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
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
P05020
|
PYRC_ECOLI
|
MTAPSQVLKIRRPDDWHLHLRDGDMLKTVVPYTSEIYGRAIVMPNLAPPVTTVEAAVAYRQRILDAVPAGHDFTPLMTCYLTDSLDPNELERGFNEGVFTAAKLYPANATTNSSHGVTSIDAIMPVLERMEKIGMPLLVHGEVTHADIDIFDREARFIESVMEPLRQRLTALKVVFEHITTKDAADYVRDGNERLAATITPQHLMFNRNHMLVGGVRPHLYCLPILKRNIHQQALRELVASGFNRVFLGTDSAPHARHRKESSCGCAGCFNAPTALGSYATVFEEMNALQHFEAFCSVNGPQFYGLPVNDTFIELVREEQQVAESIALTDDTLVPFLAGETVRWSVKQ
|
3.5.2.3
|
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000255|HAMAP-Rule:MF_00219, ECO:0000269|PubMed:11401542, ECO:0000269|PubMed:15610022, ECO:0000269|PubMed:15826651, ECO:0000269|PubMed:1671037, ECO:0000269|PubMed:6142052}; Note=Binds 2 Zn(2+) ions per subunit (PubMed:11401542, PubMed:15826651, PubMed:6142052). In vitro, can also use Co(2+) or Cd(2+) (PubMed:15610022, PubMed:1671037). {ECO:0000269|PubMed:11401542, ECO:0000269|PubMed:15610022, ECO:0000269|PubMed:15826651, ECO:0000269|PubMed:1671037, ECO:0000269|PubMed:6142052};
|
'de novo' pyrimidine nucleobase biosynthetic process [GO:0006207]; 'de novo' UMP biosynthetic process [GO:0044205]; pyrimidine nucleotide biosynthetic process [GO:0006221]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]
|
dihydroorotase activity [GO:0004151]; protein homodimerization activity [GO:0042803]; zinc ion binding [GO:0008270]
|
PF01979;
|
3.20.20.140;
|
Metallo-dependent hydrolases superfamily, DHOase family, Class II DHOase subfamily
| null | null |
CATALYTIC ACTIVITY: Reaction=(S)-dihydroorotate + H2O = H(+) + N-carbamoyl-L-aspartate; Xref=Rhea:RHEA:24296, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30864, ChEBI:CHEBI:32814; EC=3.5.2.3; Evidence={ECO:0000255|HAMAP-Rule:MF_00219, ECO:0000269|PubMed:15610022, ECO:0000269|PubMed:6142052};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.0756 mM for dihydroorotate {ECO:0000269|PubMed:6142052}; KM=0.08 mM for dihydroorotate (in the presence of Zn(2+)) {ECO:0000269|PubMed:15610022}; KM=0.7 mM for dihydroorotate (in the presence of Co(2+)) {ECO:0000269|PubMed:15610022}; KM=0.23 mM for dihydroorotate (in the presence of Cd(2+)) {ECO:0000269|PubMed:15610022}; KM=1.07 mM for N-carbamoyl-DL-aspartate {ECO:0000269|PubMed:6142052}; KM=1.7 mM for carbamoyl aspartate (in the presence of Zn(2+)) {ECO:0000269|PubMed:15610022}; KM=15 mM for carbamoyl aspartate (in the presence of Co(2+)) {ECO:0000269|PubMed:15610022}; KM=4 mM for carbamoyl aspartate (in the presence of Cd(2+)) {ECO:0000269|PubMed:15610022}; Note=kcat is 127 sec(-1) with dihydroorotate as substrate and 195 sec(-1) with N-carbamoyl-DL-aspartate as substrate (PubMed:6142052). kcat is 100 sec(-1) with dihydroorotate as substrate and 160 sec(-1) with carbamoyl aspartate as substrate in the presence of Zn(2+). kcat is 15 sec(-1) with dihydroorotate as substrate and 25 sec(-1) with carbamoyl aspartate as substrate in the presence of Co(2+). kcat is 1.9 sec(-1) with dihydroorotate as substrate and 8.2 sec(-1) with carbamoyl aspartate as substrate in the presence of Cd(2+) (PubMed:15610022). {ECO:0000269|PubMed:15610022, ECO:0000269|PubMed:6142052};
|
PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 3/3. {ECO:0000255|HAMAP-Rule:MF_00219, ECO:0000305}.
| null | null |
FUNCTION: Catalyzes the reversible cyclization of carbamoyl aspartate to dihydroorotate. {ECO:0000255|HAMAP-Rule:MF_00219, ECO:0000269|PubMed:15610022, ECO:0000269|PubMed:6142052}.
|
Escherichia coli (strain K12)
|
P05023
|
AT1A1_HUMAN
|
MGKGVGRDKYEPAAVSEQGDKKGKKGKKDRDMDELKKEVSMDDHKLSLDELHRKYGTDLSRGLTSARAAEILARDGPNALTPPPTTPEWIKFCRQLFGGFSMLLWIGAILCFLAYSIQAATEEEPQNDNLYLGVVLSAVVIITGCFSYYQEAKSSKIMESFKNMVPQQALVIRNGEKMSINAEEVVVGDLVEVKGGDRIPADLRIISANGCKVDNSSLTGESEPQTRSPDFTNENPLETRNIAFFSTNCVEGTARGIVVYTGDRTVMGRIATLASGLEGGQTPIAAEIEHFIHIITGVAVFLGVSFFILSLILEYTWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKNLEAVETLGSTSTICSDKTGTLTQNRMTVAHMWFDNQIHEADTTENQSGVSFDKTSATWLALSRIAGLCNRAVFQANQENLPILKRAVAGDASESALLKCIELCCGSVKEMRERYAKIVEIPFNSTNKYQLSIHKNPNTSEPQHLLVMKGAPERILDRCSSILLHGKEQPLDEELKDAFQNAYLELGGLGERVLGFCHLFLPDEQFPEGFQFDTDDVNFPIDNLCFVGLISMIDPPRAAVPDAVGKCRSAGIKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPVSQVNPRDAKACVVHGSDLKDMTSEQLDDILKYHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVNDSPALKKADIGVAMGIAGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSNIPEITPFLIFIIANIPLPLGTVTILCIDLGTDMVPAISLAYEQAESDIMKRQPRNPKTDKLVNERLISMAYGQIGMIQALGGFFTYFVILAENGFLPIHLLGLRVDWDDRWINDVEDSYGQQWTYEQRKIVEFTCHTAFFVSIVVVQWADLVICKTRRNSVFQQGMKNKILIFGLFEETALAAFLSYCPGMGVALRMYPLKPTWWFCAFPYSLLIFVYDEVRKLIIRRRPGGWVEKETYY
|
7.2.2.13
| null |
cardiac muscle cell action potential involved in contraction [GO:0086002]; cell communication by electrical coupling involved in cardiac conduction [GO:0086064]; cellular response to steroid hormone stimulus [GO:0071383]; establishment or maintenance of transmembrane electrochemical gradient [GO:0010248]; intracellular potassium ion homeostasis [GO:0030007]; intracellular sodium ion homeostasis [GO:0006883]; membrane repolarization [GO:0086009]; membrane repolarization during cardiac muscle cell action potential [GO:0086013]; negative regulation of glucocorticoid biosynthetic process [GO:0031947]; negative regulation of heart contraction [GO:0045822]; osmosensory signaling pathway [GO:0007231]; positive regulation of heart contraction [GO:0045823]; positive regulation of striated muscle contraction [GO:0045989]; potassium ion import across plasma membrane [GO:1990573]; proton transmembrane transport [GO:1902600]; regulation of blood pressure [GO:0008217]; regulation of sodium ion transport [GO:0002028]; regulation of the force of heart contraction [GO:0002026]; relaxation of cardiac muscle [GO:0055119]; response to glycoside [GO:1903416]; response to xenobiotic stimulus [GO:0009410]; sodium ion export across plasma membrane [GO:0036376]
|
apical plasma membrane [GO:0016324]; axon [GO:0030424]; basolateral plasma membrane [GO:0016323]; endoplasmic reticulum [GO:0005783]; extracellular exosome [GO:0070062]; extracellular vesicle [GO:1903561]; Golgi apparatus [GO:0005794]; lateral plasma membrane [GO:0016328]; melanosome [GO:0042470]; membrane [GO:0016020]; membrane raft [GO:0045121]; organelle membrane [GO:0031090]; photoreceptor inner segment membrane [GO:0060342]; plasma membrane [GO:0005886]; postsynaptic density [GO:0014069]; protein-containing complex [GO:0032991]; sarcolemma [GO:0042383]; sodium:potassium-exchanging ATPase complex [GO:0005890]; sperm flagellum [GO:0036126]; T-tubule [GO:0030315]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; P-type sodium:potassium-exchanging transporter activity [GO:0005391]; phosphatase activity [GO:0016791]; potassium ion binding [GO:0030955]; protein heterodimerization activity [GO:0046982]; protein-folding chaperone binding [GO:0051087]; sodium ion binding [GO:0031402]; steroid hormone binding [GO:1990239]; transmembrane transporter binding [GO:0044325]
|
PF13246;PF00689;PF00690;PF00122;
|
3.40.1110.10;2.70.150.10;1.20.1110.10;3.40.50.1000;
|
Cation transport ATPase (P-type) (TC 3.A.3) family, Type IIC subfamily
|
PTM: Phosphorylation on Tyr-10 modulates pumping activity. Phosphorylation of Ser-943 by PKA modulates the response of ATP1A1 to PKC. Dephosphorylation by protein phosphatase 2A (PP2A) following increases in intracellular sodium, leading to increase catalytic activity (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8VDN2}; Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane {ECO:0000250|UniProtKB:P06685}; Multi-pass membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000269|PubMed:7711835}; Multi-pass membrane protein {ECO:0000255}. Cell projection, axon {ECO:0000250|UniProtKB:P06685}. Melanosome {ECO:0000269|PubMed:17081065}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. {ECO:0000269|PubMed:17081065}.
|
CATALYTIC ACTIVITY: Reaction=ATP + H2O + K(+)(out) + Na(+)(in) = ADP + H(+) + K(+)(in) + Na(+)(out) + phosphate; Xref=Rhea:RHEA:18353, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=7.2.2.13;
| null | null | null | null |
FUNCTION: This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity). {ECO:0000250|UniProtKB:Q8VDN2, ECO:0000269|PubMed:29499166, ECO:0000269|PubMed:30388404}.
|
Homo sapiens (Human)
|
P05024
|
AT1A1_PIG
|
MGKGVGRDKYEPAAVSEHGDKKKAKKERDMDELKKEVSMDDHKLSLDELHRKYGTDLSRGLTPARAAEILARDGPNALTPPPTTPEWVKFCRQLFGGFSMLLWIGAILCFLAYGIQAATEEEPQNDNLYLGVVLSAVVIITGCFSYYQEAKSSKIMESFKNMVPQQALVIRNGEKMSINAEEVVVGDLVEVKGGDRIPADLRIISANGCKVDNSSLTGESEPQTRSPDFTNENPLETRNIAFFSTNCVEGTARGIVVYTGDRTVMGRIATLASGLEGGQTPIAAEIEHFIHIITGVAVFLGVSFFILSLILEYTWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKNLEAVETLGSTSTICSDKTGTLTQNRMTVAHMWSDNQIHEADTTENQSGVSFDKTSATWLALSRIAGLCNRAVFQANQENLPILKRAVAGDASESALLKCIELCCGSVKEMRERYTKIVEIPFNSTNKYQLSIHKNPNTAEPRHLLVMKGAPERILDRCSSILIHGKEQPLDEELKDAFQNAYLELGGLGERVLGFCHLFLPDEQFPEGFQFDTDDVNFPLDNLCFVGLISMIDPPRAAVPDAVGKCRSAGIKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPVSQVNPRDAKACVVHGSDLKDMTSEQLDDILKYHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVNDSPASKKADIGVAMGIAGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSNIPEITPFLIFIIANIPLPLGTVTILCIDLGTDMVPAISLAYEQAESDIMKRQPRNPKTDKLVNEQLISMAYGQIGMIQALGGFFTYFVILAENGFLPIHLLGLRVNWDDRWINDVEDSYGQQWTYEQRKIVEFTCHTPFFVTIVVVQWADLVICKTRRNSVFQQGMKNKILIFGLFEETALAAFLSYCPGMGVALRMYPLKPTWWFCAFPYSLLIFVYDEVRKLIIRRRPGGWVEKETYY
|
7.2.2.13
| null |
establishment or maintenance of transmembrane electrochemical gradient [GO:0010248]; intracellular potassium ion homeostasis [GO:0030007]; intracellular sodium ion homeostasis [GO:0006883]; membrane repolarization [GO:0086009]; potassium ion import across plasma membrane [GO:1990573]; proton transmembrane transport [GO:1902600]; regulation of sodium ion transport [GO:0002028]; sodium ion export across plasma membrane [GO:0036376]; transmembrane transport [GO:0055085]
|
axon [GO:0030424]; basolateral plasma membrane [GO:0016323]; melanosome [GO:0042470]; membrane [GO:0016020]; plasma membrane [GO:0005886]; sarcolemma [GO:0042383]; sodium:potassium-exchanging ATPase complex [GO:0005890]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; ATPase binding [GO:0051117]; P-type sodium:potassium-exchanging transporter activity [GO:0005391]; potassium ion binding [GO:0030955]; sodium ion binding [GO:0031402]
|
PF13246;PF00689;PF00690;PF00122;PF00702;
|
3.40.1110.10;2.70.150.10;1.20.1110.10;3.40.50.1000;
|
Cation transport ATPase (P-type) (TC 3.A.3) family, Type IIC subfamily
|
PTM: Phosphorylation on Tyr-10 modulates pumping activity. Phosphorylation of Ser-941 by PKA modulates the response of ATP1A1 to PKC. Dephosphorylation by protein phosphatase 2A (PP2A) following increases in intracellular sodium, leading to increase catalytic activity (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8VDN2}; Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane {ECO:0000250|UniProtKB:P06685}; Multi-pass membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P05023}; Multi-pass membrane protein {ECO:0000255}. Cell projection, axon {ECO:0000250|UniProtKB:P06685}. Melanosome {ECO:0000250|UniProtKB:P05023}.
|
CATALYTIC ACTIVITY: Reaction=ATP + H2O + K(+)(out) + Na(+)(in) = ADP + H(+) + K(+)(in) + Na(+)(out) + phosphate; Xref=Rhea:RHEA:18353, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=7.2.2.13; Evidence={ECO:0000269|PubMed:18075585};
| null | null | null | null |
FUNCTION: This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (By similarity). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity). {ECO:0000250|UniProtKB:P05023, ECO:0000250|UniProtKB:Q8VDN2}.
|
Sus scrofa (Pig)
|
P05026
|
AT1B1_HUMAN
|
MARGKAKEEGSWKKFIWNSEKKEFLGRTGGSWFKILLFYVIFYGCLAGIFIGTIQVMLLTISEFKPTYQDRVAPPGLTQIPQIQKTEISFRPNDPKSYEAYVLNIVRFLEKYKDSAQRDDMIFEDCGDVPSEPKERGDFNHERGERKVCRFKLEWLGNCSGLNDETYGYKEGKPCIIIKLNRVLGFKPKPPKNESLETYPVMKYNPNVLPVQCTGKRDEDKDKVGNVEYFGLGNSPGFPLQYYPYYGKLLQPKYLQPLLAVQFTNLTMDTEIRIECKAYGENIGYSEKDRFQGRFDVKIEVKS
| null | null |
ATP metabolic process [GO:0046034]; cardiac muscle contraction [GO:0060048]; cell adhesion [GO:0007155]; cell communication by electrical coupling involved in cardiac conduction [GO:0086064]; establishment or maintenance of transmembrane electrochemical gradient [GO:0010248]; innate immune response [GO:0045087]; intracellular calcium ion homeostasis [GO:0006874]; intracellular potassium ion homeostasis [GO:0030007]; intracellular sodium ion homeostasis [GO:0006883]; membrane repolarization [GO:0086009]; membrane repolarization during cardiac muscle cell action potential [GO:0086013]; monoatomic cation transmembrane transport [GO:0098655]; positive regulation of ATP-dependent activity [GO:0032781]; positive regulation of calcium:sodium antiporter activity [GO:1903281]; positive regulation of P-type sodium:potassium-exchanging transporter activity [GO:1903408]; positive regulation of potassium ion import across plasma membrane [GO:1903288]; positive regulation of potassium ion transmembrane transporter activity [GO:1901018]; positive regulation of sodium ion export across plasma membrane [GO:1903278]; potassium ion import across plasma membrane [GO:1990573]; protein localization to plasma membrane [GO:0072659]; protein stabilization [GO:0050821]; protein transport into plasma membrane raft [GO:0044861]; proton transmembrane transport [GO:1902600]; regulation of cardiac muscle contraction by calcium ion signaling [GO:0010882]; regulation of gene expression [GO:0010468]; relaxation of cardiac muscle [GO:0055119]; sodium ion export across plasma membrane [GO:0036376]; sodium ion transmembrane transport [GO:0035725]
|
apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; extracellular exosome [GO:0070062]; extracellular vesicle [GO:1903561]; intercalated disc [GO:0014704]; lateral plasma membrane [GO:0016328]; membrane [GO:0016020]; organelle membrane [GO:0031090]; plasma membrane [GO:0005886]; sarcolemma [GO:0042383]; sodium:potassium-exchanging ATPase complex [GO:0005890]; sperm flagellum [GO:0036126]; T-tubule [GO:0030315]
|
ATPase activator activity [GO:0001671]; ATPase binding [GO:0051117]; MHC class II protein complex binding [GO:0023026]; P-type sodium:potassium-exchanging transporter activity [GO:0005391]; protein heterodimerization activity [GO:0046982]; protein kinase binding [GO:0019901]; protein-macromolecule adaptor activity [GO:0030674]
|
PF00287;
|
1.20.5.170;2.60.40.1660;
|
X(+)/potassium ATPases subunit beta family
|
PTM: Glutathionylated (By similarity). N-glycosylated (By similarity). {ECO:0000250|UniProtKB:P07340, ECO:0000250|UniProtKB:P14094}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:34011520}; Single-pass type II membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000250|UniProtKB:P07340}; Single-pass type II membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P14094}. Note=Colocalizes with OBSCN at the intercalated disk and sarcolemma in cardiomyocytes. Localizes in long striations at the level of Z and M lines. {ECO:0000250|UniProtKB:P14094}.
| null | null | null | null | null |
FUNCTION: This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane (PubMed:19694409). Plays a role in innate immunity by enhancing virus-triggered induction of interferons (IFNs) and interferon stimulated genes (ISGs). Mechanistically, enhances the ubiquitination of TRAF3 and TRAF6 as well as the phosphorylation of TAK1 and TBK1 (PubMed:34011520). {ECO:0000269|PubMed:19694409, ECO:0000269|PubMed:34011520}.; FUNCTION: Involved in cell adhesion and establishing epithelial cell polarity. {ECO:0000269|PubMed:19694409}.
|
Homo sapiens (Human)
|
P05027
|
AT1B1_PIG
|
MARGKAKEEGSWKKFIWNSEKKEFLGRTGGSWFKILLFYVIFYGCLAGIFIGTIQVMLLTISEFKPTYQDRVAPPGLTQIPQSQKTEISFRPNDPQSYESYVVSIVRFLEKYKDLAQKDDMIFEDCGNVPSELKERGEYNNERGERKVCRFRLEWLGNCSGLNDETYGYKDGKPCVIIKLNRVLGFKPKPPKNESLETYPVMKYNPYVLPVHCTGKRDEDKEKVGTMEYFGLGGYPGFPLQYYPYYGKLLQPKYLQPLMAVQFTNLTMDTEIRIECKAYGENIGYSEKDRFQGRFDVKIEVKS
| null | null |
cell adhesion [GO:0007155]; establishment or maintenance of transmembrane electrochemical gradient [GO:0010248]; innate immune response [GO:0045087]; intracellular potassium ion homeostasis [GO:0030007]; intracellular sodium ion homeostasis [GO:0006883]; membrane repolarization [GO:0086009]; positive regulation of P-type sodium:potassium-exchanging transporter activity [GO:1903408]; positive regulation of potassium ion import across plasma membrane [GO:1903288]; positive regulation of sodium ion export across plasma membrane [GO:1903278]; potassium ion import across plasma membrane [GO:1990573]; proton transmembrane transport [GO:1902600]; sodium ion export across plasma membrane [GO:0036376]; transmembrane transport [GO:0055085]
|
apical plasma membrane [GO:0016324]; sarcolemma [GO:0042383]; sodium:potassium-exchanging ATPase complex [GO:0005890]
|
ATPase activator activity [GO:0001671]; ATPase binding [GO:0051117]; P-type sodium:potassium-exchanging transporter activity [GO:0005391]; protein-macromolecule adaptor activity [GO:0030674]
|
PF00287;
|
2.60.40.1660;
|
X(+)/potassium ATPases subunit beta family
|
PTM: Glutathionylated (By similarity). N-glycosylated (By similarity). {ECO:0000250|UniProtKB:P07340, ECO:0000250|UniProtKB:P14094}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Single-pass type II membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000250|UniProtKB:P07340}; Single-pass type II membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P14094}. Note=Colocalizes with OBSCN at the intercalated disk and sarcolemma in cardiomyocytes. Localizes in long striations at the level of Z and M lines. {ECO:0000250|UniProtKB:P14094}.
| null | null | null | null | null |
FUNCTION: This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. Plays a role in innate immunity by enhancing virus-triggered induction of interferons (IFNs) and interferon stimulated genes (ISGs). Mechanistically, enhances the ubiquitination of TRAF3 and TRAF6 as well as the phosphorylation of TAK1 and TBK1. {ECO:0000250|UniProtKB:P05026}.; FUNCTION: Involved in cell adhesion and establishing epithelial cell polarity. {ECO:0000250|UniProtKB:P05026}.
|
Sus scrofa (Pig)
|
P05028
|
AT1B1_SHEEP
|
MARGKAKEEGSWKKFIWNSEKKEFLGRTGGSWFKILLFYVIFYGCLAGIFIGTIQVMLLTISEFKPTYQDRVAPPGLTQIPQIQKTEIAFRPNDPKSYMTYVDNIDNFLKKYRDSAQKDDMIFEDCGNVPSELKDRGEFNNEQGERKVCRFKLEWLGNCSGINDETYGYKEGKPCVIIKLNRVLGFKPKPPKNESLETYPVMKYNPYVLPVQCTGKRDEDKEKVGSIEYFGLGGYPGFPLQYYPYYGKLLQPKYLQPLLAVQFTNLTMDTEIRIECKAYGENIGYSEKDRFQGRFDVKIEVKS
| null | null |
ATP metabolic process [GO:0046034]; cardiac muscle contraction [GO:0060048]; cell adhesion [GO:0007155]; innate immune response [GO:0045087]; intracellular calcium ion homeostasis [GO:0006874]; intracellular potassium ion homeostasis [GO:0030007]; intracellular sodium ion homeostasis [GO:0006883]; membrane repolarization [GO:0086009]; positive regulation of potassium ion import across plasma membrane [GO:1903288]; positive regulation of sodium ion export across plasma membrane [GO:1903278]; potassium ion import across plasma membrane [GO:1990573]; protein localization to plasma membrane [GO:0072659]; protein stabilization [GO:0050821]; regulation of calcium ion transmembrane transport [GO:1903169]; regulation of cardiac muscle contraction by calcium ion signaling [GO:0010882]; regulation of gene expression [GO:0010468]; relaxation of cardiac muscle [GO:0055119]; sodium ion export across plasma membrane [GO:0036376]
|
apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; intercalated disc [GO:0014704]; lateral plasma membrane [GO:0016328]; organelle membrane [GO:0031090]; sodium:potassium-exchanging ATPase complex [GO:0005890]; sperm flagellum [GO:0036126]; T-tubule [GO:0030315]
|
ATPase activator activity [GO:0001671]; ATPase binding [GO:0051117]; P-type sodium:potassium-exchanging transporter activity [GO:0005391]; protein kinase binding [GO:0019901]; protein-macromolecule adaptor activity [GO:0030674]
|
PF00287;
|
1.20.5.170;2.60.40.1660;
|
X(+)/potassium ATPases subunit beta family
|
PTM: Glutathionylated (By similarity). N-glycosylated (By similarity). {ECO:0000250|UniProtKB:P07340, ECO:0000250|UniProtKB:P14094}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Single-pass type II membrane protein {ECO:0000255}. Apical cell membrane {ECO:0000250|UniProtKB:P07340}; Single-pass type II membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P14094}. Note=Colocalizes with OBSCN at the intercalated disk and sarcolemma in cardiomyocytes. Localizes in long striations at the level of Z and M lines. {ECO:0000250|UniProtKB:P14094}.
| null | null | null | null | null |
FUNCTION: This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. Plays a role in innate immunity by enhancing virus-triggered induction of interferons (IFNs) and interferon stimulated genes (ISGs). Mechanistically, enhances the ubiquitination of TRAF3 and TRAF6 as well as the phosphorylation of TAK1 and TBK1. {ECO:0000250|UniProtKB:P05026}.; FUNCTION: Involved in cell adhesion and establishing epithelial cell polarity. {ECO:0000250|UniProtKB:P05026}.
|
Ovis aries (Sheep)
|
P05030
|
PMA1_YEAST
|
MTDTSSSSSSSSASSVSAHQPTQEKPAKTYDDAASESSDDDDIDALIEELQSNHGVDDEDSDNDGPVAAGEARPVPEEYLQTDPSYGLTSDEVLKRRKKYGLNQMADEKESLVVKFVMFFVGPIQFVMEAAAILAAGLSDWVDFGVICGLLMLNAGVGFVQEFQAGSIVDELKKTLANTAVVIRDGQLVEIPANEVVPGDILQLEDGTVIPTDGRIVTEDCFLQIDQSAITGESLAVDKHYGDQTFSSSTVKRGEGFMVVTATGDNTFVGRAAALVNKAAGGQGHFTEVLNGIGIILLVLVIATLLLVWTACFYRTNGIVRILRYTLGITIIGVPVGLPAVVTTTMAVGAAYLAKKQAIVQKLSAIESLAGVEILCSDKTGTLTKNKLSLHEPYTVEGVSPDDLMLTACLAASRKKKGLDAIDKAFLKSLKQYPKAKDALTKYKVLEFHPFDPVSKKVTAVVESPEGERIVCVKGAPLFVLKTVEEDHPIPEDVHENYENKVAELASRGFRALGVARKRGEGHWEILGVMPCMDPPRDDTAQTVSEARHLGLRVKMLTGDAVGIAKETCRQLGLGTNIYNAERLGLGGGGDMPGSELADFVENADGFAEVFPQHKYRVVEILQNRGYLVAMTGDGVNDAPSLKKADTGIAVEGATDAARSAADIVFLAPGLSAIIDALKTSRQIFHRMYSYVVYRIALSLHLEIFLGLWIAILDNSLDIDLIVFIAIFADVATLAIAYDNAPYSPKPVKWNLPRLWGMSIILGIVLAIGSWITLTTMFLPKGGIIQNFGAMNGIMFLQISLTENWLIFITRAAGPFWSSIPSWQLAGAVFAVDIIATMFTLFGWWSENWTDIVTVVRVWIWSIGIFCVLGGFYYEMSTSEAFDRLMNGKPMKEKKSTRSVEDFMAAMQRVSTQHEKET
|
7.1.2.1
| null |
positive regulation of TORC1 signaling [GO:1904263]; proteasome storage granule assembly [GO:1902906]; proton export across plasma membrane [GO:0120029]; proton transmembrane transport [GO:1902600]; regulation of intracellular pH [GO:0051453]; transmembrane transport [GO:0055085]
|
cytosol [GO:0005829]; eisosome [GO:0032126]; membrane raft [GO:0045121]; mitochondrion [GO:0005739]; plasma membrane [GO:0005886]
|
ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; metal ion binding [GO:0046872]; P-type proton-exporting transporter activity [GO:0008553]
|
PF00690;PF00122;PF00702;
|
3.40.1110.10;2.70.150.10;1.20.1110.10;3.40.50.1000;
|
Cation transport ATPase (P-type) (TC 3.A.3) family, Type IIIA subfamily
|
PTM: Phosphorylated on multiple Ser and Thr residues.
|
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
|
CATALYTIC ACTIVITY: Reaction=ATP + H(+)(in) + H2O = ADP + 2 H(+)(out) + phosphate; Xref=Rhea:RHEA:20852, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=7.1.2.1;
| null | null | null | null |
FUNCTION: The plasma membrane ATPase of plants and fungi is a hydrogen ion pump. The proton gradient it generates drives the active transport of nutrients by H(+)-symport. The resulting external acidification and/or internal alkinization may mediate growth responses.
|
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
|
P05031
|
DDC_DROME
|
MSHIPISNTIPTKQTDGNGKANISPDKLDPKVSIDMEAPEFKDFAKTMVDFIAEYLENIRERRVLPEVKPGYLKPLIPDAAPEKPEKWQDVMQDIERVIMPGVTHWHSPKFHAYFPTANSYPAIVADMLSGAIACIGFTWIASPACTELEVVMMDWLGKMLELPAEFLACSGGKGGGVIQGTASESTLVALLGAKAKKLKEVKELHPEWDEHTILGKLVGYCSDQAHSSVERAGLLGGVKLRSVQSENHRMRGAALEKAIEQDVAEGLIPFYAVVTLGTTNSCAFDYLDECGPVGNKHNLWIHVDAAYAGSAFICPEYRHLMKGIESADSFNFNPHKWMLVNFDCSAMWLKDPSWVVNAFNVDPLYLKHDMQGSAPDYRHWQIPLGRRFRALKLWFVLRLYGVENLQAHIRRHCNFAKQFGDLCVADSRFELAAEINMGLVCFRLKGSNERNEALLKRINGRGHIHLVPAKIKDVYFLRMAICSRFTQSEDMEYSWKEVSAAADEMEQEQ
|
4.1.1.28
|
COFACTOR: [Isoform Hypoderm]: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000269|PubMed:20098687, ECO:0000305|PubMed:29037755};
|
adult chitin-containing cuticle pigmentation [GO:0048085]; anesthesia-resistant memory [GO:0007615]; catecholamine metabolic process [GO:0006584]; dopamine biosynthetic process from tyrosine [GO:0006585]; long-term memory [GO:0007616]; regulation of adult chitin-containing cuticle pigmentation [GO:0048082]; response to hydrogen peroxide [GO:0042542]; response to wounding [GO:0009611]; serotonin biosynthetic process [GO:0042427]; serotonin biosynthetic process from tryptophan [GO:0006587]; thermosensory behavior [GO:0040040]; thermotaxis [GO:0043052]; wing disc development [GO:0035220]
|
cytoplasm [GO:0005737]
|
5-hydroxy-L-tryptophan decarboxylase activity [GO:0036467]; aromatic-L-amino-acid decarboxylase activity [GO:0004058]; L-dopa decarboxylase activity [GO:0036468]; pyridoxal phosphate binding [GO:0030170]
|
PF00282;
|
3.90.1150.10;1.20.1340.10;3.40.640.10;
|
Group II decarboxylase family
| null | null |
CATALYTIC ACTIVITY: [Isoform Hypoderm]: Reaction=H(+) + L-dopa = CO2 + dopamine; Xref=Rhea:RHEA:12272, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57504, ChEBI:CHEBI:59905; EC=4.1.1.28; Evidence={ECO:0000269|PubMed:29037755}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12273; Evidence={ECO:0000269|PubMed:29037755}; CATALYTIC ACTIVITY: [Isoform Hypoderm]: Reaction=5-hydroxy-L-tryptophan + H(+) = CO2 + serotonin; Xref=Rhea:RHEA:18533, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:58266, ChEBI:CHEBI:350546; EC=4.1.1.28;
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.26 mM for L-dopa {ECO:0000269|PubMed:29037755}; KM=2.2 mM for L-Dopa {ECO:0000269|PubMed:20098687}; KM=0.4 mM for 5-HTP {ECO:0000269|PubMed:20098687};
| null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7. {ECO:0000269|PubMed:20098687};
|
BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 30-60 degrees Celsius. {ECO:0000269|PubMed:20098687};
|
FUNCTION: [Isoform Hypoderm]: Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) to dopamine and L-5-hydroxytryptophan (5-HTP) to serotonin (PubMed:20098687). Catalyzes the formation of serotonin more efficiently than dopamine (PubMed:20098687). Displays no activity to tyrosine (PubMed:20098687). Variation in the synthesis of bioamines may be a factor contributing to natural variation in life span (PubMed:12881721). {ECO:0000269|PubMed:12881721, ECO:0000269|PubMed:20098687}.
|
Drosophila melanogaster (Fruit fly)
|
P05041
|
PABB_ECOLI
|
MKTLSPAVITLLWRQDAAEFYFSRLSHLPWAMLLHSGYADHPYSRFDIVVAEPICTLTTFGKETVVSESEKRTTTTDDPLQVLQQVLDRADIRPTHNEDLPFQGGALGLFGYDLGRRFESLPEIAEQDIVLPDMAVGIYDWALIVDHQRHTVSLLSHNDVNARRAWLESQQFSPQEDFTLTSDWQSNMTREQYGEKFRQVQEYLHSGDCYQVNLAQRFHATYSGDEWQAFLQLNQANRAPFSAFLRLEQGAILSLSPERFILCDNSEIQTRPIKGTLPRLPDPQEDSKQAVKLANSAKDRAENLMIVDLMRNDIGRVAVAGSVKVPELFVVEPFPAVHHLVSTITAQLPEQLHASDLLRAAFPGGSITGAPKVRAMEIIDELEPQRRNAWCGSIGYLSFCGNMDTSITIRTLTAINGQIFCSAGGGIVADSQEEAEYQETFDKVNRILKQLEK
|
2.6.1.85
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:2251281};
|
folic acid biosynthetic process [GO:0046656]; para-aminobenzoic acid biosynthetic process [GO:0008153]; tetrahydrofolate biosynthetic process [GO:0046654]; tryptophan biosynthetic process [GO:0000162]
|
aminodeoxychorismate synthase complex [GO:0009356]; cytoplasm [GO:0005737]
|
4-amino-4-deoxychorismate synthase activity [GO:0046820]; magnesium ion binding [GO:0000287]; protein heterodimerization activity [GO:0046982]; tryptophan binding [GO:0120284]
|
PF04715;PF00425;
|
3.60.120.10;
|
Anthranilate synthase component I family
| null | null |
CATALYTIC ACTIVITY: Reaction=chorismate + L-glutamine = 4-amino-4-deoxychorismate + L-glutamate; Xref=Rhea:RHEA:11672, ChEBI:CHEBI:29748, ChEBI:CHEBI:29985, ChEBI:CHEBI:58359, ChEBI:CHEBI:58406; EC=2.6.1.85; Evidence={ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:2251281};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=4.2 uM for chorismate (with PabA and glutamine as the amino donor at pH 7.5) {ECO:0000269|PubMed:14982443, ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:7592344}; KM=18.6 uM for chorismate (with PabA and ammonia as the amino donor at pH 7.5) {ECO:0000269|PubMed:14982443, ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:7592344}; KM=71 uM for chorismate {ECO:0000269|PubMed:14982443, ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:7592344}; KM=75 uM for chorismate (with PabA) {ECO:0000269|PubMed:14982443, ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:7592344}; KM=379 uM for chorismate (with PabA and ammonia) {ECO:0000269|PubMed:14982443, ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:7592344}; KM=388 uM for chorismate (with ammonia) {ECO:0000269|PubMed:14982443, ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:7592344};
|
PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 4-aminobenzoate from chorismate: step 1/2.
| null | null |
FUNCTION: Part of a heterodimeric complex that catalyzes the two-step biosynthesis of 4-amino-4-deoxychorismate (ADC), a precursor of p-aminobenzoate (PABA) and tetrahydrofolate. In the first step, a glutamine amidotransferase (PabA) generates ammonia as a substrate that, along with chorismate, is used in the second step, catalyzed by aminodeoxychorismate synthase (PabB) to produce ADC. PabB, in the absence of PabA, can catalyze the formation of ADC in the presence of exogenous ammonia. {ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:2251281, ECO:0000269|PubMed:4914080}.
|
Escherichia coli (strain K12)
|
P05042
|
FUMC_ECOLI
|
MNTVRSEKDSMGAIDVPADKLWGAQTQRSLEHFRISTEKMPTSLIHALALTKRAAAKVNEDLGLLSEEKASAIRQAADEVLAGQHDDEFPLAIWQTGSGTQSNMNMNEVLANRASELLGGVRGMERKVHPNDDVNKSQSSNDVFPTAMHVAALLALRKQLIPQLKTLTQTLNEKSRAFADIVKIGRTHLQDATPLTLGQEISGWVAMLEHNLKHIEYSLPHVAELALGGTAVGTGLNTHPEYARRVADELAVITCAPFVTAPNKFEALATCDALVQAHGALKGLAASLMKIANDVRWLASGPRCGIGEISIPENEPGSSIMPGKVNPTQCEALTMLCCQVMGNDVAINMGGASGNFELNVFRPMVIHNFLQSVRLLADGMESFNKHCAVGIEPNRERINQLLNESLMLVTALNTHIGYDKAAEIAKKAHKEGLTLKAAALALGYLSEAEFDSWVRPEQMVGSMKAGR
|
4.2.1.2
| null |
fumarate metabolic process [GO:0006106]; malate metabolic process [GO:0006108]; response to oxidative stress [GO:0006979]; tricarboxylic acid cycle [GO:0006099]
|
tricarboxylic acid cycle enzyme complex [GO:0045239]
|
fumarate hydratase activity [GO:0004333]; identical protein binding [GO:0042802]
|
PF10415;PF00206;
|
1.10.40.30;1.20.200.10;1.10.275.10;
|
Class-II fumarase/aspartase family, Fumarase subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00743, ECO:0000305}.
|
CATALYTIC ACTIVITY: Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460, ChEBI:CHEBI:15377, ChEBI:CHEBI:15589, ChEBI:CHEBI:29806; EC=4.2.1.2; Evidence={ECO:0000255|HAMAP-Rule:MF_00743, ECO:0000269|PubMed:1917897, ECO:0000269|PubMed:3282546};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=50 uM for L-malate (at pH 7.3 and 30 degrees Celsius) {ECO:0000269|PubMed:1917897}; KM=207 uM for fumarate (at pH 7.9) {ECO:0000269|PubMed:12021453}; KM=390 uM for fumarate {ECO:0000269|PubMed:3282546}; KM=857 uM for S-malate (at pH 7.9) {ECO:0000269|PubMed:12021453}; KM=2.94 mM for S-malate {ECO:0000269|PubMed:3282546}; Vmax=1 umol/min/mg enzyme for fumarate {ECO:0000269|PubMed:3282546}; Vmax=1 umol/min/mg enzyme for S-malate {ECO:0000269|PubMed:3282546}; Vmax=344.8 umol/min/mg enzyme for fumarate (at pH 7.9) {ECO:0000269|PubMed:12021453}; Vmax=176.8 umol/min/mg enzyme for S-malate (at pH 7.9) {ECO:0000269|PubMed:12021453}; Note=kcat is 1149 sec(-1) for fumarate (at pH 7.9). kcat is 595.2 sec(-1) for S-malate (at pH 7.9). {ECO:0000269|PubMed:12021453};
|
PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate from fumarate: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00743, ECO:0000305}.
