADPH; Xref=Rhea:RHEA:18625, ChEBI:CHEBI:4139, ChEBI:CHEBI:15378, ChEBI:CHEBI:15945, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.359; Evidence={ECO:0000269|PubMed:12824170, ECO:0000269|PubMed:3827812}; CATALYTIC ACTIVITY: Reaction=D-galactose + NADP(+) = D-galactono-1,5-lactone + H(+) + NADPH; Xref=Rhea:RHEA:18625, ChEBI:CHEBI:4139, ChEBI:CHEBI:15378, ChEBI:CHEBI:15945, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.120; Evidence={ECO:0000269|PubMed:12824170, ECO:0000269|PubMed:3827812}; CATALYTIC ACTIVITY: Reaction=an aldopyranose + NAD(+) = aldono-1,5-lactone + H(+) + NADH; Xref=Rhea:RHEA:15917, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:140379, ChEBI:CHEBI:140380; EC=1.1.1.359; Evidence={ECO:0000269|PubMed:12824170, ECO:0000269|PubMed:3827812}; CATALYTIC ACTIVITY: Reaction=an aldopyranose + NADP(+) = aldono-1,5-lactone + H(+) + NADPH; Xref=Rhea:RHEA:36587, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:140379, ChEBI:CHEBI:140380; EC=1.1.1.359; Evidence={ECO:0000269|PubMed:12824170, ECO:0000269|PubMed:3827812};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=8 mM for D-glucose (in the presence of NAD(+), at 70 degrees Celsius and pH 8) {ECO:0000269|PubMed:3827812}; KM=1.5 mM for D-glucose (in the presence of NAD(+), at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:12824170}; KM=0.44 mM for D-glucose (in the presence of NADP(+), at 70 degrees Celsius and pH 8) {ECO:0000269|PubMed:3827812}; KM=1.3 mM for D-glucose (in the presence of NADP(+), at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:12824170}; KM=0.57 mM for D-galactose (in the presence of NAD(+), at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:12824170}; KM=22 mM for D-galactose (in the presence of NADP(+), at 70 degrees Celsius and pH 8) {ECO:0000269|PubMed:3827812}; KM=0.44 mM for D-galactose (in the presence of NADP(+), at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:12824170}; KM=0.25 mM for D-xylose (in the presence of NAD(+), at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:16556607}; KM=0.18 mM for D-xylose (in the presence of NADP(+), at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:16556607}; KM=1.2 mM for NAD(+) (at 70 degrees Celsius and pH 8) {ECO:0000269|PubMed:3827812}; KM=0.03 mM for NADP(+) (at 70 degrees Celsius and pH 8) {ECO:0000269|PubMed:3827812}; Vmax=110 umol/min/mg enzyme for the oxidation of D-glucose by NAD(+) (at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:12824170}; Vmax=70 umol/min/mg enzyme for the oxidation of D-glucose by NADP(+) (at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:12824170}; Vmax=90 umol/min/mg enzyme for the oxidation of D-galactose by NAD(+) (at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:12824170}; Vmax=55 umol/min/mg enzyme for the oxidation of D-galactose by NADP(+) (at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:12824170}; Vmax=90 umol/min/mg enzyme for the oxidation of D-xylose by NAD(+) (at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:16556607}; Vmax=65 umol/min/mg enzyme for the oxidation of D-xylose by NADP(+) (at 70 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:16556607};
| null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 9. {ECO:0000269|PubMed:3827812};
|
BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 77 degrees Celsius. At 37 degrees Celsius, shows about 20% activity as compared with the maximal value. {ECO:0000269|PubMed:3827812};
|
FUNCTION: Catalyzes the NAD(P)(+)-dependent oxidation of D-glucose to D-gluconate via gluconolactone. Displays broad substrate specificity since it is able to catalyze the oxidation of a number of alternative aldose sugars, such as D-galactose, D-xylose and L-arabinose, to the corresponding glyconate. Can utilize both NAD(+) and NADP(+) as electron acceptor. Physiologically, seems to be involved in the degradation of both glucose and galactose through a non-phosphorylative variant of the Entner-Doudoroff pathway. {ECO:0000269|PubMed:12824170, ECO:0000269|PubMed:3827812}.
|
Saccharolobus solfataricus (Sulfolobus solfataricus)
|
O93845
|
DPOE_EMENI
|
MPSRKPSKYGNKFRSGAASFNPKRTKTVEFSSLRSSEATSQDEKFEAIRLANSIDESLGFPRFEAGEKRVGWLINMHSTSIEDPNVPGGRAGVDYYFLDDDGGSFKATVEYDPYFLIAVKTGHEAEVEEWCRRMFEGLIKKIKRVVKEDLKLPNHLLGHRRTFLQLDFANVSHLLEVRKTLLPLAEKNRKNARPNGTTNASDFIIDIREYDVPYHVRVAIDKDIRIGKWYTVEATHGIISLTCLEERLTRADPVVLAFDIETTKLPLKFPDSVIDQIMMISYMIDGQGFLITNREIVSEDIDDFEYTPKPEYSGPFMIFNEPNERAVIERFFEHIKEAKPTVIATYNGDFFDWPFVEARASVLGIDMYKEIGFRKNSEDIYQSDHCAHMDCFAWVNRDSYLPQGSRGLKAVTVAKLGYDPDELDPELMTPYASERPQTLAEYSVSDAVATYYLYMKYIHPFIFSLCTILPLNPDDTLRKGTGTLCEMLLMVQAYKGNIVLPNKHKDPPEAFYEGHLLESETYVGGHVESIEAGVFRSDIPVPFNIDPTAVDELLRDLDAALKFSIEVEEKKSLDDVTNYEEVKGQIAKLLTDLRENPHRNEVPFIYHLDVASMYPNIMITNRLQPDSLIQESNCAACDFNRPGKTCDRRLPWAWRGEFLPAKRDEYNMIRQAVQNERFPGRTKKSPMRAFTELSAEEQAAIVKKRLQDYSKKIYHKIHDSKTMVREAIICQRENPFYVDTVRSFRDRRYDFKGKQKVWKGKTESLKSSGAPAAEIEEAKKMIVLYDSLQLAHKVILNSFYGYVMRKGSRWYSMEMAGVTCLTGARIIQMARELVERIGRPLELDTDGIWCMLPGTFPENFSFTLKNGKKLGISYPCVMLNHLVHGSYTNHQYQSLANPATFRYETHSENSIFFEVDGPYRAMILPTSKEEDKNLKKRYAVFNDDGSLAELKGFEVKRRGELKLIKIFQTQIFKFFLEGTTLAETYAAVARVADRWLDVLYEHGATLADEELIELISENRSMTKTLEEYGNQKSTSITTARRLAEFLGEQMVKDKGLNCKYIISARPRNTPVTERAIPVTIFSAEDSIKRHFLRKWLKDDPGDMDPRSVIDWDYYLERLGSVVQKLITIPAALQKIRNPVPRVAHPEWLQRRINKQDDRFKQVKMTDMFGKSEKNPLSDISTNIIDHRVQHADNLDEAMADSMEKLKSSSPQKASGKRKHPENQTKTSLDPFASLPAKMPSIDDDYVGFLKYQKQKWKIQKQARLRRRQLFGERANTGGDSLSHLFRNQAELLYISTWQVLQLAETSRPGIVRAFVLIDRKIHALTIKVPRCVYINLKQDSLPDVEVPECEVEKVNHTLPNGHPSVHLFKLTLSEETFLREADKIHVLLQHPSVEGVYERNIPLNLRAVLKLGSICTFDEAQRGVLGDGLERGFDLSTLCRTSSEQQYLQDSPLAYHFLYHVSSGEKQIFAIFSSTKNEAHIVILNRARDVQGLPNVDKIYSELLARKLQGQGDQAEGAFQYQEKIHFRTTQITTRRKAYLEVSDLIKKLRNDESLPAIMIIQSQQRSRLCHDIPILKEYPILSVKPEVSDMNLPPLGWQSFIAKRLVTHYLYLSSWVQHLTMLARYGDVPLCNLESDDPRFLIDISYARRLQQNNVVLWWSSTAKPDHAGYEKDDITGPLERVGMPCVNVPGSYTTVCVELEVRNLAINTILTSSIINEAEGADSLLAPSDPSAESSGSGVLYSEKAFASAGAVVLREMVKHWWSEACQGNNMADIMVQHLIRWVESPASCLYDRSLHQYVRMLSRKSFQQLMAEFRRVGSNVVFASPTRLLLQTSKTEVGNAYAYSQYVLKSIRANPSFHFIDLDIKEYWDYLVWYDEYNYGGKGCQEVAETEEQPLETVMHWQLSRFLPTPMQTIFHDWVVEYIELMHSFKRPESDDSSTPRLTQIPIGQPEPGQENEELSAALSDRFSKPLKKQISGLIRRQREELLHPELASDYVFPILPGVLTDPNEEKRNPVLELVKLLMQVLSLSKTTALETRLLRRELLALFEVREFSKEGRFENPGSSLKIPELTCSACCLIRDLDLCRDEDVLPERGSGSGPDSATSSRPWCCPFCQTEYDRLAQEEMLIGQVWGMVVAWQTQDLKCSKCGTLKISEFMEHCSCSGQWTETMNRADIEKRLKVLESVAKFHELKLLQVVVEEVLSQT
|
2.7.7.7
|
COFACTOR: Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250|UniProtKB:P15436}; Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250|UniProtKB:P15436};
|
base-excision repair, gap-filling [GO:0006287]; CENP-A containing chromatin assembly [GO:0034080]; CMG complex assembly [GO:0140529]; DNA replication proofreading [GO:0045004]; double-strand break repair via nonhomologous end joining [GO:0006303]; error-prone translesion synthesis [GO:0042276]; gene conversion [GO:0035822]; leading strand elongation [GO:0006272]; mitotic cell cycle [GO:0000278]; mitotic DNA replication checkpoint signaling [GO:0033314]; mitotic DNA replication initiation [GO:1902975]; mitotic DNA replication leading strand elongation [GO:1903460]; mitotic intra-S DNA damage checkpoint signaling [GO:0031573]; mitotic sister chromatid cohesion [GO:0007064]; nucleotide-excision repair, DNA gap filling [GO:0006297]; premeiotic DNA replication [GO:0006279]; regulatory ncRNA-mediated heterochromatin formation [GO:0031048]
|
chromosome, telomeric repeat region [GO:0140445]; epsilon DNA polymerase complex [GO:0008622]; nuclear replication fork [GO:0043596]
|
4 iron, 4 sulfur cluster binding [GO:0051539]; DNA binding [GO:0003677]; DNA-directed DNA polymerase activity [GO:0003887]; double-stranded DNA binding [GO:0003690]; nucleotide binding [GO:0000166]; single-stranded DNA 3'-5' DNA exonuclease activity [GO:0008310]; single-stranded DNA binding [GO:0003697]; SUMO binding [GO:0032183]; zinc ion binding [GO:0008270]
|
PF00136;PF03104;PF08490;
|
1.10.132.60;3.30.342.10;3.90.1600.10;3.30.420.10;
|
DNA polymerase type-B family
| null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
|
CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000250|UniProtKB:P15436};
| null | null | null | null |
FUNCTION: DNA polymerase II participates in chromosomal DNA replication. {ECO:0000250}.
|
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans)
|
O93852
|
ALO1_CANAL
|
MTDIPESLKPFVTKKVIHSTWAGTFLCKPQAIFQPRNVEEIQELIKQARLHGKTIMTVGSGHSPSDLTMTTEWLCNLDKFNHVLLEEPYYAPKSPTDDTPEIKFVDLTVEAGTRIFELNEYLKRNNLAIQNLGSISDQSIAGLISTGTHGSTQYHGLVSQQVVSVKFLNSAGELITCSSVDKPEYFRAILLSLGKIGIITHVTLRTCPKYTIKSKQEIINFETLLNNWDNLWLESEFIRIWWFPYTNKCVLWRANKSTDPLSDPRPSWYGTKLGRFFYESLLWVSVHLFPRLTPFVEKFVFGQQYGEVETLGKGDIAVQNSVEGLNMDCLFSQFVNEWSSPLNSGPEILTELKKIITDASQTGDFFVHAPIEVRCSNVTYSDEPFTDDKNQKSLYPSQEWLSNRSKTSAGPIPGNNLRPYLDNSPKLPYSKDGKITNDQLTLFINATMYRPFGTNVETHKWFQLFEDVMSKAGGKPHWAKNFIGLTQDEKYDKQQDLKTQLEFGGKPFYTMLGFKPVMQDWFGKDLVAFNKVRKETDPDGVFLSGKVWAERNGILLD
|
1.1.3.37; 1.1.3.8; 1.3.3.12
|
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692;
|
cellular detoxification [GO:1990748]; cellular response to oxidative stress [GO:0034599]; cellular response to starvation [GO:0009267]; filamentous growth [GO:0030447]; filamentous growth of a population of unicellular organisms [GO:0044182]; filamentous growth of a population of unicellular organisms in response to starvation [GO:0036170]
|
mitochondrion [GO:0005739]; plasma membrane [GO:0005886]
|
D-arabinono-1,4-lactone oxidase activity [GO:0003885]; FAD binding [GO:0071949]; L-galactonolactone oxidase activity [GO:0050024]; L-gulono-1,4-lactone dehydrogenase activity [GO:0080049]; L-gulonolactone oxidase activity [GO:0050105]
|
PF04030;PF01565;
|
3.30.465.10;3.30.70.2520;3.30.43.10;
|
Oxygen-dependent FAD-linked oxidoreductase family
| null | null |
CATALYTIC ACTIVITY: Reaction=D-arabinono-1,4-lactone + O2 = dehydro-D-arabinono-1,4-lactone + H(+) + H2O2; Xref=Rhea:RHEA:23756, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:16292, ChEBI:CHEBI:58277; EC=1.1.3.37; Evidence={ECO:0000269|PubMed:7957197}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23757; Evidence={ECO:0000269|PubMed:7957197}; CATALYTIC ACTIVITY: Reaction=L-galactono-1,4-lactone + O2 = H(+) + H2O2 + L-ascorbate; Xref=Rhea:RHEA:20617, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17464, ChEBI:CHEBI:38290; EC=1.3.3.12; Evidence={ECO:0000269|PubMed:7957197}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20619; Evidence={ECO:0000269|PubMed:7957197}; CATALYTIC ACTIVITY: Reaction=L-gulono-1,4-lactone + O2 = H(+) + H2O2 + L-ascorbate; Xref=Rhea:RHEA:32363, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17587, ChEBI:CHEBI:38290; EC=1.1.3.8; Evidence={ECO:0000269|PubMed:7957197}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32364; Evidence={ECO:0000269|PubMed:7957197}; CATALYTIC ACTIVITY: Reaction=L-xylono-1,4-lactone + O2 = dehydro-L-arabinono-1,4-lactone + H(+) + H2O2; Xref=Rhea:RHEA:68360, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:18118, ChEBI:CHEBI:177361; Evidence={ECO:0000269|PubMed:7957197}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68361; Evidence={ECO:0000269|PubMed:7957197};
| null |
PATHWAY: Cofactor biosynthesis; D-erythroascorbate biosynthesis; dehydro-D-arabinono-1,4-lactone from D-arabinose: step 2/2. {ECO:0000269|PubMed:7957197}.