|
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8. {ECO:0000269|PubMed:1917897};
|
BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Thermostable. {ECO:0000269|PubMed:3282546};
|
FUNCTION: Involved in the TCA cycle. FumC seems to be a backup enzyme for FumA under conditions of iron limitation and oxidative stress (PubMed:7592392). Catalyzes the stereospecific interconversion of fumarate to L-malate (PubMed:1917897, PubMed:3282546). {ECO:0000269|PubMed:1917897, ECO:0000269|PubMed:3282546, ECO:0000269|PubMed:7592392, ECO:0000305|PubMed:8496960}.
|
Escherichia coli (strain K12)
|
P05043
|
SP0E_BACSU
|
MGGSSEQERLLVSIDEKRKLMIDAARKQGFTGHDTIRHSQELDCLINEYHQLMQENEHSQGIQGLVKKLGLWPRRDVMPAYDANK
|
3.1.3.-
| null |
regulation of sporulation [GO:0043937]; sporulation resulting in formation of a cellular spore [GO:0030435]
| null |
hydrolase activity [GO:0016787]; protein dimerization activity [GO:0046983]
|
PF09388;
|
4.10.280.10;
|
Spo0E family
|
PTM: Probably degraded by FtsH, the last 14 residues seem to form the FtsH recognition site.
| null | null | null | null | null | null |
FUNCTION: Aspartyl-phosphate phosphatase which specifically dephosphorylates the sporulation transcription factor Spo0A-P and negatively regulates the sporulation initiation pathway in order to control the proper timing of sporulation. {ECO:0000269|PubMed:11112444, ECO:0000269|PubMed:12067336, ECO:0000269|PubMed:15057450, ECO:0000269|PubMed:18045868, ECO:0000269|PubMed:8127878}.
|
Bacillus subtilis (strain 168)
|
P05044
|
SORCN_CRIGR
|
MAYPGHPGAGGGYYPGGYGGAPGGPSFPGQTQDPLYGYFASVAGQDGQIDADELQRCLTQSGIAGGYKPFNLETCRLMVSMLDRDMSGTMGFNEFKELWAVLNGWRQHFISFDSDRSGTVDPQELQKALTTMGFRLNPQTVNSIAKRYSTSGKITFDDYIACCVKLRALTDSFRRRDSAQQGMVNFSYDDFIQCVMTV
| null | null | null |
membrane [GO:0016020]; sarcoplasmic reticulum membrane [GO:0033017]
|
calcium ion binding [GO:0005509]
|
PF13405;PF13833;
|
6.10.140.900;1.10.238.10;
| null |
PTM: Phosphorylated; partially. {ECO:0000269|PubMed:15754088}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15754088}. Sarcoplasmic reticulum membrane {ECO:0000269|PubMed:15754088}; Peripheral membrane protein {ECO:0000269|PubMed:15754088}; Cytoplasmic side {ECO:0000269|PubMed:15754088}. Note=Relocates to the sarcoplasmic reticulum membrane in response to elevated calcium levels and phosphorylation.
| null | null | null | null | null |
FUNCTION: Calcium-binding protein that modulates excitation-contraction coupling in the heart. Contributes to calcium homeostasis in the sarcoplasmic reticulum in the heart. Modulates the activity of RYR2 calcium channels. {ECO:0000269|PubMed:15754088, ECO:0000269|PubMed:17029407}.
|
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
|
P05050
|
ALKB_ECOLI
|
MLDLFADAEPWQEPLAAGAVILRRFAFNAAEQLIRDINDVASQSPFRQMVTPGGYTMSVAMTNCGHLGWTTHRQGYLYSPIDPQTNKPWPAMPQSFHNLCQRAATAAGYPDFQPDACLINRYAPGAKLSLHQDKDEPDLRAPIVSVSLGLPAIFQFGGLKRNDPLKRLLLEHGDVVVWGGESRLFYHGIQPLKAGFHPLTIDCRYNLTFRQAGKKE
|
1.14.11.33
|
COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|PROSITE-ProRule:PRU00805, ECO:0000269|PubMed:16482161, ECO:0000269|PubMed:19706517, ECO:0000269|PubMed:20084272, ECO:0000269|PubMed:21068844}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-ProRule:PRU00805, ECO:0000269|PubMed:16482161, ECO:0000269|PubMed:19706517, ECO:0000269|PubMed:20084272, ECO:0000269|PubMed:21068844};
|
DNA dealkylation involved in DNA repair [GO:0006307]; DNA repair [GO:0006281]; oxidative demethylation [GO:0070989]; oxidative RNA demethylation [GO:0035513]; oxidative single-stranded DNA demethylation [GO:0035552]; oxidative single-stranded RNA demethylation [GO:0035553]; response to methyl methanesulfonate [GO:0072702]; RNA repair [GO:0042245]
|
cytoplasm [GO:0005737]
|
broad specificity oxidative DNA demethylase activity [GO:0035516]; dioxygenase activity [GO:0051213]; ferrous iron binding [GO:0008198]; oxidative RNA demethylase activity [GO:0035515]
|
PF13532;
|
2.60.120.590;
|
AlkB family
| null | null |
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + a methylated nucleobase within DNA + O2 = a nucleobase within DNA + CO2 + formaldehyde + succinate; Xref=Rhea:RHEA:30299, Rhea:RHEA-COMP:12192, Rhea:RHEA-COMP:12193, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:32875, ChEBI:CHEBI:64428; EC=1.14.11.33; Evidence={ECO:0000269|PubMed:12226668, ECO:0000269|PubMed:20084272, ECO:0000269|PubMed:21068844};
| null | null | null | null |
FUNCTION: Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents). {ECO:0000269|PubMed:12226668, ECO:0000269|PubMed:12594517, ECO:0000269|PubMed:16482161, ECO:0000269|PubMed:19706517, ECO:0000269|PubMed:20084272, ECO:0000269|PubMed:21068844}.
|
Escherichia coli (strain K12)
|
P05055
|
PNP_ECOLI
|
MLNPIVRKFQYGQHTVTLETGMMARQATAAVMVSMDDTAVFVTVVGQKKAKPGQDFFPLTVNYQERTYAAGRIPGSFFRREGRPSEGETLIARLIDRPIRPLFPEGFVNEVQVIATVVSVNPQVNPDIVAMIGASAALSLSGIPFNGPIGAARVGYINDQYVLNPTQDELKESKLDLVVAGTEAAVLMVESEAQLLSEDQMLGAVVFGHEQQQVVIQNINELVKEAGKPRWDWQPEPVNEALNARVAALAEARLSDAYRITDKQERYAQVDVIKSETIATLLAEDETLDENELGEILHAIEKNVVRSRVLAGEPRIDGREKDMIRGLDVRTGVLPRTHGSALFTRGETQALVTATLGTARDAQVLDELMGERTDTFLFHYNFPPYSVGETGMVGSPKRREIGHGRLAKRGVLAVMPDMDKFPYTVRVVSEITESNGSSSMASVCGASLALMDAGVPIKAAVAGIAMGLVKEGDNYVVLSDILGDEDHLGDMDFKVAGSRDGISALQMDIKIEGITKEIMQVALNQAKGARLHILGVMEQAINAPRGDISEFAPRIHTIKINPDKIKDVIGKGGSVIRALTEETGTTIEIEDDGTVKIAATDGEKAKHAIRRIEEITAEIEVGRVYTGKVTRIVDFGAFVAIGGGKEGLVHISQIADKRVEKVTDYLQMGQEVPVKVLEVDRQGRIRLSIKEATEQSQPAAAPEAPAAEQGE
|
2.7.7.8
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_01595, ECO:0000269|PubMed:19327365}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|HAMAP-Rule:MF_01595, ECO:0000269|PubMed:19327365}; Note=Magnesium. Can also use manganese. {ECO:0000255|HAMAP-Rule:MF_01595, ECO:0000269|PubMed:19327365};
|
mRNA catabolic process [GO:0006402]; response to heat [GO:0009408]; RNA catabolic process [GO:0006401]; RNA processing [GO:0006396]
|
bacterial degradosome [GO:1990061]; cytosol [GO:0005829]; membrane [GO:0016020]
|
3'-5'-RNA exonuclease activity [GO:0000175]; cyclic-di-GMP binding [GO:0035438]; identical protein binding [GO:0042802]; magnesium ion binding [GO:0000287]; polyribonucleotide nucleotidyltransferase activity [GO:0004654]; RNA binding [GO:0003723]
|
PF00013;PF03726;PF01138;PF03725;PF00575;
|
3.30.230.70;3.30.1370.10;2.40.50.140;
|
Polyribonucleotide nucleotidyltransferase family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01595, ECO:0000269|PubMed:16079137}. Note=Has also been isolated in association with the inner membrane.
|
CATALYTIC ACTIVITY: Reaction=phosphate + RNA(n+1) = a ribonucleoside 5'-diphosphate + RNA(n); Xref=Rhea:RHEA:22096, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:140395; EC=2.7.7.8; Evidence={ECO:0000255|HAMAP-Rule:MF_01595, ECO:0000269|PubMed:12162954, ECO:0000269|PubMed:18812438, ECO:0000269|PubMed:4866865};
| null | null | null | null |
FUNCTION: Involved in mRNA degradation. Catalyzes the phosphorolysis of single-stranded polyribonucleotides processively in the 3'- to 5'-direction. Also involved, along with RNase II, in tRNA processing. RNases II and R contribute to rRNA degradation during starvation, while RNase R and PNPase are the major contributors to quality control of rRNA during steady state growth (PubMed:21135037). Contributes to degradation of some small RNAs (sRNA) (PubMed:34210798). {ECO:0000255|HAMAP-Rule:MF_01595, ECO:0000269|PubMed:12162954, ECO:0000269|PubMed:18812438, ECO:0000269|PubMed:19327365, ECO:0000269|PubMed:21135037, ECO:0000269|PubMed:34210798, ECO:0000269|PubMed:4866865, ECO:0000269|PubMed:7509797}.
|
Escherichia coli (strain K12)
|
P05059
|
CMGA_BOVIN
|
MRSAAVLALLLCAGQVIALPVNSPMNKGDTEVMKCIVEVISDTLSKPSPMPVSKECFETLRGDERILSILRHQNLLKELQDLALQGAKERTHQQKKHSSYEDELSEVLEKPNDQAEPKEVTEEVSSKDAAEKRDDFKEVEKSDEDSDGDRPQASPGLGPGPKVEEDNQAPGEEEEAPSNAHPLASLPSPKYPGPQAKEDSEGPSQGPASREKGLSAEQGRQTEREEEEEKWEEAEAREKAVPEEESPPTAAFKPPPSLGNKETQRAAPGWPEDGAGKMGAEEAKPPEGKGEWAHSRQEEEEMARAPQVLFRGGKSGEPEQEEQLSKEWEDAKRWSKMDQLAKELTAEKRLEGEEEEEEDPDRSMRLSFRARGYGFRGPGLQLRRGWRPNSREDSVEAGLPLQVRGYPEEKKEEEGSANRRPEDQELESLSAIEAELEKVAHQLEELRRG
| null | null |
adenylate cyclase-activating adrenergic receptor signaling pathway involved in cardiac muscle relaxation [GO:0086030]; defense response to bacterium [GO:0042742]; defense response to fungus [GO:0050832]; defense response to Gram-negative bacterium [GO:0050829]; defense response to Gram-positive bacterium [GO:0050830]; innate immune response [GO:0045087]; killing of cells of another organism [GO:0031640]; mast cell activation [GO:0045576]; mast cell chemotaxis [GO:0002551]; mast cell degranulation [GO:0043303]; negative regulation of angiogenesis [GO:0016525]; negative regulation of catecholamine secretion [GO:0033604]; negative regulation of hormone secretion [GO:0046888]; negative regulation of insulin secretion [GO:0046676]; positive regulation of dense core granule biogenesis [GO:2000707]; regulation of cell adhesion [GO:0030155]
|
chromaffin granule [GO:0042583]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; neuronal dense core vesicle [GO:0098992]; secretory granule [GO:0030141]; transport vesicle [GO:0030133]
|
calcium ion binding [GO:0005509]; metal ion binding [GO:0046872]
|
PF01271;
| null |
Chromogranin/secretogranin protein family
|
PTM: In secretory granules, is attacked at both N- and C-terminal sides by proteolytic enzymes generating numerous peptides of various activities. Proteolytic processing can give rise to additional longer forms of catestatin peptides which display a less potent catecholamine release-inhibitory activity (PubMed:10781584). {ECO:0000269|PubMed:10781584, ECO:0000269|PubMed:8240272, ECO:0000305|PubMed:11451958}.; PTM: O-glycosylated; contains chondroitin sulfate (CS). CS attachment is pH-dependent, being observed at mildly acidic conditions of pH 5 but not at neutral pH, and promotes self-assembly in vitro. {ECO:0000250|UniProtKB:P10645}.
|
SUBCELLULAR LOCATION: [Serpinin]: Secreted {ECO:0000269|PubMed:10781584}. Cytoplasmic vesicle, secretory vesicle {ECO:0000250|UniProtKB:P26339, ECO:0000269|PubMed:11584008}. Note=Pyroglutaminated serpinin localizes to secretory vesicle. {ECO:0000250|UniProtKB:P26339}.; SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle {ECO:0000250|UniProtKB:P10354}. Cytoplasmic vesicle, secretory vesicle, neuronal dense core vesicle {ECO:0000250|UniProtKB:P10354}. Secreted {ECO:0000269|PubMed:11451958}. Note=Associated with the secretory granule membrane through direct interaction to SCG3 that in turn binds to cholesterol-enriched lipid rafts in intragranular conditions. In pituitary gonadotropes, located in large secretory granules. {ECO:0000250|UniProtKB:P10354}.
| null | null | null | null | null |
FUNCTION: [Pancreastatin]: Strongly inhibits glucose induced insulin release from the pancreas. {ECO:0000269|PubMed:2756155}.; FUNCTION: [Chromostatin]: Completely inhibits catecholamine release from chromaffin cells. {ECO:0000269|PubMed:1996343}.; FUNCTION: [Chromacin]: Has antibacterial activity against M.luteus. Not active against E.coli. {ECO:0000269|PubMed:8910482}.; FUNCTION: [Catestatin]: Inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist (PubMed:9294131, PubMed:9786174). Displays antibacterial activity against Gram-positive bacteria M.luteus and B.megaterium, and Gram-negative bacteria E.coli, and antifungal activity against a variety of filamentous fungi including A.fumigatus, N.hematococca, F.culmorum, F.oxyporum, T. mentagrophytes and several forms of Candida: C.albicans, C.tropicalis, C.glabrata and C.neoform (PubMed:15723172). Can induce mast cell migration, degranulation and production of cytokines and chemokines (By similarity). {ECO:0000250|UniProtKB:P10645, ECO:0000269|PubMed:15723172, ECO:0000269|PubMed:9294131, ECO:0000269|PubMed:9786174}.; FUNCTION: [Vasostatin-1]: Has antibacterial activity against Gram-positive bacteria M.luteus, B.megaterium. Not active against Gram-positive bacteria B.cereus, B.subtilis, S.pyogenes, M.fortuitum, S.aureus and L.monocytogenes and against Gram-negative bacteria E.coli, E.cloacae, S.typhimurium, K.pneumoniae and P.aeruginosa. Possesses antifungal activity against N.crassa, A.fumigatus, A.brassicicola, N.hematococca, F.culmorum and F.oxyporum and against the yeast S.cerevisiae and C.albicans. Inactive against A.benhamiae. {ECO:0000269|PubMed:10753865}.; FUNCTION: [Chromofungin]: Has antifungal activity against N.crassa, A.fumigatus, A.brassicicola, N.hematococca, F.culmorum, F.oxyporum, A.benhamiae, C.neoformans, as well as against yeasts C.albicans, and C.tropicalis. Seems to be inactive against C.glabrata. Interacts with the fungal cell wall, crosses the plasma membrane and accumulates in fungal cells where it inhibits calcineurin activity. {ECO:0000269|PubMed:11451958}.; FUNCTION: [Serpinin]: Regulates granule biogenesis in endocrine cells by up-regulating the transcription of protease nexin 1 (SERPINE2) via a cAMP-PKA-SP1 pathway. This leads to inhibition of granule protein degradation in the Golgi complex which in turn promotes granule formation (PubMed:21436258). {ECO:0000269|PubMed:21436258}.
|
Bos taurus (Bovine)
|
P05060
|
SCG1_HUMAN
|
MQPTLLLSLLGAVGLAAVNSMPVDNRNHNEGMVTRCIIEVLSNALSKSSAPPITPECRQVLKTSRKDVKDKETTENENTKFEVRLLRDPADASEAHESSSRGEAGAPGEEDIQGPTKADTEKWAEGGGHSRERADEPQWSLYPSDSQVSEEVKTRHSEKSQREDEEEEEGENYQKGERGEDSSEEKHLEEPGETQNAFLNERKQASAIKKEELVARSETHAAGHSQEKTHSREKSSQESGEETGSQENHPQESKGQPRSQEESEEGEEDATSEVDKRRTRPRHHHGRSRPDRSSQGGSLPSEEKGHPQEESEESNVSMASLGEKRDHHSTHYRASEEEPEYGEEIKGYPGVQAPEDLEWERYRGRGSEEYRAPRPQSEESWDEEDKRNYPSLELDKMAHGYGEESEEERGLEPGKGRHHRGRGGEPRAYFMSDTREEKRFLGEGHHRVQENQMDKARRHPQGAWKELDRNYLNYGEEGAPGKWQQQGDLQDTKENREEARFQDKQYSSHHTAEKRKRLGELFNPYYDPLQWKSSHFERRDNMNDNFLEGEEENELTLNEKNFFPEYNYDWWEKKPFSEDVNWGYEKRNLARVPKLDLKRQYDRVAQLDQLLHYRKKSAEFPDFYDSEEPVSTHQEAENEKDRADQTVLTEDEKKELENLAAMDLELQKIAEKFSQRG
| null | null | null |
endoplasmic reticulum lumen [GO:0005788]; extracellular space [GO:0005615]; secretory granule [GO:0030141]
|
hormone activity [GO:0005179]
|
PF01271;
| null |
Chromogranin/secretogranin protein family
|
PTM: Extensively processed by limited proteolysis at conserved basic residues. Alternative processing are seen in different tissues (By similarity). {ECO:0000250}.; PTM: O-glycosylated. {ECO:0000269|PubMed:23234360, ECO:0000269|PubMed:25326458}.
|
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25326458, ECO:0000269|PubMed:37453717}. Note=Neuroendocrine and endocrine secretory granules.
| null | null | null | null | null |
FUNCTION: Secretogranin-1 is a neuroendocrine secretory granule protein, which may be the precursor for other biologically active peptides.
|
Homo sapiens (Human)
|
P05062
|
ALDOB_HUMAN
|
MAHRFPALTQEQKKELSEIAQSIVANGKGILAADESVGTMGNRLQRIKVENTEENRRQFREILFSVDSSINQSIGGVILFHETLYQKDSQGKLFRNILKEKGIVVGIKLDQGGAPLAGTNKETTIQGLDGLSERCAQYKKDGVDFGKWRAVLRIADQCPSSLAIQENANALARYASICQQNGLVPIVEPEVIPDGDHDLEHCQYVTEKVLAAVYKALNDHHVYLEGTLLKPNMVTAGHACTKKYTPEQVAMATVTALHRTVPAAVPGICFLSGGMSEEDATLNLNAINLCPLPKPWKLSFSYGRALQASALAAWGGKAANKEATQEAFMKRAMANCQAAKGQYVHTGSSGAASTQSLFTACYTY
|
4.1.2.13
| null |
fructose 1,6-bisphosphate metabolic process [GO:0030388]; fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate [GO:0061624]; fructose metabolic process [GO:0006000]; gluconeogenesis [GO:0006094]; glycolytic process [GO:0006096]; NADH oxidation [GO:0006116]; negative regulation of pentose-phosphate shunt [GO:1905856]; positive regulation of ATP-dependent activity [GO:0032781]; vacuolar proton-transporting V-type ATPase complex assembly [GO:0070072]
|
centriolar satellite [GO:0034451]; cytosol [GO:0005829]; extracellular exosome [GO:0070062]; microtubule organizing center [GO:0005815]
|
ATPase binding [GO:0051117]; cytoskeletal protein binding [GO:0008092]; fructose binding [GO:0070061]; fructose-1-phosphate aldolase activity [GO:0061609]; fructose-bisphosphate aldolase activity [GO:0004332]; identical protein binding [GO:0042802]; molecular adaptor activity [GO:0060090]
|
PF00274;
|
3.20.20.70;
|
Class I fructose-bisphosphate aldolase family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:35122041}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriolar satellite {ECO:0000269|PubMed:18000879}.
|
CATALYTIC ACTIVITY: Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3-phosphate + dihydroxyacetone phosphate; Xref=Rhea:RHEA:14729, ChEBI:CHEBI:32966, ChEBI:CHEBI:57642, ChEBI:CHEBI:59776; EC=4.1.2.13; Evidence={ECO:0000269|PubMed:10970798, ECO:0000269|PubMed:12205126, ECO:0000269|PubMed:20848650}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14730; Evidence={ECO:0000305|PubMed:10970798, ECO:0000305|PubMed:12205126, ECO:0000305|PubMed:20848650}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14731; Evidence={ECO:0000305}; CATALYTIC ACTIVITY: Reaction=beta-D-fructose 1-phosphate = D-glyceraldehyde + dihydroxyacetone phosphate; Xref=Rhea:RHEA:30851, ChEBI:CHEBI:17378, ChEBI:CHEBI:57642, ChEBI:CHEBI:138881; Evidence={ECO:0000269|PubMed:10970798, ECO:0000269|PubMed:12205126, ECO:0000269|PubMed:20848650}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30852; Evidence={ECO:0000305|PubMed:10970798, ECO:0000305|PubMed:12205126, ECO:0000305|PubMed:20848650}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30853; Evidence={ECO:0000305};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.6 uM for fructose 1,6-bisphosphate {ECO:0000269|PubMed:10970798}; KM=0.95 uM for fructose 1,6-bisphosphate {ECO:0000269|PubMed:20848650}; KM=2.3 mM for fructose 1-phosphate {ECO:0000269|PubMed:10970798}; KM=0.73 mM for fructose 1-phosphate {ECO:0000269|PubMed:20848650};
|
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 4/4. {ECO:0000305|PubMed:10970798, ECO:0000305|PubMed:12205126, ECO:0000305|PubMed:20848650}.; PATHWAY: Carbohydrate biosynthesis; gluconeogenesis. {ECO:0000305|PubMed:10970798, ECO:0000305|PubMed:12205126, ECO:0000305|PubMed:20848650}.; PATHWAY: Carbohydrate metabolism; fructose metabolism. {ECO:0000269|PubMed:10970798, ECO:0000269|PubMed:12205126, ECO:0000269|PubMed:20848650}.
| null | null |
FUNCTION: Catalyzes the aldol cleavage of fructose 1,6-biphosphate to form two triosephosphates dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate in glycolysis as well as the reverse stereospecific aldol addition reaction in gluconeogenesis. In fructolysis, metabolizes fructose 1-phosphate derived from the phosphorylation of dietary fructose by fructokinase into dihydroxyacetone phosphate and D-glyceraldehyde (PubMed:10970798, PubMed:12205126, PubMed:20848650). Acts as an adapter independently of its enzymatic activity, exerts a tumor suppressor role by stabilizing the ternary complex with G6PD and TP53 to inhibit G6PD activity and keep oxidative pentose phosphate metabolism in check (PubMed:35122041). {ECO:0000269|PubMed:10970798, ECO:0000269|PubMed:12205126, ECO:0000269|PubMed:20848650, ECO:0000269|PubMed:35122041}.
|
Homo sapiens (Human)
|
P05063
|
ALDOC_MOUSE
|
MPHSYPALSAEQKKELSDIALRIVTPGKGILAADESVGSMAKRLSQIGVENTEENRRLYRQVLFSADDRVKKCIGGVIFFHETLYQKDDNGVPFVRTIQDKGILVGIKVDKGVVPLAGTDGETTTQGLDGLLERCAQYKKDGADFAKWRCVLKISDRTPSALAILENANVLARYASICQQNGIVPIVEPEILPDGDHDLKRCQYVTEKVLAAVYKALSDHHVYLEGTLLKPNMVTPGHACPIKYSPEEIAMATVTALRRTVPPAVPGVTFLSGGQSEEEASLNLNAINRCPLPRPWALTFSYGRALQASALNAWRGQRDNAGAATEEFIKRAEMNGLAAQGRYEGSGDGGAAAQSLYIANHAY
|
4.1.2.13
| null |
epithelial cell differentiation [GO:0030855]; fructose 1,6-bisphosphate metabolic process [GO:0030388]; gluconeogenesis [GO:0006094]; glycolytic process [GO:0006096]
|
axon [GO:0030424]; cytosol [GO:0005829]; mitochondrion [GO:0005739]; postsynaptic cytosol [GO:0099524]
|
cytoskeletal protein binding [GO:0008092]; fructose-bisphosphate aldolase activity [GO:0004332]; identical protein binding [GO:0042802]; protein-containing complex binding [GO:0044877]
|
PF00274;
|
3.20.20.70;
|
Class I fructose-bisphosphate aldolase family
| null | null |
CATALYTIC ACTIVITY: Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3-phosphate + dihydroxyacetone phosphate; Xref=Rhea:RHEA:14729, ChEBI:CHEBI:32966, ChEBI:CHEBI:57642, ChEBI:CHEBI:59776; EC=4.1.2.13;
| null |
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 4/4.
| null | null | null |
Mus musculus (Mouse)
|
P05064
|
ALDOA_MOUSE
|
MPHPYPALTPEQKKELSDIAHRIVAPGKGILAADESTGSIAKRLQSIGTENTEENRRFYRQLLLTADDRVNPCIGGVILFHETLYQKADDGRPFPQVIKSKGGVVGIKVDKGVVPLAGTNGETTTQGLDGLSERCAQYKKDGADFAKWRCVLKIGEHTPSALAIMENANVLARYASICQQNGIVPIVEPEILPDGDHDLKRCQYVTEKVLAAVYKALSDHHVYLEGTLLKPNMVTPGHACTQKFSNEEIAMATVTALRRTVPPAVTGVTFLSGGQSEEEASINLNAINKCPLLKPWALTFSYGRALQASALKAWGGKKENLKAAQEEYIKRALANSLACQGKYTPSGQSGAAASESLFISNHAY
|
4.1.2.13
| null |
canonical glycolysis [GO:0061621]; fructose 1,6-bisphosphate metabolic process [GO:0030388]; glycolytic process [GO:0006096]; glycolytic process through fructose-6-phosphate [GO:0061615]; methylglyoxal biosynthetic process [GO:0019242]; positive regulation of cell migration [GO:0030335]; protein homotetramerization [GO:0051289]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular space [GO:0005615]; heterochromatin [GO:0000792]; M band [GO:0031430]; membrane [GO:0016020]; myelin sheath [GO:0043209]; plasma membrane [GO:0005886]; protein-containing complex [GO:0032991]; sperm fibrous sheath [GO:0035686]; Z disc [GO:0030018]
|
fructose-bisphosphate aldolase activity [GO:0004332]; protease binding [GO:0002020]
|
PF00274;
|
3.20.20.70;
|
Class I fructose-bisphosphate aldolase family
| null |
SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, I band {ECO:0000250|UniProtKB:P00883}. Cytoplasm, myofibril, sarcomere, M line {ECO:0000250|UniProtKB:P00883}. Note=In skeletal muscle, accumulates around the M line and within the I band, colocalizing with FBP2 on both sides of the Z line in the absence of Ca(2+). {ECO:0000250|UniProtKB:P00883}.
|
CATALYTIC ACTIVITY: Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3-phosphate + dihydroxyacetone phosphate; Xref=Rhea:RHEA:14729, ChEBI:CHEBI:32966, ChEBI:CHEBI:57642, ChEBI:CHEBI:59776; EC=4.1.2.13; Evidence={ECO:0000250|UniProtKB:P04075}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14730; Evidence={ECO:0000250|UniProtKB:P04075};
| null |
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 4/4.
| null | null |
FUNCTION: Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also function as scaffolding protein (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P04075}.
|
Mus musculus (Mouse)
|
P05065
|
ALDOA_RAT
|
MPHPYPALTPEQKKELADIAHRIVAPGKGILAADESTGSIAKRLQSIGTENTEENRRFYRQLLLTADDRVNPCIGGVILFHETLYQKADDGRPFPQVIKSKGGVVGIKVDKGVVPLAGTNGETTTQGLDGLSERCAQYKKDGADFAKWRCVLKIGEHTPSSLAIMENANVLARYASICQQNGIVPIVEPEILPDGDHDLKRCQYVTEKVLAAVYKALSDHHVYLEGTLLKPNMVTPGHACTQKFSNEEIAMATVTALRRTVPPAVPGVTFLSGGQSEEEASINLNAINKCPLLKPWALTFSYGRALQASALKAWGGKKENLKAAQEEYIKRALANSLACQGKYTPSGQSGAAASESLFISNHAY
|
4.1.2.13
| null |
ATP biosynthetic process [GO:0006754]; binding of sperm to zona pellucida [GO:0007339]; fructose 1,6-bisphosphate metabolic process [GO:0030388]; fructose metabolic process [GO:0006000]; glycolytic process [GO:0006096]; methylglyoxal biosynthetic process [GO:0019242]; muscle cell cellular homeostasis [GO:0046716]; protein homotetramerization [GO:0051289]; regulation of cell shape [GO:0008360]; response to estrogen [GO:0043627]; response to hypoxia [GO:0001666]; response to lipopolysaccharide [GO:0032496]; response to nicotine [GO:0035094]; striated muscle contraction [GO:0006941]
|
actin cytoskeleton [GO:0015629]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular exosome [GO:0070062]; heterochromatin [GO:0000792]; I band [GO:0031674]; M band [GO:0031430]; sperm head [GO:0061827]
|
cytoskeletal protein binding [GO:0008092]; fructose binding [GO:0070061]; fructose-bisphosphate aldolase activity [GO:0004332]; identical protein binding [GO:0042802]
|
PF00274;
|
3.20.20.70;
|
Class I fructose-bisphosphate aldolase family
| null |
SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, I band {ECO:0000250|UniProtKB:P00883}. Cytoplasm, myofibril, sarcomere, M line {ECO:0000250|UniProtKB:P00883}. Note=In skeletal muscle, accumulates around the M line and within the I band, colocalizing with FBP2 on both sides of the Z line in the absence of Ca(2+). {ECO:0000250|UniProtKB:P00883}.
|
CATALYTIC ACTIVITY: Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3-phosphate + dihydroxyacetone phosphate; Xref=Rhea:RHEA:14729, ChEBI:CHEBI:32966, ChEBI:CHEBI:57642, ChEBI:CHEBI:59776; EC=4.1.2.13; Evidence={ECO:0000250|UniProtKB:P04075}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14730; Evidence={ECO:0000250|UniProtKB:P04075};
| null |
PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 4/4.
| null | null |
FUNCTION: Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also function as scaffolding protein (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P04075}.
|
Rattus norvegicus (Rat)
|
P05066
|
PHR_YEAST
|
MKRTVISSSNAYASKRSRLDIEHDFEQYHSLNKKYYPRPITRTGANQFNNKSRAKPMEIVEKLQKKQKTSFENVSTVMHWFRNDLRLYDNVGLYKSVALFQQLRQKNAKAKLYAVYVINEDDWRAHMDSGWKLMFIMGALKNLQQSLAELHIPLLLWEFHTPKSTLSNSKEFVEFFKEKCMNVSSGTGTIITANIEYQTDELYRDIRLLENEDHRLQLKYYHDSCIVAPGLITTDRGTNYSVFTPWYKKWVLYVNNYKKSTSEICHLHIIEPLKYNETFELKPFQYSLPDEFLQYIPKSKWCLPDVSEEAALSRLKDFLGTKSSKYNNEKDMLYLGGTSGLSVYITTGRISTRLIVNQAFQSCNGQIMSKALKDNSSTQNFIKEVAWRDFYRHCMCNWPYTSMGMPYRLDTLDIKWENNPVAFEKWCTGNTGIPIVDAIMRKLLYTGYINNRSRMITASFLSKNLLIDWRWGERWFMKHLIDGDSSSNVGGWGFCSSTGIDAQPYFRVFNMDIQAKKYDPQMIFVKQWVPELISSENKRPENYPKPLVDLKHSRERALKVYKDAM
|
4.1.99.3
|
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD per subunit.; COFACTOR: Name=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate; Xref=ChEBI:CHEBI:15636; Note=Binds 1 5,10-methenyltetrahydrofolate (MTHF) non-covalently per subunit.;
|
circadian regulation of gene expression [GO:0032922]; entrainment of circadian clock by photoperiod [GO:0043153]; photoreactive repair [GO:0000719]
|
cytoplasm [GO:0005737]; mitochondrion [GO:0005739]; nucleus [GO:0005634]
|
deoxyribodipyrimidine photo-lyase activity [GO:0003904]; DNA binding [GO:0003677]; FAD binding [GO:0071949]; mRNA binding [GO:0003729]
|
PF00875;PF03441;
|
1.25.40.80;1.10.579.10;3.40.50.620;
|
DNA photolyase class-1 family
| null |
SUBCELLULAR LOCATION: Nucleus. Mitochondrion.
|
CATALYTIC ACTIVITY: Reaction=cyclobutadipyrimidine (in DNA) = 2 pyrimidine residues (in DNA).; EC=4.1.99.3;
| null | null | null | null |
FUNCTION: Involved in repair of UV radiation-induced DNA damage. Catalyzes the light-dependent monomerization (300-600 nm) of cyclobutyl pyrimidine dimers (in cis-syn configuration), which are formed between adjacent bases on the same DNA strand upon exposure to ultraviolet radiation.
|
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
|
P05067
|
A4_HUMAN
|
MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
| null | null |
adult locomotory behavior [GO:0008344]; amyloid fibril formation [GO:1990000]; astrocyte activation [GO:0048143]; astrocyte activation involved in immune response [GO:0002265]; axo-dendritic transport [GO:0008088]; axon midline choice point recognition [GO:0016199]; axonogenesis [GO:0007409]; cell adhesion [GO:0007155]; cellular response to amyloid-beta [GO:1904646]; central nervous system development [GO:0007417]; cholesterol metabolic process [GO:0008203]; cognition [GO:0050890]; collateral sprouting in absence of injury [GO:0048669]; cytoplasmic polyadenylation [GO:0180011]; dendrite development [GO:0016358]; endocytosis [GO:0006897]; extracellular matrix organization [GO:0030198]; forebrain development [GO:0030900]; G2/M transition of mitotic cell cycle [GO:0000086]; intracellular copper ion homeostasis [GO:0006878]; ionotropic glutamate receptor signaling pathway [GO:0035235]; learning [GO:0007612]; learning or memory [GO:0007611]; locomotory behavior [GO:0007626]; mating behavior [GO:0007617]; microglia development [GO:0014005]; microglial cell activation [GO:0001774]; modulation of excitatory postsynaptic potential [GO:0098815]; mRNA polyadenylation [GO:0006378]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of gene expression [GO:0010629]; negative regulation of long-term synaptic potentiation [GO:1900272]; negative regulation of neuron differentiation [GO:0045665]; neuromuscular process controlling balance [GO:0050885]; neuron apoptotic process [GO:0051402]; neuron cellular homeostasis [GO:0070050]; neuron projection development [GO:0031175]; neuron projection maintenance [GO:1990535]; neuron remodeling [GO:0016322]; NMDA selective glutamate receptor signaling pathway [GO:0098989]; Notch signaling pathway [GO:0007219]; positive regulation of amyloid fibril formation [GO:1905908]; positive regulation of calcium-mediated signaling [GO:0050850]; positive regulation of chemokine production [GO:0032722]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of G2/M transition of mitotic cell cycle [GO:0010971]; positive regulation of gene expression [GO:0010628]; positive regulation of glycolytic process [GO:0045821]; positive regulation of inflammatory response [GO:0050729]; positive regulation of interleukin-1 beta production [GO:0032731]; positive regulation of interleukin-6 production [GO:0032755]; positive regulation of JNK cascade [GO:0046330]; positive regulation of long-term synaptic potentiation [GO:1900273]; positive regulation of mitotic cell cycle [GO:0045931]; positive regulation of non-canonical NF-kappaB signal transduction [GO:1901224]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of peptidyl-threonine phosphorylation [GO:0010800]; positive regulation of protein metabolic process [GO:0051247]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of T cell migration [GO:2000406]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of tumor necrosis factor production [GO:0032760]; protein phosphorylation [GO:0006468]; regulation of epidermal growth factor-activated receptor activity [GO:0007176]; regulation of gene expression [GO:0010468]; regulation of long-term neuronal synaptic plasticity [GO:0048169]; regulation of multicellular organism growth [GO:0040014]; regulation of peptidyl-tyrosine phosphorylation [GO:0050730]; regulation of presynapse assembly [GO:1905606]; regulation of spontaneous synaptic transmission [GO:0150003]; regulation of synapse structure or activity [GO:0050803]; regulation of translation [GO:0006417]; regulation of Wnt signaling pathway [GO:0030111]; response to interleukin-1 [GO:0070555]; response to oxidative stress [GO:0006979]; smooth endoplasmic reticulum calcium ion homeostasis [GO:0051563]; suckling behavior [GO:0001967]; synapse organization [GO:0050808]; synaptic assembly at neuromuscular junction [GO:0051124]; visual learning [GO:0008542]
|
apical part of cell [GO:0045177]; axon [GO:0030424]; cell surface [GO:0009986]; cell-cell junction [GO:0005911]; ciliary rootlet [GO:0035253]; clathrin-coated pit [GO:0005905]; COPII-coated ER to Golgi transport vesicle [GO:0030134]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; dendrite [GO:0030425]; dendritic shaft [GO:0043198]; dendritic spine [GO:0043197]; early endosome [GO:0005769]; endoplasmic reticulum [GO:0005783]; endoplasmic reticulum lumen [GO:0005788]; endosome [GO:0005768]; endosome lumen [GO:0031904]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; Golgi apparatus [GO:0005794]; Golgi lumen [GO:0005796]; Golgi-associated vesicle [GO:0005798]; growth cone [GO:0030426]; membrane [GO:0016020]; membrane raft [GO:0045121]; mitochondrial inner membrane [GO:0005743]; neuromuscular junction [GO:0031594]; nuclear envelope lumen [GO:0005641]; perikaryon [GO:0043204]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; platelet alpha granule lumen [GO:0031093]; presynaptic active zone [GO:0048786]; receptor complex [GO:0043235]; recycling endosome [GO:0055037]; smooth endoplasmic reticulum [GO:0005790]; spindle midzone [GO:0051233]; synapse [GO:0045202]; synaptic vesicle [GO:0008021]; trans-Golgi network membrane [GO:0032588]
|
DNA binding [GO:0003677]; enzyme binding [GO:0019899]; heparin binding [GO:0008201]; identical protein binding [GO:0042802]; protein serine/threonine kinase binding [GO:0120283]; PTB domain binding [GO:0051425]; receptor ligand activity [GO:0048018]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; 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;
|
1.20.120.770;4.10.230.10;3.30.1490.140;3.90.570.10;4.10.410.10;2.30.29.30;
|
APP family
|
PTM: Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid-beta proteins, amyloid-beta protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). PSEN1 cleavage is more efficient with C83 than with C99 as substrate (in vitro) (PubMed:30630874). Amyloid-beta protein 40 and Amyloid-beta protein 42 are cleaved by ACE (PubMed:11604391, PubMed:16154999). Many other minor amyloid-beta peptides, amyloid-beta 1-X peptides, are found in cerebral spinal fluid (CSF) including the amyloid-beta X-15 peptides, produced from the cleavage by alpha-secretase and all terminating at Gln-686. {ECO:0000269|PubMed:10656250, ECO:0000269|PubMed:11604391, ECO:0000269|PubMed:16154999, ECO:0000269|PubMed:30630874}.; PTM: Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either CASP6, CASP8 or CASP9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides. {ECO:0000269|PubMed:10319819}.; PTM: N-glycosylated (PubMed:2900137). N- and O-glycosylated (PubMed:2649245). O-glycosylation on Ser and Thr residues with core 1 or possibly core 8 glycans. Partial tyrosine glycosylation (Tyr-681) is found on some minor, short amyloid-beta peptides (amyloid-beta 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on amyloid-beta protein 38, amyloid-beta protein 40 nor on amyloid-beta protein 42. Modification on a tyrosine is unusual and is more prevelant in AD patients. Glycans had Neu5AcHex(Neu5Ac)HexNAc-O-Tyr, Neu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr and O-AcNeu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr structures, where O-Ac is O-acetylation of Neu5Ac. Neu5AcNeu5Ac is most likely Neu5Ac 2,8Neu5Ac linked. O-glycosylations in the vicinity of the cleavage sites may influence the proteolytic processing. Appicans are L-APP isoforms with O-linked chondroitin sulfate. {ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:21712440, ECO:0000269|PubMed:22576872, ECO:0000269|PubMed:2649245, ECO:0000269|PubMed:2900137}.; PTM: Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific (PubMed:10341243). Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins (PubMed:10341243). Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta (PubMed:11146006, PubMed:8131745). The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members (PubMed:11517218). In dopaminergic (DA) neurons, phosphorylation on Thr-743 by LRKK2 promotes the production and the nuclear translocation of the APP intracellular domain (AICD) which induces DA neuron apoptosis (PubMed:28720718). Phosphorylation on Tyr-757 is required for SHC binding (PubMed:11877420). Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin (PubMed:8999878). {ECO:0000269|PubMed:10341243, ECO:0000269|PubMed:11146006, ECO:0000269|PubMed:11517218, ECO:0000269|PubMed:11877420, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:8131745, ECO:0000269|PubMed:8999878}.; PTM: Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu(+) complex in the presence of hydrogen peroxide results in an increased production of amyloid-beta-containing peptides.; PTM: Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP).; PTM: Amyloid-beta peptides are degraded by IDE. {ECO:0000250|UniProtKB:P12023}.; PTM: Sulfated on tyrosine residues. {ECO:0000269|PubMed:2649245}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10383380, ECO:0000269|PubMed:20580937, ECO:0000269|PubMed:2649245, ECO:0000305|PubMed:25122912}; Single-pass type I membrane protein {ECO:0000269|PubMed:30630874, ECO:0000305|PubMed:10383380, ECO:0000305|PubMed:25122912}. Membrane {ECO:0000269|PubMed:2900137, ECO:0000305|PubMed:22584060}; Single-pass type I membrane protein {ECO:0000269|PubMed:2900137, ECO:0000269|PubMed:30630874, ECO:0000305|PubMed:22584060}. Perikaryon {ECO:0000269|PubMed:10341243}. Cell projection, growth cone {ECO:0000269|PubMed:10341243}. Membrane, clathrin-coated pit {ECO:0000269|PubMed:20580937}. Early endosome {ECO:0000269|PubMed:20580937}. Cytoplasmic vesicle {ECO:0000269|PubMed:20580937, ECO:0000269|PubMed:25122912}. Note=Cell surface protein that rapidly becomes internalized via clathrin-coated pits. Only a minor proportion is present at the cell membrane; most of the protein is present in intracellular vesicles (PubMed:20580937). During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body (PubMed:10341243). Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment. Associates with GPC1 in perinuclear compartments. Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions. {ECO:0000269|PubMed:10341243, ECO:0000269|PubMed:20580937}.; SUBCELLULAR LOCATION: [C83]: Endoplasmic reticulum {ECO:0000269|PubMed:14527950}. Golgi apparatus {ECO:0000269|PubMed:14527950}. Early endosome {ECO:0000269|PubMed:14527950}.; SUBCELLULAR LOCATION: [C99]: Early endosome {ECO:0000269|PubMed:14527950}.; SUBCELLULAR LOCATION: [Soluble APP-beta]: Secreted {ECO:0000269|PubMed:10656250, ECO:0000269|PubMed:2649245}.; SUBCELLULAR LOCATION: [Amyloid-beta protein 40]: Cell surface {ECO:0000269|PubMed:16154999}.; SUBCELLULAR LOCATION: [Amyloid-beta protein 42]: Cell surface {ECO:0000269|PubMed:11689470, ECO:0000269|PubMed:16154999}. Note=Associates with FPR2 at the cell surface and the complex is then rapidly internalized. {ECO:0000269|PubMed:11689470}.; SUBCELLULAR LOCATION: [Gamma-secretase C-terminal fragment 59]: Nucleus {ECO:0000269|PubMed:11544248}. Cytoplasm {ECO:0000269|PubMed:11544248}. Note=Located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65) (PubMed:11544248). In dopaminergic neurons, the phosphorylated Thr-743 form is localized to the nucleus (By similarity). {ECO:0000250|UniProtKB:P12023, ECO:0000269|PubMed:11544248}.