| null | null |
FUNCTION: D-arabinono-1,4-lactone oxidase that catalyzes the final step of biosynthesis of D-erythroascorbic acid, an important antioxidant and one of the virulence factors enhancing the pathogenicity (PubMed:11349062, PubMed:7957197). Is also able to oxidize L-galactono-1,4-lactone, L-xylono-1,4-lactone and L-gulono-1,4-lactone (PubMed:7957197). {ECO:0000269|PubMed:11349062, ECO:0000269|PubMed:7957197}.
|
Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast)
|
O93875
|
ERG3_CANAX
|
MDIVLEICDYYLFDKVYADVFPKDGAVHEFLKPAIQSFSQIDFPSLPNLDSFDTNSTLISSNNFNISNVNPATIPSYLFSKIASYQDKSEIYGLAPKFFPATDFINTSFLARSNIFRETLSLFIITTIFGWLLYFIVAYLSYVFVFDKKIFNHPRYLKNQMSLEIKRATTAIPVMVLLTIPFFLLELNGYSFLYLDINECTGGYKAILWQIPKFILFTDCGIYFLHRWLHWPSVYKVLHKPHHKWIVCTPFASHAFHPVDGFFQSLPYHLYPLLFPLHKVLYLFLFTFVNFWTVMIHDGSYWSNDPVVNGTACHTVHHLYFNYNYGQFTTLWDRLGNSYRRPDDSLFVKDVKAEEEKKIWKEQTRKMEEIRGEVEGKVDDREYVEQ
|
1.14.19.20
|
COFACTOR: Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000250|UniProtKB:P53045};
|
cholesterol biosynthetic process via lathosterol [GO:0033490]; ergosterol biosynthetic process [GO:0006696]; sphingolipid biosynthetic process [GO:0030148]
|
endoplasmic reticulum lumen [GO:0005788]; endoplasmic reticulum membrane [GO:0005789]
|
C-4 methylsterol oxidase activity [GO:0000254]; C-5 sterol desaturase activity [GO:0000248]; delta7-sterol 5(6)-desaturase activity [GO:0050046]; iron ion binding [GO:0005506]; sphingolipid delta-4 desaturase activity [GO:0042284]; sphingosine hydroxylase activity [GO:0000170]
|
PF04116;
| null |
Sterol desaturase family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000255}.
|
CATALYTIC ACTIVITY: Reaction=a Delta(7)-sterol + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = a Delta(5),Delta(7)-sterol + 2 Fe(III)-[cytochrome b5] + 2 H2O; Xref=Rhea:RHEA:54320, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:138130, ChEBI:CHEBI:138131; EC=1.14.19.20; Evidence={ECO:0000305|PubMed:10433965}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54321; Evidence={ECO:0000305|PubMed:10433965};
| null |
PATHWAY: Steroid metabolism; ergosterol biosynthesis; ergosterol from zymosterol: step 3/5.
| null | null |
FUNCTION: C-5 sterol desaturase; part of the third module of ergosterol biosynthesis pathway that includes the late steps of the pathwa (PubMed:10433965, PubMed:20733039, PubMed:9000517). ERG3 catalyzes the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol (PubMed:10433965). The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane. Firstly, the squalene synthase ERG9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to form squalene, which is the precursor of all steroids. Squalene synthase is crucial for balancing the incorporation of farnesyl diphosphate (FPP) into sterol and nonsterol isoprene synthesis. Secondly, the squalene epoxidase ERG1 catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, which is considered to be a rate-limiting enzyme in steroid biosynthesis. Then, the lanosterol synthase ERG7 catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol core. In the next steps, lanosterol is transformed to zymosterol through a complex process involving various demethylation, reduction and desaturation reactions. The lanosterol 14-alpha-demethylase ERG11 (also known as CYP51) catalyzes C14-demethylation of lanosterol to produce 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol, which is critical for ergosterol biosynthesis. The C-14 reductase ERG24 reduces the C14=C15 double bond of 4,4-dimethyl-cholesta-8,14,24-trienol to produce 4,4-dimethyl-cholesta-8,24-dienol. 4,4-dimethyl-cholesta-8,24-dienol is substrate of the C-4 demethylation complex ERG25-ERG26-ERG27 in which ERG25 catalyzes the three-step monooxygenation required for the demethylation of 4,4-dimethyl and 4alpha-methylsterols, ERG26 catalyzes the oxidative decarboxylation that results in a reduction of the 3-beta-hydroxy group at the C-3 carbon to an oxo group, and ERG27 is responsible for the reduction of the keto group on the C-3. ERG28 has a role as a scaffold to help anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum and ERG29 regulates the activity of the iron-containing C4-methylsterol oxidase ERG25. Then, the sterol 24-C-methyltransferase ERG6 catalyzes the methyl transfer from S-adenosyl-methionine to the C-24 of zymosterol to form fecosterol. The C-8 sterol isomerase ERG2 catalyzes the reaction which results in unsaturation at C-7 in the B ring of sterols and thus converts fecosterol to episterol. The sterol-C5-desaturase ERG3 then catalyzes the introduction of a C-5 double bond in the B ring to produce 5-dehydroepisterol. The C-22 sterol desaturase ERG5 further converts 5-dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-3beta-ol by forming the C-22(23) double bond in the sterol side chain. Finally, ergosta-5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-24(28) sterol reductase ERG4 to produce ergosterol (Probable). {ECO:0000269|PubMed:10433965, ECO:0000269|PubMed:20733039, ECO:0000269|PubMed:9000517, ECO:0000305}.