| null | null | null | null | null |
FUNCTION: Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(o) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapses in axons (PubMed:17062754, PubMed:23011729). Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1. {ECO:0000250, ECO:0000250|UniProtKB:P12023, ECO:0000269|PubMed:17062754, ECO:0000269|PubMed:23011729, ECO:0000269|PubMed:25122912}.; FUNCTION: Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.; FUNCTION: Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain. {ECO:0000250}.; FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.; FUNCTION: N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
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Homo sapiens (Human)
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P05081
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KAD1_CHICK
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MSTEKLKHHKIIFVVGGPGSGKGTQCEKIVHKYGYTHLSTGDLLRAEVSSGSERGKKLQAIMEKGELVPLDTVLDMLRDAMLAKADTSKGFLIDGYPREVKQGEEFEKKIAPPTLLLYVDAGKETMVKRLLKRGETSGRVDDNEETIKKRLETYYKATEPVIAFYKGRGIVRQLNAEGTVDEVFQQVCSYLDKL
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2.7.4.10; 2.7.4.3; 2.7.4.6
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COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305|PubMed:1958702};
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ADP biosynthetic process [GO:0006172]; AMP metabolic process [GO:0046033]; ATP metabolic process [GO:0046034]; nucleoside triphosphate biosynthetic process [GO:0009142]; phosphorylation [GO:0016310]
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cytoplasm [GO:0005737]; cytosol [GO:0005829]
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adenylate kinase activity [GO:0004017]; ATP binding [GO:0005524]; cytidylate kinase activity [GO:0004127]; magnesium ion binding [GO:0000287]; nucleoside diphosphate kinase activity [GO:0004550]; nucleoside triphosphate adenylate kinase activity [GO:0046899]
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PF00406;
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3.40.50.300;
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Adenylate kinase family, AK1 subfamily
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:2229026}.
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CATALYTIC ACTIVITY: Reaction=AMP + ATP = 2 ADP; Xref=Rhea:RHEA:12973, ChEBI:CHEBI:30616, ChEBI:CHEBI:456215, ChEBI:CHEBI:456216; EC=2.7.4.3; Evidence={ECO:0000255|HAMAP-Rule:MF_03171, ECO:0000269|PubMed:1958702, ECO:0000269|PubMed:2161682, ECO:0000269|PubMed:2229026, ECO:0000269|PubMed:2542324, ECO:0000269|PubMed:8431472}; CATALYTIC ACTIVITY: Reaction=a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-deoxyribonucleoside 5'-triphosphate + ADP; Xref=Rhea:RHEA:44640, ChEBI:CHEBI:30616, ChEBI:CHEBI:61560, ChEBI:CHEBI:73316, ChEBI:CHEBI:456216; EC=2.7.4.6; Evidence={ECO:0000255|HAMAP-Rule:MF_03171}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-diphosphate + ATP = a ribonucleoside 5'-triphosphate + ADP; Xref=Rhea:RHEA:18113, ChEBI:CHEBI:30616, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557, ChEBI:CHEBI:456216; EC=2.7.4.6; Evidence={ECO:0000255|HAMAP-Rule:MF_03171}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + AMP = a ribonucleoside 5'-diphosphate + ADP; Xref=Rhea:RHEA:13749, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557, ChEBI:CHEBI:456215, ChEBI:CHEBI:456216; EC=2.7.4.10; Evidence={ECO:0000269|PubMed:1958702, ECO:0000269|PubMed:2161682, ECO:0000269|PubMed:2229026, ECO:0000269|PubMed:2542324, ECO:0000269|PubMed:8431472}; CATALYTIC ACTIVITY: Reaction=ATP + GDP = ADP + GTP; Xref=Rhea:RHEA:27686, ChEBI:CHEBI:30616, ChEBI:CHEBI:37565, ChEBI:CHEBI:58189, ChEBI:CHEBI:456216; EC=2.7.4.6; Evidence={ECO:0000250|UniProtKB:P00568}; CATALYTIC ACTIVITY: Reaction=ATP + UDP = ADP + UTP; Xref=Rhea:RHEA:25098, ChEBI:CHEBI:30616, ChEBI:CHEBI:46398, ChEBI:CHEBI:58223, ChEBI:CHEBI:456216; EC=2.7.4.6; Evidence={ECO:0000250|UniProtKB:P00568}; CATALYTIC ACTIVITY: Reaction=ATP + dGDP = ADP + dGTP; Xref=Rhea:RHEA:27690, ChEBI:CHEBI:30616, ChEBI:CHEBI:58595, ChEBI:CHEBI:61429, ChEBI:CHEBI:456216; EC=2.7.4.6; Evidence={ECO:0000250|UniProtKB:P00568}; CATALYTIC ACTIVITY: Reaction=ATP + dTDP = ADP + dTTP; Xref=Rhea:RHEA:27682, ChEBI:CHEBI:30616, ChEBI:CHEBI:37568, ChEBI:CHEBI:58369, ChEBI:CHEBI:456216; EC=2.7.4.6; Evidence={ECO:0000250|UniProtKB:P00568}; CATALYTIC ACTIVITY: Reaction=ADP + thiamine diphosphate = AMP + thiamine triphosphate; Xref=Rhea:RHEA:69180, ChEBI:CHEBI:58937, ChEBI:CHEBI:58938, ChEBI:CHEBI:456215, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:1958702, ECO:0000269|PubMed:2229026, ECO:0000269|PubMed:8431472};
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BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.17 mM for ATP {ECO:0000269|PubMed:2542324}; KM=0.6 mM for ADP {ECO:0000269|PubMed:2542324}; KM=0.17 mM for AMP {ECO:0000269|PubMed:2542324}; KM=0.094 mM for AMP {ECO:0000269|PubMed:2161682}; KM=2.25 mM for ThDP {ECO:0000269|PubMed:2229026}; KM=2.3 mM for ThDP {ECO:0000269|PubMed:1958702, ECO:0000269|PubMed:8431472}; KM=0.17 mM for ADP {ECO:0000269|PubMed:8431472}; Vmax=1.9 umol/h/mg enzyme for ThDP {ECO:0000269|PubMed:1958702}; Vmax=1900 nmol/h/mg enzyme for ThDP {ECO:0000269|PubMed:8431472}; Vmax=1000 umol/min/mg enzyme for ADP {ECO:0000269|PubMed:8431472};
| null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 9.0 for ThTP synthesis. {ECO:0000269|PubMed:1958702, ECO:0000269|PubMed:8431472};
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BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Thermostable. {ECO:0000269|PubMed:1958702, ECO:0000269|PubMed:8431472};
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FUNCTION: Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP (PubMed:1958702, PubMed:2161682, PubMed:2229026, PubMed:2542324). Exhibits nucleoside diphosphate kinase catalyzing the production of ATP, CTP, GTP, UTP, dATP, dCTP, dGTP and dTTP from the corresponding diphosphate substrates with either ATP or GTP as phosphate donor (By similarity). Also catalyzes at a very low rate the synthesis of thiamine triphosphate (ThTP) from thiamine diphosphate (ThDP) and ADP (PubMed:2229026, PubMed:8431472). {ECO:0000250|UniProtKB:P00568, ECO:0000269|PubMed:1958702, ECO:0000269|PubMed:2161682, ECO:0000269|PubMed:2229026, ECO:0000269|PubMed:2542324, ECO:0000269|PubMed:8431472}.
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Gallus gallus (Chicken)
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P05084
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HUNB_DROME
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MQNWETTATTNYEQHNAWYNSMFAANIKQEPGHHLDGNSVASSPRQSPIPSTNHLEQFLKQQQQQLQQQPMDTLCAMTPSPSQNDQNSLQHYDANLQQQLLQQQQYQQHFQAAQQQHHHHHHLMGGFNPLTPPGLPNPMQHFYGGNLRPSPQPTPTSASTIAPVAVATGSSEKLQALTPPMDVTPPKSPAKSSQSNIEPEKEHDQMSNSSEDMKYMAESEDDDTNIRMPIYNSHGKMKNYKCKTCGVVAITKVDFWAHTRTHMKPDKILQCPKCPFVTEFKHHLEYHIRKHKNQKPFQCDKCSYTCVNKSMLNSHRKSHSSVYQYRCADCDYATKYCHSFKLHLRKYGHKPGMVLDEDGTPNPSLVIDVYGTRRGPKSKNGGPIASGGSGSGSRKSNVAAVAPQQQQSQPAQPVATSQLSAALQGFPLVQGNSAPPAASPVLPLPASPAKSVASVEQTPSLPSPANLLPPLASLLQQNRNMAFFPYWNLNLQMLAAQQQAAVLAQLSPRMREQLQQQNQQQSDNEEEEQDDEYERKSVDSAMDLSQGTPVKEDEQQQQPQQPLAMNLKVEEEATPLMSSSNASRRKGRVLKLDTLLQLRSEAMTSPEQLKVPSTPMPTASSPIAGRKPMPEEHCSGTSSADESMETAHVPQANTSASSTASSSGNSSNASSNSNGNSSSNSSSNGTTSAVAAPPSGTPAAAGAIYECKYCDIFFKDAVLYTIHMGYHSCDDVFKCNMCGEKCDGPVGLFVHMARNAHS
| null | null |
anterior/posterior axis specification [GO:0009948]; ganglion mother cell fate determination [GO:0007402]; generation of neurons [GO:0048699]; negative regulation of transcription by RNA polymerase II [GO:0000122]; neuroblast fate determination [GO:0007400]; positive regulation of transcription by RNA polymerase II [GO:0045944]; posterior head segmentation [GO:0035289]; regulation of development, heterochronic [GO:0040034]; regulation of neural precursor cell proliferation [GO:2000177]; regulation of neurogenesis [GO:0050767]; regulation of transcription by RNA polymerase II [GO:0006357]; salivary gland development [GO:0007431]; trunk segmentation [GO:0035290]; ventral cord development [GO:0007419]; zygotic determination of anterior/posterior axis, embryo [GO:0007354]
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nucleus [GO:0005634]
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DNA-binding transcription factor activity [GO:0003700]; 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]; RNA polymerase II transcription regulatory region sequence-specific DNA binding [GO:0000977]; sequence-specific DNA binding [GO:0043565]
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PF00096;
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3.30.160.60;
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Hunchback C2H2-type zinc-finger protein family
| null |
SUBCELLULAR LOCATION: Nucleus.
| null | null | null | null | null |
FUNCTION: Gap class segmentation protein that controls development of head structures.
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Drosophila melanogaster (Fruit fly)
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P05089
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ARGI1_HUMAN
|
MSAKSRTIGIIGAPFSKGQPRGGVEEGPTVLRKAGLLEKLKEQECDVKDYGDLPFADIPNDSPFQIVKNPRSVGKASEQLAGKVAEVKKNGRISLVLGGDHSLAIGSISGHARVHPDLGVIWVDAHTDINTPLTTTSGNLHGQPVSFLLKELKGKIPDVPGFSWVTPCISAKDIVYIGLRDVDPGEHYILKTLGIKYFSMTEVDRLGIGKVMEETLSYLLGRKKRPIHLSFDVDGLDPSFTPATGTPVVGGLTYREGLYITEEIYKTGLLSGLDIMEVNPSLGKTPEEVTRTVNTAVAITLACFGLAREGNHKPIDYLNPPK
|
3.5.3.1
|
COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:16141327, ECO:0000269|PubMed:17469833, ECO:0000269|PubMed:17562323, ECO:0000269|PubMed:18802628}; Note=Binds 2 manganese ions per subunit. {ECO:0000269|PubMed:16141327, ECO:0000269|PubMed:17469833, ECO:0000269|PubMed:17562323, ECO:0000269|PubMed:18802628, ECO:0000269|PubMed:21728378};
|
adaptive immune response [GO:0002250]; arginine catabolic process [GO:0006527]; arginine catabolic process to ornithine [GO:0019547]; defense response to protozoan [GO:0042832]; innate immune response [GO:0045087]; negative regulation of activated T cell proliferation [GO:0046007]; negative regulation of T cell proliferation [GO:0042130]; negative regulation of T-helper 2 cell cytokine production [GO:2000552]; negative regulation of type II interferon-mediated signaling pathway [GO:0060336]; positive regulation of neutrophil mediated killing of fungus [GO:0070965]; urea cycle [GO:0000050]
|
azurophil granule lumen [GO:0035578]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; nucleus [GO:0005634]; specific granule lumen [GO:0035580]
|
arginase activity [GO:0004053]; manganese ion binding [GO:0030145]
|
PF00491;
|
3.40.800.10;
|
Arginase family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16141327}. Cytoplasmic granule {ECO:0000269|PubMed:15546957}. Note=Localized in azurophil granules of neutrophils (PubMed:15546957). {ECO:0000269|PubMed:15546957}.
|
CATALYTIC ACTIVITY: Reaction=H2O + L-arginine = L-ornithine + urea; Xref=Rhea:RHEA:20569, ChEBI:CHEBI:15377, ChEBI:CHEBI:16199, ChEBI:CHEBI:32682, ChEBI:CHEBI:46911; EC=3.5.3.1; Evidence={ECO:0000269|PubMed:16141327, ECO:0000269|PubMed:17562323, ECO:0000269|PubMed:21728378};
| null |
PATHWAY: Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine: step 1/1. {ECO:0000305|PubMed:16141327}.
| null | null |
FUNCTION: Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathways critical for cell proliferation, respectively; the urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys. {ECO:0000305}.; FUNCTION: Functions in L-arginine homeostasis in nonhepatic tissues characterized by the competition between nitric oxide synthase (NOS) and arginase for the available intracellular substrate arginine. Arginine metabolism is a critical regulator of innate and adaptive immune responses. Involved in an antimicrobial effector pathway in polymorphonuclear granulocytes (PMN). Upon PMN cell death is liberated from the phagolysosome and depletes arginine in the microenvironment leading to suppressed T cell and natural killer (NK) cell proliferation and cytokine secretion (PubMed:15546957, PubMed:16709924, PubMed:19380772). In group 2 innate lymphoid cells (ILC2s) promotes acute type 2 inflammation in the lung and is involved in optimal ILC2 proliferation but not survival (By similarity). In humans, the immunological role in the monocytic/macrophage/dendritic cell (DC) lineage is unsure. {ECO:0000250|UniProtKB:Q61176, ECO:0000269|PubMed:15546957, ECO:0000269|PubMed:16709924, ECO:0000269|PubMed:19380772}.
|
Homo sapiens (Human)
|
P05090
|
APOD_HUMAN
|
MVMLLLLLSALAGLFGAAEGQAFHLGKCPNPPVQENFDVNKYLGRWYEIEKIPTTFENGRCIQANYSLMENGKIKVLNQELRADGTVNQIEGEATPVNLTEPAKLEVKFSWFMPSAPYWILATDYENYALVYSCTCIIQLFHVDFAWILARNPNLPPETVDSLKNILTSNNIDVKKMTVTDQVNCPKLS
| null | null |
angiogenesis [GO:0001525]; brain development [GO:0007420]; glucose metabolic process [GO:0006006]; lipid metabolic process [GO:0006629]; negative regulation of cytokine production involved in inflammatory response [GO:1900016]; negative regulation of focal adhesion assembly [GO:0051895]; negative regulation of lipoprotein lipid oxidation [GO:0060588]; negative regulation of monocyte chemotactic protein-1 production [GO:0071638]; negative regulation of platelet-derived growth factor receptor signaling pathway [GO:0010642]; negative regulation of protein import into nucleus [GO:0042308]; negative regulation of smooth muscle cell proliferation [GO:0048662]; negative regulation of smooth muscle cell-matrix adhesion [GO:2000098]; negative regulation of T cell migration [GO:2000405]; peripheral nervous system axon regeneration [GO:0014012]; response to axon injury [GO:0048678]; response to reactive oxygen species [GO:0000302]; tissue regeneration [GO:0042246]
|
cytoplasm [GO:0005737]; cytosolic ribosome [GO:0022626]; dendrite [GO:0030425]; endoplasmic reticulum [GO:0005783]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; neuronal cell body [GO:0043025]; perinuclear region of cytoplasm [GO:0048471]
|
cholesterol binding [GO:0015485]; lipid transporter activity [GO:0005319]
|
PF08212;
|
2.40.128.20;
|
Calycin superfamily, Lipocalin family
|
PTM: N-glycosylatd. N-glycan heterogeneity at Asn-65: Hex5HexNAc4 (major) and Hex6HexNAc5 (minor); at Asn-98: Hex5HexNAc4 (minor), dHex1Hex5HexNAc4 (major), dHex1Hex6HexNAc5 (minor) and dHex1Hex7HexNAc6 (minor). {ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:7613477, ECO:0000269|PubMed:7918467}.
|
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: APOD occurs in the macromolecular complex with lecithin-cholesterol acyltransferase. It is probably involved in the transport and binding of bilin. Appears to be able to transport a variety of ligands in a number of different contexts.
|
Homo sapiens (Human)
|
P05091
|
ALDH2_HUMAN
|
MLRAAARFGPRLGRRLLSAAATQAVPAPNQQPEVFCNQIFINNEWHDAVSRKTFPTVNPSTGEVICQVAEGDKEDVDKAVKAARAAFQLGSPWRRMDASHRGRLLNRLADLIERDRTYLAALETLDNGKPYVISYLVDLDMVLKCLRYYAGWADKYHGKTIPIDGDFFSYTRHEPVGVCGQIIPWNFPLLMQAWKLGPALATGNVVVMKVAEQTPLTALYVANLIKEAGFPPGVVNIVPGFGPTAGAAIASHEDVDKVAFTGSTEIGRVIQVAAGSSNLKRVTLELGGKSPNIIMSDADMDWAVEQAHFALFFNQGQCCCAGSRTFVQEDIYDEFVERSVARAKSRVVGNPFDSKTEQGPQVDETQFKKILGYINTGKQEGAKLLCGGGIAADRGYFIQPTVFGDVQDGMTIAKEEIFGPVMQILKFKTIEEVVGRANNSTYGLAAAVFTKDLDKANYLSQALQAGTVWVNCYDVFGAQSPFGGYKMSGSGRELGEYGLQAYTEVKTVTVKVPQKNS
|
1.2.1.3
| null |
alcohol metabolic process [GO:0006066]; aldehyde catabolic process [GO:0046185]; carbohydrate metabolic process [GO:0005975]; ethanol catabolic process [GO:0006068]; regulation of dopamine biosynthetic process [GO:1903179]; regulation of serotonin biosynthetic process [GO:1905627]
|
extracellular exosome [GO:0070062]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
|
aldehyde dehydrogenase (NAD+) activity [GO:0004029]; aldehyde dehydrogenase [NAD(P)+] activity [GO:0004030]; carboxylesterase activity [GO:0106435]; electron transfer activity [GO:0009055]; glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity [GO:0043878]; NAD binding [GO:0051287]; nitroglycerin reductase activity [GO:0018547]; phenylacetaldehyde dehydrogenase activity [GO:0008957]
|
PF00171;
| null |
Aldehyde dehydrogenase family
| null |
SUBCELLULAR LOCATION: Mitochondrion matrix.
|
CATALYTIC ACTIVITY: Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH; Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.3;
| null |
PATHWAY: Alcohol metabolism; ethanol degradation; acetate from ethanol: step 2/2.
| null | null |
FUNCTION: Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage. {ECO:0000269|PubMed:33355142}.
|
Homo sapiens (Human)
|
P05093
|
CP17A_HUMAN
|
MWELVALLLLTLAYLFWPKRRCPGAKYPKSLLSLPLVGSLPFLPRHGHMHNNFFKLQKKYGPIYSVRMGTKTTVIVGHHQLAKEVLIKKGKDFSGRPQMATLDIASNNRKGIAFADSGAHWQLHRRLAMATFALFKDGDQKLEKIICQEISTLCDMLATHNGQSIDISFPVFVAVTNVISLICFNTSYKNGDPELNVIQNYNEGIIDNLSKDSLVDLVPWLKIFPNKTLEKLKSHVKIRNDLLNKILENYKEKFRSDSITNMLDTLMQAKMNSDNGNAGPDQDSELLSDNHILTTIGDIFGAGVETTTSVVKWTLAFLLHNPQVKKKLYEEIDQNVGFSRTPTISDRNRLLLLEATIREVLRLRPVAPMLIPHKANVDSSIGEFAVDKGTEVIINLWALHHNEKEWHQPDQFMPERFLNPAGTQLISPSVSYLPFGAGPRSCIGEILARQELFLIMAWLLQRFDLEVPDDGQLPSLEGIPKVVFLIDSFKVKIKVRQAWREAQAEGST
|
1.14.14.19; 1.14.14.32
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938};
|
androgen biosynthetic process [GO:0006702]; glucocorticoid biosynthetic process [GO:0006704]; hormone biosynthetic process [GO:0042446]; progesterone metabolic process [GO:0042448]; sex differentiation [GO:0007548]; steroid biosynthetic process [GO:0006694]; steroid metabolic process [GO:0008202]
|
axon [GO:0030424]; endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; neuronal cell body [GO:0043025]
|
17-alpha-hydroxyprogesterone aldolase activity [GO:0047442]; heme binding [GO:0020037]; iron ion binding [GO:0005506]; oxygen binding [GO:0019825]; steroid 17-alpha-monooxygenase activity [GO:0004508]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
|
PTM: Phosphorylation is necessary for 17,20-lyase, but not for 17-alpha-hydroxylase activity. {ECO:0000269|PubMed:10720067}.
|
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305|PubMed:2808364}. Microsome membrane {ECO:0000305|PubMed:2808364}.
|
CATALYTIC ACTIVITY: Reaction=a C21-steroid + O2 + reduced [NADPH--hemoprotein reductase] = a 17alpha-hydroxy-C21-steroid + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:65760, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:61313, ChEBI:CHEBI:138141; EC=1.14.14.19; Evidence={ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:27339894}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65761; Evidence={ECO:0000305}; CATALYTIC ACTIVITY: Reaction=O2 + progesterone + reduced [NADPH--hemoprotein reductase] = 17alpha-hydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46308, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17026, ChEBI:CHEBI:17252, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.19; Evidence={ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:36640554, ECO:0000269|PubMed:9452426}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46309; Evidence={ECO:0000305|PubMed:9452426}; CATALYTIC ACTIVITY: Reaction=O2 + pregnenolone + reduced [NADPH--hemoprotein reductase] = 17alpha-hydroxypregnenolone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50236, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16581, ChEBI:CHEBI:28750, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.19; Evidence={ECO:0000269|PubMed:36640554, ECO:0000269|PubMed:9452426}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50237; Evidence={ECO:0000305|PubMed:9452426}; CATALYTIC ACTIVITY: Reaction=17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein reductase] = acetate + androst-4-ene-3,17-dione + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:14753, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16422, ChEBI:CHEBI:17252, ChEBI:CHEBI:30089, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.32; Evidence={ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:27339894, ECO:0000269|PubMed:36640554}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14754; Evidence={ECO:0000305|PubMed:22266943}; CATALYTIC ACTIVITY: Reaction=17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha,17alpha-dihydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53216, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:763, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17252, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:27339894}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53217; Evidence={ECO:0000305|PubMed:27339894}; CATALYTIC ACTIVITY: Reaction=16alpha,17alpha-dihydroxyprogesterone + O2 + reduced [NADPH--hemoprotein reductase] = 6beta,16alpha,17alpha-trihydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53220, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:763, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137046; Evidence={ECO:0000269|PubMed:27339894}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53221; Evidence={ECO:0000305|PubMed:27339894}; CATALYTIC ACTIVITY: Reaction=17alpha-hydroxypregnenolone + O2 + reduced [NADPH--hemoprotein reductase] = 3beta-hydroxyandrost-5-en-17-one + acetate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50244, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:28689, ChEBI:CHEBI:28750, ChEBI:CHEBI:30089, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.32; Evidence={ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:27339894}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50245; Evidence={ECO:0000305|PubMed:22266943}; CATALYTIC ACTIVITY: Reaction=16alpha,17alpha-dihydroxypregnenolone + O2 + reduced [NADPH--hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-en-17-one + acetate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53224, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:27771, ChEBI:CHEBI:30089, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137049; Evidence={ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:27339894}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53225; Evidence={ECO:0000305|PubMed:27339894}; CATALYTIC ACTIVITY: Reaction=3beta-hydroxyandrost-5-en-17-one + O2 + reduced [NADPH--hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-en-17-one + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47220, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:27771, ChEBI:CHEBI:28689, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:27339894}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47221; Evidence={ECO:0000305|PubMed:27339894}; CATALYTIC ACTIVITY: Reaction=androst-4-ene-3,17-dione + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha-hydroxyandrost-4-ene-3,17-dione + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53228, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16422, ChEBI:CHEBI:27582, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:27339894}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53229; Evidence={ECO:0000305|PubMed:27339894};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=10.5 uM for progesterone (17-alpha hydroxylation) {ECO:0000269|PubMed:25301938}; KM=5.87 uM for progesterone (17-alpha hydroxylation) {ECO:0000269|PubMed:36640554}; KM=0.93 uM for pregnenolone (17-alpha hydroxylation) {ECO:0000269|PubMed:25301938}; KM=1.19 uM for pregnenolone (17-alpha hydroxylation) {ECO:0000269|PubMed:36640554}; KM=1.2 uM for 17alpha-hydroxypregnenolone (17,20 lyase activity) {ECO:0000269|PubMed:25301938}; KM=21.9 uM for 17alpha-hydroxyprogesterone (17,20 lyase activity) {ECO:0000269|PubMed:36640554}; Note=kcat is 1.01 min(-1) with progesterone as substrate. kcat is 0.39 min(-1) with pregnenolone as substrate. kcat is 0.24 min(-1) with 17alpha-hydroxypregnenolone as substrate.;
|
PATHWAY: Steroid hormone biosynthesis. {ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:27339894, ECO:0000269|PubMed:9452426}.; PATHWAY: Steroid biosynthesis; glucocorticoid biosynthesis. {ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:9452426}.
| null | null |
FUNCTION: A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426). Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (Probable) (PubMed:25301938, PubMed:9452426). Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:36640554, PubMed:9452426). Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA (PubMed:36640554). Also 16-alpha hydroxylates androgens, relevant for estriol synthesis (PubMed:25301938, PubMed:27339894). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426). {ECO:0000269|PubMed:22266943, ECO:0000269|PubMed:25301938, ECO:0000269|PubMed:27339894, ECO:0000269|PubMed:36640554, ECO:0000269|PubMed:9452426, ECO:0000305|PubMed:8027220}.
|
Homo sapiens (Human)
|
P05094
|
ACTN1_CHICK
|
MDHHYDPQQTNDYMQPEEDWDRDLLLDPAWEKQQRKTFTAWCNSHLRKAGTQIENIEEDFRDGLKLMLLLEVISGERLAKPERGKMRVHKISNVNKALDFIASKGVKLVSIGAEEIVDGNVKMTLGMIWTIILRFAIQDISVEETSAKEGLLLWCQRKTAPYKNVNIQNFHISWKDGLGFCALIHRHRPELIDYGKLRKDDPLTNLNTAFDVAEKYLDIPKMLDAEDIVGTARPDEKAIMTYVSSFYHAFSGAQKAETAANRICKVLAVNQENEQLMEDYEKLASDLLEWIRRTIPWLENRAPENTMQAMQQKLEDFRDYRRLHKPPKVQEKCQLEINFNTLQTKLRLSNRPAFMPSEGKMVSDINNAWGGLEQAEKGYEEWLLNEIRRLERLDHLAEKFRQKASIHESWTDGKEAMLQQKDYETATLSEIKALLKKHEAFESDLAAHQDRVEQIAAIAQELNELDYYDSPSVNARCQKICDQWDNLGALTQKRREALERTEKLLETIDQLYLEYAKRAAPFNNWMEGAMEDLQDTFIVHTIEEIQGLTTAHEQFKATLPDADKERQAILGIHNEVSKIVQTYHVNMAGTNPYTTITPQEINGKWEHVRQLVPRRDQALMEEHARQQQNERLRKQFGAQANVIGPWIQTKMEEIGRISIEMHGTLEDQLNHLRQYEKSIVNYKPKIDQLEGDHQQIQEALIFDNKHTNYTMEHIRVGWEQLLTTIARTINEVENQILTRDAKGISQEQMNEFRASFNHFDRDHSGTLGPEEFKACLISLGYDIGNDAQGEAEFARIMSIVDPNRMGVVTFQAFIDFMSRETADTDTADQVMASFKILAGDKNYITVDELRRELPPDQAEYCIARMAPYNGRDAVPGALDYMSFSTALYGESDL
| null | null |
actin cytoskeleton organization [GO:0030036]; muscle cell development [GO:0055001]; sarcomere organization [GO:0045214]; skeletal muscle fiber development [GO:0048741]
|
bicellular tight junction [GO:0005923]; cell junction [GO:0030054]; cell leading edge [GO:0031252]; cell projection [GO:0042995]; cortical actin cytoskeleton [GO:0030864]; dense body [GO:0097433]; focal adhesion [GO:0005925]; inner dense plaque of desmosome [GO:0090637]; lamellipodium [GO:0030027]; lateral plasma membrane [GO:0016328]; outer dense plaque of desmosome [GO:0090636]; plasma membrane [GO:0005886]; ruffle [GO:0001726]; sarcolemma [GO:0042383]; smooth muscle dense body [GO:0030486]; stress fiber [GO:0001725]; terminal web [GO:1990357]; Z disc [GO:0030018]; zonula adherens [GO:0005915]
|
actin filament binding [GO:0051015]; alpha-actinin binding [GO:0051393]; calcium ion binding [GO:0005509]; LIM domain binding [GO:0030274]; phosphoprotein binding [GO:0051219]; protein homodimerization activity [GO:0042803]; vinculin binding [GO:0017166]
|
PF00307;PF13405;PF08726;PF00435;
|
1.20.58.60;1.10.418.10;1.10.238.10;
|
Alpha-actinin family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q9Z1P2}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000250|UniProtKB:P12814}. Cell membrane {ECO:0000250|UniProtKB:Q9Z1P2}. Cell junction {ECO:0000250|UniProtKB:Q9Z1P2}. Cell projection, ruffle {ECO:0000250|UniProtKB:Q7TPR4}.
| null | null | null | null | null |
FUNCTION: F-actin cross-linking protein is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.
|
Gallus gallus (Chicken)
|
P05095
|
ACTNA_DICDI
|
MSEEPTPVSGNDKQLLNKAWEITQKKTFTAWCNSHLRKLGSSIEQIDTDFTDGIKLAQLLEVISNDPVFKVNKTPKLRIHNIQNVGLCLKHIESHGVKLVGIGAEELVDKNLKMTLGMIWTIILRFAIQDISIEELSAKEALLLWCQRKTEGYDRVKVGNFHTSFQDGLAFCALIHKHRPDLINFDSLNKDDKAGNLQLAFDIAEKELDIPKMLDVSDMLDVVRPDERSVMTYVAQYYHHFSASRKAETAGKQVGKVLDTFMLLEQTKSDYLKRANELVQWINDKQASLESRDFGDSIESVQSFMNAHKEYKKTEKPPKGQEVSELEAIYNSLQTKLRLIKREPFVAPAGLTPNEIDSTWSALEKAEQEHAEALRIELKRQKKIAVLLQKYNRILKKLENWATTKSVYLGSNETGDSITAVQAKLKNLEAFDGECQSLEGQSNSDLLSILAQLTELNYNGVPELTERKDTFFAQQWTGVKSSAETYKNTLLAELERLQKIEDSLVEFAKRAAQLNVWIEAADDHVFDPINVDSVQGVQEIQEKFDAFLHDQSQQFAELEALAALTQQLRELGRSENDYSVISYDELSAKWNNLLAGIEERKVQLANELTTQTNNDVLCQSFSVKANEISDYVRVTLDAISQNTSSDPQEQLNNIRAIITAHAEKKPELDELYTIASQLEEAQVVDNKHTQHSLESIKLKWDKLNTLAKKNEQVVEGEILAKQLTGVTAEELSEFKACFSHFDKDNDNKLNRLEFSSCLKSIGDELTEEQLNQVISKIDTDGNGTISFEEFIDYMVSSRKGTDSVESTKAAFKVMAEDKDFITEAQIRAAISDSKQIDYLLASMPAVEGGFDYNSFAEKLYQ
| null | null |
actin crosslink formation [GO:0051764]; actin cytoskeleton organization [GO:0030036]; actin filament bundle assembly [GO:0051017]; cell motility [GO:0048870]; cellular response to starvation [GO:0009267]; hyperosmotic response [GO:0006972]; phagocytosis [GO:0006909]; sorocarp development [GO:0030587]
|
actin filament [GO:0005884]; cell cortex [GO:0005938]; cell junction [GO:0030054]; cell leading edge [GO:0031252]; cell projection [GO:0042995]; contractile vacuole [GO:0000331]; cortical actin cytoskeleton [GO:0030864]; cytosol [GO:0005829]; extracellular matrix [GO:0031012]; macropinocytic cup [GO:0070685]; phagocytic vesicle [GO:0045335]; plasma membrane [GO:0005886]; pseudopodium [GO:0031143]
|
actin filament binding [GO:0051015]; calcium ion binding [GO:0005509]; protein-macromolecule adaptor activity [GO:0030674]; structural constituent of cytoskeleton [GO:0005200]
|
PF00307;PF13499;PF08726;PF00435;
|
1.20.58.60;1.10.418.10;1.10.238.10;
|
Alpha-actinin family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7820857}. Cytoplasm, cell cortex {ECO:0000269|PubMed:7820857}. Contractile vacuole {ECO:0000269|PubMed:7820857}. Cytoplasmic vesicle, phagosome {ECO:0000269|PubMed:7820857}. Note=Expressed diffusely throughout the cytoplasm. Accumulates in the cell cortex, contractile vesicle and phagosome.
| null | null | null | null | null |
FUNCTION: F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. Increases the actin-stimulated ATPase activity of myosin. Involved in vegetative cell growth, phagocytosis, motility and development, probably through stabilization of the actin network in the cortical cytoskeleton. {ECO:0000269|PubMed:10411959, ECO:0000269|PubMed:10413681, ECO:0000269|PubMed:10704840, ECO:0000269|PubMed:1732064, ECO:0000269|PubMed:3956480, ECO:0000269|PubMed:6746725, ECO:0000269|PubMed:8486739, ECO:0000269|PubMed:8937986}.
|
Dictyostelium discoideum (Social amoeba)
|
P05102
|
MTH1_HAEPH
|
MIEIKDKQLTGLRFIDLFAGLGGFRLALESCGAECVYSNEWDKYAQEVYEMNFGEKPEGDITQVNEKTIPDHDILCAGFPCQAFSISGKQKGFEDSRGTLFFDIARIVREKKPKVVFMENVKNFASHDNGNTLEVVKNTMNELDYSFHAKVLNALDYGIPQKRERIYMICFRNDLNIQNFQFPKPFELNTFVKDLLLPDSEVEHLVIDRKDLVMTNQEIEQTTPKTVRLGIVGKGGQGERIYSTRGIAITLSAYGGGIFAKTGGYLVNGKTRKLHPRECARVMGYPDSYKVHPSTSQAYKQFGNSVVINVLQYIAYNIGSSLNFKPY
|
2.1.1.37
| null |
DNA restriction-modification system [GO:0009307]; methylation [GO:0032259]
| null |
DNA (cytosine-5-)-methyltransferase activity [GO:0003886]; DNA binding [GO:0003677]
|
PF00145;
|
3.90.120.10;3.40.50.150;
|
Class I-like SAM-binding methyltransferase superfamily, C5-methyltransferase family
| null | null |
CATALYTIC ACTIVITY: Reaction=a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-methyl-2'-deoxycytidine in DNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:13681, Rhea:RHEA-COMP:11369, Rhea:RHEA-COMP:11370, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:85452, ChEBI:CHEBI:85454; EC=2.1.1.37; Evidence={ECO:0000255|PROSITE-ProRule:PRU10018, ECO:0000269|PubMed:7899082};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=69 nM for DNA {ECO:0000269|PubMed:7899082}; KM=15 nM for S-adenosyl-L-methionine (SAM) {ECO:0000269|PubMed:7899082}; Vmax=87 nmol/min/mg enzyme {ECO:0000269|PubMed:7899082};
| null | null | null |
FUNCTION: A methylase, recognizes the double-stranded sequence 5'-GCGC-3', methylates C-2 on both strands, and protects the DNA from cleavage by the HhaI endonuclease. {ECO:0000269|PubMed:3549710, ECO:0000269|PubMed:7899082, ECO:0000303|PubMed:12654995}.
|
Haemophilus parahaemolyticus
|
P05106
|
ITB3_HUMAN
|
MRARPRPRPLWATVLALGALAGVGVGGPNICTTRGVSSCQQCLAVSPMCAWCSDEALPLGSPRCDLKENLLKDNCAPESIEFPVSEARVLEDRPLSDKGSGDSSQVTQVSPQRIALRLRPDDSKNFSIQVRQVEDYPVDIYYLMDLSYSMKDDLWSIQNLGTKLATQMRKLTSNLRIGFGAFVDKPVSPYMYISPPEALENPCYDMKTTCLPMFGYKHVLTLTDQVTRFNEEVKKQSVSRNRDAPEGGFDAIMQATVCDEKIGWRNDASHLLVFTTDAKTHIALDGRLAGIVQPNDGQCHVGSDNHYSASTTMDYPSLGLMTEKLSQKNINLIFAVTENVVNLYQNYSELIPGTTVGVLSMDSSNVLQLIVDAYGKIRSKVELEVRDLPEELSLSFNATCLNNEVIPGLKSCMGLKIGDTVSFSIEAKVRGCPQEKEKSFTIKPVGFKDSLIVQVTFDCDCACQAQAEPNSHRCNNGNGTFECGVCRCGPGWLGSQCECSEEDYRPSQQDECSPREGQPVCSQRGECLCGQCVCHSSDFGKITGKYCECDDFSCVRYKGEMCSGHGQCSCGDCLCDSDWTGYYCNCTTRTDTCMSSNGLLCSGRGKCECGSCVCIQPGSYGDTCEKCPTCPDACTFKKECVECKKFDRGALHDENTCNRYCRDEIESVKELKDTGKDAVNCTYKNEDDCVVRFQYYEDSSGKSILYVVEEPECPKGPDILVVLLSVMGAILLIGLAALLIWKLLITIHDRKEFAKFEEERARAKWDTANNPLYKEATSTFTNITYRGT
| null | null |
activation of protein kinase activity [GO:0032147]; angiogenesis involved in wound healing [GO:0060055]; apolipoprotein A-I-mediated signaling pathway [GO:0038027]; apoptotic cell clearance [GO:0043277]; blood coagulation [GO:0007596]; blood coagulation, fibrin clot formation [GO:0072378]; cell adhesion [GO:0007155]; cell adhesion mediated by integrin [GO:0033627]; cell-matrix adhesion [GO:0007160]; cell-substrate adhesion [GO:0031589]; cell-substrate junction assembly [GO:0007044]; cellular response to insulin-like growth factor stimulus [GO:1990314]; cellular response to mechanical stimulus [GO:0071260]; cellular response to platelet-derived growth factor stimulus [GO:0036120]; cellular response to xenobiotic stimulus [GO:0071466]; embryo implantation [GO:0007566]; heterotypic cell-cell adhesion [GO:0034113]; integrin-mediated signaling pathway [GO:0007229]; maintenance of postsynaptic specialization structure [GO:0098880]; mesodermal cell differentiation [GO:0048333]; negative chemotaxis [GO:0050919]; negative regulation of endothelial cell apoptotic process [GO:2000352]; negative regulation of lipid storage [GO:0010888]; negative regulation of lipid transport [GO:0032369]; negative regulation of lipoprotein metabolic process [GO:0050748]; negative regulation of low-density lipoprotein receptor activity [GO:1905598]; negative regulation of macrophage derived foam cell differentiation [GO:0010745]; platelet activation [GO:0030168]; platelet aggregation [GO:0070527]; platelet-derived growth factor receptor signaling pathway [GO:0048008]; positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway [GO:1900731]; positive regulation of angiogenesis [GO:0045766]; positive regulation of bone resorption [GO:0045780]; positive regulation of cell adhesion mediated by integrin [GO:0033630]; positive regulation of cell-matrix adhesion [GO:0001954]; positive regulation of endothelial cell migration [GO:0010595]; positive regulation of endothelial cell proliferation [GO:0001938]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of fibroblast migration [GO:0010763]; positive regulation of fibroblast proliferation [GO:0048146]; positive regulation of gene expression [GO:0010628]; positive regulation of glomerular mesangial cell proliferation [GO:0072126]; positive regulation of osteoblast proliferation [GO:0033690]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of smooth muscle cell migration [GO:0014911]; positive regulation of smooth muscle cell proliferation [GO:0048661]; positive regulation of substrate adhesion-dependent cell spreading [GO:1900026]; positive regulation of T cell migration [GO:2000406]; positive regulation of vascular endothelial growth factor receptor signaling pathway [GO:0030949]; regulation of actin cytoskeleton organization [GO:0032956]; regulation of bone resorption [GO:0045124]; regulation of extracellular matrix organization [GO:1903053]; regulation of postsynaptic neurotransmitter receptor diffusion trapping [GO:0150054]; regulation of postsynaptic neurotransmitter receptor internalization [GO:0099149]; regulation of protein localization [GO:0032880]; regulation of release of sequestered calcium ion into cytosol [GO:0051279]; regulation of serotonin uptake [GO:0051611]; regulation of trophoblast cell migration [GO:1901163]; response to activity [GO:0014823]; smooth muscle cell migration [GO:0014909]; substrate adhesion-dependent cell spreading [GO:0034446]; symbiont entry into host cell [GO:0046718]; tube development [GO:0035295]; wound healing [GO:0042060]; wound healing, spreading of epidermal cells [GO:0035313]
|
alpha9-beta1 integrin-ADAM8 complex [GO:0071133]; alphav-beta3 integrin-HMGB1 complex [GO:0035868]; alphav-beta3 integrin-IGF-1-IGF1R complex [GO:0035867]; alphav-beta3 integrin-PKCalpha complex [GO:0035866]; alphav-beta3 integrin-vitronectin complex [GO:0071062]; apical plasma membrane [GO:0016324]; cell surface [GO:0009986]; cell-cell junction [GO:0005911]; external side of plasma membrane [GO:0009897]; extracellular exosome [GO:0070062]; filopodium membrane [GO:0031527]; focal adhesion [GO:0005925]; glutamatergic synapse [GO:0098978]; glycinergic synapse [GO:0098690]; integrin alphav-beta3 complex [GO:0034683]; integrin complex [GO:0008305]; lamellipodium membrane [GO:0031258]; melanosome [GO:0042470]; microvillus membrane [GO:0031528]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; platelet alpha granule membrane [GO:0031092]; postsynaptic membrane [GO:0045211]; protein-containing complex [GO:0032991]; receptor complex [GO:0043235]; ruffle membrane [GO:0032587]; synapse [GO:0045202]
|
cell adhesion molecule binding [GO:0050839]; coreceptor activity [GO:0015026]; enzyme binding [GO:0019899]; extracellular matrix binding [GO:0050840]; fibrinogen binding [GO:0070051]; fibronectin binding [GO:0001968]; identical protein binding [GO:0042802]; integrin binding [GO:0005178]; metal ion binding [GO:0046872]; platelet-derived growth factor receptor binding [GO:0005161]; protease binding [GO:0002020]; protein disulfide isomerase activity [GO:0003756]; protein kinase C binding [GO:0005080]; vascular endothelial growth factor receptor 2 binding [GO:0043184]; virus receptor activity [GO:0001618]
|
PF07974;PF18372;PF08725;PF07965;PF00362;PF17205;
|
4.10.1240.30;1.20.5.100;2.10.25.10;3.30.1680.10;2.60.40.1510;3.40.50.410;
|
Integrin beta chain family
|
PTM: Phosphorylated on tyrosine residues in response to thrombin-induced platelet aggregation. Probably involved in outside-in signaling. A peptide (AA 740-762) is capable of binding GRB2 only when both Tyr-773 and Tyr-785 are phosphorylated. Phosphorylation of Thr-779 inhibits SHC binding. {ECO:0000269|PubMed:10896934}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20020534, ECO:0000269|PubMed:20702409, ECO:0000269|PubMed:9195946}; Single-pass type I membrane protein {ECO:0000269|PubMed:20020534, ECO:0000269|PubMed:20702409, ECO:0000269|PubMed:9195946}. Cell projection, lamellipodium membrane {ECO:0000269|PubMed:20702409}. Cell junction, focal adhesion {ECO:0000269|PubMed:20702409, ECO:0000269|PubMed:35687021}. Postsynaptic cell membrane {ECO:0000250|UniProtKB:O54890}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:O54890}. Synapse {ECO:0000250|UniProtKB:O54890}.
| null | null | null | null | null |
FUNCTION: Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Fibrinogen binding enhances SELP expression in activated platelets (By similarity). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415, PubMed:24789099). ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (PubMed:18441324). ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (PubMed:28302677). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:19578119). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (PubMed:29030430). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGAV:ITGB3 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887). In brain, plays a role in synaptic transmission and plasticity. Involved in the regulation of the serotonin neurotransmission, is required to localize to specific compartments within the synapse the serotonin receptor SLC6A4 and for an appropriate reuptake of serotonin. Controls excitatory synaptic strength by regulating GRIA2-containing AMPAR endocytosis, which affects AMPAR abundance and composition (By similarity). ITGAV:ITGB3 act as a receptor for CD40LG (PubMed:31331973). ITGAV:ITGB3 acts as a receptor for IBSP and promotes cell adhesion and migration to IBSP (PubMed:10640428). {ECO:0000250|UniProtKB:O54890, ECO:0000269|PubMed:10640428, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19578119, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:24789099, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:28302677, ECO:0000269|PubMed:28873464, ECO:0000269|PubMed:29030430, ECO:0000269|PubMed:31331973, ECO:0000269|PubMed:9195946, ECO:0000303|PubMed:16322781, ECO:0000303|PubMed:17635696}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Herpes virus 8/HHV-8. {ECO:0000269|PubMed:18045938}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Coxsackievirus A9. {ECO:0000269|PubMed:7519807}.; FUNCTION: (Microbial infection) Acts as a receptor for Hantaan virus. {ECO:0000269|PubMed:9618541}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Cytomegalovirus/HHV-5. {ECO:0000269|PubMed:15834425}.; FUNCTION: (Microbial infection) Integrin ITGA5:ITGB3 acts as a receptor for Human metapneumovirus. {ECO:0000269|PubMed:24478423}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts aP05556s a receptor for Human parechovirus 1. {ECO:0000269|PubMed:11160695}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus. {ECO:0000269|PubMed:23658209}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. {ECO:0000269|PubMed:10397733}.
|
Homo sapiens (Human)
|
P05107
|
ITB2_HUMAN
|
MLGLRPPLLALVGLLSLGCVLSQECTKFKVSSCRECIESGPGCTWCQKLNFTGPGDPDSIRCDTRPQLLMRGCAADDIMDPTSLAETQEDHNGGQKQLSPQKVTLYLRPGQAAAFNVTFRRAKGYPIDLYYLMDLSYSMLDDLRNVKKLGGDLLRALNEITESGRIGFGSFVDKTVLPFVNTHPDKLRNPCPNKEKECQPPFAFRHVLKLTNNSNQFQTEVGKQLISGNLDAPEGGLDAMMQVAACPEEIGWRNVTRLLVFATDDGFHFAGDGKLGAILTPNDGRCHLEDNLYKRSNEFDYPSVGQLAHKLAENNIQPIFAVTSRMVKTYEKLTEIIPKSAVGELSEDSSNVVHLIKNAYNKLSSRVFLDHNALPDTLKVTYDSFCSNGVTHRNQPRGDCDGVQINVPITFQVKVTATECIQEQSFVIRALGFTDIVTVQVLPQCECRCRDQSRDRSLCHGKGFLECGICRCDTGYIGKNCECQTQGRSSQELEGSCRKDNNSIICSGLGDCVCGQCLCHTSDVPGKLIYGQYCECDTINCERYNGQVCGGPGRGLCFCGKCRCHPGFEGSACQCERTTEGCLNPRRVECSGRGRCRCNVCECHSGYQLPLCQECPGCPSPCGKYISCAECLKFEKGPFGKNCSAACPGLQLSNNPVKGRTCKERDSEGCWVAYTLEQQDGMDRYLIYVDESRECVAGPNIAAIVGGTVAGIVLIGILLLVIWKALIHLSDLREYRRFEKEKLKSQWNNDNPLFKSATTTVMNPKFAES
| null | null |
amyloid-beta clearance [GO:0097242]; apoptotic process [GO:0006915]; cell adhesion [GO:0007155]; cell adhesion mediated by integrin [GO:0033627]; cell-cell adhesion [GO:0098609]; cell-cell adhesion via plasma-membrane adhesion molecules [GO:0098742]; cell-cell signaling [GO:0007267]; cell-matrix adhesion [GO:0007160]; cellular response to low-density lipoprotein particle stimulus [GO:0071404]; endodermal cell differentiation [GO:0035987]; heterotypic cell-cell adhesion [GO:0034113]; inflammatory response [GO:0006954]; integrin-mediated signaling pathway [GO:0007229]; leukocyte cell-cell adhesion [GO:0007159]; microglial cell activation [GO:0001774]; negative regulation of dopamine metabolic process [GO:0045963]; neutrophil chemotaxis [GO:0030593]; neutrophil migration [GO:1990266]; phagocytosis, engulfment [GO:0006911]; positive regulation of leukocyte adhesion to vascular endothelial cell [GO:1904996]; positive regulation of neutrophil degranulation [GO:0043315]; positive regulation of prostaglandin-E synthase activity [GO:2000363]; positive regulation of protein targeting to membrane [GO:0090314]; positive regulation of superoxide anion generation [GO:0032930]; receptor clustering [GO:0043113]; receptor internalization [GO:0031623]; receptor-mediated endocytosis [GO:0006898]; regulation of cell shape [GO:0008360]; regulation of peptidyl-tyrosine phosphorylation [GO:0050730]
|
cell surface [GO:0009986]; external side of plasma membrane [GO:0009897]; extracellular exosome [GO:0070062]; extracellular vesicle [GO:1903561]; ficolin-1-rich granule membrane [GO:0101003]; focal adhesion [GO:0005925]; integrin alphaL-beta2 complex [GO:0034687]; integrin alphaM-beta2 complex [GO:0034688]; integrin alphaX-beta2 complex [GO:0034689]; integrin complex [GO:0008305]; membrane [GO:0016020]; plasma membrane [GO:0005886]; plasma membrane raft [GO:0044853]; receptor complex [GO:0043235]; specific granule membrane [GO:0035579]; tertiary granule membrane [GO:0070821]
|
amyloid-beta binding [GO:0001540]; cell adhesion molecule binding [GO:0050839]; complement component C3b binding [GO:0001851]; heat shock protein binding [GO:0031072]; ICAM-3 receptor activity [GO:0030369]; integrin binding [GO:0005178]; metal ion binding [GO:0046872]; protein kinase binding [GO:0019901]
|
PF08725;PF07965;PF00362;PF17205;
|
6.20.50.10;1.20.5.100;2.10.25.10;3.30.1680.10;2.60.40.1510;3.40.50.410;
|
Integrin beta chain family
|
PTM: Both Ser-745 and Ser-756 become phosphorylated when T-cells are exposed to phorbol esters (PubMed:11700305). Phosphorylation on Thr-758 (but not on Ser-756) allows interaction with 14-3-3 proteins (PubMed:11700305, PubMed:16301335). {ECO:0000269|PubMed:11700305, ECO:0000269|PubMed:16301335}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21193407, ECO:0000269|PubMed:28807980}; Single-pass type I membrane protein {ECO:0000305}. Membrane raft {ECO:0000269|PubMed:21193407}; Single-pass type I membrane protein {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin ITGAL/ITGB2 is also a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL (PubMed:29100055). Integrins ITGAM/ITGB2 and ITGAX/ITGB2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin ITGAX/ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin ITGAM/ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin ITGAM/ITGB2 is also a receptor for factor X. Integrin ITGAD/ITGB2 is a receptor for ICAM3 and VCAM1. Contributes to natural killer cell cytotoxicity (PubMed:15356110). Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils (PubMed:11812992, PubMed:28807980). Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation (PubMed:18587400). Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages (PubMed:23775590). In association with alpha subunit ITGAM/CD11b, required for CD177-PRTN3-mediated activation of TNF primed neutrophils (PubMed:21193407). {ECO:0000269|PubMed:11812992, ECO:0000269|PubMed:15356110, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:21193407, ECO:0000269|PubMed:23775590, ECO:0000269|PubMed:28807980, ECO:0000269|PubMed:29100055}.
|
Homo sapiens (Human)
|
P05108
|
CP11A_HUMAN
|
MLAKGLPPRSVLVKGCQTFLSAPREGLGRLRVPTGEGAGISTRSPRPFNEIPSPGDNGWLNLYHFWRETGTHKVHLHHVQNFQKYGPIYREKLGNVESVYVIDPEDVALLFKSEGPNPERFLIPPWVAYHQYYQRPIGVLLKKSAAWKKDRVALNQEVMAPEATKNFLPLLDAVSRDFVSVLHRRIKKAGSGNYSGDISDDLFRFAFESITNVIFGERQGMLEEVVNPEAQRFIDAIYQMFHTSVPMLNLPPDLFRLFRTKTWKDHVAAWDVIFSKADIYTQNFYWELRQKGSVHHDYRGILYRLLGDSKMSFEDIKANVTEMLAGGVDTTSMTLQWHLYEMARNLKVQDMLRAEVLAARHQAQGDMATMLQLVPLLKASIKETLRLHPISVTLQRYLVNDLVLRDYMIPAKTLVQVAIYALGREPTFFFDPENFDPTRWLSKDKNITYFRNLGFGWGVRQCLGRRIAELEMTIFLINMLENFRVEIQHLSDVGTTFNLILMPEKPISFTFWPFNQEATQQ
|
1.14.15.6
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269|PubMed:21636783};
|
C21-steroid hormone biosynthetic process [GO:0006700]; cellular response to peptide hormone stimulus [GO:0071375]; cholesterol metabolic process [GO:0008203]; cortisol metabolic process [GO:0034650]; glucocorticoid biosynthetic process [GO:0006704]; sterol metabolic process [GO:0016125]; vitamin D metabolic process [GO:0042359]
|
mitochondrial inner membrane [GO:0005743]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
|
cholesterol monooxygenase (side-chain-cleaving) activity [GO:0008386]; heme binding [GO:0020037]; iron ion binding [GO:0005506]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250|UniProtKB:P14137}; Peripheral membrane protein {ECO:0000305}. Note=Localizes to the matrix side of the mitochondrion inner membrane. {ECO:0000250|UniProtKB:P14137}.
|
CATALYTIC ACTIVITY: Reaction=cholesterol + 6 H(+) + 3 O2 + 6 reduced [adrenodoxin] = 4-methylpentanal + 4 H2O + 6 oxidized [adrenodoxin] + pregnenolone; Xref=Rhea:RHEA:35739, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16113, ChEBI:CHEBI:16581, ChEBI:CHEBI:17998, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; EC=1.14.15.6; Evidence={ECO:0000269|PubMed:21636783}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35740; Evidence={ECO:0000305|PubMed:21636783}; CATALYTIC ACTIVITY: Reaction=cholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (22R)-hydroxycholesterol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:34335, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16113, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:67237; Evidence={ECO:0000269|PubMed:21636783}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34336; Evidence={ECO:0000305|PubMed:21636783}; CATALYTIC ACTIVITY: Reaction=(22R)-hydroxycholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (20R,22R)-20,22-dihydroxycholesterol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:34339, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:1294, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:67237; Evidence={ECO:0000269|PubMed:21636783}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34340; Evidence={ECO:0000305|PubMed:21636783}; CATALYTIC ACTIVITY: Reaction=(20R,22R)-20,22-dihydroxycholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 4-methylpentanal + 2 H2O + 2 oxidized [adrenodoxin] + pregnenolone; Xref=Rhea:RHEA:34343, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:1294, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16581, ChEBI:CHEBI:17998, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; Evidence={ECO:0000269|PubMed:21636783}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34344; Evidence={ECO:0000305|PubMed:21636783};
| null |
PATHWAY: Lipid metabolism; C21-steroid hormone metabolism. {ECO:0000269|PubMed:21636783}.; PATHWAY: Steroid metabolism; cholesterol metabolism. {ECO:0000269|PubMed:21636783}.
| null | null |
FUNCTION: A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones (PubMed:21636783). Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal (PubMed:21636783). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:21636783). {ECO:0000269|PubMed:21636783}.
|
Homo sapiens (Human)
|
P05109
|
S10A8_HUMAN
|
MLTELEKALNSIIDVYHKYSLIKGNFHAVYRDDLKKLLETECPQYIRKKGADVWFKELDINTDGAVNFQEFLILVIKMGVAAHKKSHEESHKE
| null | null |
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919]; apoptotic process [GO:0006915]; astrocyte development [GO:0014002]; autocrine signaling [GO:0035425]; autophagy [GO:0006914]; chronic inflammatory response [GO:0002544]; defense response to bacterium [GO:0042742]; defense response to fungus [GO:0050832]; inflammatory response [GO:0006954]; innate immune response [GO:0045087]; leukocyte migration involved in inflammatory response [GO:0002523]; neutrophil aggregation [GO:0070488]; neutrophil chemotaxis [GO:0030593]; peptide secretion [GO:0002790]; peptidyl-cysteine S-nitrosylation [GO:0018119]; positive regulation of cell growth [GO:0030307]; positive regulation of inflammatory response [GO:0050729]; positive regulation of intrinsic apoptotic signaling pathway [GO:2001244]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of peptide secretion [GO:0002793]; regulation of cytoskeleton organization [GO:0051493]; regulation of toll-like receptor signaling pathway [GO:0034121]; response to ethanol [GO:0045471]; response to lipopolysaccharide [GO:0032496]; response to zinc ion [GO:0010043]; sequestering of zinc ion [GO:0032119]
|
calprotectin complex [GO:1990660]; collagen-containing extracellular matrix [GO:0062023]; cytoskeleton [GO:0005856]; cytosol [GO:0005829]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; intermediate filament cytoskeleton [GO:0045111]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; secretory granule lumen [GO:0034774]
|
arachidonic acid binding [GO:0050544]; calcium ion binding [GO:0005509]; calcium-dependent protein binding [GO:0048306]; microtubule binding [GO:0008017]; RAGE receptor binding [GO:0050786]; Toll-like receptor 4 binding [GO:0035662]; zinc ion binding [GO:0008270]
|
PF01023;
|
1.10.238.10;
|
S-100 family
| null |
SUBCELLULAR LOCATION: Secreted. Cytoplasm. Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Note=Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway.
| null | null | null | null | null |
FUNCTION: S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its pro-inflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the pro-inflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. The iNOS-S100A8/A9 transnitrosylase complex directs selective inflammatory stimulus-dependent S-nitrosylation of GAPDH and probably multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity. {ECO:0000269|PubMed:12626582, ECO:0000269|PubMed:15331440, ECO:0000269|PubMed:15598812, ECO:0000269|PubMed:15642721, ECO:0000269|PubMed:16258195, ECO:0000269|PubMed:19087201, ECO:0000269|PubMed:19122197, ECO:0000269|PubMed:19935772, ECO:0000269|PubMed:21487906, ECO:0000269|PubMed:22363402, ECO:0000269|PubMed:22808130, ECO:0000269|PubMed:25417112}.; FUNCTION: (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, may induce expansion of aberrant immature neutrophils in a TLR4-dependent manner. {ECO:0000305|PubMed:33388094}.
|
Homo sapiens (Human)
|
P05110
|
GLUC_CAVPO
|
MKSVYFVAGLFIMLAQGSWQRSLQDTEEKPRSVSASQTDMLDDPDQMNEDKRHSQGTFTSDYSKYLDSRRAQQFLKWLLNVKRNRNNIAKRHDEFERHAEGTFTSDVSSYLEGQAAKEFIAWLVKGRGRRDFPEEVAIVEELGRRHADGSFSDEMNTILDNLATRDFINWLIQTKITDRK
| null | null |
adenylate cyclase-activating G protein-coupled receptor signaling pathway [GO:0007189]; cellular response to glucagon stimulus [GO:0071377]; gluconeogenesis [GO:0006094]; glucose homeostasis [GO:0042593]; negative regulation of execution phase of apoptosis [GO:1900118]; positive regulation of calcium ion import [GO:0090280]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of gluconeogenesis [GO:0045722]; positive regulation of insulin secretion involved in cellular response to glucose stimulus [GO:0035774]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of peptidyl-threonine phosphorylation [GO:0010800]; protein kinase A signaling [GO:0010737]; regulation of insulin secretion [GO:0050796]; response to activity [GO:0014823]; response to starvation [GO:0042594]
|
cytoplasm [GO:0005737]; extracellular space [GO:0005615]; plasma membrane [GO:0005886]
|
glucagon receptor binding [GO:0031769]; hormone activity [GO:0005179]; identical protein binding [GO:0042802]
|
PF00123;
|
6.10.250.590;
|
Glucagon family
|
PTM: Proglucagon is post-translationally processed in a tissue-specific manner in pancreatic A cells and intestinal L cells. In pancreatic A cells, the major bioactive hormone is glucagon cleaved by PCSK2/PC2. In the intestinal L cells PCSK1/PC1 liberates GLP-1, GLP-2, glicentin and oxyntomodulin. GLP-1 is further N-terminally truncated by post-translational processing in the intestinal L cells resulting in GLP-1(7-37) GLP-1-(7-36)amide. The C-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P01275}.; SUBCELLULAR LOCATION: [Glucagon-like peptide 1]: Secreted {ECO:0000250|UniProtKB:P01275}.
| null | null | null | null | null |
FUNCTION: [Glucagon]: Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes. {ECO:0000250|UniProtKB:P55095}.; FUNCTION: [Glucagon-like peptide 1]: Potent stimulator of glucose-dependent insulin release. Also stimulates insulin release in response to IL6. Plays important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Has growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis. {ECO:0000250|UniProtKB:P55095}.; FUNCTION: [Glucagon-like peptide 2]: Stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability. {ECO:0000250|UniProtKB:P55095}.; FUNCTION: [Oxyntomodulin]: Significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness. {ECO:0000250|UniProtKB:P55095}.; FUNCTION: [Glicentin]: May modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life. {ECO:0000250|UniProtKB:P55095}.
|
Cavia porcellus (Guinea pig)
|
P05111
|
INHA_HUMAN
|
MVLHLLLFLLLTPQGGHSCQGLELARELVLAKVRALFLDALGPPAVTREGGDPGVRRLPRRHALGGFTHRGSEPEEEEDVSQAILFPATDASCEDKSAARGLAQEAEEGLFRYMFRPSQHTRSRQVTSAQLWFHTGLDRQGTAASNSSEPLLGLLALSPGGPVAVPMSLGHAPPHWAVLHLATSALSLLTHPVLVLLLRCPLCTCSARPEATPFLVAHTRTRPPSGGERARRSTPLMSWPWSPSALRLLQRPPEEPAAHANCHRVALNISFQELGWERWIVYPPSFIFHYCHGGCGLHIPPNLSLPVPGAPPTPAQPYSLLPGAQPCCAALPGTMRPLHVRTTSDGGYSFKYETVPNLLTQHCACI
| null | null |
cell differentiation [GO:0030154]; cell surface receptor signaling pathway [GO:0007166]; cell-cell signaling [GO:0007267]; erythrocyte differentiation [GO:0030218]; hemoglobin biosynthetic process [GO:0042541]; male gonad development [GO:0008584]; negative regulation of B cell differentiation [GO:0045578]; negative regulation of cell cycle [GO:0045786]; negative regulation of follicle-stimulating hormone secretion [GO:0046882]; negative regulation of macrophage differentiation [GO:0045650]; negative regulation of phosphorylation [GO:0042326]; negative regulation of type II interferon production [GO:0032689]; ovarian follicle development [GO:0001541]; positive regulation of follicle-stimulating hormone secretion [GO:0046881]; regulation of cell cycle [GO:0051726]; regulation of cell population proliferation [GO:0042127]; signal transduction [GO:0007165]; skeletal system development [GO:0001501]
|
extracellular region [GO:0005576]; extracellular space [GO:0005615]; inhibin A complex [GO:0043512]; inhibin B complex [GO:0043513]; inhibin-betaglycan-ActRII complex [GO:0034673]; neuronal cell body [GO:0043025]; photoreceptor inner segment [GO:0001917]; photoreceptor outer segment [GO:0001750]
|
cytokine activity [GO:0005125]; growth factor activity [GO:0008083]; hormone activity [GO:0005179]; inhibin binding [GO:0034711]; protein-containing complex binding [GO:0044877]; signaling receptor binding [GO:0005102]
|
PF00019;
|
2.10.90.10;
|
TGF-beta family
|
PTM: Proteolytic processing yields a number of bioactive forms. The 20/23 kDa forms consist solely of the mature alpha chain, the 26/29 kDa forms consist of the most N-terminal propeptide linked through a disulfide bond to the mature alpha chain, the 50/53 kDa forms encompass the entire proprotein. Each type can be furthermore either mono- or diglycosylated, causing the mass difference. {ECO:0000269|PubMed:8885240}.
|
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.
|
Homo sapiens (Human)
|
P05112
|
IL4_HUMAN
|
MGLTSQLLPPLFFLLACAGNFVHGHKCDITLQEIIKTLNSLTEQKTLCTELTVTDIFAASKNTTEKETFCRAATVLRQFYSHHEKDTRCLGATAQQFHRHKQLIRFLKRLDRNLWGLAGLNSCPVKEANQSTLENFLERLKTIMREKYSKCSS
| null | null |
activation of Janus kinase activity [GO:0042976]; B cell costimulation [GO:0031296]; B cell differentiation [GO:0030183]; cholesterol metabolic process [GO:0008203]; dendritic cell differentiation [GO:0097028]; extrinsic apoptotic signaling pathway in absence of ligand [GO:0097192]; immune response [GO:0006955]; innate immune response in mucosa [GO:0002227]; interleukin-4-mediated signaling pathway [GO:0035771]; macrophage activation [GO:0042116]; microglial cell activation [GO:0001774]; myeloid dendritic cell differentiation [GO:0043011]; negative regulation of acute inflammatory response [GO:0002674]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cellular response to transforming growth factor beta stimulus [GO:1903845]; negative regulation of chronic inflammatory response [GO:0002677]; negative regulation of complement-dependent cytotoxicity [GO:1903660]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of endothelial cell apoptotic process [GO:2000352]; negative regulation of epithelial cell migration [GO:0010633]; negative regulation of extrinsic apoptotic signaling pathway [GO:2001237]; negative regulation of inflammatory response [GO:0050728]; negative regulation of macrophage activation [GO:0043031]; negative regulation of neuroinflammatory response [GO:0150079]; negative regulation of osteoclast differentiation [GO:0045671]; negative regulation of T-helper 17 cell differentiation [GO:2000320]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of tumor necrosis factor production [GO:0032720]; neuroinflammatory response [GO:0150076]; positive regulation of amyloid-beta clearance [GO:1900223]; positive regulation of ATP biosynthetic process [GO:2001171]; positive regulation of B cell proliferation [GO:0030890]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cellular respiration [GO:1901857]; positive regulation of cold-induced thermogenesis [GO:0120162]; positive regulation of defense response to virus by host [GO:0002230]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of eosinophil chemotaxis [GO:2000424]; positive regulation of gene expression [GO:0010628]; positive regulation of interleukin-10 production [GO:0032733]; positive regulation of interleukin-13 production [GO:0032736]; positive regulation of isotype switching to IgE isotypes [GO:0048295]; positive regulation of isotype switching to IgG isotypes [GO:0048304]; positive regulation of macroautophagy [GO:0016239]; positive regulation of mast cell degranulation [GO:0043306]; positive regulation of MHC class II biosynthetic process [GO:0045348]; positive regulation of mononuclear cell migration [GO:0071677]; positive regulation of myoblast fusion [GO:1901741]; positive regulation of receptor-mediated endocytosis [GO:0048260]; positive regulation of T cell differentiation [GO:0045582]; positive regulation of T cell proliferation [GO:0042102]; positive regulation of T-helper 2 cell cytokine production [GO:2000553]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of tyrosine phosphorylation of STAT protein [GO:0042531]; regulation of immune response [GO:0050776]; regulation of isotype switching [GO:0045191]; regulation of phosphorylation [GO:0042325]; T cell activation [GO:0042110]; T-helper 2 cell differentiation [GO:0045064]; type 2 immune response [GO:0042092]
|
extracellular region [GO:0005576]; extracellular space [GO:0005615]
|
cytokine activity [GO:0005125]; growth factor activity [GO:0008083]; interleukin-4 receptor binding [GO:0005136]
|
PF00727;
|
1.20.1250.10;
|
IL-4/IL-13 family
| null |
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Cytokine secreted primarily by mast cells, T-cells, eosinophils, and basophils that plays a role in regulating antibody production, hematopoiesis and inflammation, and the development of effector T-cell responses (PubMed:1993171, PubMed:3016727). Induces the expression of class II MHC molecules on resting B-cells. Enhances both secretion and cell surface expression of IgE and IgG1 (PubMed:1993171). Regulates also the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes (PubMed:2521231). Positively regulates IL31RA expression in macrophages. Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4. In addition, plays a critical role in higher functions of the normal brain, such as memory and learning (By similarity). Upon binding to IL4, IL4R receptor dimerizes either with the common IL2R gamma chain/IL2RG to produce the type 1 signaling complex, located mainly on hematopoietic cells, or with the IL13RA1 to produce the type 2 complex, which is expressed also on nonhematopoietic cells (PubMed:10219247, PubMed:11526337, PubMed:18243101). Engagement of both types of receptors initiates JAK3 and to a lower extend JAK1 phosphorylation leading to activation of the signal transducer and activator of transcription 6/STAT6 (PubMed:7721895). {ECO:0000250|UniProtKB:P07750, ECO:0000269|PubMed:10219247, ECO:0000269|PubMed:11526337, ECO:0000269|PubMed:18243101}.
|
Homo sapiens (Human)
|
P05113
|
IL5_HUMAN
|
MRMLLHLSLLALGAAYVYAIPTEIPTSALVKETLALLSTHRTLLIANETLRIPVPVHKNHQLCTEEIFQGIGTLESQTVQGGTVERLFKNLSLIKKYIDGQKKKCGEERRRVNQFLDYLQEFLGVMNTEWIIES
| null | null |
immune response [GO:0006955]; inflammatory response [GO:0006954]; interleukin-5-mediated signaling pathway [GO:0038043]; positive regulation of B cell proliferation [GO:0030890]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of eosinophil differentiation [GO:0045645]; positive regulation of immunoglobulin production [GO:0002639]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of podosome assembly [GO:0071803]; positive regulation of receptor signaling pathway via JAK-STAT [GO:0046427]
|
extracellular region [GO:0005576]; extracellular space [GO:0005615]
|
cytokine activity [GO:0005125]; growth factor activity [GO:0008083]; interleukin-5 receptor binding [GO:0005137]
|
PF02025;
|
1.20.1250.10;
|
IL-5 family
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2653458}.
| null | null | null | null | null |
FUNCTION: Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils (PubMed:2653458, PubMed:9010276). Acts also on activated and resting B-cells to induce immunoglobulin production, growth, and differentiation (By similarity). Mechanistically, exerts its biological effects through a receptor composed of IL5RA subunit and the cytokine receptor common subunit beta/CSF2RB (PubMed:1495999, PubMed:22528658). Binding to the receptor leads to activation of various kinases including LYN, SYK and JAK2 and thereby propagates signals through the RAS-MAPK and JAK-STAT5 pathways respectively (PubMed:7613138). {ECO:0000250|UniProtKB:P04401, ECO:0000269|PubMed:1495999, ECO:0000269|PubMed:22528658, ECO:0000269|PubMed:2653458, ECO:0000269|PubMed:7613138, ECO:0000269|PubMed:9010276}.
|
Homo sapiens (Human)
|
P05114
|
HMGN1_HUMAN
|
MPKRKVSSAEGAAKEEPKRRSARLSAKPPAKVEAKPKKAAAKDKSSDKKVQTKGKRGAKGKQAEVANQETKEDLPAENGETKTEESPASDEAGEKEAKSD
| null | null |
chromatin organization [GO:0006325]; positive regulation of DNA-templated transcription, elongation [GO:0032786]; post-embryonic camera-type eye morphogenesis [GO:0048597]; pyrimidine dimer repair by nucleotide-excision repair [GO:0000720]; regulation of development, heterochronic [GO:0040034]; regulation of epithelial cell proliferation [GO:0050678]; regulation of transcription by RNA polymerase II [GO:0006357]; response to UV-B [GO:0010224]; response to UV-C [GO:0010225]; transcription-coupled nucleotide-excision repair [GO:0006283]
|
chromatin [GO:0000785]; cytoplasm [GO:0005737]; female germ cell nucleus [GO:0001674]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
chromatin binding [GO:0003682]; DNA binding [GO:0003677]; nucleosomal DNA binding [GO:0031492]
|
PF01101;
| null |
HMGN family
|
PTM: Phosphorylation on Ser-21 and Ser-25 weakens binding to nucleosomes and increases the rate of H3 phosphorylation (By similarity). Phosphorylation favors cytoplasmic localization. {ECO:0000250, ECO:0000269|PubMed:10739259}.