|
Candida albicans (Yeast)
|
O93922
|
ATG7_PICPA
|
MTSMDIPYSQISSFVNSSFFQKVSQLKLNKYRLDDTDKAIVGSVDFKFIGKNQPTSLSVDESSFNDNITYTHAQFPVKGILKNLNTVEDFRKVDKNEFLQSQGLVVHKSIQDRSCLKDLSKLTQFFILSFSDLKGFKFIYWFGFPSLVSRWKVNKLSGLTESQIEPYESKLNEWLNARLPIEQKQAFIIDNLEFKPFEQLSSFSPDDQLNIGFIDTSSILNKCSTQLRNILYMLAYYGFENIKVYNFRFNNTTSFTLDITLAEPLTSEPKTTGWERTAQGKLGPKLADIGALVDPARLADQSVDLNLKLMKWRVMPELDLDIIKNSKVLLLGAGTLGSYVSRVLLGYGVRHITFVDNGKVSFSNPVRQPLFNFTDCLEGGAPKAETAAKALKLIFPLITSQGYNLEVPMAGHPVTDEKRQYEDYQRLVTLIKEHDVVFLLMDSRETRWLPTVLCNVFDKICITAALGFDSYLVMRHGNLFNTEHIEAEENSHRLGCYFCNDIIAPKDSTTDRTLDQMCTVTRPGVALLASSLAAELFVSILQHPLKSHAPASLHDNATVLGCLPQQLRGFLHNFETSKLEANNYEYCSACSIQVLNEYKSRTWDFVKDALNENNYLEDLTGLTKVKQESEIAEKKFQEFENGLEFSDEDSEWIN
| null | null |
autophagosome assembly [GO:0000045]; cellular response to nitrogen starvation [GO:0006995]; micropexophagy [GO:0000426]; pexophagy [GO:0000425]; piecemeal microautophagy of the nucleus [GO:0034727]; protein modification by small protein conjugation [GO:0032446]; protein transport [GO:0015031]
|
phagophore assembly site [GO:0000407]
|
Atg12 activating enzyme activity [GO:0019778]; Atg8 activating enzyme activity [GO:0019779]
|
PF16420;PF00899;
|
3.40.50.720;3.40.140.100;3.40.140.70;
|
ATG7 family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Preautophagosomal structure {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 and ATG8 for its conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Autophagy is essential for maintenance of amino acid levels and protein synthesis under nitrogen starvation. Required for selective autophagic degradation of the nucleus (nucleophagy) as well as for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Plays a role in the regulation of filamentous growth and chronological longevity (By similarity). Involved in glucose-induced micropexophagy. {ECO:0000250, ECO:0000269|PubMed:10233149, ECO:0000269|PubMed:11856375}.
|
Komagataella pastoris (Yeast) (Pichia pastoris)
|
O93927
|
FKS1_CRYNH
|
MSYPNPPPPPKGSASFSSSSSDPFNQTNQLPYDSQFPPQHAFAHPSAPNPGAGGAGVAPPGQGGQYAPYYDNEPEMGGRWEGGGMGRETWASESGWSQNEPNYPPSDYHGGPGYLPSRASTPTFEGSNAGHRPRDPYPAWTVDANIPLSKEEIEDVLIDLANKFGFQKDSSRNVYDFLMIQLDSRASRMSPNQALLTLHADYIGGEHANYRKWYFAAQLDLDDAIGAVQNPGLNRVRSVARRGGKTKNPLATAQEKSLESATSRWRTAMNNMSQYDRLRQVALYLLCWGEAAQVRFMPECLCFIFKCADDYYRSPECQNRQEAVPEGLYLRAVIKPLYRFLRDQGYEVVDGKFLRRERDHDKVIGYDDVNQLFWYPEGISRITLNDNTRLVDIPPAQRFMKFDRIDWNKVFFKTYLEKRSFFHLLVNFNRIWVLHISVFWFFTAYNAPSIYAPSGSTTATTPMAWSMTGLGGFVATLIMIAATLAEFSYIPTTWNNTSHLTRRLIFLLIILAITGGPSIYIAFFNQTGHVALILGIVQFFCSVVATIAFATLPSGRMFGDRVAGKSRKYLANQTFTASYPALGFYPRVASFLLWFLVFGCKFTESYFFLTLSFRDPMKVMNGMKVQNCHDKYFGNGLCTNQPAFALAVMFVMDLTLFFLDTFLWYVIWNTVFSIARSFAIGMSIWTPWKDIFARLPKRIYAKILATDDMEVKYKPKVLVSQVWNAVIISMYREHLLSIEHVQKLLYHQIQSDQPGKRTLRAPAFFISQSEKGSKAEFFPKGSEAERRICFFAQSLTTSIPAPIPVDAMPTFTVLVPHYSEKILLSLREIIREEDQNTRVTLLEYLKQLHPVEWDNFVRDTKILAEESDAFNGGNPFASDEKEEAKKADDIPFYTIGFKSAAPEYTLRTRIWASLRAQTLYRTVSGFMNYSKAIKLLYRVENPEVVQLFGGNTDQLERELERMARRKFKFVVSMQRYSKFNKEEHENAEFLLRAYPDLQIAYLDEEPPRKDGGESRIFSALIDGHSEIMPNGRRRPKFRIELPGNPILGDGKSDNQNHAIVFYRGEYLQLIDANQDNYLEECLKIRNVLGEFEEFKVSTQSPYAAQGHADFAKFPVAILGAREYIFSENIGILGDIAAGKEQTFGTLAARSLSYIGGKLHYGHPDFLNAIYMNTRGGVSKAQKGLHLNEDIFAGMLAFGRGGRIKHSEYYQCGKGRDLGFGTILNFQTKIGTGMGEQMLSREYYYLGTQLPIDRFLTFYYGHPGFHINNILVMMSVQVFMLALVFLGTLNKQLTVCRYSSGGDILPGQSGCYNLVPVFKWIKRCIISIFIVFWIAFVPLFVQELTERGTGRAILRLCKHFLSLSPVFEVFSTQIYMHSILNDLTFGGARYIATGRGFATTRISFSILYSRFAGPSIYLGMRTLVLLLFITLTVWVPHLIYFWITVVGLCVAPFLFNPHQFAIADFIIDYREFLRWMSRGNSRTHANSWVGYCRLSRTRVTGFKRKRLGLPSEKLSSDVPRAPWKAILIGEIIGPICLAILFVICYLFIKSFAVDGQIQPGLVRIAIIALGPIVWNMALLITLFLISVFLGPCLNSYTHQFGATMAALAHFGAVAGMLVFFELLWFLELWNTSHAVLGIIAVISVQRCIFKFLIAVFLSREFKHDETNRAWWTGVWFNRGLGSHALSQPAREFVVKTIEMGLYSADFIACHLLLALLTIPMFIPYFDRVHATMLFWLAPNQQIRPPIYSFRQRSQRRKIVFKYGLLYLIIQGIFIALIVVPIIFKDVAGLTPKSVPFNGII
|
2.4.1.34
| null |
(1->3)-beta-D-glucan biosynthetic process [GO:0006075]; cell wall biogenesis [GO:0042546]; cell wall organization [GO:0071555]; fungal-type cell wall polysaccharide biosynthetic process [GO:0051278]
|
1,3-beta-D-glucan synthase complex [GO:0000148]; perinuclear endoplasmic reticulum [GO:0097038]; plasma membrane [GO:0005886]
|
1,3-beta-D-glucan synthase activity [GO:0003843]; alpha-1,3-glucan synthase activity [GO:0047657]
|
PF14288;PF02364;
| null |
Glycosyltransferase 48 family
| null |
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P38631}; Multi-pass membrane protein {ECO:0000255}.
|
CATALYTIC ACTIVITY: Reaction=[(1->3)-beta-D-glucosyl](n) + UDP-alpha-D-glucose = [(1->3)-beta-D-glucosyl](n+1) + H(+) + UDP; Xref=Rhea:RHEA:21476, Rhea:RHEA-COMP:11146, Rhea:RHEA-COMP:14303, ChEBI:CHEBI:15378, ChEBI:CHEBI:37671, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885; EC=2.4.1.34; Evidence={ECO:0000269|PubMed:15980360};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.21 mM for UDP-glucose (at pH 7.75) {ECO:0000269|PubMed:15980360};
| null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.75. {ECO:0000269|PubMed:15980360};
| null |
FUNCTION: Catalytic subunit of the 1,3-beta-glucan synthase (GS) complex (PubMed:15980360). Synthesizes 1,3-beta-glucan, a major structural component of the yeast cell wall (PubMed:15980360). Involved in cell wall synthesis, maintenance and remodeling (By similarity). {ECO:0000250|UniProtKB:P38631, ECO:0000269|PubMed:15980360}.
|
Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 / CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii)
|
O93937
|
PYR1_EMENI
|
MPETVGHEEPALPSSPQAGGAVAYNAISKELQPLPPTETANGGIIPPASSRIEGSTGRLCALELEDGTVYQGYNFGAEKSVAGELVFQTGMVGYPESITDPSYRGQILVITFPLVGNYGVPSRETMDELLKTLPKHFESTEIHIAALVVATYAGENYSHFLAESSLGQWLKEQGVPAIHGVDTRALTKRIRQKGSMLGRLLLHKADVAETDAALAQDTWKSSFEQIDWVDPNTKNLVSEVSIREPKLFSPPENVALKHPSSRPIRVLCLDVGLKFNQLRCLVARGVEVLVVPWDYDFPTLAGKDYDGLFVSNGPGDPATMTTTVNNLAKTMQEARTPIFGICLGHQLIARSVGAQTLKMKFGNRGHNIPCTSLVTGKCHITSQNHGYAVDSSTLPSDWQELFVNANDGSNEGIRHVSRPYFSVQFHPESTPGPRDTEYLFDVFINAIKDTIASPEALQKPVNFPGGAVAENIKASPRVSVKKVLILGSGGLSIGQAGEFDYSGSQAIKALKEEGIYTILINPNIATIQTSKGLADKVYFLPVNADFVRKVIKHERPDAIYVTFGGQTALQVGIQLKDEFESLGVKVLGTPIDTIITTEDRELFARSMDSIGEKCAKSASASSLEEALQVVESIGFPVIVRAAYALGGLGSGFADNLDELKDLCAKAFAASPQVLIERSMKGWKEIEYEVVRDARDNCITVCNMENFDPLGIHTGDSIVVAPSQTLSDEDYNMLRTTAVNVIRHLGVVGECNIQYALNPYSKEYCIIEVNARLSRSSALASKATGYPLAFIAAKLGLNIPLNEIKNSVTKVTCACFEPSLDYCVVKIPRWDLKKFTRVSTQLGSSMKSVGEVMAIGRTFEEAIQKAIRSVDFHNLGFNETNALMSIKTELQTPSDQRLFAIANAMAAGYSVDDIWKLTNIDKWFLTRLKGLSDFGKLMTNYNASTVTAPLLRQAKQLGFSDRQLAKFLSSNELAIRRLRVEAGIIPIVKQIDTVAAEFPSVTNYLYLTYNASEHDVRFDDNGIMVLGSGVYRIGSSVEFDWCSVRTIRTLREQGHKTVMVNYNPETVSTDYDEADRLYFENINLETVLDIYQLESSSGVIMSMGGQTPNNIALPLHRLNVRILGTSPEMIDGAENRYKFSRMLDRIGVDQPAWKELTSIEEAREFCDKVGYPVLVRPSYVLSGAAMNTVYSEHDLASYLNQAADVSREHPVVITKYIENAKEIEMDAVARNGVMVGHFISEHVENAGVHSGDATLILPPQDLDPETVRRIEEATRKIGNALNVTGPFNIQFIAKDNDIKVIECNVRASRSFPFVSKVMGVDLIEMATKAMIGAPFAEYPPVTIPKDYVGVKVPQFSFSRLAGADPVLGVEMASTGEVASFGRDKYEAYLKALLSTGFKLPKRNILLSIGSYKEKMEMLPSIIKLRDVGFELFATSGTADFLKENGVPVKYLEILPGEDEDIKSEYSLTQHLANNLIDLYINLPSSNRFRRPANYMSKGYRTRRMAVDYQTPLVTNVKNAKILIEAIARHYALNVQTIDYQTSHRSIILPGLINVGAFVPGLGSADSKDFEAVTKASIAAGFSMIRVMPVGVDSSITDARTLKLVQQNAGKASFCDYNFSVVATSSNSAEVGQLTGEVGSLFIPFNHLSGNISKVAAVTSHFGAWPSSKPIITDAKSTDLASVLLLASLHSRNIHVMSVTSKEDIGLIALSKEKGLKVTCDVSIYCLFLSRDDYPEAAFLPTAEDQKALWEHLSTIDIFSIGSIPYQLAGEKGSPAAGIAEALPLLFTAVSEGRLTVEDIIARLYENPKKIFELHDQSDSSVEVEIDRPYLFQSAQAWSPFSGKSVKGLVQRVIFQGKTSCLDSEITPDAPKGSDMSGHRIVPASPSLKAMSPRVDGALDRRQSISIAGTPARLGRKPVDHFPAATGAELGPPLYTPVPRASSPLLQMLSRSPFKQKHVLSVNQFNRADLHLLFTVAQEMRLGVQREGVLDILKGRLLCTLFYEPSTRTSASFDAAMQRLGGRTIAISTEHSSTKKGETLQDTLRTLGCYGDAVVLRHPEPSSTEVAAKFSPVPVINGGNGSVEHPTQAFLDLFTIREELGTVGGLTITFTGDLKYGRPVHSLIKLLQFYDVRVQLVAPKDLSLPADIRQQLLATGQLLTESEELTPEIVARSDVLYSTRVQKERFADLEQYERLKNSFIIDNALLKHAKSHMVVMHPLPRNAEVSEEVDFDQRAAYFRQVSLQSRGPSSEFDMLMWMQMRYGLYCRMALLALIMAP
|
2.1.3.2; 3.5.1.2; 6.3.4.16; 6.3.5.5
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|PROSITE-ProRule:PRU00409}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|PROSITE-ProRule:PRU00409}; Note=Binds 4 Mg(2+) or Mn(2+) ions per subunit. {ECO:0000255|PROSITE-ProRule:PRU00409};
|
'de novo' pyrimidine nucleobase biosynthetic process [GO:0006207]; 'de novo' UMP biosynthetic process [GO:0044205]; amino acid metabolic process [GO:0006520]; citrulline biosynthetic process [GO:0019240]; glutamine metabolic process [GO:0006541]; nitrogen compound metabolic process [GO:0006807]; UTP biosynthetic process [GO:0006228]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]
|
amino acid binding [GO:0016597]; aspartate carbamoyltransferase activity [GO:0004070]; ATP binding [GO:0005524]; carbamoyl-phosphate synthase (ammonia) activity [GO:0004087]; carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity [GO:0004088]; dihydroorotase activity [GO:0004151]; glutaminase activity [GO:0004359]; metal ion binding [GO:0046872]
|
PF02786;PF02787;PF00988;PF00117;PF02142;PF00185;PF02729;
|
3.40.50.20;3.40.50.880;3.40.50.1370;3.30.1490.20;3.30.470.20;3.50.30.20;1.10.1030.10;3.20.20.140;3.40.50.1380;
|
Metallo-dependent hydrolases superfamily, DHOase family, CAD subfamily; CarA family; CarB family; Metallo-dependent hydrolases superfamily, DHOase family, CAD subfamily; Aspartate/ornithine carbamoyltransferase superfamily, ATCase family