|
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Cytoplasmic enrichment upon phosphorylation. The RNA edited version localizes to the nucleus.
| null | null | null | null | null |
FUNCTION: Binds to the inner side of the nucleosomal DNA thus altering the interaction between the DNA and the histone octamer. May be involved in the process which maintains transcribable genes in a unique chromatin conformation. Inhibits the phosphorylation of nucleosomal histones H3 and H2A by RPS6KA5/MSK1 and RPS6KA3/RSK2 (By similarity). {ECO:0000250}.
|
Homo sapiens (Human)
|
P05117
|
PGLR_SOLLC
|
MVIQRNSILLLIIIFASSISTCRSNVIDDNLFKQVYDNILEQEFAHDFQAYLSYLSKNIESNNNIDKVDKNGIKVINVLSFGAKGDGKTYDNIAFEQAWNEACSSRTPVQFVVPKNKNYLLKQITFSGPCRSSISVKIFGSLEASSKISDYKDRRLWIAFDSVQNLVVGGGGTINGNGQVWWPSSCKINKSLPCRDAPTALTFWNCKNLKVNNLKSKNAQQIHIKFESCTNVVASNLMINASAKSPNTDGVHVSNTQYIQISDTIIGTGDDCISIVSGSQNVQATNITCGPGHGISIGSLGSGNSEAYVSNVTVNEAKIIGAENGVRIKTWQGGSGQASNIKFLNVEMQDVKYPIIIDQNYCDRVEPCIQQFSAVQVKNVVYENIKGTSATKVAIKFDCSTNFPCEGIIMENINLVGESGKPSEATCKNVHFNNAEHVTPHCTSLEISEDEALLYNY
|
3.2.1.15
| null |
anther dehiscence [GO:0009901]; cell wall organization [GO:0071555]; fruit dehiscence [GO:0010047]; fruit ripening [GO:0009835]; pectin catabolic process [GO:0045490]
|
apoplast [GO:0048046]
|
polygalacturonase activity [GO:0004650]
|
PF00295;
|
2.160.20.10;
|
Glycosyl hydrolase 28 family
|
PTM: N-glycosylated. PG2B isozyme has a greater degree of glycosylation than PG2A. {ECO:0000269|PubMed:16666031, ECO:0000269|PubMed:2152163, ECO:0000269|PubMed:6617647}.
|
SUBCELLULAR LOCATION: Secreted, extracellular space, apoplast {ECO:0000269|PubMed:2152163}. Secreted, cell wall {ECO:0000269|PubMed:2152163}. Note=Associated to the cell wall.
|
CATALYTIC ACTIVITY: Reaction=(1,4-alpha-D-galacturonosyl)n+m + H2O = (1,4-alpha-D-galacturonosyl)n + (1,4-alpha-D-galacturonosyl)m.; EC=3.2.1.15; Evidence={ECO:0000269|PubMed:9701584};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=38 uM for polygalacturonic acid (for PG2 at pH 4.6 and 35 degrees Celsius) {ECO:0000269|PubMed:15007842, ECO:0000269|PubMed:6489331, ECO:0000269|PubMed:6617647, ECO:0000269|PubMed:7449759}; KM=75 uM for polygalacturonic acid (for PG1 at pH 4.6 and 35 degrees Celsius) {ECO:0000269|PubMed:15007842, ECO:0000269|PubMed:6489331, ECO:0000269|PubMed:6617647, ECO:0000269|PubMed:7449759}; Vmax=58.8 umol/min/mg enzyme (for PG2 at pH 4.6 and 35 degrees Celsius) {ECO:0000269|PubMed:15007842, ECO:0000269|PubMed:6489331, ECO:0000269|PubMed:6617647, ECO:0000269|PubMed:7449759}; Vmax=7 umol/min/mg enzyme (for PG2 at pH 3.8 and 25 degrees Celsius) {ECO:0000269|PubMed:15007842, ECO:0000269|PubMed:6489331, ECO:0000269|PubMed:6617647, ECO:0000269|PubMed:7449759}; Vmax=27.7 umol/min/mg enzyme (for PG1 at pH 4.6 and 35 degrees Celsius) {ECO:0000269|PubMed:15007842, ECO:0000269|PubMed:6489331, ECO:0000269|PubMed:6617647, ECO:0000269|PubMed:7449759}; Vmax=4 umol/min/mg enzyme (for PG1 at pH 3.8 and 25 degrees Celsius) {ECO:0000269|PubMed:15007842, ECO:0000269|PubMed:6489331, ECO:0000269|PubMed:6617647, ECO:0000269|PubMed:7449759};
| null |
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 4.4-4.8 at 35 degrees Celsius. PG1 is resistant to acidic but not to alkaline conditions, at which PG2 is released from the beta subunit. {ECO:0000269|PubMed:15007842, ECO:0000269|PubMed:6489331, ECO:0000269|PubMed:6617647, ECO:0000269|PubMed:7449759};
|
BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 55-60 degrees Celsius at pH 4.4. PG1 is more thermostable than PG2. {ECO:0000269|PubMed:15007842, ECO:0000269|PubMed:6489331, ECO:0000269|PubMed:6617647, ECO:0000269|PubMed:7449759};
|
FUNCTION: Catalytic subunit of the polygalacturonase isozyme 1 and 2 (PG1 and PG2). Acts in concert with the pectinesterase, in the ripening process. Is involved in cell wall metabolism, specifically in polyuronide degradation. The depolymerization and solubilization of cell wall polyuronides mediated by PG2 during ripening seems to be limited by the beta subunit GP1, probably by recruiting PG2 to form PG1. {ECO:0000269|PubMed:2152163, ECO:0000269|PubMed:7827495, ECO:0000269|PubMed:9747798}.
|
Solanum lycopersicum (Tomato) (Lycopersicon esculentum)
|
P05120
|
PAI2_HUMAN
|
MEDLCVANTLFALNLFKHLAKASPTQNLFLSPWSISSTMAMVYMGSRGSTEDQMAKVLQFNEVGANAVTPMTPENFTSCGFMQQIQKGSYPDAILQAQAADKIHSSFRSLSSAINASTGNYLLESVNKLFGEKSASFREEYIRLCQKYYSSEPQAVDFLECAEEARKKINSWVKTQTKGKIPNLLPEGSVDGDTRMVLVNAVYFKGKWKTPFEKKLNGLYPFRVNSAQRTPVQMMYLREKLNIGYIEDLKAQILELPYAGDVSMFLLLPDEIADVSTGLELLESEITYDKLNKWTSKDKMAEDEVEVYIPQFKLEEHYELRSILRSMGMEDAFNKGRANFSGMSERNDLFLSEVFHQAMVDVNEEGTEAAAGTGGVMTGRTGHGGPQFVADHPFLFLIMHKITNCILFFGRFSSP
| null | null |
fibrinolysis [GO:0042730]; negative regulation of apoptotic process [GO:0043066]
|
cornified envelope [GO:0001533]; cytoplasm [GO:0005737]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; plasma membrane [GO:0005886]
|
serine-type endopeptidase inhibitor activity [GO:0004867]
|
PF00079;
|
2.30.39.10;3.30.497.10;
|
Serpin family, Ov-serpin subfamily
|
PTM: The signal sequence is not cleaved.
|
SUBCELLULAR LOCATION: Cytoplasm. Secreted, extracellular space.
| null | null | null | null | null |
FUNCTION: Inhibits urokinase-type plasminogen activator. The monocyte derived PAI-2 is distinct from the endothelial cell-derived PAI-1.
|
Homo sapiens (Human)
|
P05121
|
PAI1_HUMAN
|
MQMSPALTCLVLGLALVFGEGSAVHHPPSYVAHLASDFGVRVFQQVAQASKDRNVVFSPYGVASVLAMLQLTTGGETQQQIQAAMGFKIDDKGMAPALRHLYKELMGPWNKDEISTTDAIFVQRDLKLVQGFMPHFFRLFRSTVKQVDFSEVERARFIINDWVKTHTKGMISNLLGKGAVDQLTRLVLVNALYFNGQWKTPFPDSSTHRRLFHKSDGSTVSVPMMAQTNKFNYTEFTTPDGHYYDILELPYHGDTLSMFIAAPYEKEVPLSALTNILSAQLISHWKGNMTRLPRLLVLPKFSLETEVDLRKPLENLGMTDMFRQFQADFTSLSDQEPLHVAQALQKVKIEVNESGTVASSSTAVIVSARMAPEEIIMDRPFLFVVRHNPTGTVLFMGQVMEP
| null | null |
angiogenesis [GO:0001525]; cellular response to lipopolysaccharide [GO:0071222]; defense response to Gram-negative bacterium [GO:0050829]; dentinogenesis [GO:0097187]; fibrinolysis [GO:0042730]; negative regulation of blood coagulation [GO:0030195]; negative regulation of cell adhesion mediated by integrin [GO:0033629]; negative regulation of cell migration [GO:0030336]; negative regulation of endopeptidase activity [GO:0010951]; negative regulation of endothelial cell apoptotic process [GO:2000352]; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902042]; negative regulation of fibrinolysis [GO:0051918]; negative regulation of plasminogen activation [GO:0010757]; negative regulation of smooth muscle cell migration [GO:0014912]; negative regulation of smooth muscle cell-matrix adhesion [GO:2000098]; negative regulation of vascular wound healing [GO:0061044]; negative regulation of wound healing [GO:0061045]; positive regulation of angiogenesis [GO:0045766]; positive regulation of blood coagulation [GO:0030194]; positive regulation of inflammatory response [GO:0050729]; positive regulation of interleukin-8 production [GO:0032757]; positive regulation of leukotriene production involved in inflammatory response [GO:0035491]; positive regulation of monocyte chemotaxis [GO:0090026]; positive regulation of odontoblast differentiation [GO:1901331]; positive regulation of receptor-mediated endocytosis [GO:0048260]; regulation of signaling receptor activity [GO:0010469]; replicative senescence [GO:0090399]
|
collagen-containing extracellular matrix [GO:0062023]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; peptidase inhibitor complex [GO:1904090]; plasma membrane [GO:0005886]; platelet alpha granule lumen [GO:0031093]; serine protease inhibitor complex [GO:0097180]
|
protease binding [GO:0002020]; serine-type endopeptidase inhibitor activity [GO:0004867]; signaling receptor binding [GO:0005102]
|
PF00079;
|
2.30.39.10;3.30.497.10;
|
Serpin family
|
PTM: Inactivated by proteolytic attack of the urokinase-type (u-PA) and the tissue-type (TPA), cleaving the 369-Arg-|-Met-370 bond.
|
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2430793}.
| null | null | null | null | null |
FUNCTION: Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots (PubMed:17912461, PubMed:8481516, PubMed:9207454). As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading (PubMed:9175705). Acts as a regulator of cell migration, independently of its role as protease inhibitor (PubMed:15001579, PubMed:9168821). It is required for stimulation of keratinocyte migration during cutaneous injury repair (PubMed:18386027). It is involved in cellular and replicative senescence (PubMed:16862142). Plays a role in alveolar type 2 cells senescence in the lung (By similarity). Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis (PubMed:25808697, PubMed:27046084). {ECO:0000250|UniProtKB:P22777, ECO:0000269|PubMed:15001579, ECO:0000269|PubMed:15853774, ECO:0000269|PubMed:16862142, ECO:0000269|PubMed:17912461, ECO:0000269|PubMed:18386027, ECO:0000269|PubMed:25808697, ECO:0000269|PubMed:27046084, ECO:0000269|PubMed:8481516, ECO:0000269|PubMed:9168821, ECO:0000269|PubMed:9175705, ECO:0000269|PubMed:9207454}.
|
Homo sapiens (Human)
|
P05122
|
KCRB_CHICK
|
MPFSNSHNLLKMKYSVDDEYPDLSVHNNHMAKVLTLDLYKKLRDRQTSSGFTLDDVIQTGVDNPGHPFIMTVGCVAGDEESYEVFKELFDPVIEDRHGGYKPTDEHKTDLNADNLQGGDDLDPNYVLSSRVRTGRSIRGFCLPPHCSRGERRAIEKLSVEALGSLGGDLKGKYYALRNMTDAEQQQLIDDHFLFDKPVSPLLLASGMARDWPDARGIWHNDNKTFLVWINEEDHLRVISMQKGGNMKEVFTRFCTGLTQIETLFKSKNYEFMWNPHLGYILTCPSNLGTGLRAGVHIKLPNLGKHEKFGEVLKRLRLQKRGTGGVDTAAVGGVFDVSNADRLGFSEVELVQMVVDGVKLLIEMEKRLEKGQSIDDLMPAQK
|
2.7.3.2
| null |
ATP biosynthetic process [GO:0006754]; phosphocreatine biosynthetic process [GO:0046314]; phosphorylation [GO:0016310]
|
cytosol [GO:0005829]; extracellular membrane-bounded organelle [GO:0065010]; extracellular space [GO:0005615]; mitochondrion [GO:0005739]; plasma membrane [GO:0005886]
|
ATP binding [GO:0005524]; creatine kinase activity [GO:0004111]
|
PF00217;PF02807;
|
1.10.135.10;3.30.590.10;
|
ATP:guanido phosphotransferase family
|
PTM: Ba-CK and Bb-CK are phosphorylated. {ECO:0000269|PubMed:2307674}.; PTM: The N-terminus of BA-CK is blocked. {ECO:0000269|PubMed:2365692}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q04447}. Mitochondrion {ECO:0000250|UniProtKB:Q04447}. Cell membrane {ECO:0000250|UniProtKB:P12277}.
|
CATALYTIC ACTIVITY: Reaction=ATP + creatine = ADP + H(+) + N-phosphocreatine; Xref=Rhea:RHEA:17157, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57947, ChEBI:CHEBI:58092, ChEBI:CHEBI:456216; EC=2.7.3.2; Evidence={ECO:0000255|PROSITE-ProRule:PRU10029, ECO:0000269|PubMed:20026305, ECO:0000269|PubMed:8525081}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17158; Evidence={ECO:0000269|PubMed:20026305, ECO:0000269|PubMed:8525081};
| null | null | null | null |
FUNCTION: Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:20026305, PubMed:8525081). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa (Probable). {ECO:0000269|PubMed:20026305, ECO:0000269|PubMed:8525081, ECO:0000305}.
|
Gallus gallus (Chicken)
|
P05125
|
ANF_MOUSE
|
MGSFSITLGFFLVLAFWLPGHIGANPVYSAVSNTDLMDFKNLLDHLEEKMPVEDEVMPPQALSEQTEEAGAALSSLPEVPPWTGEVNPPLRDGSALGRSPWDPSDRSALLKSKLRALLAGPRSLRRSSCFGGRIDRIGAQSGLGCNSFRYRR
| null | null |
cardiac muscle hypertrophy in response to stress [GO:0014898]; cGMP biosynthetic process [GO:0006182]; cGMP-mediated signaling [GO:0019934]; female pregnancy [GO:0007565]; negative regulation of blood pressure [GO:0045776]; negative regulation of cell growth [GO:0030308]; negative regulation of collecting lymphatic vessel constriction [GO:1903815]; negative regulation of systemic arterial blood pressure [GO:0003085]; neuropeptide signaling pathway [GO:0007218]; positive regulation of cardiac muscle contraction [GO:0060452]; positive regulation of cGMP-mediated signaling [GO:0010753]; positive regulation of heart rate [GO:0010460]; positive regulation of histamine secretion by mast cell [GO:1903595]; positive regulation of potassium ion export across plasma membrane [GO:1903766]; protein folding [GO:0006457]; receptor guanylyl cyclase signaling pathway [GO:0007168]; regulation of atrial cardiac muscle cell membrane repolarization [GO:0060372]; regulation of blood pressure [GO:0008217]; regulation of calcium ion transmembrane transport via high voltage-gated calcium channel [GO:1902514]; sodium ion export across plasma membrane [GO:0036376]; synaptic signaling via neuropeptide [GO:0099538]; vasodilation [GO:0042311]
|
brush border [GO:0005903]; cell projection [GO:0042995]; cytoplasm [GO:0005737]; extracellular space [GO:0005615]; glycinergic synapse [GO:0098690]; mast cell granule [GO:0042629]; perikaryon [GO:0043204]; perinuclear region of cytoplasm [GO:0048471]; protein-containing complex [GO:0032991]
|
hormone activity [GO:0005179]; hormone receptor binding [GO:0051427]; neuropeptide hormone activity [GO:0005184]; neuropeptide receptor binding [GO:0071855]; signaling receptor binding [GO:0005102]
|
PF00212;
| null |
Natriuretic peptide family
|
PTM: The precursor molecule is proteolytically cleaved by CORIN at Arg-122 to produce atrial natriuretic peptide (PubMed:11884416, PubMed:15637153). Undergoes further proteolytic cleavage by unknown proteases to give rise to long-acting natriuretic peptide, vessel dilator and kaliuretic peptide (By similarity). Additional processing gives rise to the auriculin and atriopeptin peptides (By similarity). In the kidneys, alternative processing by an unknown protease results in the peptide urodilatin (By similarity). {ECO:0000250|UniProtKB:P01160, ECO:0000250|UniProtKB:P01161, ECO:0000269|PubMed:11884416, ECO:0000269|PubMed:15637153}.; PTM: [Atrial natriuretic peptide]: Cleavage by MME initiates degradation of the factor and thereby regulates its activity. Degradation by IDE results in reduced activation of NPR1 (in vitro). During IDE degradation, the resulting products can temporarily stimulate NPR2 to produce cGMP, before the fragments are completely degraded and inactivated by IDE (in vitro). {ECO:0000250|UniProtKB:P01160}.; PTM: [Urodilatin]: Degraded by IDE. {ECO:0000250|UniProtKB:P01160}.; PTM: [Urodilatin]: Phosphorylation on Ser-128 decreases vasorelaxant activity. {ECO:0000250|UniProtKB:P01160}.
|
SUBCELLULAR LOCATION: [Long-acting natriuretic peptide]: Secreted {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood. {ECO:0000250|UniProtKB:P01160}.; SUBCELLULAR LOCATION: [Vessel dilator]: Secreted {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood. {ECO:0000250|UniProtKB:P01160}.; SUBCELLULAR LOCATION: [Kaliuretic peptide]: Secreted {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood. {ECO:0000250|UniProtKB:P01160}.; SUBCELLULAR LOCATION: [Urodilatin]: Secreted {ECO:0000250|UniProtKB:P01160}. Note=Detected in urine. Not detected in blood. Increased electrolytes, osmolality and intracellular cAMP levels increase peptide secretion/excretion. {ECO:0000250|UniProtKB:P01160}.; SUBCELLULAR LOCATION: [Atrial natriuretic peptide]: Secreted {ECO:0000250|UniProtKB:P01160}. Perikaryon {ECO:0000250|UniProtKB:P01160}. Cell projection {ECO:0000250|UniProtKB:P01160}. Note=Detected in blood. Detected in urine in one study. However, in another study, was not detected in urine. Detected in cytoplasmic bodies and neuronal processes of pyramidal neurons (layers II-VI) (By similarity). Increased secretion in response to the vasopressin AVP (By similarity). Likely to be secreted in response to an increase in atrial pressure or atrial stretch. In kidney cells, secretion increases in response to activated guanylyl cyclases and increased intracellular cAMP levels. Plasma levels increase 15 minutes after a high-salt meal, and decrease back to normal plasma levels 1 hr later (By similarity). {ECO:0000250|UniProtKB:P01160, ECO:0000250|UniProtKB:P01161}.; SUBCELLULAR LOCATION: [Atriopeptin-3]: Secreted {ECO:0000250|UniProtKB:P01161}. Note=Detected in blood. Slight increase in secretion in response to the vasopressin AVP. {ECO:0000250|UniProtKB:P01161}.
| null | null | null | null | null |
FUNCTION: [Atrial natriuretic peptide]: Hormone that plays a key role in mediating cardio-renal homeostasis, and is involved in vascular remodeling and regulating energy metabolism (PubMed:12890708, PubMed:22437503, PubMed:8760210). Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins, such as PRKG1, that drive various biological responses (PubMed:12890708). Regulates vasodilation, natriuresis, diuresis and aldosterone synthesis and is therefore essential for regulating blood pressure, controlling the extracellular fluid volume and maintaining the fluid-electrolyte balance (PubMed:22437503, PubMed:8760210). Also involved in inhibiting cardiac remodeling and cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating the growth of cardiomyocytes and fibroblasts (By similarity). Plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus, and thus prevents pregnancy-induced hypertension (PubMed:22437503). In adipose tissue, acts in various cGMP- and PKG-dependent pathways to regulate lipid metabolism and energy homeostasis (By similarity). This includes up-regulating lipid metabolism and mitochondrial oxygen utilization by activating the AMP-activated protein kinase (AMPK), and increasing energy expenditure by acting via MAPK11 to promote the UCP1-dependent thermogenesis of brown adipose tissue (By similarity). Binds the clearance receptor NPR3 which removes the hormone from circulation (By similarity). {ECO:0000250|UniProtKB:P01160, ECO:0000269|PubMed:12890708, ECO:0000269|PubMed:22437503, ECO:0000269|PubMed:8760210}.; FUNCTION: [Long-acting natriuretic peptide]: May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, vasodilation, and inhibiting aldosterone synthesis. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (By similarity). However reports on the involvement of this peptide in mammal blood volume and blood pressure homeostasis are conflicting; according to a report, in vivo it is not sufficient to activate cGMP and does not inhibit collecting duct transport nor effect diuresis and natriuresis (By similarity). Appears to bind to specific receptors that are distinct from the receptors bound by atrial natriuretic peptide and vessel dilator. Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption (By similarity). {ECO:0000250|UniProtKB:P01160, ECO:0000250|UniProtKB:P01161}.; FUNCTION: [Vessel dilator]: May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, and vasodilation. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. However reports on the involvement of this peptide in mammal blood volume and blood pressure homeostasis are conflicting; according to a report it is not sufficient to activate cGMP and does not inhibit collecting duct transport nor effect diuresis and natriuresis. Appears to bind to specific receptors that are distinct from the receptors bound by the atrial natriuretic and long-acting natriuretic peptides. Possibly functions in protein excretion in urine by maintaining the integrity of the proximal tubules and enhancing protein excretion by decreasing proximal tubular protein reabsorption. {ECO:0000250|UniProtKB:P01160}.; FUNCTION: [Kaliuretic peptide]: May have a role in cardio-renal homeostasis through regulation of diuresis and inhibiting aldosterone synthesis. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. May have a role in potassium excretion but not sodium excretion (natriuresis). Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption. {ECO:0000250|UniProtKB:P01160}.; FUNCTION: [Urodilatin]: Hormone produced in the kidneys that appears to be important for maintaining cardio-renal homeostasis. Mediates vasodilation, natriuresis and diuresis primarily in the renal system, in order to maintain the extracellular fluid volume and control the fluid-electrolyte balance. Specifically binds and stimulates cGMP production by renal transmembrane receptors, likely NPR1. Urodilatin not ANP, may be the natriuretic peptide responsible for the regulation of sodium and water homeostasis in the kidney. {ECO:0000250|UniProtKB:P01160}.; FUNCTION: [Auriculin-D]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips. {ECO:0000250|UniProtKB:P01161}.; FUNCTION: [Auriculin-B]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips. {ECO:0000250|UniProtKB:P01161}.; FUNCTION: [Auriculin-A]: May have a role in cardio-renal homeostasis through regulation of regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, vasodilates intestinal smooth muscle but not smooth muscle strips. {ECO:0000250|UniProtKB:P01161}.; FUNCTION: [Atriopeptin-2]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, selectively vasodilates intestinal and vascular smooth muscle strips. {ECO:0000250|UniProtKB:P01161}.; FUNCTION: [Atriopeptin-1]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, selectively vasodilates intestinal smooth muscle but not vascular smooth muscle strips. {ECO:0000250|UniProtKB:P01161}.
|
Mus musculus (Mouse)
|
P05126
|
KPCB_BOVIN
|
MADPAAGPPPSEGEESTVRFARKGALRQKNVHEVKNHKFTARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPASDDPRSKHKFKIHTYSSPTFCDHCGSLLYGLIHQGMKCDTCMMNVHKRCVMNVPSLCGTDHTERRGRIYIQAHIEREVLIVVVRDAKNLVPMDPNGLSDPYVKLKLIPDPKSESKQKTKTIKCSLNPEWNETFRFQLKESDKDRRLSVEIWDWDLTSRNDFMGSLSFGISELQKAGVDGWFKLLSQEEGEYFNVPVPPEGSEGNEELRQKFERAKIGPGPKTPEEKTTNTISKFDNNGNRDRMKLTDFNFLMVLGKGSFGKVMLSERKGTDELYAVKILKKDVVIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTMDRLYFVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTKTFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTKHPGKRLGCGPEGERDIKEHAFFRYIDWEKLERKEIQPPYKPKARDKRDTSNFDKEFTRQPVELTPTDKLFIMNLDQNEFAGFSYTNPEFVINV
|
2.7.11.13
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE-ProRule:PRU00041}; Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain. {ECO:0000250|UniProtKB:P68403};
|
adaptive immune response [GO:0002250]; apoptotic process [GO:0006915]; B cell activation [GO:0042113]; B cell receptor signaling pathway [GO:0050853]; intracellular signal transduction [GO:0035556]; negative regulation of glucose transmembrane transport [GO:0010829]; negative regulation of insulin receptor signaling pathway [GO:0046627]; phosphorylation [GO:0016310]; positive regulation of angiogenesis [GO:0045766]; positive regulation of B cell receptor signaling pathway [GO:0050861]; positive regulation of canonical NF-kappaB signal transduction [GO:0043123]; positive regulation of vascular endothelial growth factor receptor signaling pathway [GO:0030949]; post-translational protein modification [GO:0043687]; regulation of glucose transmembrane transport [GO:0010827]; regulation of transcription by RNA polymerase II [GO:0006357]
|
cytoplasm [GO:0005737]; membrane [GO:0016020]; nucleus [GO:0005634]
|
ATP binding [GO:0005524]; chromatin binding [GO:0003682]; diacylglycerol-dependent serine/threonine kinase activity [GO:0004697]; histone binding [GO:0042393]; histone H3T6 kinase activity [GO:0035403]; nuclear androgen receptor binding [GO:0050681]; nuclear receptor coactivator activity [GO:0030374]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]; zinc ion binding [GO:0008270]
|
PF00130;PF00168;PF00069;PF00433;
|
3.30.60.20;2.60.40.150;1.10.510.10;
|
Protein kinase superfamily, AGC Ser/Thr protein kinase family, PKC subfamily
|
PTM: Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade (By similarity). {ECO:0000250}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. 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=2.7.11.13; 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=2.7.11.13;
| null | null | null | null |
FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (By similarity). {ECO:0000250|UniProtKB:P05771, ECO:0000250|UniProtKB:P68404}.
|
Bos taurus (Bovine)
|
P05128
|
KPCG_BOVIN
|
RPLFCRKGALRQKVVHEVKSHKFTARFFKQPTFCSHCTDFIWGIGKQGLQCQVCSFVVHRRCHEFVTFECPGAGKGPQTDDPRNKHKFRLHSYSSPTFCDHCGSLLYGLVHQGMKCSCCEMNVHRRCVRSVPSLCGVDHTERRGRLQLEIRAPTSDEIHVTVGEARNLIPMDPNGLSDPYVKLKLIPDPRNLTKQKTRTVKATLNPVWNETFVFNLKPGDVERRLSVEVWDWDRTSRNDFMGAMSFGVSELLKAPVDGWYKLLNQEEGEYYNVPVADADNCNLLQKFEACNYPLELYERVRTGPSSSPIPSPSPSPTDSKRCFFGASPGRLHISDFSFLMVLGKGSFGKVMLAERRGSDELYAIKILKKDVIVQDDDVDCTLVEKRVLALGGRGPGGRPHFLTQLHSTFQTPDRLYFVMEYVTGGDLMYHIQQLGKFKEPHAAFYAAEIAIGLFFLHNQGIIYRDLKLDNVMLDAEGHIKITDFGMCKENVFPGSTTRTFCGTPDYIAPEIIAYQPYGKSVDWWSFGVLLYEMLAGQPPFDGEDEEELFQAIMEQTVTYPKSLSREAVAICKGFLTKHPAKRLGSGPDGEPTIRAHGFFRWIDWDRLERLEIAPPFRPRPCGRSGENFDKFFTRAAPALTPPDRLVLASIDQAEFQGFTYVNPDFVHPDARSPISPTPVPVM
|
2.7.11.13
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE-ProRule:PRU00041}; Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain. {ECO:0000250|UniProtKB:P05129};
|
intracellular signal transduction [GO:0035556]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of proteasomal protein catabolic process [GO:1901799]; negative regulation of protein ubiquitination [GO:0031397]; phosphorylation [GO:0016310]; regulation of circadian rhythm [GO:0042752]; regulation of response to food [GO:0032095]; response to morphine [GO:0043278]; response to pain [GO:0048265]; rhythmic process [GO:0048511]
|
cytosol [GO:0005829]; dendrite [GO:0030425]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; synapse [GO:0045202]
|
ATP binding [GO:0005524]; diacylglycerol-dependent serine/threonine kinase activity [GO:0004697]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]; zinc ion binding [GO:0008270]
|
PF00130;PF00168;PF00069;PF00433;
|
3.30.60.20;2.60.40.150;1.10.510.10;
|
Protein kinase superfamily, AGC Ser/Thr protein kinase family, PKC subfamily
|
PTM: Autophosphorylation on Thr-659 appears to regulate motor functions of junctophilins, JPH3 and JPH4. {ECO:0000250|UniProtKB:P63318}.; PTM: Ubiquitinated. {ECO:0000250|UniProtKB:P05129}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P63318}. Cytoplasm, perinuclear region {ECO:0000250}. Cell membrane {ECO:0000250|UniProtKB:P63318}; Peripheral membrane protein {ECO:0000250}. Synapse, synaptosome {ECO:0000250|UniProtKB:P63318}. Cell projection, dendrite {ECO:0000250|UniProtKB:P63319}. Note=Translocates to synaptic membranes on stimulation. {ECO:0000250|UniProtKB:P63318}.
|
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=2.7.11.13; 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=2.7.11.13;
| null | null | null | null |
FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contributes to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress. Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock. {ECO:0000250|UniProtKB:P05129, ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319}.
|
Bos taurus (Bovine)
|
P05129
|
KPCG_HUMAN
|
MAGLGPGVGDSEGGPRPLFCRKGALRQKVVHEVKSHKFTARFFKQPTFCSHCTDFIWGIGKQGLQCQVCSFVVHRRCHEFVTFECPGAGKGPQTDDPRNKHKFRLHSYSSPTFCDHCGSLLYGLVHQGMKCSCCEMNVHRRCVRSVPSLCGVDHTERRGRLQLEIRAPTADEIHVTVGEARNLIPMDPNGLSDPYVKLKLIPDPRNLTKQKTRTVKATLNPVWNETFVFNLKPGDVERRLSVEVWDWDRTSRNDFMGAMSFGVSELLKAPVDGWYKLLNQEEGEYYNVPVADADNCSLLQKFEACNYPLELYERVRMGPSSSPIPSPSPSPTDPKRCFFGASPGRLHISDFSFLMVLGKGSFGKVMLAERRGSDELYAIKILKKDVIVQDDDVDCTLVEKRVLALGGRGPGGRPHFLTQLHSTFQTPDRLYFVMEYVTGGDLMYHIQQLGKFKEPHAAFYAAEIAIGLFFLHNQGIIYRDLKLDNVMLDAEGHIKITDFGMCKENVFPGTTTRTFCGTPDYIAPEIIAYQPYGKSVDWWSFGVLLYEMLAGQPPFDGEDEEELFQAIMEQTVTYPKSLSREAVAICKGFLTKHPGKRLGSGPDGEPTIRAHGFFRWIDWERLERLEIPPPFRPRPCGRSGENFDKFFTRAAPALTPPDRLVLASIDQADFQGFTYVNPDFVHPDARSPTSPVPVPVM
|
2.7.11.13
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE-ProRule:PRU00041, ECO:0000269|Ref.14}; Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain. {ECO:0000269|Ref.14};
|
chemical synaptic transmission [GO:0007268]; chemosensory behavior [GO:0007635]; innervation [GO:0060384]; intracellular signal transduction [GO:0035556]; learning or memory [GO:0007611]; long-term synaptic potentiation [GO:0060291]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of proteasomal protein catabolic process [GO:1901799]; negative regulation of protein catabolic process [GO:0042177]; negative regulation of protein ubiquitination [GO:0031397]; phosphorylation [GO:0016310]; positive regulation of mismatch repair [GO:0032425]; presynaptic modulation of chemical synaptic transmission [GO:0099171]; protein phosphorylation [GO:0006468]; regulation of circadian rhythm [GO:0042752]; regulation of phagocytosis [GO:0050764]; regulation of response to food [GO:0032095]; regulation of synaptic vesicle exocytosis [GO:2000300]; response to morphine [GO:0043278]; response to pain [GO:0048265]; response to psychosocial stress [GO:1990911]; response to toxic substance [GO:0009636]; rhythmic process [GO:0048511]
|
calyx of Held [GO:0044305]; cell-cell junction [GO:0005911]; cytosol [GO:0005829]; dendrite [GO:0030425]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; postsynaptic cytosol [GO:0099524]; postsynaptic density [GO:0014069]; presynaptic cytosol [GO:0099523]; synaptic membrane [GO:0097060]
|
ATP binding [GO:0005524]; calcium,diacylglycerol-dependent serine/threonine kinase activity [GO:0004698]; diacylglycerol-dependent serine/threonine kinase activity [GO:0004697]; protein kinase activity [GO:0004672]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]; protein serine/threonine/tyrosine kinase activity [GO:0004712]; zinc ion binding [GO:0008270]
|
PF00130;PF00168;PF00069;PF00433;
|
3.30.60.20;2.60.40.150;1.10.510.10;
|
Protein kinase superfamily, AGC Ser/Thr protein kinase family, PKC subfamily
|
PTM: Autophosphorylation on Thr-674 appears to regulate motor functions of junctophilins, JPH3 and JPH4. {ECO:0000250|UniProtKB:P63318}.; PTM: Ubiquitinated. {ECO:0000269|PubMed:20596523}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P63318}. Cytoplasm, perinuclear region {ECO:0000250}. Cell membrane {ECO:0000269|PubMed:29053796}; Peripheral membrane protein {ECO:0000250}. Synapse, synaptosome {ECO:0000250|UniProtKB:P63318}. Cell projection, dendrite {ECO:0000250|UniProtKB:P63319}. Note=Translocates to synaptic membranes on stimulation. {ECO:0000250|UniProtKB:P63318}.
|
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=2.7.11.13; 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=2.7.11.13;
| null | null | null | null |
FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contributes to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress (By similarity). Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity). {ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319, ECO:0000269|PubMed:16377624}.
|
Homo sapiens (Human)
|
P05130
|
KPC1_DROME
|
MSEGSDNNGDPQQQGAEGEAVGENKMKSRLRKGALKKKNVFNVKDHCFIARFFKQPTFCSHCKDFICGYQSGYAWMGFGKQGFQCQVCSYVVHKRCHEYVTFICPGKDKGIDSDSPKTQHNFEPFTYAGPTFCDHCGSLLYGIYHQGLKCSACDMNVHARCKENVPSLCGCDHTERRGRIYLEINVKENLLTVQIKEGRNLIPMDPNGLSDPYVKVKLIPDDKDQSKKKTRTIKACLNPVWNETLTYDLKPEDKDRRILIEVWDWDRTSRNDFMGALSFGISEIIKNPTNGWFKLLTQDEGEYYNVPCADDEQDLLKLKQKPSQKKPMVMRSDTNTHTSSKKDMIRATDFNFIKVLGKGSFGKVLLAERKGSEELYAIKILKKDVIIQDDDVECTMIEKRVLALGEKPPFLVQLHSCFQTMDRLFFVMEYVNGGDLMFQIQQFGKFKEPVAVFYAAEIAAGLFFLHTKGILYRDLKLDNVLLDADGHVKIADFGMCKENIVGDKTTKTFCGTPDYIAPEIILYQPYGKSVDWWAYGVLLYEMLVGQPPFDGEDEEELFAAITDHNVSYPKSLSKEAKEACKGFLTKQPNKRLGCGSSGEEDVRLHPFFRRIDWEKIENREVQPPFKPKIKHRKDVSNFDKQFTSEKTDLTPTDKVFMMNLDQSEFVGFSYMNPEYVFSP
|
2.7.11.13
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE-ProRule:PRU00041}; Note=Binds 3 Ca(2+) ions per C2 domain. {ECO:0000255|PROSITE-ProRule:PRU00041};
|
intracellular signal transduction [GO:0035556]; positive regulation of clathrin-dependent endocytosis [GO:2000370]; protein phosphorylation [GO:0006468]; regulation of hemocyte proliferation [GO:0035206]
|
cytoplasm [GO:0005737]; nucleus [GO:0005634]; plasma membrane [GO:0005886]
|
ATP binding [GO:0005524]; diacylglycerol-dependent serine/threonine kinase activity [GO:0004697]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]; zinc ion binding [GO:0008270]
|
PF00130;PF00168;PF00069;PF00433;
|
3.30.60.20;2.60.40.150;1.10.510.10;
|
Protein kinase superfamily, AGC Ser/Thr protein kinase family, PKC subfamily
| 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=2.7.11.13; 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=2.7.11.13;
| null | null | null | null |
FUNCTION: PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins (By similarity). PKC also serves as the receptor for phorbol esters, a class of tumor promoters (By similarity). Acts in a hh-signaling pathway which regulates the Duox-dependent gut immune response to bacterial uracil; required for the activation of Cad99C and consequently Cad99C-dependent endosome formation, which is essential for the Duox-dependent production of reactive oxygen species (ROS) in response to intestinal bacterial infection (PubMed:25639794). {ECO:0000250|UniProtKB:P34885, ECO:0000269|PubMed:25639794}.
|
Drosophila melanogaster (Fruit fly)
|
P05131
|
KAPCB_BOVIN
|
MGNAATAKKGSEVESVKEFLAKAKEDFLKKWENPAPNNAGLEDFERKKTLGTGSFGRVMLVKHKATEQYYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVRLEYAFKDNSNLYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDHQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVSDIKTHKWFATTDWIAIYQRKVEAPFIPKFRGSGDTSNFDDYEEEDIRVSITEKCGKEFCEF
|
2.7.11.11
| null |
negative regulation of TORC1 signaling [GO:1904262]; protein kinase A signaling [GO:0010737]; protein phosphorylation [GO:0006468]
|
cAMP-dependent protein kinase complex [GO:0005952]; cytosol [GO:0005829]; nucleus [GO:0005634]; plasma membrane [GO:0005886]
|
AMP-activated protein kinase activity [GO:0004679]; ATP binding [GO:0005524]; cAMP-dependent protein kinase activity [GO:0004691]; protein serine kinase activity [GO:0106310]
|
PF00069;
|
1.10.510.10;
|
Protein kinase superfamily, AGC Ser/Thr protein kinase family, cAMP subfamily
|
PTM: Asn-3 is deaminated to Asp in more than 25% of the proteins, giving rise to 2 major isoelectric variants, called CB and CA respectively (0.4 pH unit change). Deamidation proceeds via the so-called beta-aspartyl shift mechanism and yields either 'D-Asp-2' (major) or 'D-isoAsp-2' (minor), in addition to L-isomers. Deamidation occurs after the addition of myristate. The Asn-3 form reaches a significantly larger nuclear/cytoplasmic ratio than the 'Asp-2' form. {ECO:0000269|PubMed:10684253, ECO:0000269|PubMed:11152138, ECO:0000269|PubMed:9521123}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10684253}. Cell membrane {ECO:0000250|UniProtKB:P22694}. Membrane {ECO:0000250|UniProtKB:P22694}; Lipid-anchor {ECO:0000250|UniProtKB:P22694}. Nucleus {ECO:0000269|PubMed:10684253}. Note=Translocates into the nucleus (monomeric catalytic subunit). The inactive holoenzyme is found in the cytoplasm. {ECO:0000269|PubMed:10684253}.