| null | null |
CATALYTIC ACTIVITY: Reaction=2 ATP + H2O + hydrogencarbonate + L-glutamine = 2 ADP + carbamoyl phosphate + 2 H(+) + L-glutamate + phosphate; Xref=Rhea:RHEA:18633, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58228, ChEBI:CHEBI:58359, ChEBI:CHEBI:456216; EC=6.3.5.5; Evidence={ECO:0000250|UniProtKB:P07259}; CATALYTIC ACTIVITY: Reaction=H2O + L-glutamine = L-glutamate + NH4(+); Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; EC=3.5.1.2; Evidence={ECO:0000250|UniProtKB:P07259}; CATALYTIC ACTIVITY: Reaction=2 ATP + hydrogencarbonate + NH4(+) = 2 ADP + carbamoyl phosphate + 2 H(+) + phosphate; Xref=Rhea:RHEA:18029, ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:28938, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58228, ChEBI:CHEBI:456216; EC=6.3.4.16; Evidence={ECO:0000250|UniProtKB:P07259}; CATALYTIC ACTIVITY: Reaction=carbamoyl phosphate + L-aspartate = H(+) + N-carbamoyl-L-aspartate + phosphate; Xref=Rhea:RHEA:20013, ChEBI:CHEBI:15378, ChEBI:CHEBI:29991, ChEBI:CHEBI:32814, ChEBI:CHEBI:43474, ChEBI:CHEBI:58228; EC=2.1.3.2; Evidence={ECO:0000250|UniProtKB:P07259};
| null |
PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3. {ECO:0000250|UniProtKB:P07259}.; PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 2/3. {ECO:0000250|UniProtKB:P07259}.
| null | null |
FUNCTION: Multifunctional protein that encodes the first 2 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5) and aspartate transcarbamylase (ATCase; EC 2.1.3.2). The CPSase-function is accomplished in 2 steps, by a glutamine-dependent amidotransferase activity (GATase) that binds and cleaves glutamine to produce ammonia, followed by an ammonium-dependent carbamoyl phosphate synthetase, which reacts with the ammonia, hydrogencarbonate and ATP to form carbamoyl phosphate. The endogenously produced carbamoyl phosphate is sequestered and channeled to the ATCase active site. ATCase then catalyzes the formation of carbamoyl-L-aspartate from L-aspartate and carbamoyl phosphate. {ECO:0000250|UniProtKB:P07259}.
|
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans)
|
O94168
|
SNF1_CANTR
|
MSEQNQGQPDQQHSGDHQHHHHHHHHHHHSQQPAQPIPIDPNVNPANRIGRYQIIKTLGEGSFGKVKLAQHVGTGQKVALKIINRKTLAKSDMQGRVEREISYLRLLRHPHIIKLYDVIKSKDEIIMVIEFAGKELFDYIVQRGKMPEDEARRFFQQIIAAVEYCHRHKIVHRDLKPENLLLDDQLNVKIADFGLSNIMTDGNFLKTSCGSPNYAAPEVISGKLYAGPEVDVWSSGVILYVMLCGRLPFDDEFIPALFKKISNGVYTLPNYLSPGAKHLLTRMLVVNPLNRITIHEIMEDEWFKQDMPDYLLPPDLSKIKTSKIDIDEDVISALSVTMGYDRDEIISVIEKANREAAAGGATPTNQSKSTNEVLDAYLLMKENHTLVKDLKKSKSENIESFLSLSPPPSSSFPNPGSTSSAPGVQQSLTYQTLATVPDLSTLPNSTIAILPTSLPSIHRAYMMETKVNDPQQQIPAPQPTKKLKTRWHFGIRSRSYPLDVMGEIYRALKNLGAEWAKPTEEELWTIRVRWKYDSTPQLRVWQRTNLMKMQIQLFQLEPNNYLVDFKFDGWEQTSDESKNDASLDYKQQDLDEVGSFSAYPFLHLATRLIMELAVNSQSG
|
2.7.11.1
| null |
CAMKK-AMPK signaling cascade [GO:0061762]; establishment of mitotic spindle orientation [GO:0000132]; fungal-type cell wall assembly [GO:0071940]; invasive growth in response to glucose limitation [GO:0001403]; negative regulation of TORC1 signaling [GO:1904262]; negative regulation of translation [GO:0017148]; phosphorylation [GO:0016310]; positive regulation of ascus development [GO:0075319]; positive regulation of filamentous growth of a population of unicellular organisms in response to starvation [GO:1900436]; positive regulation of gluconeogenesis [GO:0045722]; positive regulation of macroautophagy [GO:0016239]; positive regulation of pseudohyphal growth [GO:2000222]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of invasive growth in response to glucose limitation [GO:2000217]; response to endoplasmic reticulum stress [GO:0034976]; response to unfolded protein [GO:0006986]; single-species surface biofilm formation [GO:0090606]; SREBP signaling pathway [GO:0032933]
|
cellular bud neck septin ring [GO:0000144]; nuclear envelope lumen [GO:0005641]; nuclear membrane [GO:0031965]; nucleotide-activated protein kinase complex [GO:0031588]; vacuolar membrane [GO:0005774]
|
AMP-activated protein kinase activity [GO:0004679]; ATP binding [GO:0005524]; guanyl-nucleotide exchange factor activity [GO:0005085]; identical protein binding [GO:0042802]; protein serine kinase activity [GO:0106310]
|
PF16579;PF00069;PF08587;
|
3.30.310.80;1.10.510.10;
|
Protein kinase superfamily, CAMK Ser/Thr protein kinase family, SNF1 subfamily
| null |
SUBCELLULAR LOCATION: Nucleus membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
|
CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
| null | null | null | null |
FUNCTION: Essential for release from glucose repression. It interacts and has functional relationship to the regulatory protein SNF4. Could phosphorylate CAT8 (By similarity). {ECO:0000250}.