|
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=2.7.11.11; 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=2.7.11.11;
| null | null | null | null |
FUNCTION: Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates GPKOW which regulates its ability to bind RNA. Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR. {ECO:0000250|UniProtKB:P22694}.
|
Bos taurus (Bovine)
|
P05132
|
KAPCA_MOUSE
|
MGNAAAAKKGSEQESVKEFLAKAKEDFLKKWETPSQNTAQLDQFDRIKTLGTGSFGRVMLVKHKESGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVAGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLIYRDLKPENLLIDQQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWFATTDWIAIYQRKVEAPFIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFTEF
|
2.7.11.11
| null |
adenylate cyclase-activating G protein-coupled receptor signaling pathway [GO:0007189]; cellular response to cold [GO:0070417]; cellular response to glucagon stimulus [GO:0071377]; cellular response to glucose stimulus [GO:0071333]; cellular response to heat [GO:0034605]; cellular response to parathyroid hormone stimulus [GO:0071374]; mesoderm formation [GO:0001707]; modulation of chemical synaptic transmission [GO:0050804]; mRNA processing [GO:0006397]; negative regulation of glycolytic process through fructose-6-phosphate [GO:1904539]; negative regulation of meiotic cell cycle [GO:0051447]; negative regulation of smoothened signaling pathway [GO:0045879]; negative regulation of TORC1 signaling [GO:1904262]; negative regulation of transcription by RNA polymerase II [GO:0000122]; neural tube closure [GO:0001843]; peptidyl-serine phosphorylation [GO:0018105]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of gluconeogenesis [GO:0045722]; positive regulation of insulin secretion [GO:0032024]; positive regulation of protein export from nucleus [GO:0046827]; postsynaptic modulation of chemical synaptic transmission [GO:0099170]; protein export from nucleus [GO:0006611]; protein kinase A signaling [GO:0010737]; protein localization to lipid droplet [GO:1990044]; regulation of bicellular tight junction assembly [GO:2000810]; regulation of cell cycle [GO:0051726]; regulation of cellular respiration [GO:0043457]; regulation of osteoblast differentiation [GO:0045667]; regulation of proteasomal protein catabolic process [GO:0061136]; regulation of protein processing [GO:0070613]; regulation of synaptic transmission, glutamatergic [GO:0051966]; sperm capacitation [GO:0048240]; spontaneous exocytosis of neurotransmitter [GO:0048792]
|
acrosomal vesicle [GO:0001669]; axoneme [GO:0005930]; cAMP-dependent protein kinase complex [GO:0005952]; centrosome [GO:0005813]; ciliary base [GO:0097546]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; dendritic spine [GO:0043197]; glutamatergic synapse [GO:0098978]; mitochondrion [GO:0005739]; neuromuscular junction [GO:0031594]; nuclear speck [GO:0016607]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane [GO:0005886]; plasma membrane raft [GO:0044853]; postsynapse [GO:0098794]; presynapse [GO:0098793]; protein-containing complex [GO:0032991]; sperm flagellum [GO:0036126]; sperm midpiece [GO:0097225]
|
AMP-activated protein kinase activity [GO:0004679]; ATP binding [GO:0005524]; cAMP-dependent protein kinase activity [GO:0004691]; magnesium ion binding [GO:0000287]; manganese ion binding [GO:0030145]; protein domain specific binding [GO:0019904]; protein kinase A regulatory subunit binding [GO:0034237]; protein kinase activity [GO:0004672]; protein kinase binding [GO:0019901]; protein serine kinase activity [GO:0106310]; protein serine/threonine kinase activity [GO:0004674]; protein serine/threonine/tyrosine kinase activity [GO:0004712]; protein-containing complex binding [GO:0044877]; small GTPase binding [GO:0031267]; ubiquitin protein ligase binding [GO:0031625]
|
PF00069;
|
1.10.510.10;
|
Protein kinase superfamily, AGC Ser/Thr protein kinase family, cAMP subfamily
|
PTM: Autophosphorylated; phosphorylation is enhanced by vitamin K(2) (By similarity). Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity (PubMed:8395513, PubMed:9707564). Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency (PubMed:21866565). {ECO:0000250|UniProtKB:P17612, ECO:0000269|PubMed:21866565, ECO:0000269|PubMed:8395513, ECO:0000269|PubMed:9707564}.; PTM: Asn-3 is partially deaminated to Asp-3 giving rise to 2 major isoelectric variants, called CB and CA respectively. {ECO:0000269|PubMed:11141074}.; PTM: When myristoylated, Ser-11 is autophosphorylated probably in conjunction with deamidation of Asn-3. {ECO:0000269|PubMed:11141074, ECO:0000269|PubMed:8395513}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18367160}. Cell membrane {ECO:0000269|PubMed:33886552}. Nucleus {ECO:0000250|UniProtKB:P17612}. Mitochondrion {ECO:0000269|PubMed:18367160}. Membrane {ECO:0000250|UniProtKB:P17612}; Lipid-anchor {ECO:0000250|UniProtKB:P17612}. Note=Translocates into the nucleus (monomeric catalytic subunit) (By similarity). The inactive holoenzyme is found in the cytoplasm. Distributed throughout the cytoplasm in meiotically incompetent oocytes. Associated to mitochondrion as meiotic competence is acquired. Aggregates around the germinal vesicles (GV) at the immature GV stage oocytes. Colocalizes with HSF1 in nuclear stress bodies (nSBs) upon heat shock (By similarity). Recruited to the cell membrane through interaction with SMO (PubMed:33886552). {ECO:0000250|UniProtKB:P17612, ECO:0000269|PubMed:33886552}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell projection, cilium, flagellum {ECO:0000269|PubMed:27105888}. Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000269|PubMed:27105888}. Note=Expressed in the midpiece region of the sperm flagellum (By similarity). Colocalizes with MROH2B and TCP11 on the acrosome and tail regions in round spermatids and spermatozoa regardless of the capacitation status of the sperm (PubMed:27105888). {ECO:0000250, ECO:0000269|PubMed:27105888}.
|
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=2.7.11.11; Evidence={ECO:0000269|PubMed:10805756, ECO:0000269|PubMed:19223768}; 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=2.7.11.11; Evidence={ECO:0000269|PubMed:10805756, ECO:0000269|PubMed:19223768};
| null | null | null | null |
FUNCTION: Phosphorylates a large number of substrates in the cytoplasm and the nucleus (By similarity). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:10805756, PubMed:19223768). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (By similarity). RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (By similarity). Involved in chondrogenesis by mediating phosphorylation of SOX9 (PubMed:10805756). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes (PubMed:33886552). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (PubMed:33886552). Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis (By similarity). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (PubMed:19223768). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA. Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (By similarity). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (By similarity). {ECO:0000250|UniProtKB:P17612, ECO:0000250|UniProtKB:P27791, ECO:0000269|PubMed:10805756, ECO:0000269|PubMed:19223768, ECO:0000269|PubMed:33886552}.; FUNCTION: [Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. {ECO:0000269|PubMed:15340140, ECO:0000269|PubMed:19560455}.
|
Mus musculus (Mouse)
|
P05133
|
NCAP_HANTV
|
MATMEELQREINAHEGQLVIARQKVRDAEKQYEKDPDELNKRTLTDREGVAVSIQAKIDELKRQLADRIATGKNLGKEQDPTGVEPGDHLKERSMLSYGNVLDLNHLDIDEPTGQTADWLSIIVYLTSFVVPILLKALYMLTTRGRQTTKDNKGTRIRFKDDSSFEDVNGIRKPKHLYVSLPNAQSSMKAEEITPGRYRTAVCGLYPAQIKARQMISPVMSVIGFLALAKDWSDRIEQWLIEPCKLLPDTAAVSLLGGPATNRDYLRQRQVALGNMETKESKAIRQHAEAAGCSMIEDIESPSSIWVFAGAPDRCPPTCLFIAGIAELGAFFSILQDMRNTIMASKTVGTSEEKLRKKSSFYQSYLRRTQSMGIQLGQRIIVLFMVAWGKEAVDNFHLGDDMDPELRTLAQSLIDVKVKEISNQEPLKL
|
3.1.-.-
| null |
symbiont-mediated suppression of host apoptosis [GO:0033668]
|
helical viral capsid [GO:0019029]; host cell Golgi apparatus [GO:0044177]; host cell perinuclear region of cytoplasm [GO:0044220]; ribonucleoprotein complex [GO:1990904]; viral nucleocapsid [GO:0019013]
|
endonuclease activity [GO:0004519]; RNA binding [GO:0003723]
|
PF00846;
|
1.20.58.90;
|
Hantavirus nucleocapsid protein family
| null |
SUBCELLULAR LOCATION: Virion {ECO:0000305}. Host cytoplasm, host perinuclear region {ECO:0000269|PubMed:12573574}. Host Golgi apparatus, host cis-Golgi network {ECO:0000269|PubMed:24070985}. Note=Internal protein of virus particle. {ECO:0000305}.
| null | null | null | null | null |
FUNCTION: Encapsidates the genome protecting it from nucleases (PubMed:26923588). The encapsidated genomic RNA is termed the nucleocapsid (NC) and serves as template for transcription and replication (Probable). The nucleocapsid has a left-handed helical structure (PubMed:30638449). As a trimer, specifically binds and acts as a chaperone to unwind the panhandle structure formed by the viral RNA (vRNA) termini (By similarity). Involved in the transcription and replication initiation of vRNA by mediating primer annealing (By similarity). Plays a role in cap snatching by sequestering capped RNAs in P bodies for use by the viral RdRp during transcription initiation (By similarity). Substitutes for the cellular cap-binding complex (eIF4F) to preferentially facilitate the translation of capped mRNAs (By similarity). Initiates the translation by specifically binding to the cap and 40S ribosomal subunit (By similarity). Prevents the viral glycoprotein N (Gn) from autophagy-dependent breakdown maybe by blocking autophagosome formation (PubMed:31091447). Inhibits host EIF2AK2/PKR dimerization to prevent PKR-induced translational shutdown in cells and thus the activation of the antiviral state (By similarity). Also displays sequence-unspecific DNA endonuclease activity (By similarity). Suppresses apoptosis probably through the inhibition of nuclear import of NF-kappa-B (PubMed:20227103). {ECO:0000250|UniProtKB:O36307, ECO:0000250|UniProtKB:Q89462, ECO:0000269|PubMed:20227103, ECO:0000269|PubMed:26923588, ECO:0000269|PubMed:30638449, ECO:0000269|PubMed:31091447, ECO:0000305}.
|
Hantaan virus (strain 76-118) (Korean hemorrhagic fever virus)
|
P05141
|
ADT2_HUMAN
|
MTDAAVSFAKDFLAGGVAAAISKTAVAPIERVKLLLQVQHASKQITADKQYKGIIDCVVRIPKEQGVLSFWRGNLANVIRYFPTQALNFAFKDKYKQIFLGGVDKRTQFWLYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKAGAEREFRGLGDCLVKIYKSDGIKGLYQGFNVSVQGIIIYRAAYFGIYDTAKGMLPDPKNTHIVISWMIAQTVTAVAGLTSYPFDTVRRRMMMQSGRKGTDIMYTGTLDCWRKIARDEGGKAFFKGAWSNVLRGMGGAFVLVLYDEIKKYT
| null | null |
adaptive thermogenesis [GO:1990845]; adenine nucleotide transport [GO:0051503]; B cell differentiation [GO:0030183]; cellular response to leukemia inhibitory factor [GO:1990830]; chromosome segregation [GO:0007059]; erythrocyte differentiation [GO:0030218]; mitochondrial ADP transmembrane transport [GO:0140021]; mitochondrial ATP transmembrane transport [GO:1990544]; negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway [GO:1901029]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of mitophagy [GO:1901526]; regulation of mitochondrial membrane permeability [GO:0046902]
|
membrane [GO:0016020]; mitochondrial inner membrane [GO:0005743]; mitochondrial nucleoid [GO:0042645]; mitochondrial permeability transition pore complex [GO:0005757]; mitochondrion [GO:0005739]; MMXD complex [GO:0071817]; nucleus [GO:0005634]; plasma membrane [GO:0005886]
|
adenine nucleotide transmembrane transporter activity [GO:0000295]; adenine transmembrane transporter activity [GO:0015207]; ATP:ADP antiporter activity [GO:0005471]; oxidative phosphorylation uncoupler activity [GO:0017077]; proton transmembrane transporter activity [GO:0015078]; RNA binding [GO:0003723]; ubiquitin protein ligase binding [GO:0031625]
|
PF00153;
|
1.50.40.10;
|
Mitochondrial carrier (TC 2.A.29) family
|
PTM: Trimethylated by ANTKMT at Lys-52. {ECO:0000269|PubMed:31213526}.
|
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250|UniProtKB:P02722}; Multi-pass membrane protein {ECO:0000255}. Membrane {ECO:0000269|PubMed:27641616}; Multi-pass membrane protein {ECO:0000255}. Note=May localize to non-mitochondrial membranes. {ECO:0000269|PubMed:27641616}.
|
CATALYTIC ACTIVITY: Reaction=ADP(in) + ATP(out) = ADP(out) + ATP(in); Xref=Rhea:RHEA:34999, ChEBI:CHEBI:30616, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P51881}; CATALYTIC ACTIVITY: Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378; Evidence={ECO:0000250|UniProtKB:P51881};
| null | null | null | null |
FUNCTION: ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (By similarity). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (By similarity). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A5/ANT2 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (By similarity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity). Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (By similarity). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (PubMed:31883789). It is however unclear if SLC25A5/ANT2 constitutes a pore-forming component of mPTP or regulates it (By similarity). Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity). As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation (PubMed:20797633). {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P51881, ECO:0000269|PubMed:20797633, ECO:0000269|PubMed:31883789}.
|
Homo sapiens (Human)
|
P05150
|
OTC_YEAST
|
MSTTASTPSSLRHLISIKDLSDEEFRILVQRAQHFKNVFKANKTNDFQSNHLKLLGRTIALIFTKRSTRTRISTEGAATFFGAQPMFLGKEDIQLGVNESFYDTTKVVSSMVSCIFARVNKHEDILAFCKDSSVPIINSLCDKFHPLQAICDLLTIIENFNISLDEVNKGINSKLKMAWIGDANNVINDMCIACLKFGISVSISTPPGIEMDSDIVDEAKKVAERNGATFELTHDSLKASTNANILVTDTFVSMGEEFAKQAKLKQFKGFQINQELVSVADPNYKFMHCLPRHQEEVSDDVFYGEHSIVFEEAENRLYAAMSAIDIFVNNKGNFKDLK
|
2.1.3.3
| null |
arginine biosynthetic process [GO:0006526]; arginine biosynthetic process via ornithine [GO:0042450]; citrulline biosynthetic process [GO:0019240]
|
cytosol [GO:0005829]; mitochondrion [GO:0005739]; ornithine carbamoyltransferase inhibitor complex [GO:1903269]
|
amino acid binding [GO:0016597]; ornithine carbamoyltransferase activity [GO:0004585]
|
PF00185;PF02729;
|
3.40.50.1370;
|
Aspartate/ornithine carbamoyltransferase superfamily, OTCase family
| null |
SUBCELLULAR LOCATION: Cytoplasm.
|
CATALYTIC ACTIVITY: Reaction=carbamoyl phosphate + L-ornithine = H(+) + L-citrulline + phosphate; Xref=Rhea:RHEA:19513, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:46911, ChEBI:CHEBI:57743, ChEBI:CHEBI:58228; EC=2.1.3.3;
| null |
PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine from L-ornithine and carbamoyl phosphate: step 1/3.
| null | null | null |
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
|
P05153
|
PCKGC_CHICK
|
MAPELKTEVNIISKVIQGDLESLPPQVREFIESNAKLCQPESIHICDGSEEENKKILDIMVEQGMIKKLSKYENCWLALTNPRDVARIESKTVIITQEQRDTIPIPKTGSSQLGRWMSEEDFEKAFNTRFPGCMQGRTMYVIPFSMGPIGSPLAKIGIELTDSPYVVASMRMMTRMGTAALKALGNGEFVKCLHSVGCPLPLKEPLINNWPCNPELTLIAHLPDRREIISFGSGYGGNSLLGKKCFALRIASRIAKEEGWLAEHMLILGITNPEGEKKYFAAAFPSACGKTNLAMMNPSRPGWKIECVGDDIAWMKFDELGNLRAINPENGFFGVAPGTSIKTNPNAIKTIFKNTIFTNVAETSDGGVYWEGIDEPLPPGVTLTSWKNKDWTPDNGEPCAHPNSRFCTPASQCPIMDPAWESPEGVPIEGIIFGGRRPAGVPLVYEAFNWQHGVFIGAAMRSEATAAAEHKGKIIMHDPFAMRPFFGYNFGKYLAHWLSMAHRPAAKLPRIFHVNWFRKDSQGKFLWPGYGENSRVLEWMFNRIQGKASAKSTAIGYIPADTALNLKGLEDINLTELFNISKEFWEKEVEEIKQYFEGQVNADLPYEIERELLALEMRIKQL
|
2.7.11.-; 4.1.1.32
|
COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250|UniProtKB:P35558}; Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000250|UniProtKB:P35558};
|
adult feeding behavior [GO:0008343]; alanine metabolic process [GO:0006522]; aspartate metabolic process [GO:0006531]; cellular response to cAMP [GO:0071320]; cellular response to dexamethasone stimulus [GO:0071549]; cellular response to ethanol [GO:0071361]; cellular response to fructose stimulus [GO:0071332]; cellular response to glucagon stimulus [GO:0071377]; cellular response to glucose starvation [GO:0042149]; cellular response to glucose stimulus [GO:0071333]; cellular response to hypoxia [GO:0071456]; cellular response to insulin stimulus [GO:0032869]; cellular response to interleukin-1 [GO:0071347]; cellular response to parathyroid hormone stimulus [GO:0071374]; cellular response to retinoic acid [GO:0071300]; cellular response to tumor necrosis factor [GO:0071356]; developmental growth [GO:0048589]; digestion [GO:0007586]; egg-laying behavior [GO:0018991]; eggshell formation [GO:0030703]; embryo development ending in birth or egg hatching [GO:0009792]; embryonic organ morphogenesis [GO:0048562]; gluconeogenesis [GO:0006094]; glutamate metabolic process [GO:0006536]; glutamine metabolic process [GO:0006541]; glycerol biosynthetic process from pyruvate [GO:0046327]; glycerol catabolic process [GO:0019563]; glycine metabolic process [GO:0006544]; hepatocyte differentiation [GO:0070365]; intestinal absorption [GO:0050892]; lactate metabolic process [GO:0006089]; NADH regeneration [GO:0006735]; negative regulation of carbohydrate metabolic process [GO:0045912]; oxaloacetate metabolic process [GO:0006107]; peptidyl-serine phosphorylation [GO:0018105]; positive regulation of carbohydrate metabolic process [GO:0045913]; positive regulation of gluconeogenesis [GO:0045722]; positive regulation of memory T cell differentiation [GO:0043382]; proline metabolic process [GO:0006560]; propionate catabolic process [GO:0019543]; pyruvate metabolic process [GO:0006090]; regulation of feeding behavior [GO:0060259]; regulation of gluconeogenesis [GO:0006111]; regulation of lipid biosynthetic process [GO:0046890]; regulation of transcription by glucose [GO:0046015]; response to cAMP [GO:0051591]; response to cycloheximide [GO:0046898]; response to glucocorticoid [GO:0051384]; response to interleukin-6 [GO:0070741]; response to lipid [GO:0033993]; response to lipopolysaccharide [GO:0032496]; response to methionine [GO:1904640]; response to starvation [GO:0042594]; serine family amino acid metabolic process [GO:0009069]; sexual reproduction [GO:0019953]; vitellogenesis [GO:0007296]
|
cytosol [GO:0005829]; endoplasmic reticulum [GO:0005783]
|
epinephrine binding [GO:0051379]; GTP binding [GO:0005525]; manganese ion binding [GO:0030145]; nucleoside diphosphate kinase activity [GO:0004550]; phosphoenolpyruvate carboxykinase (GTP) activity [GO:0004613]; protein serine kinase activity (using GTP as donor) [GO:0106264]
|
PF00821;PF17297;
|
3.90.228.20;3.40.449.10;2.170.8.10;
|
Phosphoenolpyruvate carboxykinase [GTP] family
|
PTM: Phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and promotes the protein kinase activity. {ECO:0000250|UniProtKB:P35558}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P35558}.
|
CATALYTIC ACTIVITY: Reaction=GTP + oxaloacetate = CO2 + GDP + phosphoenolpyruvate; Xref=Rhea:RHEA:10388, ChEBI:CHEBI:16452, ChEBI:CHEBI:16526, ChEBI:CHEBI:37565, ChEBI:CHEBI:58189, ChEBI:CHEBI:58702; EC=4.1.1.32; Evidence={ECO:0000250|UniProtKB:P35558}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10389; Evidence={ECO:0000250|UniProtKB:P35558}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10390; Evidence={ECO:0000250|UniProtKB:P35558}; CATALYTIC ACTIVITY: Reaction=GTP + L-seryl-[protein] = GDP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:64020, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:37565, ChEBI:CHEBI:58189, ChEBI:CHEBI:83421; Evidence={ECO:0000250|UniProtKB:P35558}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64021; Evidence={ECO:0000250|UniProtKB:P35558};
| null |
PATHWAY: Carbohydrate biosynthesis; gluconeogenesis. {ECO:0000250|UniProtKB:P35558}.
| null | null |
FUNCTION: Regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle. At low glucose levels, it catalyzes the cataplerotic conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. At high glucose levels, it catalyzes the anaplerotic conversion of phosphoenolpyruvate to oxaloacetate. In addition to the phosphoenolpyruvate carboxykinase activity, also acts as a protein kinase when phosphorylated at Ser-90: phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and promotes an atypical serine protein kinase activity using GTP as donor. {ECO:0000250|UniProtKB:P35558}.
|
Gallus gallus (Chicken)
|
P05154
|
IPSP_HUMAN
|
MQLFLLLCLVLLSPQGASLHRHHPREMKKRVEDLHVGATVAPSSRRDFTFDLYRALASAAPSQSIFFSPVSISMSLAMLSLGAGSSTKMQILEGLGLNLQKSSEKELHRGFQQLLQELNQPRDGFQLSLGNALFTDLVVDLQDTFVSAMKTLYLADTFPTNFRDSAGAMKQINDYVAKQTKGKIVDLLKNLDSNAVVIMVNYIFFKAKWETSFNHKGTQEQDFYVTSETVVRVPMMSREDQYHYLLDRNLSCRVVGVPYQGNATALFILPSEGKMQQVENGLSEKTLRKWLKMFKKRQLELYLPKFSIEGSYQLEKVLPSLGISNVFTSHADLSGISNHSNIQVSEMVHKAVVEVDESGTRAAAATGTIFTFRSARLNSQRLVFNRPFLMFIVDNNILFLGKVNRP
| null | null |
fusion of sperm to egg plasma membrane involved in single fertilization [GO:0007342]; lipid transport [GO:0006869]; negative regulation of hydrolase activity [GO:0051346]; spermatogenesis [GO:0007283]
|
acrosomal membrane [GO:0002080]; external side of plasma membrane [GO:0009897]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; membrane [GO:0016020]; platelet alpha granule [GO:0031091]; platelet dense tubular network [GO:0031094]; protein C inhibitor-coagulation factor V complex [GO:0097181]; protein C inhibitor-coagulation factor Xa complex [GO:0097182]; protein C inhibitor-coagulation factor XI complex [GO:0097183]; protein C inhibitor-KLK3 complex [GO:0036029]; protein C inhibitor-plasma kallikrein complex [GO:0036030]; protein C inhibitor-PLAT complex [GO:0036026]; protein C inhibitor-PLAU complex [GO:0036027]; protein C inhibitor-thrombin complex [GO:0036028]; protein C inhibitor-TMPRSS11E complex [GO:0036025]; protein C inhibitor-TMPRSS7 complex [GO:0036024]; protein-containing complex [GO:0032991]
|
acrosin binding [GO:0032190]; glycosaminoglycan binding [GO:0005539]; heparin binding [GO:0008201]; phosphatidylcholine binding [GO:0031210]; protease binding [GO:0002020]; retinoic acid binding [GO:0001972]; serine-type endopeptidase inhibitor activity [GO:0004867]
|
PF00079;
|
2.30.39.10;3.30.497.10;
|
Serpin family
|
PTM: N- and O-glycosylated. N-glycosylation consists of a mixture of sialylated bi- (including sialyl-Lewis X epitopes), tri- and tetra-antennary complex-type chains; affects the maximal heparin- and thrombomodulin-enhanced rates of thrombin inhibition. O-glycosylated with core 1 or possibly core 8 glycans. Further modified with 2 sialic acid residues. {ECO:0000269|PubMed:12575940, ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:18467335, ECO:0000269|PubMed:21056543, ECO:0000269|PubMed:22171320}.; PTM: Proteolytically cleaved. Inhibition of proteases is accompanied by formation of a stable enzyme-inhibitor complex and by degradation of the serpin to lower molecular weight derivatives. Proteolytically cleaved at the N-terminus; inhibits slightly the heparin- and thrombomodulin-enhanced rates of thrombin inhibition. {ECO:0000269|PubMed:15328353, ECO:0000269|PubMed:18467335}.
|
SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000269|PubMed:1725227, ECO:0000269|PubMed:18467335, ECO:0000269|PubMed:7521127, ECO:0000269|PubMed:8536714, ECO:0000269|PubMed:9510955, ECO:0000269|PubMed:9556620}. Note=Localized on the plasma membrane overlying the acrosomal head of spermatozoa of ependymal spermatozoa and ejaculated sperm. Localized at the equatorial segment of acrosome-reacted spermatozoa. Localized in alpha granules in resting platelets and on the external plasma membrane and within the surface-connected cannalicular system in activated platelets.
| null | null | null | null | null |
FUNCTION: Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and pro-inflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue- and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid. {ECO:0000269|PubMed:10340997, ECO:0000269|PubMed:11722589, ECO:0000269|PubMed:14696115, ECO:0000269|PubMed:15140131, ECO:0000269|PubMed:15328353, ECO:0000269|PubMed:15853774, ECO:0000269|PubMed:1725227, ECO:0000269|PubMed:18467335, ECO:0000269|PubMed:2844223, ECO:0000269|PubMed:3501295, ECO:0000269|PubMed:6323392, ECO:0000269|PubMed:7521127, ECO:0000269|PubMed:7548057, ECO:0000269|PubMed:8536714, ECO:0000269|PubMed:8665956, ECO:0000269|PubMed:9473218, ECO:0000269|PubMed:9510955, ECO:0000269|PubMed:9556620}.
|
Homo sapiens (Human)
|
P05155
|
IC1_HUMAN
|
MASRLTLLTLLLLLLAGDRASSNPNATSSSSQDPESLQDRGEGKVATTVISKMLFVEPILEVSSLPTTNSTTNSATKITANTTDEPTTQPTTEPTTQPTIQPTQPTTQLPTDSPTQPTTGSFCPGPVTLCSDLESHSTEAVLGDALVDFSLKLYHAFSAMKKVETNMAFSPFSIASLLTQVLLGAGENTKTNLESILSYPKDFTCVHQALKGFTTKGVTSVSQIFHSPDLAIRDTFVNASRTLYSSSPRVLSNNSDANLELINTWVAKNTNNKISRLLDSLPSDTRLVLLNAIYLSAKWKTTFDPKKTRMEPFHFKNSVIKVPMMNSKKYPVAHFIDQTLKAKVGQLQLSHNLSLVILVPQNLKHRLEDMEQALSPSVFKAIMEKLEMSKFQPTLLTLPRIKVTTSQDMLSIMEKLEFFDFSYDLNLCGLTEDPDLQVSAMQHQTVLELTETGVEAAAASAISVARTLLVFEVQQPFLFVLWDQQHKFPVFMGRVYDPRA
| null | null |
blood circulation [GO:0008015]; blood coagulation [GO:0007596]; complement activation, classical pathway [GO:0006958]; fibrinolysis [GO:0042730]; innate immune response [GO:0045087]; negative regulation of complement activation, lectin pathway [GO:0001869]
|
blood microparticle [GO:0072562]; collagen-containing extracellular matrix [GO:0062023]; endoplasmic reticulum lumen [GO:0005788]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; platelet alpha granule lumen [GO:0031093]
|
serine-type endopeptidase inhibitor activity [GO:0004867]
|
PF00079;
|
2.30.39.10;3.30.497.10;
|
Serpin family
|
PTM: Highly glycosylated (49%) with N- and O-glycosylation. O-glycosylated with core 1 or possibly core 8 glycans. N-glycan heterogeneity at Asn-25: Hex5HexNAc4 (minor), dHex1Hex5HexNAc4 (minor), Hex6HexNAc5 (major) and dHex1Hex6HexNAc5 (minor). {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16040958, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:17488724, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:23234360, ECO:0000269|PubMed:3756141}.; PTM: Can be proteolytically cleaved by E.coli stcE. {ECO:0000269|PubMed:12123444, ECO:0000269|PubMed:15096536}.
|
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Activation of the C1 complex is under control of the C1-inhibitor. It forms a proteolytically inactive stoichiometric complex with the C1r or C1s proteases. May play a potentially crucial role in regulating important physiological pathways including complement activation, blood coagulation, fibrinolysis and the generation of kinins. Very efficient inhibitor of FXIIa. Inhibits chymotrypsin and kallikrein. {ECO:0000269|PubMed:8495195}.
|
Homo sapiens (Human)
|
P05156
|
CFAI_HUMAN
|
MKLLHVFLLFLCFHLRFCKVTYTSQEDLVEKKCLAKKYTHLSCDKVFCQPWQRCIEGTCVCKLPYQCPKNGTAVCATNRRSFPTYCQQKSLECLHPGTKFLNNGTCTAEGKFSVSLKHGNTDSEGIVEVKLVDQDKTMFICKSSWSMREANVACLDLGFQQGADTQRRFKLSDLSINSTECLHVHCRGLETSLAECTFTKRRTMGYQDFADVVCYTQKADSPMDDFFQCVNGKYISQMKACDGINDCGDQSDELCCKACQGKGFHCKSGVCIPSQYQCNGEVDCITGEDEVGCAGFASVTQEETEILTADMDAERRRIKSLLPKLSCGVKNRMHIRRKRIVGGKRAQLGDLPWQVAIKDASGITCGGIYIGGCWILTAAHCLRASKTHRYQIWTTVVDWIHPDLKRIVIEYVDRIIFHENYNAGTYQNDIALIEMKKDGNKKDCELPRSIPACVPWSPYLFQPNDTCIVSGWGREKDNERVFSLQWGEVKLISNCSKFYGNRFYEKEMECAGTYDGSIDACKGDSGGPLVCMDANNVTYVWGVVSWGENCGKPEFPGVYTKVANYFDWISYHVGRPFISQYNV
|
3.4.21.45
| null |
complement activation, classical pathway [GO:0006958]; innate immune response [GO:0045087]; proteolysis [GO:0006508]
|
extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; membrane [GO:0016020]
|
metal ion binding [GO:0046872]; serine-type endopeptidase activity [GO:0004252]
|
PF21286;PF21287;PF00057;PF00530;PF00089;
|
3.30.60.30;4.10.400.10;3.10.250.10;2.40.10.10;
|
Peptidase S1 family
| null |
SUBCELLULAR LOCATION: Secreted, extracellular space. Secreted {ECO:0000269|PubMed:6327681}.
|
CATALYTIC ACTIVITY: Reaction=Inactivates complement subcomponents C3b, iC3b and C4b by proteolytic cleavage.; EC=3.4.21.45;
| null | null | null | null |
FUNCTION: Trypsin-like serine protease that plays an essential role in regulating the immune response by controlling all complement pathways. Inhibits these pathways by cleaving three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b thereby inactivating these proteins (PubMed:17320177, PubMed:7360115). Essential cofactors for these reactions include factor H and C4BP in the fluid phase and membrane cofactor protein/CD46 and CR1 on cell surfaces (PubMed:12055245, PubMed:2141838, PubMed:9605165). The presence of these cofactors on healthy cells allows degradation of deposited C3b by CFI in order to prevent undesired complement activation, while in apoptotic cells or microbes, the absence of such cofactors leads to C3b-mediated complement activation and subsequent opsonization (PubMed:28671664). {ECO:0000269|PubMed:12055245, ECO:0000269|PubMed:17320177, ECO:0000269|PubMed:2141838, ECO:0000269|PubMed:28671664, ECO:0000269|PubMed:7360115, ECO:0000269|PubMed:9605165}.
|
Homo sapiens (Human)
|
P05160
|
F13B_HUMAN
|
MRLKNLTFIIILIISGELYAEEKPCGFPHVENGRIAQYYYTFKSFYFPMSIDKKLSFFCLAGYTTESGRQEEQTTCTTEGWSPEPRCFKKCTKPDLSNGYISDVKLLYKIQENMRYGCASGYKTTGGKDEEVVQCLSDGWSSQPTCRKEHETCLAPELYNGNYSTTQKTFKVKDKVQYECATGYYTAGGKKTEEVECLTYGWSLTPKCTKLKCSSLRLIENGYFHPVKQTYEEGDVVQFFCHENYYLSGSDLIQCYNFGWYPESPVCEGRRNRCPPPPLPINSKIQTHSTTYRHGEIVHIECELNFEIHGSAEIRCEDGKWTEPPKCIEGQEKVACEEPPFIENGAANLHSKIYYNGDKVTYACKSGYLLHGSNEITCNRGKWTLPPECVENNENCKHPPVVMNGAVADGILASYATGSSVEYRCNEYYLLRGSKISRCEQGKWSSPPVCLEPCTVNVDYMNRNNIEMKWKYEGKVLHGDLIDFVCKQGYDLSPLTPLSELSVQCNRGEVKYPLCTRKESKGMCTSPPLIKHGVIISSTVDTYENGSSVEYRCFDHHFLEGSREAYCLDGMWTTPPLCLEPCTLSFTEMEKNNLLLKWDFDNRPHILHGEYIEFICRGDTYPAELYITGSILRMQCDRGQLKYPRCIPRQSTLSYQEPLRT
| null | null |
blood coagulation [GO:0007596]; blood coagulation, fibrin clot formation [GO:0072378]
|
extracellular region [GO:0005576]; extracellular space [GO:0005615]; transferase complex [GO:1990234]
| null |
PF00084;
|
2.10.70.10;
| null | null |
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26247044, ECO:0000269|PubMed:4405643}.
| null | null | null | null | null |
FUNCTION: The B chain of factor XIII is not catalytically active, but is thought to stabilize the A subunits and regulate the rate of transglutaminase formation by thrombin. {ECO:0000303|PubMed:21742792, ECO:0000303|PubMed:3021194}.
|
Homo sapiens (Human)
|
P05161
|
ISG15_HUMAN
|
MGWDLTVKMLAGNEFQVSLSSSMSVSELKAQITQKIGVHAFQQRLAVHPSGVALQDRVPLASQGLGPGSTVLLVVDKCDEPLSILVRNNKGRSSTYEVRLTQTVAHLKQQVSGLEGVQDDLFWLTFEGKPLEDQLPLGEYGLKPLSTVFMNLRLRGGGTEPGGRS
| null | null |
defense response to bacterium [GO:0042742]; defense response to virus [GO:0051607]; innate immune response [GO:0045087]; integrin-mediated signaling pathway [GO:0007229]; ISG15-protein conjugation [GO:0032020]; modification-dependent protein catabolic process [GO:0019941]; negative regulation of protein ubiquitination [GO:0031397]; negative regulation of type I interferon-mediated signaling pathway [GO:0060339]; negative regulation of viral genome replication [GO:0045071]; positive regulation of bone mineralization [GO:0030501]; positive regulation of erythrocyte differentiation [GO:0045648]; positive regulation of interferon-beta production [GO:0032728]; positive regulation of interleukin-10 production [GO:0032733]; positive regulation of protein oligomerization [GO:0032461]; positive regulation of type II interferon production [GO:0032729]; protein localization to mitochondrion [GO:0070585]; regulation of type II interferon production [GO:0032649]; response to type I interferon [GO:0034340]; response to virus [GO:0009615]; ubiquitin-dependent protein catabolic process [GO:0006511]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular region [GO:0005576]; nucleoplasm [GO:0005654]
|
integrin binding [GO:0005178]; polyubiquitin modification-dependent protein binding [GO:0031593]; protein tag activity [GO:0031386]; ubiquitin protein ligase binding [GO:0031625]
|
PF00240;
| null | null |
PTM: S-nitrosylation decreases its dimerization, thereby increasing the availability as well as the solubility of monomeric ISG15 for its conjugation to cellular proteins. {ECO:0000269|PubMed:18606809}.; PTM: Induced as an inactive, precursor protein that is cleaved by specific proteases to expose the C-terminal diglycine (LRLRGG) motif. This motif is essential not only for its conjugation to substrates but also for its recognition by the relevant processing proteases. {ECO:0000269|PubMed:2477469, ECO:0000269|PubMed:3350799}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22859821}. Secreted {ECO:0000269|PubMed:22859821}. Note=Exists in three distinct states: free within the cell, released into the extracellular space, or conjugated to target proteins.
| null | null | null | null | null |
FUNCTION: Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein (PubMed:27564865). ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein (PubMed:33727702). Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Isgylation of the viral sensor IFIH1/MDA5 promotes IFIH1/MDA5 oligomerization and triggers activation of innate immunity against a range of viruses, including coronaviruses, flaviviruses and picornaviruses (PubMed:33727702). Can also isgylate: EIF2AK2/PKR which results in its activation, RIGI which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade thereby inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL (PubMed:29100055). {ECO:0000269|PubMed:1373138, ECO:0000269|PubMed:16009940, ECO:0000269|PubMed:16112642, ECO:0000269|PubMed:16428300, ECO:0000269|PubMed:16434471, ECO:0000269|PubMed:16872604, ECO:0000269|PubMed:18305167, ECO:0000269|PubMed:19270716, ECO:0000269|PubMed:19357168, ECO:0000269|PubMed:2005397, ECO:0000269|PubMed:20133869, ECO:0000269|PubMed:20308324, ECO:0000269|PubMed:20639253, ECO:0000269|PubMed:21543490, ECO:0000269|PubMed:22693631, ECO:0000269|PubMed:22859821, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:27564865, ECO:0000269|PubMed:29100055, ECO:0000269|PubMed:33727702, ECO:0000269|PubMed:7526157, ECO:0000269|PubMed:8550581}.