|
Candida tropicalis (Yeast)
|
O94200
|
PFKA2_CANAX
|
MISIVNGTSTLSLVAGSVETLNQAINFYTNILGLSVHSEQNDWTYLSNDDNKMIVKIQLDTKSGLSLDQVNDRRTEIIAKLNVTDWRSLDTTSVLKVQNLVALIETLTTFNYTLQITPNELYPNEVYCVGPIGYIIGFTACDEPLTLVPPLQKSHPKPGLVSNLMSKSGSQSRNIEETKAVRRNIAVMTSGGDSQGMNAAVRAVVRATIFHGSKAFAVQEGYAGLVKGGPEYIKEMKWQDVRGFLSEGGTNIGTARCMEFKERWGRLKGCKNLIDAGIDGLIVCGGDGSLTGADLFRHEWPSLIQELKDKGEITNEQFERHKHLYICGMVGSIDNDMAMTDATIGGYSALERICRAIDYIDATANSHSRAFVVEVMGRHCGWLALMAGIATSADYIFIPEKPASSKDWQDQMCDIVGKHRAQGKRKTIVIVAEGAITSDLKPITSDEVKDVLVDRLGLDTRITVLGHVQRGGTAVAFDRTLATLQGVEAVKAILELTPDVPSPLIAIDENKICRRPLVEAVRITKSVASAIEAKDFEKAMSLRDHEFKEHLANFMAMNTANHEKPTLPREKRKKIAIINIGAPAGGMNSAVYAMATYCMSRGHTPYAIHNGFAGLSRHESVKSIEWIDIEGWNSIGGSEIGTNRQTPEETDIGMIAHYFEKYQFDGLIIVGGFEAFVSLEQLERSRAMYPSFRIPMVLIPATISNNVPGTEYSLGADTCLNSLMEYCDIVKQSASATRGTAFIIDVQGGNSGYIATFASLISGAQASYVPEEGISLQQLEMDINSLREAFAVEQGMTKSGKLIIKSSNASKVLTPHTLADIFNDECHGDFDTKTAIPGHVQQGGLPSPIDRSRGDRFAIRAVQFIEDHCDVLAPYRYELDFPIDDKKILNTAAVLGIKSSRLRFTSIRHLFDFETELGRRMPKTIYWNTIRDISDQLVGRTRLDKP
|
2.7.1.11
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_03184};
|
canonical glycolysis [GO:0061621]; fructose 1,6-bisphosphate metabolic process [GO:0030388]; fructose 6-phosphate metabolic process [GO:0006002]; vacuolar acidification [GO:0007035]; vacuolar proton-transporting V-type ATPase complex assembly [GO:0070072]
|
6-phosphofructokinase complex [GO:0005945]; membrane [GO:0016020]; mitochondrion [GO:0005739]
|
6-phosphofructokinase activity [GO:0003872]; AMP binding [GO:0016208]; ATP binding [GO:0005524]; fructose-6-phosphate binding [GO:0070095]; identical protein binding [GO:0042802]; metal ion binding [GO:0046872]; monosaccharide binding [GO:0048029]; mRNA binding [GO:0003729]; proton-transporting ATPase activity, rotational mechanism [GO:0046961]
|
PF00365;
|
3.40.50.450;3.10.180.10;3.40.50.460;
|
Phosphofructokinase type A (PFKA) family, ATP-dependent PFK group I subfamily, Eukaryotic two domain clade 'E' sub-subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
|
CATALYTIC ACTIVITY: Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 1,6-bisphosphate + H(+); Xref=Rhea:RHEA:16109, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:32966, ChEBI:CHEBI:57634, ChEBI:CHEBI:456216; EC=2.7.1.11; Evidence={ECO:0000255|HAMAP-Rule:MF_03184};
| null |
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 3/4. {ECO:0000255|HAMAP-Rule:MF_03184}.
| null | null |
FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.
|
Candida albicans (Yeast)
|
O94201
|
PFKA1_CANAX
|
MPSSSDAINRISYISLVTSDNDKFNQTFQFYSQLGFRLTKSFSKVSSYGSGLGANHPEFQLGVSHDSLKEVWLESYPLQNVDSNGNLRPWQEMEVYDGDNCERLNESTVIKVRLLGETPLKSISQKQFVFFTTQLNKIEKILTDANVKYGKVVDNVILAEDPLNNIISFSNTQNELCKTRFQSPEEYVEKTTAEILAKRKKSQLGSKFGSFEEISPSEVGGGNGLRKKKIGVMTSGGDAPGMNPAVRAVVRAGIYYGCDVYAVYEGYEGLVKGGDLLKKMEWSDVRSYMSLGGTSIGTARCKEFRERAGRLQGAYNMIKNGIDALVVCGGDGSLTGADLFRSEWPSLVKELVDTGKLTKEEVSPYEHLTIVGLVGSIDNDMSGTDVTIGAFSALERITEMVDYIGATAASHSRAFVVEVMGRHCGWLALLSGLATGADFVFIPERPPKAGLWKEQLKEVCLRHREYGRRKTTVIVAEGAIDDELNPITSEEVKQVLADLGLDTRNTILGHVQRGGTAVAFDRRLATLQGVEAVKAVLEMTPDTPSPMIGILKHKIVRIPLVDAVKQTKAVAEAISNKDFDKAMSLRDNSFYDDYRYFRDISIYDDGSKQLSEDKRLNIAIVHVGAASAGLNAATRAVALYSLSRGHKLYAVQDGFAGLVKGDLKNLTWMDVEGWHSLGGSEIGTNRSLPSQNIGKVAYNLQKFNIQGLLIVGGFEAFTSLHELSEQKANYPIFEIPMVVVPATVSNNVPGTEYSLGADTCLNQLVSYCDAVQQSASSTRRRVFVVEVQGGHSGYVASYCGLITGALATYTPESNINLRELQGDIDLLQKVFATDRGEDHNGTLIVRNEQASAVYSTQLIADILKENANKRFETRTAIPGHVQQGFTPSANDRVMAVKFSLKAMEFIETRNGCYGKHDRKFSDEEISEHSQVVIGIHGDVVKFTCIKHLYDNEANVALRKGKTVHWTDMIDVANILNGKSLLKKQERY
|
2.7.1.11
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_03184};
|
canonical glycolysis [GO:0061621]; fructose 1,6-bisphosphate metabolic process [GO:0030388]; fructose 6-phosphate metabolic process [GO:0006002]; regulation of intracellular pH [GO:0051453]
|
6-phosphofructokinase complex [GO:0005945]; mitochondrion [GO:0005739]
|
6-phosphofructokinase activity [GO:0003872]; AMP binding [GO:0016208]; ATP binding [GO:0005524]; fructose-6-phosphate binding [GO:0070095]; identical protein binding [GO:0042802]; metal ion binding [GO:0046872]; monosaccharide binding [GO:0048029]; proton-transporting ATPase activity, rotational mechanism [GO:0046961]
|
PF00365;PF18468;
|
3.10.180.90;3.40.50.450;3.40.50.460;
|
Phosphofructokinase type A (PFKA) family, ATP-dependent PFK group I subfamily, Eukaryotic two domain clade 'E' sub-subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
|
CATALYTIC ACTIVITY: Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 1,6-bisphosphate + H(+); Xref=Rhea:RHEA:16109, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:32966, ChEBI:CHEBI:57634, ChEBI:CHEBI:456216; EC=2.7.1.11; Evidence={ECO:0000255|HAMAP-Rule:MF_03184};
| null |
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 3/4. {ECO:0000255|HAMAP-Rule:MF_03184}.
| null | null |
FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.
|
Candida albicans (Yeast)
|
O94220
|
INU2_ASPFI
|
MLNPKVAYMVWMTCLGLTLPSQAQSNDYRPSYHFTPDQYWMNEPNGLIKIGSTWHLFFQHNPTANVWGNICWGHATSTDLMHWAHKPTAIADENGVEAFTGTAYYDPNNTSGLGDSANPPYLAWFTGYTTSSQTQDQRLAFSVDNGATWTKFQGNPIISTSQEAPHDITGGLESRDPKVFFHRQSGNWIMVLAHGGQDKLSFWTSADTINWTWQSDLKSTSINGLSSDITGWEVPDMFELPVEGTEETTWVVMMTPAEGSPAGGNGVLAITGSFDGKSFTADPVDASTMWLDNGRDFDGALSWVNVPASDGRRIIAAVMNSYGSNPPTTTWKGMLSFPRTLSLKKVGTQQHFVQQPITELDTISTSLQILANQTITPGQTLLSSIRGTALDVRVAFYPDAGSVLSLAVRKGASEQTVIKYTQSDATLSVDRTESGDISYDPAAGGVHTAKLEEDGTGLVSIRVLVDTCSVEVFGGQGEAVISDLIFPSDSSDGLALEVTGGNAVLQSVDVRSVSLE
|
3.2.1.7
| null |
polysaccharide catabolic process [GO:0000272]; sucrose catabolic process [GO:0005987]
|
cytoplasm [GO:0005737]; extracellular region [GO:0005576]
|
inulinase activity [GO:0051670]; sucrose alpha-glucosidase activity [GO:0004575]
|
PF08244;PF00251;
| null |
Glycosyl hydrolase 32 family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24251113}.
|
CATALYTIC ACTIVITY: Reaction=Endohydrolysis of (2->1)-beta-D-fructosidic linkages in inulin.; EC=3.2.1.7; Evidence={ECO:0000269|PubMed:22750808, ECO:0000269|PubMed:24251113};
| null | null | null | null |
FUNCTION: Endo-inulinase involved in utilization of the plant storage polymer inulin, consisting of fructooligosaccharides with a degree of polymerization (DP) value from 2 to 60. {ECO:0000269|PubMed:24251113}.
|
Aspergillus ficuum
|
O94235
|
MPH1L_SCHPO
|
MSKRNPPVTNIADLVSDSSLDEDSLSFLEELQDPELYFKNDTFSSKSSHSDGTVTGDTLRRQSSGATALERLVSHPRTKNFDLQGNGGQNSALKEVNTPAYQSMHHFEHLITPLPSTNASHSEVSLSAGVNDLNSNSEHDLLPKSVNKTPGSLSISRRRRIGRIGLGPPKRAEYTLTDPSKTSDTKNSTEADEDIEMKSREVSPASNSVAATTLKPLQLHNTPLQTSQEHPKPSFHPSQFESSFSPRVQFDHDVERRASELHSRPVTVFQEPQRSASQPYESHALSPKVAPLFDNSQATPIPKRQQDVVTVANLQFIKLGVVGKGGSSMVYRIFSPDNSRLYALKEVNFINADQTTIQGYKNEIALLRKLSGNDRIIKLYAAEVNDTLGQLNMVMECGETDLANLLMKNMKKPINLNFIRMYWEQMLEAVQVVHDQNIVHSDLKPANFLLVEGNLKLIDFGIAKAIGNDTTNIHRDSHIGTINYMAPEALTDMNAHTNSGVKLVKLGRPSDVWSLGCILYQMVYGRAPFAHLKMIQAIAAIPNEQYHIHFPEVALPANAVQEKEGSLPGVTVGPDLMDVMKRCLERDQRKRLTIPELLVHPFLNPLPSYLTPLAKKPLPVSGHTNNAHPLRLSTEISASQLSMIIERSVELSKHKRLNKELIDSMAYDCVSNLRKMPE
|
2.7.12.1
| null |
cell division [GO:0051301]; chromosome segregation [GO:0007059]; meiosis I [GO:0007127]; meiotic centromeric cohesion protection in anaphase I [GO:1990813]; meiotic spindle assembly checkpoint signaling [GO:0033316]; mitotic spindle assembly checkpoint signaling [GO:0007094]; phosphorylation [GO:0016310]; protein localization to kinetochore [GO:0034501]
|
cytosol [GO:0005829]; kinetochore [GO:0000776]; nucleus [GO:0005634]
|
ATP binding [GO:0005524]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]; protein serine/threonine/tyrosine kinase activity [GO:0004712]; protein tyrosine kinase activity [GO:0004713]
|
PF00069;
|
1.10.510.10;
|
Protein kinase superfamily, Ser/Thr protein kinase family
| null | null |
CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.1; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.12.1; CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;
| null | null | null | null |
FUNCTION: Involved in the regulation of the onset of mitosis. Involved in a pathway that coordinates cell proliferation and differentiation. {ECO:0000269|PubMed:9601094}.
|
Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
|
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