|
Homo sapiens (Human)
|
P05162
|
LEG2_HUMAN
|
MTGELEVKNMDMKPGSTLKITGSIADGTDGFVINLGQGTDKLNLHFNPRFSESTIVCNSLDGSNWGQEQREDHLCFSPGSEVKFTVTFESDKFKVKLPDGHELTFPNRLGHSHLSYLSVRGGFNMSSFKLKE
| null | null |
cell-cell adhesion [GO:0098609]; positive regulation of apoptotic process [GO:0043065]; positive regulation of inflammatory response [GO:0050729]; T cell homeostasis [GO:0043029]
|
galectin complex [GO:1990724]
|
carbohydrate binding [GO:0030246]; galactoside binding [GO:0016936]
|
PF00337;
|
2.60.120.200;
| null | null | null | null | null | null | null | null |
FUNCTION: This protein binds beta-galactoside. Its physiological function is not yet known.
|
Homo sapiens (Human)
|
P05164
|
PERM_HUMAN
|
MGVPFFSSLRCMVDLGPCWAGGLTAEMKLLLALAGLLAILATPQPSEGAAPAVLGEVDTSLVLSSMEEAKQLVDKAYKERRESIKQRLRSGSASPMELLSYFKQPVAATRTAVRAADYLHVALDLLERKLRSLWRRPFNVTDVLTPAQLNVLSKSSGCAYQDVGVTCPEQDKYRTITGMCNNRRSPTLGASNRAFVRWLPAEYEDGFSLPYGWTPGVKRNGFPVALARAVSNEIVRFPTDQLTPDQERSLMFMQWGQLLDHDLDFTPEPAARASFVTGVNCETSCVQQPPCFPLKIPPNDPRIKNQADCIPFFRSCPACPGSNITIRNQINALTSFVDASMVYGSEEPLARNLRNMSNQLGLLAVNQRFQDNGRALLPFDNLHDDPCLLTNRSARIPCFLAGDTRSSEMPELTSMHTLLLREHNRLATELKSLNPRWDGERLYQEARKIVGAMVQIITYRDYLPLVLGPTAMRKYLPTYRSYNDSVDPRIANVFTNAFRYGHTLIQPFMFRLDNRYQPMEPNPRVPLSRVFFASWRVVLEGGIDPILRGLMATPAKLNRQNQIAVDEIRERLFEQVMRIGLDLPALNMQRSRDHGLPGYNAWRRFCGLPQPETVGQLGTVLRNLKLARKLMEQYGTPNNIDIWMGGVSEPLKRKGRVGPLLACIIGTQFRKLRDGDRFWWENEGVFSMQQRQALAQISLPRIICDNTGITTVSKNNIFMSNSYPRDFVNCSTLPALNLASWREAS
|
1.11.2.2
|
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Note=Binds 1 Ca(2+) ion per monomer.; COFACTOR: Name=heme b; Xref=ChEBI:CHEBI:60344; Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per monomer.;
|
defense response [GO:0006952]; defense response to bacterium [GO:0042742]; defense response to fungus [GO:0050832]; hydrogen peroxide catabolic process [GO:0042744]; hypochlorous acid biosynthetic process [GO:0002149]; low-density lipoprotein particle remodeling [GO:0034374]; negative regulation of apoptotic process [GO:0043066]; removal of superoxide radicals [GO:0019430]; respiratory burst involved in defense response [GO:0002679]; response to food [GO:0032094]; response to gold nanoparticle [GO:1990268]; response to lipopolysaccharide [GO:0032496]; response to mechanical stimulus [GO:0009612]; response to oxidative stress [GO:0006979]; response to yeast [GO:0001878]
|
azurophil granule [GO:0042582]; azurophil granule lumen [GO:0035578]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; intracellular membrane-bounded organelle [GO:0043231]; lysosome [GO:0005764]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; phagocytic vesicle lumen [GO:0097013]; secretory granule [GO:0030141]
|
chromatin binding [GO:0003682]; heme binding [GO:0020037]; heparin binding [GO:0008201]; metal ion binding [GO:0046872]; peroxidase activity [GO:0004601]
|
PF03098;
|
1.10.640.10;
|
Peroxidase family, XPO subfamily
| null |
SUBCELLULAR LOCATION: Lysosome.
|
CATALYTIC ACTIVITY: Reaction=chloride + H(+) + H2O2 = H2O + hypochlorous acid; Xref=Rhea:RHEA:28218, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:17996, ChEBI:CHEBI:24757; EC=1.11.2.2; Evidence={ECO:0000269|PubMed:9922160};
| null | null | null | null |
FUNCTION: Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity (PubMed:9922160). Mediates the proteolytic cleavage of alpha-1-microglobulin to form t-alpha-1-microglobulin, which potently inhibits oxidation of low-density lipoprotein particles and limits vascular damage (PubMed:25698971). {ECO:0000269|PubMed:25698971, ECO:0000269|PubMed:9922160}.
|
Homo sapiens (Human)
|
P05165
|
PCCA_HUMAN
|
MAGFWVGTAPLVAAGRRGRWPPQQLMLSAALRTLKHVLYYSRQCLMVSRNLGSVGYDPNEKTFDKILVANRGEIACRVIRTCKKMGIKTVAIHSDVDASSVHVKMADEAVCVGPAPTSKSYLNMDAIMEAIKKTRAQAVHPGYGFLSENKEFARCLAAEDVVFIGPDTHAIQAMGDKIESKLLAKKAEVNTIPGFDGVVKDAEEAVRIAREIGYPVMIKASAGGGGKGMRIAWDDEETRDGFRLSSQEAASSFGDDRLLIEKFIDNPRHIEIQVLGDKHGNALWLNERECSIQRRNQKVVEEAPSIFLDAETRRAMGEQAVALARAVKYSSAGTVEFLVDSKKNFYFLEMNTRLQVEHPVTECITGLDLVQEMIRVAKGYPLRHKQADIRINGWAVECRVYAEDPYKSFGLPSIGRLSQYQEPLHLPGVRVDSGIQPGSDISIYYDPMISKLITYGSDRTEALKRMADALDNYVIRGVTHNIALLREVIINSRFVKGDISTKFLSDVYPDGFKGHMLTKSEKNQLLAIASSLFVAFQLRAQHFQENSRMPVIKPDIANWELSVKLHDKVHTVVASNNGSVFSVEVDGSKLNVTSTWNLASPLLSVSVDGTQRTVQCLSREAGGNMSIQFLGTVYKVNILTRLAAELNKFMLEKVTEDTSSVLRSPMPGVVVAVSVKPGDAVAEGQEICVIEAMKMQNSMTAGKTGTVKSVHCQAGDTVGEGDLLVELE
|
6.4.1.3
|
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 2 magnesium or manganese ions per subunit. {ECO:0000255|PROSITE-ProRule:PRU00409}; COFACTOR: Name=biotin; Xref=ChEBI:CHEBI:57586; Evidence={ECO:0000255|PROSITE-ProRule:PRU01066, ECO:0000269|PubMed:6765947};
|
branched-chain amino acid metabolic process [GO:0009081]; fatty acid metabolic process [GO:0006631]; short-chain fatty acid catabolic process [GO:0019626]
|
catalytic complex [GO:1902494]; cytosol [GO:0005829]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
|
ATP binding [GO:0005524]; biotin binding [GO:0009374]; enzyme binding [GO:0019899]; metal ion binding [GO:0046872]; methylcrotonoyl-CoA carboxylase activity [GO:0004485]; propionyl-CoA carboxylase activity [GO:0004658]; urea carboxylase activity [GO:0004847]
|
PF02785;PF00289;PF00364;PF02786;PF18140;
|
2.40.50.100;3.30.700.30;3.40.50.20;3.30.1490.20;3.30.470.20;
| null |
PTM: Acetylated. {ECO:0000250|UniProtKB:Q91ZA3}.; PTM: The biotin cofactor is covalently attached to the C-terminal biotinyl-binding domain and is required for the catalytic activity (PubMed:10329019). Biotinylation is catalyzed by HLCS (PubMed:20443544, PubMed:7753853). {ECO:0000269|PubMed:10329019, ECO:0000269|PubMed:20443544, ECO:0000269|PubMed:7753853}.
|
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:10101253, ECO:0000269|PubMed:16023992}.
|
CATALYTIC ACTIVITY: Reaction=ATP + hydrogencarbonate + propanoyl-CoA = (S)-methylmalonyl-CoA + ADP + H(+) + phosphate; Xref=Rhea:RHEA:23720, ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57327, ChEBI:CHEBI:57392, ChEBI:CHEBI:456216; EC=6.4.1.3; Evidence={ECO:0000269|PubMed:6765947, ECO:0000269|PubMed:8434582}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23721; Evidence={ECO:0000269|PubMed:6765947, ECO:0000269|PubMed:8434582}; CATALYTIC ACTIVITY: Reaction=ATP + butanoyl-CoA + hydrogencarbonate = (2S)-ethylmalonyl-CoA + ADP + H(+) + phosphate; Xref=Rhea:RHEA:59520, ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57371, ChEBI:CHEBI:60909, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P0DTA4}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59521; Evidence={ECO:0000250|UniProtKB:P0DTA4};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.08 mM for ATP {ECO:0000269|PubMed:6765947}; KM=3 mM for hydrogencarbonate {ECO:0000269|PubMed:6765947};
|
PATHWAY: Metabolic intermediate metabolism; propanoyl-CoA degradation; succinyl-CoA from propanoyl-CoA: step 1/3. {ECO:0000269|PubMed:6765947, ECO:0000269|PubMed:8434582}.
|
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.2-8.8 for the propionyl-CoA carboxylase activity measured for the holoenzyme. {ECO:0000269|PubMed:6765947};
| null |
FUNCTION: This is one of the 2 subunits of the biotin-dependent propionyl-CoA carboxylase (PCC), a mitochondrial enzyme involved in the catabolism of odd chain fatty acids, branched-chain amino acids isoleucine, threonine, methionine, and valine and other metabolites (PubMed:6765947, PubMed:8434582). Propionyl-CoA carboxylase catalyzes the carboxylation of propionyl-CoA/propanoyl-CoA to D-methylmalonyl-CoA/(S)-methylmalonyl-CoA (PubMed:10101253, PubMed:6765947, PubMed:8434582). Within the holoenzyme, the alpha subunit catalyzes the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain, while the beta subunit then transfers the carboxyl group from carboxylated biotin to propionyl-CoA (By similarity). Propionyl-CoA carboxylase also significantly acts on butyryl-CoA/butanoyl-CoA, which is converted to ethylmalonyl-CoA/(2S)-ethylmalonyl-CoA at a much lower rate (PubMed:6765947). Other alternative minor substrates include (2E)-butenoyl-CoA/crotonoyl-CoA (By similarity). {ECO:0000250|UniProtKB:P0DTA4, ECO:0000250|UniProtKB:Q5LUF3, ECO:0000269|PubMed:10101253, ECO:0000269|PubMed:6765947, ECO:0000269|PubMed:8434582}.
|
Homo sapiens (Human)
|
P05166
|
PCCB_HUMAN
|
MAAALRVAAVGARLSVLASGLRAAVRSLCSQATSVNERIENKRRTALLGGGQRRIDAQHKRGKLTARERISLLLDPGSFVESDMFVEHRCADFGMAADKNKFPGDSVVTGRGRINGRLVYVFSQDFTVFGGSLSGAHAQKICKIMDQAITVGAPVIGLNDSGGARIQEGVESLAGYADIFLRNVTASGVIPQISLIMGPCAGGAVYSPALTDFTFMVKDTSYLFITGPDVVKSVTNEDVTQEELGGAKTHTTMSGVAHRAFENDVDALCNLRDFFNYLPLSSQDPAPVRECHDPSDRLVPELDTIVPLESTKAYNMVDIIHSVVDEREFFEIMPNYAKNIIVGFARMNGRTVGIVGNQPKVASGCLDINSSVKGARFVRFCDAFNIPLITFVDVPGFLPGTAQEYGGIIRHGAKLLYAFAEATVPKVTVITRKAYGGAYDVMSSKHLCGDTNYAWPTAEIAVMGAKGAVEIIFKGHENVEAAQAEYIEKFANPFPAAVRGFVDDIIQPSSTRARICCDLDVLASKKVQRPWRKHANIPL
|
6.4.1.3
| null |
branched-chain amino acid metabolic process [GO:0009081]; fatty acid metabolic process [GO:0006631]; short-chain fatty acid catabolic process [GO:0019626]
|
catalytic complex [GO:1902494]; cytosol [GO:0005829]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
|
ATP binding [GO:0005524]; propionyl-CoA carboxylase activity [GO:0004658]
|
PF01039;
| null |
AccD/PCCB family
| null |
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305|PubMed:16023992}.
|
CATALYTIC ACTIVITY: Reaction=ATP + hydrogencarbonate + propanoyl-CoA = (S)-methylmalonyl-CoA + ADP + H(+) + phosphate; Xref=Rhea:RHEA:23720, ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57327, ChEBI:CHEBI:57392, ChEBI:CHEBI:456216; EC=6.4.1.3; Evidence={ECO:0000269|PubMed:15890657, ECO:0000269|PubMed:6765947}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23721; Evidence={ECO:0000269|PubMed:15890657, ECO:0000269|PubMed:6765947}; CATALYTIC ACTIVITY: Reaction=ATP + butanoyl-CoA + hydrogencarbonate = (2S)-ethylmalonyl-CoA + ADP + H(+) + phosphate; Xref=Rhea:RHEA:59520, ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57371, ChEBI:CHEBI:60909, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P79384}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59521; Evidence={ECO:0000250|UniProtKB:P79384};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.29 mM for propanoyl-CoA {ECO:0000269|PubMed:6765947}; KM=0.41 mM for propanoyl-CoA (at 37 degrees Celsius and pH 8.0) {ECO:0000269|PubMed:15890657};
|
PATHWAY: Metabolic intermediate metabolism; propanoyl-CoA degradation; succinyl-CoA from propanoyl-CoA: step 1/3. {ECO:0000269|PubMed:15890657, ECO:0000269|PubMed:6765947}.
|
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.2-8.8 for the propionyl-CoA carboxylase activity as measured for the holoenzyme. {ECO:0000269|PubMed:6765947};
| null |
FUNCTION: This is one of the 2 subunits of the biotin-dependent propionyl-CoA carboxylase (PCC), a mitochondrial enzyme involved in the catabolism of odd chain fatty acids, branched-chain amino acids isoleucine, threonine, methionine, and valine and other metabolites (PubMed:15890657, PubMed:6765947). Propionyl-CoA carboxylase catalyzes the carboxylation of propionyl-CoA/propanoyl-CoA to D-methylmalonyl-CoA/(S)-methylmalonyl-CoA (PubMed:15890657, PubMed:6765947). Within the holoenzyme, the alpha subunit catalyzes the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain, while the beta subunit then transfers the carboxyl group from carboxylated biotin to propionyl-CoA (By similarity). Propionyl-CoA carboxylase also significantly acts on butyryl-CoA/butanoyl-CoA, which is converted to ethylmalonyl-CoA/(2S)-ethylmalonyl-CoA at a much lower rate (PubMed:6765947). Other alternative minor substrates include (2E)-butenoyl-CoA/crotonoyl-CoA (By similarity). {ECO:0000250|UniProtKB:P79384, ECO:0000250|UniProtKB:Q168G2, ECO:0000269|PubMed:15890657, ECO:0000269|PubMed:6765947}.
|
Homo sapiens (Human)
|
P05176
|
CP1A1_RABIT
|
MVSDFGLPTFISATELLLASAVFCLVFWVAGASKPRVPKGLKRLPGPWGWPLLGHVLTLGKNPHVALARLSRRYGDVFQIRLGSTPVVVLSGLDTIKQALVRQGDDFKGRPDLYSFSFVTKGQSMIFGSDSGPVWAARRRLAQNALNSFSVASDPASSSSCYLEEHVSQEAENLISKFQELMAAVGHFDPYRYVVMSVANVICAMCFGRRYDHDDQELLSLVNLNDEFGKVAASGSPADFFLILRYLPNPALDTFKDLNERFYSFTQERVKEHCRSFEKGHIRDITDSLIKHYRVDRLDENANVQVSDEKTVGIVLDLFGAGFDTVTTAISWSLMYLVTKPRIQRKIQEELDAVVGRARRPRFSDRPQLPYLEAVIMETFRHTSFLPFTIPHSTTRDTSLGGFYIPKGRCVFVNQWQNNHDPELWGDPEAFRPERFLTPSGAVDKALTEKVLLFGLGKRKCIGETIGRLEVFLFLATLLQQVEFSVSPGTTVDMTPIYGLTMKHARCEHFQAKLRFEA
|
1.14.14.1; 4.2.1.152
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
|
amine metabolic process [GO:0009308]; cellular response to organic cyclic compound [GO:0071407]; estrogen metabolic process [GO:0008210]; heterocycle metabolic process [GO:0046483]; hormone biosynthetic process [GO:0042446]; hydrogen peroxide biosynthetic process [GO:0050665]; lipid hydroxylation [GO:0002933]; long-chain fatty acid metabolic process [GO:0001676]; progesterone metabolic process [GO:0042448]; response to toxic substance [GO:0009636]; retinol metabolic process [GO:0042572]; steroid biosynthetic process [GO:0006694]; toxin metabolic process [GO:0009404]; xenobiotic metabolic process [GO:0006805]
|
endoplasmic reticulum membrane [GO:0005789]; mitochondrial inner membrane [GO:0005743]
|
17-alpha-hydroxyprogesterone aldolase activity [GO:0047442]; arachidonic acid monooxygenase activity [GO:0008391]; aromatase activity [GO:0070330]; estrogen 16-alpha-hydroxylase activity [GO:0101020]; estrogen 2-hydroxylase activity [GO:0101021]; heme binding [GO:0020037]; Hsp70 protein binding [GO:0030544]; Hsp90 protein binding [GO:0051879]; hydroperoxy icosatetraenoate dehydratase activity [GO:0106256]; iron ion binding [GO:0005506]; long-chain fatty acid omega-1 hydroxylase activity [GO:0120319]; long-chain fatty acid omega-hydroxylase activity [GO:0102033]; steroid 17-alpha-monooxygenase activity [GO:0004508]; vitamin D 24-hydroxylase activity [GO:0070576]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P00185}; Peripheral membrane protein {ECO:0000250|UniProtKB:P00185}. Mitochondrion inner membrane {ECO:0000250|UniProtKB:P00185}; Peripheral membrane protein {ECO:0000250|UniProtKB:P00185}. Microsome membrane {ECO:0000250|UniProtKB:P00185}; Peripheral membrane protein {ECO:0000250|UniProtKB:P00185}. Cytoplasm {ECO:0000250|UniProtKB:P00185}.
|
CATALYTIC ACTIVITY: Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:142491; EC=1.14.14.1; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17151; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 2-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47208, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:1156, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 4-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47292, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87602; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47293; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 6alpha-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47308, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87605; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47309; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 15alpha-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47312, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87618; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47313; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47204, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:776, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47205; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 2-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:28744, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 4-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47280, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:62845; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47281; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 6alpha-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47284, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:62847; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47285; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 7alpha-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47288, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87598; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47289; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 15alpha-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47276, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87593; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47277; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z)-eicosatrienoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50076, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:78043, ChEBI:CHEBI:132024; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50077; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 16-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49972, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:132019; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49973; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 17-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49968, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:132016; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49969; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 18-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39811, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:63590; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39812; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39759, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:76627; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39760; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39787, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:76636; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39788; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49884, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131975; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49885; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131970; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49856, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131964; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131965; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39779, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:76634; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (19S,20R)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52124, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, ChEBI:CHEBI:136411; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52125; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52120, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, ChEBI:CHEBI:136410; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=all-trans-retinol + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-retinal + H(+) + 2 H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42092, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=all-trans-retinal + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-retinoate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42088, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17898, ChEBI:CHEBI:35291, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42089; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 13-oxo-(9Z,11E)-octadecadienoate + H2O; Xref=Rhea:RHEA:48716, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466, ChEBI:CHEBI:90781; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48717; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = 12-oxo-(5Z,8Z,10E,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:37947, ChEBI:CHEBI:15377, ChEBI:CHEBI:57444, ChEBI:CHEBI:75231; EC=4.2.1.152; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37948; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48636, ChEBI:CHEBI:15377, ChEBI:CHEBI:57410, ChEBI:CHEBI:57446; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637; Evidence={ECO:0000250|UniProtKB:P04798}; CATALYTIC ACTIVITY: Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = 5-oxo-(6E,8Z,11Z,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48632, ChEBI:CHEBI:15377, ChEBI:CHEBI:57450, ChEBI:CHEBI:65342; Evidence={ECO:0000250|UniProtKB:P04798}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48633; Evidence={ECO:0000250|UniProtKB:P04798};
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PATHWAY: Steroid hormone biosynthesis. {ECO:0000250|UniProtKB:P04798}.; PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000250|UniProtKB:P04798}.; PATHWAY: Cofactor metabolism; retinol metabolism. {ECO:0000250|UniProtKB:P04798}.
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FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15alpha and C16alpha positions. Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation. Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system. Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer. May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid. May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent). {ECO:0000250|UniProtKB:P04798}.
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Oryctolagus cuniculus (Rabbit)
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P05177
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CP1A2_HUMAN
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MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKNPHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDGQSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELMAGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFPILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGNLIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLSDRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPELWEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLEFSVPPGVKVDLTPIYGLTMKHARCEHVQARLRFSIN
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1.14.14.1; 4.2.1.152
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COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413;
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aflatoxin metabolic process [GO:0046222]; alkaloid metabolic process [GO:0009820]; cellular respiration [GO:0045333]; cellular response to cadmium ion [GO:0071276]; cholesterol metabolic process [GO:0008203]; dibenzo-p-dioxin metabolic process [GO:0018894]; epoxygenase P450 pathway [GO:0019373]; estrogen metabolic process [GO:0008210]; heterocycle metabolic process [GO:0046483]; hormone biosynthetic process [GO:0042446]; hydrogen peroxide biosynthetic process [GO:0050665]; long-chain fatty acid biosynthetic process [GO:0042759]; lung development [GO:0030324]; methylation [GO:0032259]; monocarboxylic acid metabolic process [GO:0032787]; monoterpenoid metabolic process [GO:0016098]; omega-hydroxylase P450 pathway [GO:0097267]; oxidative demethylation [GO:0070989]; porphyrin-containing compound metabolic process [GO:0006778]; post-embryonic development [GO:0009791]; progesterone metabolic process [GO:0042448]; regulation of gene expression [GO:0010468]; retinol metabolic process [GO:0042572]; steroid catabolic process [GO:0006706]; toxin biosynthetic process [GO:0009403]; xenobiotic catabolic process [GO:0042178]; xenobiotic metabolic process [GO:0006805]
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endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]
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17-alpha-hydroxyprogesterone aldolase activity [GO:0047442]; aromatase activity [GO:0070330]; caffeine oxidase activity [GO:0034875]; demethylase activity [GO:0032451]; electron transfer activity [GO:0009055]; enzyme binding [GO:0019899]; estrogen 16-alpha-hydroxylase activity [GO:0101020]; estrogen 2-hydroxylase activity [GO:0101021]; heme binding [GO:0020037]; hydroperoxy icosatetraenoate dehydratase activity [GO:0106256]; iron ion binding [GO:0005506]; monooxygenase activity [GO:0004497]; oxidoreductase activity [GO:0016491]; oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen [GO:0016712]; steroid 17-alpha-monooxygenase activity [GO:0004508]
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PF00067;
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1.10.630.10;
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Cytochrome P450 family
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SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane {ECO:0000269|PubMed:21576599}; Peripheral membrane protein.
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CATALYTIC ACTIVITY: Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:142491; EC=1.14.14.1; Evidence={ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:9435160}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150; Evidence={ECO:0000305|PubMed:11555828, ECO:0000305|PubMed:12865317, ECO:0000305|PubMed:9435160}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 2-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:28744, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:12865317}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213; Evidence={ECO:0000305|PubMed:11555828, ECO:0000305|PubMed:12865317}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 4-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47280, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:62845; Evidence={ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:12865317}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47281; Evidence={ECO:0000305|PubMed:11555828, ECO:0000305|PubMed:12865317}; CATALYTIC ACTIVITY: Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 2-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47208, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:1156, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:12865317}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209; Evidence={ECO:0000305|PubMed:12865317}; CATALYTIC ACTIVITY: Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 4-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47292, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87602; Evidence={ECO:0000269|PubMed:12865317}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47293; Evidence={ECO:0000305|PubMed:12865317}; CATALYTIC ACTIVITY: Reaction=cholesterol + O2 + reduced [NADPH--hemoprotein reductase] = 25-hydroxycholesterol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50256, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16113, ChEBI:CHEBI:42977, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:21576599}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50257; Evidence={ECO:0000305|PubMed:21576599}; CATALYTIC ACTIVITY: Reaction=all-trans-retinol + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-retinal + H(+) + 2 H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42092, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:10681376}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093; Evidence={ECO:0000305|PubMed:10681376}; CATALYTIC ACTIVITY: Reaction=all-trans-retinal + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-retinoate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42088, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17898, ChEBI:CHEBI:35291, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:10681376}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42089; Evidence={ECO:0000305|PubMed:10681376}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131965; Evidence={ECO:0000269|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861; Evidence={ECO:0000305|PubMed:19965576}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49856, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131964; Evidence={ECO:0000269|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857; Evidence={ECO:0000305|PubMed:19965576}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39779, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:76634; Evidence={ECO:0000269|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780; Evidence={ECO:0000305|PubMed:19965576}; CATALYTIC ACTIVITY: Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52120, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, ChEBI:CHEBI:136410; Evidence={ECO:0000269|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121; Evidence={ECO:0000305|PubMed:19965576}; CATALYTIC ACTIVITY: Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = 5-oxo-(6E,8Z,11Z,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48632, ChEBI:CHEBI:15377, ChEBI:CHEBI:57450, ChEBI:CHEBI:65342; Evidence={ECO:0000269|PubMed:21068195}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48633; Evidence={ECO:0000305|PubMed:21068195}; CATALYTIC ACTIVITY: Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = 12-oxo-(5Z,8Z,10E,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:37947, ChEBI:CHEBI:15377, ChEBI:CHEBI:57444, ChEBI:CHEBI:75231; EC=4.2.1.152; Evidence={ECO:0000269|PubMed:21068195}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37948; Evidence={ECO:0000305|PubMed:21068195}; CATALYTIC ACTIVITY: Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48636, ChEBI:CHEBI:15377, ChEBI:CHEBI:57410, ChEBI:CHEBI:57446; Evidence={ECO:0000269|PubMed:21068195}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637; Evidence={ECO:0000305|PubMed:21068195}; CATALYTIC ACTIVITY: Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 13-oxo-(9Z,11E)-octadecadienoate + H2O; Xref=Rhea:RHEA:48716, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466, ChEBI:CHEBI:90781; Evidence={ECO:0000269|PubMed:21068195}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48717; Evidence={ECO:0000305|PubMed:21068195}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 13-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52292, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136524; Evidence={ECO:0000269|PubMed:9435160}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52293; Evidence={ECO:0000305|PubMed:9435160}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39759, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:76627; Evidence={ECO:0000269|PubMed:9435160}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39760; Evidence={ECO:0000305|PubMed:9435160}; CATALYTIC ACTIVITY: Reaction=(9Z,12Z)-octadecadienoate + O2 + reduced [NADPH--hemoprotein reductase] = 11-hydroxy-(9Z,12Z)-octadecadienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52284, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30245, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136522; Evidence={ECO:0000269|PubMed:9435160}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52285; Evidence={ECO:0000305|PubMed:9435160};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=19 uM for 17beta-estradiol (2-hydroxylation) {ECO:0000269|PubMed:11555828}; KM=9 uM for all-trans retinol {ECO:0000269|PubMed:10681376}; KM=4 uM for 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole {ECO:0000269|PubMed:14725854}; KM=21 uM for 2-amino-3-methylimidazo[4,5-f]quinoline {ECO:0000269|PubMed:14725854}; KM=26 uM for 2-amino-2,4-dimethylimidazo[4,5-f]quinoline {ECO:0000269|PubMed:14725854}; KM=27 uM for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline {ECO:0000269|PubMed:14725854}; KM=71 uM for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine {ECO:0000269|PubMed:14725854}; KM=25 uM for phenacetin {ECO:0000269|PubMed:14725854}; Vmax=9.2 nmol/min/nmol enzyme toward 17beta-estradiol (2-hydroxylation) {ECO:0000269|PubMed:11555828}; Vmax=491 pmol/min/nmol enzyme toward all-trans retinol {ECO:0000269|PubMed:10681376};
|
PATHWAY: Cofactor metabolism; retinol metabolism. {ECO:0000269|PubMed:10681376}.; PATHWAY: Steroid metabolism; cholesterol metabolism. {ECO:0000269|PubMed:21576599}.; PATHWAY: Lipid metabolism; arachidonate metabolism. {ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:21068195, ECO:0000269|PubMed:9435160}.
| null | null |
FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable). {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14725854, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:21068195, ECO:0000269|PubMed:21576599, ECO:0000269|PubMed:9435160, ECO:0000305|PubMed:16522833}.
|
Homo sapiens (Human)
|
P05178
|
CP2C6_RAT
|
MDLVMLLVLTLTCLILLSIWRQSSGRGKLPPGPIPLPIIGNIFQLNVKNITQSLTSFSKVYGPVFTLYFGTKPTVILHGYEAVKEALIDHGEEFAERGSFPVAEKINKDLGIVFSHGNRWKEIRRFTLTTLRNLGMGKRNIEDRVQEEARCLVEELRKTNGSPCDPTFILGCAPCNVICSIIFQNRFDYKDQDFLNLMEKLNENMKILSSPWTQFCSFFPVLIDYCPGSHTTLAKNVYHIRNYLLKKIKEHQESLDVTNPRDFIDYYLIKWKQENHNPHSEFTLENLSITVTDLFGAGTETTSTTLRYALLLLLKCPEVTAKVQEEIDRVVGKHRSPCMQDRSRMPYTDAHDHEVQRFIDLIPTNLPHAVTCDIKFRNYLIPKGTTIITSLSSVLHDSKEFPDPEIFDPGHFLDGNGKFKKSDYFMPFSAGKRMCAGEGLARMELFLFLTTILQNFKLKSVLHPKDIDTTPVFNGFASLPPFYELCFIPL
|
1.14.14.1
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
|
arachidonic acid metabolic process [GO:0019369]; epoxygenase P450 pathway [GO:0019373]; heterocycle metabolic process [GO:0046483]; long-chain fatty acid metabolic process [GO:0001676]; monoterpenoid metabolic process [GO:0016098]; response to xenobiotic stimulus [GO:0009410]; steroid metabolic process [GO:0008202]; xenobiotic catabolic process [GO:0042178]; xenobiotic metabolic process [GO:0006805]
|
cytoplasm [GO:0005737]; endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]
|
arachidonic acid 11,12-epoxygenase activity [GO:0008405]; arachidonic acid 14,15-epoxygenase activity [GO:0008404]; arachidonic acid epoxygenase activity [GO:0008392]; aromatase activity [GO:0070330]; enzyme binding [GO:0019899]; heme binding [GO:0020037]; iron ion binding [GO:0005506]; long-chain fatty acid omega-1 hydroxylase activity [GO:0120319]; monooxygenase activity [GO:0004497]; oxidoreductase activity [GO:0016491]; oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen [GO:0016712]; steroid hydroxylase activity [GO:0008395]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
|
CATALYTIC ACTIVITY: Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:142491; EC=1.14.14.1;
| null | null | null | null |
FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
|
Rattus norvegicus (Rat)
|
P05179
|
CP2C7_RAT
|
MDLVTFLVLTLSSLILLSLWRQSSRRRKLPPGPTPLPIIGNFLQIDVKNISQSLTKFSKTYGPVFTLYLGSQPTVILHGYEAIKEALIDNGEKFSGRGSYPMNENVTKGFGIVFSNGNRWKEMRRFTIMNFRNLGIGKRNIEDRVQEEAQCLVEELRKTKGSPCDPSLILNCAPCNVICSITFQNHFDYKDKEMLTFMEKVNENLKIMSSPWMQVCNSFPSLIDYFPGTHHKIAKNINYMKSYLLKKIEEHQESLDVTNPRDFVDYYLIKQKQANNIEQSEYSHENLTCSIMDLIGAGTETMSTTLRYALLLLMKYPHVTAKVQEEIDRVIGRHRSPCMQDRKHMPYTDAMIHEVQRFINFVPTNLPHAVTCDIKFRNYLIPKGTKVLTSLTSVLHDSKEFPNPEMFDPGHFLDENGNFKKSDYFLPFSAGKRACVGEGLARMQLFLFLTTILQNFNLKSLVHPKDIDTMPVLNGFASLPPTYQLCFIPS
|
1.14.14.1
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
|
epoxygenase P450 pathway [GO:0019373]; response to ethanol [GO:0045471]; response to lipopolysaccharide [GO:0032496]; response to nutrient [GO:0007584]; response to organic cyclic compound [GO:0014070]; response to organonitrogen compound [GO:0010243]; response to peptide hormone [GO:0043434]; response to retinoic acid [GO:0032526]; response to xenobiotic stimulus [GO:0009410]; xenobiotic metabolic process [GO:0006805]
|
cytoplasm [GO:0005737]; endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]
|
arachidonic acid epoxygenase activity [GO:0008392]; aromatase activity [GO:0070330]; heme binding [GO:0020037]; iron ion binding [GO:0005506]; oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen [GO:0016712]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
|
CATALYTIC ACTIVITY: Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:142491; EC=1.14.14.1;
| null | null | null | null |
FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
|
Rattus norvegicus (Rat)
|
P05180
|
CP2H1_CHICK
|
MDFLGLPTILLLVCISCLLIAAWRSTSQRGKEPPGPTPIPIIGNVFQLNPWDLMGSFKELSKKYGPIFTIHLGPKKIVVLYGYDIVKEALIDNGEAFSGRGILPLIEKLFKGTGIVTSNGETWRQLRRFALTTLRDFGMGKKGIEERIQEEAHFLVERIRKTHEEPFNPGKFLIHAVANIICSIVFGDRFDYEDKKFLDLIEMLEENNKYQNRIQTLLYNFFPTILDSLPGPHKTLIKNTETVDDFIKEIVIAHQESFDASCPRDFIDAFINKMEQEKENSYFTVESLTRTTLDLFLAGTGTTSTTLRYGLLILLKHPEIEEKMHKEIDRVVGRDRSPCMADRSQLPYTDAVIHEIQRFIDFLPLNVPHAVIKDTKLRDYFIPKDTMIFPLLSPILQDCKEFPNPEKFDPGHFLNANGTFRRSDYFMPFSAGKRICAGEGLARMEIFLFLTSILQNFSLKPVKDRKDIDISPIITSLANMPRPYEVSFIPR
|
1.14.14.1
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
|
epoxygenase P450 pathway [GO:0019373]; response to xenobiotic stimulus [GO:0009410]; xenobiotic metabolic process [GO:0006805]
|
cytoplasm [GO:0005737]; endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]
|
arachidonic acid epoxygenase activity [GO:0008392]; aromatase activity [GO:0070330]; heme binding [GO:0020037]; iron ion binding [GO:0005506]; oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen [GO:0016712]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
|
CATALYTIC ACTIVITY: Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:142491; EC=1.14.14.1;
| null | null | null | null |
FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
|
Gallus gallus (Chicken)
|
P05181
|
CP2E1_HUMAN
|
MSALGVTVALLVWAAFLLLVSMWRQVHSSWNLPPGPFPLPIIGNLFQLELKNIPKSFTRLAQRFGPVFTLYVGSQRMVVMHGYKAVKEALLDYKDEFSGRGDLPAFHAHRDRGIIFNNGPTWKDIRRFSLTTLRNYGMGKQGNESRIQREAHFLLEALRKTQGQPFDPTFLIGCAPCNVIADILFRKHFDYNDEKFLRLMYLFNENFHLLSTPWLQLYNNFPSFLHYLPGSHRKVIKNVAEVKEYVSERVKEHHQSLDPNCPRDLTDCLLVEMEKEKHSAERLYTMDGITVTVADLFFAGTETTSTTLRYGLLILMKYPEIEEKLHEEIDRVIGPSRIPAIKDRQEMPYMDAVVHEIQRFITLVPSNLPHEATRDTIFRGYLIPKGTVVVPTLDSVLYDNQEFPDPEKFKPEHFLNENGKFKYSDYFKPFSTGKRVCAGEGLARMELFLLLCAILQHFNLKPLVDPKDIDLSPIHIGFGCIPPRYKLCVIPRS
|
1.14.13.n7; 1.14.14.1
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413;
|
4-nitrophenol metabolic process [GO:0018960]; benzene metabolic process [GO:0018910]; carbon tetrachloride metabolic process [GO:0018885]; epoxygenase P450 pathway [GO:0019373]; halogenated hydrocarbon metabolic process [GO:0042197]; heterocycle metabolic process [GO:0046483]; lipid hydroxylation [GO:0002933]; long-chain fatty acid biosynthetic process [GO:0042759]; long-chain fatty acid metabolic process [GO:0001676]; monoterpenoid metabolic process [GO:0016098]; response to bacterium [GO:0009617]; steroid metabolic process [GO:0008202]; xenobiotic metabolic process [GO:0006805]
|
cytoplasm [GO:0005737]; endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]; mitochondrial inner membrane [GO:0005743]
|
4-nitrophenol 2-monooxygenase activity [GO:0018601]; arachidonic acid epoxygenase activity [GO:0008392]; aromatase activity [GO:0070330]; enzyme binding [GO:0019899]; heme binding [GO:0020037]; Hsp70 protein binding [GO:0030544]; Hsp90 protein binding [GO:0051879]; iron ion binding [GO:0005506]; long-chain fatty acid omega-1 hydroxylase activity [GO:0120319]; monooxygenase activity [GO:0004497]; oxidoreductase activity [GO:0016491]; oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen [GO:0016709]; oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen [GO:0016712]; oxygen binding [GO:0019825]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein {ECO:0000250|UniProtKB:P05182}. Microsome membrane {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein {ECO:0000250|UniProtKB:P05182}. Mitochondrion inner membrane {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein {ECO:0000250|UniProtKB:P05182}. Note=Post-translationally targeted to mitochondria. TOMM70 is required for the translocation across the mitochondrial outer membrane. After translocation into the matrix, associates with the inner membrane as a membrane extrinsic protein. {ECO:0000250|UniProtKB:P05182}.
|
CATALYTIC ACTIVITY: Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:142491; EC=1.14.14.1; Evidence={ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150; Evidence={ECO:0000305|PubMed:10553002, ECO:0000305|PubMed:18577768}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z)-eicosatrienoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50076, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:78043, ChEBI:CHEBI:132024; Evidence={ECO:0000269|PubMed:18577768}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50077; Evidence={ECO:0000305|PubMed:18577768}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39787, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:76636; Evidence={ECO:0000269|PubMed:18577768}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39788; Evidence={ECO:0000305|PubMed:18577768}; CATALYTIC ACTIVITY: Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 21-hydroxy-(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50088, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, ChEBI:CHEBI:132025; Evidence={ECO:0000269|PubMed:18577768}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50089; Evidence={ECO:0000305|PubMed:18577768}; CATALYTIC ACTIVITY: Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 11-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39751, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:18262, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:76628; Evidence={ECO:0000269|PubMed:10553002}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39752; Evidence={ECO:0000305|PubMed:10553002}; CATALYTIC ACTIVITY: Reaction=O2 + reduced [NADPH--hemoprotein reductase] + tetradecanoate = 13-hydroxytetradecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50096, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30807, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:132031; Evidence={ECO:0000269|PubMed:10553002}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50097; Evidence={ECO:0000305|PubMed:10553002}; CATALYTIC ACTIVITY: Reaction=4-nitrophenol + H(+) + NADPH + O2 = 4-nitrocatechol + H2O + NADP(+); Xref=Rhea:RHEA:26205, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57730, ChEBI:CHEBI:57783, ChEBI:CHEBI:57917, ChEBI:CHEBI:58349; EC=1.14.13.n7; Evidence={ECO:0000269|PubMed:9348445};
| null |
PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768}.
| null | null |
FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable). {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768, ECO:0000305|PubMed:9348445}.
|
Homo sapiens (Human)
|
P05182
|
CP2E1_RAT
|
MAVLGITIALLVWVATLLVISIWKQIYNSWNLPPGPFPLPILGNIFQLDLKDIPKSFTKLAKRFGPVFTLHLGSRRIVVLHGYKAVKEVLLNHKNEFSGRGDIPVFQEYKNKGIIFNNGPTWKDVRRFSLSILRDWGMGKQGNEARIQREAQFLVEELKKTKGQPFDPTFLIGCAPCNVIADILFNKRFDYNDKKCLRLMSLFNENFYLLSTPWIQLYNNFADYLRYLPGSHRKIMKNVSEIKQYTLEKAKEHLQSLDINCARDVTDCLLIEMEKEKHSQEPMYTMENVSVTLADLFFAGTETTSTTLRYGLLILMKYPEIEEKLHEEIDRVIGPSRVPAVRDRLDMPYMDAVVHEIQRFINLVPSNLPHEATRDTVFQGYVIPKGTVVIPTLDSLLYDSHEFPDPEKFKPEHFLNENGKFKYSDYFKAFSAGKRVCVGEGLARMELFLLLSAILQHFNLKSLVDPKDIDLSPVTVGFGSIPPQFKLCVIPRS
|
1.14.13.n7; 1.14.14.1
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
|
4-nitrophenol metabolic process [GO:0018960]; epoxygenase P450 pathway [GO:0019373]; heterocycle metabolic process [GO:0046483]; lipid hydroxylation [GO:0002933]; long-chain fatty acid metabolic process [GO:0001676]; monoterpenoid metabolic process [GO:0016098]; response to 3-methylcholanthrene [GO:1904681]; response to bacterium [GO:0009617]; response to ethanol [GO:0045471]; response to organonitrogen compound [GO:0010243]; response to ozone [GO:0010193]; response to xenobiotic stimulus [GO:0009410]; steroid metabolic process [GO:0008202]; triglyceride metabolic process [GO:0006641]; xenobiotic metabolic process [GO:0006805]
|
cytoplasm [GO:0005737]; endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; Golgi membrane [GO:0000139]; intracellular membrane-bounded organelle [GO:0043231]; mitochondrial inner membrane [GO:0005743]
|
4-nitrophenol 2-monooxygenase activity [GO:0018601]; arachidonic acid epoxygenase activity [GO:0008392]; aromatase activity [GO:0070330]; enzyme binding [GO:0019899]; heme binding [GO:0020037]; Hsp70 protein binding [GO:0030544]; Hsp90 protein binding [GO:0051879]; iron ion binding [GO:0005506]; long-chain fatty acid omega-1 hydroxylase activity [GO:0120319]; monooxygenase activity [GO:0004497]; oxidoreductase activity [GO:0016491]; oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen [GO:0016712]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305|PubMed:19401463}; Peripheral membrane protein. Microsome membrane {ECO:0000305|PubMed:19401463}; Peripheral membrane protein. Mitochondrion inner membrane {ECO:0000305|PubMed:19401463}; Peripheral membrane protein {ECO:0000305|PubMed:19401463}. Note=Post-translationally targeted to mitochondria. TOMM70 is required for the translocation across the mitochondrial outer membrane. After translocation into the matrix, associates with the inner membrane as a membrane extrinsic protein. {ECO:0000305|PubMed:19401463}.
|
CATALYTIC ACTIVITY: Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:142491; EC=1.14.14.1; Evidence={ECO:0000250|UniProtKB:P05181}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150; Evidence={ECO:0000250|UniProtKB:P05181}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z)-eicosatrienoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50076, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:78043, ChEBI:CHEBI:132024; Evidence={ECO:0000250|UniProtKB:P05181}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50077; Evidence={ECO:0000250|UniProtKB:P05181}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39787, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:76636; Evidence={ECO:0000250|UniProtKB:P05181}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39788; Evidence={ECO:0000250|UniProtKB:P05181}; CATALYTIC ACTIVITY: Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 21-hydroxy-(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50088, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, ChEBI:CHEBI:132025; Evidence={ECO:0000250|UniProtKB:P05181}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50089; Evidence={ECO:0000250|UniProtKB:P05181}; CATALYTIC ACTIVITY: Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 11-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39751, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:18262, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:76628; Evidence={ECO:0000250|UniProtKB:P05181}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39752; Evidence={ECO:0000250|UniProtKB:P05181}; CATALYTIC ACTIVITY: Reaction=O2 + reduced [NADPH--hemoprotein reductase] + tetradecanoate = 13-hydroxytetradecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50096, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30807, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:132031; Evidence={ECO:0000250|UniProtKB:P05181}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50097; Evidence={ECO:0000250|UniProtKB:P05181}; CATALYTIC ACTIVITY: Reaction=4-nitrophenol + H(+) + NADPH + O2 = 4-nitrocatechol + H2O + NADP(+); Xref=Rhea:RHEA:26205, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57730, ChEBI:CHEBI:57783, ChEBI:CHEBI:57917, ChEBI:CHEBI:58349; EC=1.14.13.n7; Evidence={ECO:0000250|UniProtKB:P05181}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26206; Evidence={ECO:0000250|UniProtKB:P05181};
| null |
PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000250|UniProtKB:P05181}.
| null | null |
FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of fatty acids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids. May be involved in the oxidative metabolism of xenobiotics. {ECO:0000250|UniProtKB:P05181}.
|
Rattus norvegicus (Rat)
|
P05183
|
CP3A2_RAT
|
MDLLSALTLETWVLLAVILVLLYRLGTHRHGIFKKQGIPGPKPLPFLGTVLNYYKGLGRFDMECYKKYGKIWGLFDGQTPVFAIMDTEMIKNVLVKECFSVFTNRRDFGPVGIMGKAVSVAKDEEWKRYRALLSPTFTSGRLKEMFPIIEQYGDILVKYLKQEAETGKPVTMKKVFGAYSMDVITSTSFGVNVDSLNNPKDPFVEKTKKLLRFDFFDPLFLSVVLFPFLTPIYEMLNICMFPKDSIAFFQKFVHRIKETRLDSKHKHRVDFLQLMLNAHNNSKDEVSHKALSDVEIIAQSVIFIFAGYETTSSTLSFVLYFLATHPDIQKKLQEEIDGALPSKAPPTYDIVMEMEYLDMVLNETLRLYPIGNRLERVCKKDIELDGLFIPKGSVVTIPTYALHHDPQHWPKPEEFHPERFSKENKGSIDPYVYLPFGNGPRNCIGMRFALMNMKLALTKVLQNFSFQPCKETQIPLKLSRQAILEPEKPIVLKVLPRDAVINGA
|
1.14.14.1
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
|
alkaloid catabolic process [GO:0009822]; estrogen metabolic process [GO:0008210]; heterocycle metabolic process [GO:0046483]; lipid hydroxylation [GO:0002933]; monoterpenoid metabolic process [GO:0016098]; oxidative demethylation [GO:0070989]; retinoic acid metabolic process [GO:0042573]; retinol metabolic process [GO:0042572]; steroid catabolic process [GO:0006706]; steroid metabolic process [GO:0008202]; vitamin D catabolic process [GO:0042369]; xenobiotic catabolic process [GO:0042178]; xenobiotic metabolic process [GO:0006805]
|
cytoplasm [GO:0005737]; endoplasmic reticulum membrane [GO:0005789]
|
1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity [GO:0062181]; aromatase activity [GO:0070330]; caffeine oxidase activity [GO:0034875]; demethylase activity [GO:0032451]; enzyme binding [GO:0019899]; estrogen 16-alpha-hydroxylase activity [GO:0101020]; estrogen 2-hydroxylase activity [GO:0101021]; heme binding [GO:0020037]; iron ion binding [GO:0005506]; monooxygenase activity [GO:0004497]; oxidoreductase activity [GO:0016491]; retinoic acid 4-hydroxylase activity [GO:0008401]; steroid binding [GO:0005496]; steroid hydroxylase activity [GO:0008395]; testosterone 6-beta-hydroxylase activity [GO:0050649]; vitamin D 24-hydroxylase activity [GO:0070576]; vitamin D3 25-hydroxylase activity [GO:0030343]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
|
CATALYTIC ACTIVITY: Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:142491; EC=1.14.14.1;
| null | null | null | null |
FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
|
Rattus norvegicus (Rat)
|
P05185
|
CP17A_BOVIN
|
MWLLLAVFLLTLAYLFWPKTKHSGAKYPRSLPSLPLVGSLPFLPRRGQQHKNFFKLQEKYGPIYSFRLGSKTTVMIGHHQLAREVLLKKGKEFSGRPKVATLDILSDNQKGIAFADHGAHWQLHRKLALNAFALFKDGNLKLEKIINQEANVLCDFLATQHGEAIDLSEPLSLAVTNIISFICFNFSFKNEDPALKAIQNVNDGILEVLSKEVLLDIFPVLKIFPSKAMEKMKGCVQTRNELLNEILEKCQENFSSDSITNLLHILIQAKVNADNNNAGPDQDSKLLSNRHMLATIGDIFGAGVETTTSVIKWIVAYLLHHPSLKKRIQDDIDQIIGFNRTPTISDRNRLVLLEATIREVLRIRPVAPTLIPHKAVIDSSIGDLTIDKGTDVVVNLWALHHSEKEWQHPDLFMPERFLDPTGTQLISPSLSYLPFGAGPRSCVGEMLARQELFLFMSRLLQRFNLEIPDDGKLPSLEGHASLVLQIKPFKVKIEVRQAWKEAQAEGSTP
|
1.14.14.19; 1.14.14.32
|
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250|UniProtKB:P05093};
|
glucocorticoid biosynthetic process [GO:0006704]; hormone biosynthetic process [GO:0042446]; progesterone metabolic process [GO:0042448]; steroid metabolic process [GO:0008202]
|
endoplasmic reticulum membrane [GO:0005789]
|
17-alpha-hydroxyprogesterone aldolase activity [GO:0047442]; heme binding [GO:0020037]; iron ion binding [GO:0005506]; steroid 17-alpha-monooxygenase activity [GO:0004508]
|
PF00067;
|
1.10.630.10;
|
Cytochrome P450 family
| null |
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P05093}. Microsome membrane {ECO:0000250|UniProtKB:P05093}.
|
CATALYTIC ACTIVITY: Reaction=a C21-steroid + O2 + reduced [NADPH--hemoprotein reductase] = a 17alpha-hydroxy-C21-steroid + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:65760, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:61313, ChEBI:CHEBI:138141; EC=1.14.14.19; Evidence={ECO:0000250|UniProtKB:P05093}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65761; Evidence={ECO:0000250|UniProtKB:P05093}; CATALYTIC ACTIVITY: Reaction=O2 + progesterone + reduced [NADPH--hemoprotein reductase] = 17alpha-hydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46308, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17026, ChEBI:CHEBI:17252, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.19; Evidence={ECO:0000250|UniProtKB:P05093}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46309; Evidence={ECO:0000250|UniProtKB:P05093}; CATALYTIC ACTIVITY: Reaction=O2 + pregnenolone + reduced [NADPH--hemoprotein reductase] = 17alpha-hydroxypregnenolone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50236, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16581, ChEBI:CHEBI:28750, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.19; Evidence={ECO:0000250|UniProtKB:P05093}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50237; Evidence={ECO:0000250|UniProtKB:P05093}; CATALYTIC ACTIVITY: Reaction=17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein reductase] = acetate + androst-4-ene-3,17-dione + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:14753, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16422, ChEBI:CHEBI:17252, ChEBI:CHEBI:30089, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.32; Evidence={ECO:0000250|UniProtKB:P05093}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14754; Evidence={ECO:0000250|UniProtKB:P05093}; CATALYTIC ACTIVITY: Reaction=17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha,17alpha-dihydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53216, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:763, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17252, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:P05093}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53217; Evidence={ECO:0000250|UniProtKB:P05093}; CATALYTIC ACTIVITY: Reaction=16alpha,17alpha-dihydroxyprogesterone + O2 + reduced [NADPH--hemoprotein reductase] = 6beta,16alpha,17alpha-trihydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53220, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:763, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137046; Evidence={ECO:0000250|UniProtKB:P05093}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53221; Evidence={ECO:0000250|UniProtKB:P05093}; CATALYTIC ACTIVITY: Reaction=17alpha-hydroxypregnenolone + O2 + reduced [NADPH--hemoprotein reductase] = 3beta-hydroxyandrost-5-en-17-one + acetate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50244, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:28689, ChEBI:CHEBI:28750, ChEBI:CHEBI:30089, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.32; Evidence={ECO:0000250|UniProtKB:P05093}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50245; Evidence={ECO:0000250|UniProtKB:P05093}; CATALYTIC ACTIVITY: Reaction=16alpha,17alpha-dihydroxypregnenolone + O2 + reduced [NADPH--hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-en-17-one + acetate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53224, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:27771, ChEBI:CHEBI:30089, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137049; Evidence={ECO:0000250|UniProtKB:P05093}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53225; Evidence={ECO:0000250|UniProtKB:P05093}; CATALYTIC ACTIVITY: Reaction=3beta-hydroxyandrost-5-en-17-one + O2 + reduced [NADPH--hemoprotein reductase] = 3beta,16alpha-dihydroxy-androst-5-en-17-one + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47220, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:27771, ChEBI:CHEBI:28689, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:P05093}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47221; Evidence={ECO:0000250|UniProtKB:P05093}; CATALYTIC ACTIVITY: Reaction=androst-4-ene-3,17-dione + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha-hydroxyandrost-4-ene-3,17-dione + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53228, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16422, ChEBI:CHEBI:27582, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:P05093}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53229; Evidence={ECO:0000250|UniProtKB:P05093};
| null |
PATHWAY: Steroid hormone biosynthesis. {ECO:0000250|UniProtKB:P05093}.; PATHWAY: Steroid biosynthesis; glucocorticoid biosynthesis. {ECO:0000250|UniProtKB:P05093}.
| null | null |
FUNCTION: A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis. Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol. Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione. Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA. Also 16-alpha hydroxylates androgens, relevant for estriol synthesis. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). {ECO:0000250|UniProtKB:P05093}.
|
Bos taurus (Bovine)
|
P05186
|
PPBT_HUMAN
|
MISPFLVLAIGTCLTNSLVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGDGMGVSTVTAARILKGQLHHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCGVKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDEKARGTRLDGLDLVDTWKSFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFEPGDMQYELNRNNVTDPSLSEMVVVAIQILRKNPKGFFLLVEGGRIDHGHHEGKAKQALHEAVEMDRAIGQAGSLTSSEDTLTVVTADHSHVFTFGGYTPRGNSIFGLAPMLSDTDKKPFTAILYGNGPGYKVVGGERENVSMVDYAHNNYQAQSAVPLRHETHGGEDVAVFSKGPMAHLLHGVHEQNYVPHVMAYAACIGANLGHCAPASSAGSLAAGPLLLALALYPLSVLF
|
3.1.3.1; 3.9.1.1
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P05187}; Note=Binds 1 Mg(2+) ion. {ECO:0000250|UniProtKB:P05187}; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:25775211}; Note=Binds 2 Zn(2+) ions. {ECO:0000269|PubMed:25775211}; COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:11395499, ECO:0000269|PubMed:25775211};
|
bone mineralization [GO:0030282]; calcium ion homeostasis [GO:0055074]; cellular homeostasis [GO:0019725]; cellular response to organic cyclic compound [GO:0071407]; cementum mineralization [GO:0071529]; dephosphorylation [GO:0016311]; developmental process involved in reproduction [GO:0003006]; endochondral ossification [GO:0001958]; futile creatine cycle [GO:0140651]; inhibition of non-skeletal tissue mineralization [GO:0140928]; osteoblast differentiation [GO:0001649]; phosphate ion homeostasis [GO:0055062]; positive regulation of cold-induced thermogenesis [GO:0120162]; pyridoxal phosphate metabolic process [GO:0042822]; response to antibiotic [GO:0046677]; response to glucocorticoid [GO:0051384]; response to insulin [GO:0032868]; response to lipopolysaccharide [GO:0032496]; response to macrophage colony-stimulating factor [GO:0036005]; response to sodium phosphate [GO:1904383]; response to vitamin B6 [GO:0034516]; response to vitamin D [GO:0033280]; skeletal system development [GO:0001501]
|
extracellular exosome [GO:0070062]; extracellular matrix [GO:0031012]; extracellular region [GO:0005576]; membrane [GO:0016020]; mitochondrial intermembrane space [GO:0005758]; mitochondrial membrane [GO:0031966]; plasma membrane [GO:0005886]; side of membrane [GO:0098552]
|
ADP phosphatase activity [GO:0043262]; alkaline phosphatase activity [GO:0004035]; ATP hydrolysis activity [GO:0016887]; calcium ion binding [GO:0005509]; inorganic diphosphate phosphatase activity [GO:0004427]; phosphoamidase activity [GO:0050187]; phosphoethanolamine phosphatase activity [GO:0052732]; pyridoxal phosphatase activity [GO:0033883]; pyrophosphatase activity [GO:0016462]
|
PF00245;
|
3.40.720.10;
|
Alkaline phosphatase family
|
PTM: N-glycosylated. {ECO:0000269|PubMed:1458595, ECO:0000269|PubMed:19159218}.
|
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2220817, ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064, ECO:0000269|PubMed:33821301}; Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064}. Extracellular vesicle membrane {ECO:0000250|UniProtKB:P09242}; Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P09242}. Mitochondrion membrane {ECO:0000250|UniProtKB:P09242}; Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P09242}. Mitochondrion intermembrane space {ECO:0000250|UniProtKB:P09242}. Note=Localizes to special class of extracellular vesicles, named matrix vesicles (MVs), which are released by osteogenic cells. Localizes to the mitochondria of thermogenic fat cells: tethered to mitochondrial membranes via a GPI-anchor and probably resides in the mitochondrion intermembrane space. {ECO:0000250|UniProtKB:P09242}.
|
CATALYTIC ACTIVITY: Reaction=a phosphate monoester + H2O = an alcohol + phosphate; Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879, ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=3.1.3.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10042, ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:2220817, ECO:0000269|PubMed:23039266, ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25775211, ECO:0000269|PubMed:25982064, ECO:0000269|PubMed:33821301}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15018; Evidence={ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:2220817, ECO:0000269|PubMed:23039266, ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25775211, ECO:0000269|PubMed:25982064, ECO:0000269|PubMed:33821301}; CATALYTIC ACTIVITY: Reaction=diphosphate + H2O = H(+) + 2 phosphate; Xref=Rhea:RHEA:24576, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:43474; Evidence={ECO:0000269|PubMed:12162492}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24577; Evidence={ECO:0000269|PubMed:12162492}; CATALYTIC ACTIVITY: Reaction=H2O + pyridoxal 5'-phosphate = phosphate + pyridoxal; Xref=Rhea:RHEA:20533, ChEBI:CHEBI:15377, ChEBI:CHEBI:17310, ChEBI:CHEBI:43474, ChEBI:CHEBI:597326; Evidence={ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:2220817}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20534; Evidence={ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:2220817}; CATALYTIC ACTIVITY: Reaction=H2O + phosphoethanolamine = ethanolamine + phosphate; Xref=Rhea:RHEA:16089, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57603, ChEBI:CHEBI:58190; Evidence={ECO:0000269|PubMed:2220817}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16090; Evidence={ECO:0000269|PubMed:2220817}; CATALYTIC ACTIVITY: Reaction=H2O + N-phosphocreatine = creatine + phosphate; Xref=Rhea:RHEA:12977, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57947, ChEBI:CHEBI:58092; EC=3.9.1.1; Evidence={ECO:0000250|UniProtKB:P09242}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12978; Evidence={ECO:0000250|UniProtKB:P09242}; 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:0000250|UniProtKB:P09242}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; Evidence={ECO:0000250|UniProtKB:P09242}; CATALYTIC ACTIVITY: Reaction=ADP + H2O = AMP + H(+) + phosphate; Xref=Rhea:RHEA:61436, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:456215, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P09242}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61437; Evidence={ECO:0000250|UniProtKB:P09242}; CATALYTIC ACTIVITY: Reaction=AMP + H2O = adenosine + phosphate; Xref=Rhea:RHEA:29375, ChEBI:CHEBI:15377, ChEBI:CHEBI:16335, ChEBI:CHEBI:43474, ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:P09242}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29376; Evidence={ECO:0000250|UniProtKB:P09242};
| null | null | null | null |
FUNCTION: Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:12162492, PubMed:23688511, PubMed:25982064). Has broad substrate specificity and can hydrolyze a considerable variety of compounds: however, only a few substrates, such as diphosphate (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate (PLP) and N-phosphocreatine are natural substrates (PubMed:12162492, PubMed:2220817). Plays an essential role in skeletal and dental mineralization via its ability to hydrolyze extracellular diphosphate, a potent mineralization inhibitor, to phosphate: it thereby promotes hydroxyapatite crystal formation and increases inorganic phosphate concentration (PubMed:23688511, PubMed:25982064). Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix (By similarity). Also promotes dephosphorylation of osteopontin (SSP1), an inhibitor of hydroxyapatite crystallization in its phosphorylated state; it is however unclear whether ALPL/TNAP mediates SSP1 dephosphorylation via a direct or indirect manner (By similarity). Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable form of vitamin B6, in order to provide a sufficient amount of PLP in the brain, an essential cofactor for enzymes catalyzing the synthesis of diverse neurotransmitters (PubMed:20049532, PubMed:2220817). Additionally, also able to mediate ATP degradation in a stepwise manner to adenosine, thereby regulating the availability of ligands for purinergic receptors (By similarity). Also capable of dephosphorylating microbial products, such as lipopolysaccharides (LPS) as well as other phosphorylated small-molecules, such as poly-inosine:cytosine (poly I:C) (PubMed:28448526). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating hydrolysis of N-phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation (By similarity). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity). {ECO:0000250|UniProtKB:P09242, ECO:0000269|PubMed:12162492, ECO:0000269|PubMed:20049532, ECO:0000269|PubMed:2220817, ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064, ECO:0000269|PubMed:28448526}.
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Homo sapiens (Human)
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P05187
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PPB1_HUMAN
|
MLGPCMLLLLLLLGLRLQLSLGIIPVEEENPDFWNREAAEALGAAKKLQPAQTAAKNLIIFLGDGMGVSTVTAARILKGQKKDKLGPEIPLAMDRFPYVALSKTYNVDKHVPDSGATATAYLCGVKGNFQTIGLSAAARFNQCNTTRGNEVISVMNRAKKAGKSVGVVTTTRVQHASPAGTYAHTVNRNWYSDADVPASARQEGCQDIATQLISNMDIDVILGGGRKYMFRMGTPDPEYPDDYSQGGTRLDGKNLVQEWLAKRQGARYVWNRTELMQASLDPSVTHLMGLFEPGDMKYEIHRDSTLDPSLMEMTEAALRLLSRNPRGFFLFVEGGRIDHGHHESRAYRALTETIMFDDAIERAGQLTSEEDTLSLVTADHSHVFSFGGYPLRGSSIFGLAPGKARDRKAYTVLLYGNGPGYVLKDGARPDVTESESGSPEYRQQSAVPLDEETHAGEDVAVFARGPQAHLVHGVQEQTFIAHVMAFAACLEPYTACDLAPPAGTTDAAHPGRSVVPALLPLLAGTLLLLETATAP
|
3.1.3.1
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:11124260, ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, ECO:0000269|PubMed:20693656}; Note=Binds 1 Mg(2+) ion. {ECO:0000269|PubMed:11124260, ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, ECO:0000269|PubMed:20693656}; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:11124260, ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, ECO:0000269|PubMed:20693656}; Note=Binds 2 Zn(2+) ions. {ECO:0000269|PubMed:11124260, ECO:0000269|PubMed:15946677, ECO:0000269|PubMed:16815919, ECO:0000269|PubMed:20693656}; COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000305|PubMed:25775211};
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dephosphorylation [GO:0016311]
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cell surface [GO:0009986]; plasma membrane [GO:0005886]; side of membrane [GO:0098552]
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alkaline phosphatase activity [GO:0004035]; magnesium ion binding [GO:0000287]; zinc ion binding [GO:0008270]
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PF00245;
|
3.40.720.10;
|
Alkaline phosphatase family
| null |
SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:1730777, ECO:0000269|PubMed:2153284}.
|
CATALYTIC ACTIVITY: Reaction=a phosphate monoester + H2O = an alcohol + phosphate; Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879, ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=3.1.3.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10042, ECO:0000269|PubMed:1939159, ECO:0000269|PubMed:25775211}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15018; Evidence={ECO:0000269|PubMed:1939159, ECO:0000269|PubMed:25775211};
| null | null | null | null |
FUNCTION: Alkaline phosphatase that can hydrolyze various phosphate compounds. {ECO:0000269|PubMed:1939159, ECO:0000269|PubMed:25775211}.
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Homo sapiens (Human)
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P05189
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IPNA_HAPCH
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MGSVPVPVANVPRIDVSPLFGDDKEKKLEVARAIDAASRDTGFFYAVNHGVDLPWLSRETNKFHMSITDEEKWQLAIRAYNKEHESQIRAGYYLPIPGKKAVESFCYLNPSFSPDHPRIKEPTPMHEVNVWPDEAKHPGFRAFAEKYYWDVFGLSSAVLRGYALALGRDEDFFTRHSRRDTTLSSVVLIRYPYLDPYPEPAIKTADDGTKLSFEWHEDVSLITVLYQSDVQNLQVKTPQGWQDIQADDTGFLINCGSYMAHITDDYYPAPIHRVKWVNEERQSLPFFVNLGWEDTIQPWDPATAKDGAKDAAKDKPAISYGEYLQGGLRGLINKNGQT
|
1.21.3.1
|
COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|PROSITE-ProRule:PRU00805, ECO:0000269|PubMed:3839755}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-ProRule:PRU00805};
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penicillin biosynthetic process [GO:0042318]
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cytosol [GO:0005829]
|
iron ion binding [GO:0005506]; isopenicillin-N synthase activity [GO:0016216]
|
PF03171;PF14226;
| null |
Iron/ascorbate-dependent oxidoreductase family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P08703}.
|
CATALYTIC ACTIVITY: Reaction=N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine + O2 = 2 H2O + isopenicillin N; Xref=Rhea:RHEA:22428, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:58399, ChEBI:CHEBI:58572; EC=1.21.3.1; Evidence={ECO:0000269|PubMed:3839755, ECO:0000269|PubMed:3903520, ECO:0000269|PubMed:8076799, ECO:0000269|PubMed:8557701, ECO:0000269|PubMed:9418249, ECO:0000269|PubMed:9530516, ECO:0000269|PubMed:9703965, ECO:0000269|PubMed:9826554, ECO:0000269|PubMed:9841222}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22429; Evidence={ECO:0000269|PubMed:3839755, ECO:0000269|PubMed:3903520, ECO:0000269|PubMed:8076799, ECO:0000269|PubMed:8557701, ECO:0000269|PubMed:9418249, ECO:0000269|PubMed:9530516, ECO:0000269|PubMed:9703965, ECO:0000269|PubMed:9826554, ECO:0000269|PubMed:9841222};
| null |
PATHWAY: Antibiotic biosynthesis; penicillin G biosynthesis; penicillin G from L-alpha-aminoadipate and L-cysteine and L-valine: step 2/3. {ECO:0000269|PubMed:3903520}.
| null | null |
FUNCTION: Isopenicillin N synthase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic (PubMed:3903520). IpnA catalyzes the cyclization of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) to form isopenicillin N (IPN) that contains the beta-lactam nucleus (PubMed:3839755, PubMed:3903520, PubMed:8076799, PubMed:8557701, PubMed:9418249, PubMed:9530516, PubMed:9703965, PubMed:9826554, PubMed:9841222). The penicillin biosynthesis occurs via 3 enzymatic steps, the first corresponding to the production of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) by the NRPS pcbAB. The tripeptide ACV is then cyclized to isopenicillin N (IPN) by the isopenicillin N synthase pcbC that forms the beta-lactam nucleus. Finally, the alpha-aminoadipyl side chain is exchanged for phenylacetic acid by the isopenicillin N acyltransferase penDE to yield penicillin in the peroxisomal matrix (By similarity). {ECO:0000250|UniProtKB:P08703, ECO:0000269|PubMed:3839755, ECO:0000269|PubMed:3903520, ECO:0000269|PubMed:8076799, ECO:0000269|PubMed:8557701, ECO:0000269|PubMed:9418249, ECO:0000269|PubMed:9530516, ECO:0000269|PubMed:9703965, ECO:0000269|PubMed:9826554, ECO:0000269|PubMed:9841222}.
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Hapsidospora chrysogena (Acremonium chrysogenum)
|
P05193
|
AMPC_CITFR
|
MMKKSICCALLLTASFSTFAAAKTEQQIADIVNRTITPLMQEQAIPGMAVAIIYEGKPYYFTWGKADIANNHPVTQQTLFELGSVSKTFNGVLGGDRIARGEIKLSDPVTKYWPELTGKQWRGISLLHLATYTAGGLPLQIPGDVTDKAELLRFYQNWQPQWTPGAKRLYANSSIGLFGALAVKSSGMSYEEAMTRRVLQPLKLAHTWITVPQSEQKNYAWGYLEGKPVHVSPGQLDAEAYGVKSSVIDMARWVQANMDASHVQEKTLQQGIELAQSRYWRIGDMYQGLGWEMLNWPLKADSIINGSDSKVALAALPAVEVNPPAPAVKASWVHKTGSTGGFGSYVAFVPEKNLGIVMLANKSYPNPARVEAAWRILEKLQ
|
3.5.2.6
| null |
antibiotic catabolic process [GO:0017001]; response to antibiotic [GO:0046677]
|
outer membrane-bounded periplasmic space [GO:0030288]
|
beta-lactamase activity [GO:0008800]
|
PF00144;
|
3.40.710.10;
|
Class-C beta-lactamase family
| null |
SUBCELLULAR LOCATION: Periplasm {ECO:0000250}.
|
CATALYTIC ACTIVITY: Reaction=a beta-lactam + H2O = a substituted beta-amino acid; Xref=Rhea:RHEA:20401, ChEBI:CHEBI:15377, ChEBI:CHEBI:35627, ChEBI:CHEBI:140347; EC=3.5.2.6; Evidence={ECO:0000255|PROSITE-ProRule:PRU10102};
| null | null | null | null |
FUNCTION: This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
|
Citrobacter freundii
|
P05194
|
AROD_ECOLI
|
MKTVTVKDLVIGTGAPKIIVSLMAKDIASVKSEALAYREADFDILEWRVDHYADLSNVESVMAAAKILRETMPEKPLLFTFRSAKEGGEQAISTEAYIALNRAAIDSGLVDMIDLELFTGDDQVKETVAYAHAHDVKVVMSNHDFHKTPEAEEIIARLRKMQSFDADIPKIALMPQSTSDVLTLLAATLEMQEQYADRPIITMSMAKTGVISRLAGEVFGSAATFGAVKKASAPGQISVNDLRTVLTILHQA
|
4.2.1.10
| null |
3,4-dihydroxybenzoate biosynthetic process [GO:0046279]; amino acid biosynthetic process [GO:0008652]; aromatic amino acid family biosynthetic process [GO:0009073]; chorismate biosynthetic process [GO:0009423]
|
cytosol [GO:0005829]
|
3-dehydroquinate dehydratase activity [GO:0003855]; protein homodimerization activity [GO:0042803]
|
PF01487;
|
3.20.20.70;
|
Type-I 3-dehydroquinase family
| null | null |
CATALYTIC ACTIVITY: Reaction=3-dehydroquinate = 3-dehydroshikimate + H2O; Xref=Rhea:RHEA:21096, ChEBI:CHEBI:15377, ChEBI:CHEBI:16630, ChEBI:CHEBI:32364; EC=4.2.1.10; Evidence={ECO:0000255|HAMAP-Rule:MF_00214, ECO:0000269|PubMed:2950851, ECO:0000269|PubMed:7592767};
|
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=17 uM for 3-dehydroquinate (at pH 7 and 25 degrees Celsius) {ECO:0000269|PubMed:7592767}; KM=18 uM for 3-dehydroquinate (at pH 7 and 25 degrees Celsius) {ECO:0000269|PubMed:2950851}; Note=kcat is 142 sec(-1) for dehydratase activity with 3-dehydroquinate (at pH 7 and 25 degrees Celsius). {ECO:0000269|PubMed:7592767};
|
PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis; chorismate from D-erythrose 4-phosphate and phosphoenolpyruvate: step 3/7. {ECO:0000255|HAMAP-Rule:MF_00214}.
| null | null |
FUNCTION: Involved in the third step of the chorismate pathway, which leads to the biosynthesis of aromatic amino acids (AroAA). Catalyzes the cis-dehydration of 3-dehydroquinate (DHQ) and introduces the first double bond of the aromatic ring to yield 3-dehydroshikimate. The reaction involves the formation of an imine intermediate between the keto group of 3-dehydroquinate and the epsilon-amino group of a Lys-170 at the active site. {ECO:0000255|HAMAP-Rule:MF_00214, ECO:0000269|PubMed:13198937, ECO:0000269|PubMed:2950851, ECO:0000269|PubMed:3541912, ECO:0000269|PubMed:7592767}.
|
Escherichia coli (strain K12)
|
P05197
|
EF2_RAT
|
MVNFTVDQIRAIMDKKANIRNMSVIAHVDHGKSTLTDSLVCKAGIIASARAGETRFTDTRKDEQERCITIKSTAISLFYELSENDLNFIKQSKDGSGFLINLIDSPGHVDFSSEVTAALRVTDGALVVVDCVSGVCVQTETVLRQAIAERIKPVLMMNKMDRALLELQLEPEELYQTFQRIVENVNVIISTYGEGESGPMGNIMIDPVLGTVGFGSGLHGWAFTLKQFAEMYVAKFAAKGEGQLGAAERAKKVEDMMKKLWGDRYFDPANGKFSKSANSPDGKKLPRTFCQLILDPIFKVFDAIMNFRKEETAKLIEKLDIKLDSEDKDKEGKPLLKAVMRRWLPAGDALLQMITIHLPSPVTAQKYRCELLYEGPPDDEAAMGIKSCDPKGPLMMYISKMVPTSDKGRFYAFGRVFSGVVSTGLKVRIMGPNYTPGKKEDLYLKPIQRTILMMGRYVEPIEDVPCGNIVGLVGVDQFLVKTGTITTFEHAHNMRVMKFSVSPVVRVAVEAKNPADLPKLVEGLKRLAKSDPMVQCIIEESGEHIIAGAGELHLEICLKDLEEDHACIPIKKSDPVVSYRETVSEESNVLCLSKSPNKHNRLYMKARPFPDGLAEDIDKGEVSARQELKARARYLAEKYEWDVAEARKIWCFGPDGTGPNILTDITKGVQYLNEIKDSVVAGFQWATKEGALCEENMRGVRFDVHDVTLHADAIHRGGGQIIPTARRCLYASVLTAQPRLMEPIYLVEIQCPEQVVGGIYGVLNRKRGHVFEESQVAGTPMFVVKAYLPVNESFGFTADLRSNTGGQAFPQCVFDHWQILPGDPFDNSSRPSQVVAETRKRKGLKEGIPALDNFLDKL
|
3.6.5.-
| null |
cellular response to brain-derived neurotrophic factor stimulus [GO:1990416]; glial cell proliferation [GO:0014009]; hematopoietic progenitor cell differentiation [GO:0002244]; positive regulation of cytoplasmic translation [GO:2000767]; positive regulation of translation [GO:0045727]; response to endoplasmic reticulum stress [GO:0034976]; response to estradiol [GO:0032355]; response to ethanol [GO:0045471]; response to folic acid [GO:0051593]; response to hydrogen peroxide [GO:0042542]; response to ischemia [GO:0002931]; response to xenobiotic stimulus [GO:0009410]; skeletal muscle cell differentiation [GO:0035914]; skeletal muscle contraction [GO:0003009]; translation at postsynapse [GO:0140242]; translational elongation [GO:0006414]
|
cytoplasm [GO:0005737]; cytosol [GO:0005829]; glutamatergic synapse [GO:0098978]; postsynapse [GO:0098794]; ribonucleoprotein complex [GO:1990904]; ribosome [GO:0005840]; synapse [GO:0045202]
|
5S rRNA binding [GO:0008097]; actin filament binding [GO:0051015]; GTP binding [GO:0005525]; GTPase activity [GO:0003924]; p53 binding [GO:0002039]; protein kinase binding [GO:0019901]; ribosome binding [GO:0043022]; RNA binding [GO:0003723]; translation elongation factor activity [GO:0003746]
|
PF00679;PF14492;PF03764;PF00009;PF03144;
|
3.30.230.10;3.30.70.240;3.30.70.870;3.40.50.300;2.40.30.10;
|
TRAFAC class translation factor GTPase superfamily, Classic translation factor GTPase family, EF-G/EF-2 subfamily
|
PTM: Diphthamide is 2-[3-carboxyamido-3-(trimethyl-ammonio)propyl]histidine. {ECO:0000269|PubMed:4368673}.; PTM: Phosphorylation by EF-2 kinase completely inactivates EF-2; it requires prior phosphorylation by CDK2 at Ser-595 during mitotic prometaphase. Phosphorylation by CSK promotes SUMOylation, proteolytic cleavage, and nuclear translocation if the C-terminal fragment. {ECO:0000250|UniProtKB:P13639}.; PTM: Proteolytically processed at two sites following phosphorylation by CSK. {ECO:0000250|UniProtKB:P13639}.; PTM: SUMOylated following phosphorylation by CSK, promotes proteolytic cleavage. {ECO:0000250|UniProtKB:P13639}.; PTM: ISGylated. {ECO:0000250|UniProtKB:P13639}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P13639}. Nucleus {ECO:0000250|UniProtKB:P13639}. Note=Phosphorylation by CSK promotes cleavage and SUMOylation-dependent nuclear translocation of the C-terminal cleavage product. {ECO:0000250|UniProtKB:P13639}.
|
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:P13639}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000250|UniProtKB:P13639};
| null | null | null | null |
FUNCTION: Catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome. {ECO:0000250|UniProtKB:P13639}.
|
Rattus norvegicus (Rat)
|
P05198
|
IF2A_HUMAN
|
MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSINKLIRIGRNECVVVIRVDKEKGYIDLSKRRVSPEEAIKCEDKFTKSKTVYSILRHVAEVLEYTKDEQLESLFQRTAWVFDDKYKRPGYGAYDAFKHAVSDPSILDSLDLNEDEREVLINNINRRLTPQAVKIRADIEVACYGYEGIDAVKEALRAGLNCSTENMPIKINLIAPPRYVMTTTTLERTEGLSVLSQAMAVIKEKIEEKRGVFNVQMEPKVVTDTDETELARQMERLERENAEVDGDDDAEEMEAKAED
| null | null |
cellular response to amino acid starvation [GO:0034198]; cellular response to heat [GO:0034605]; cellular response to oxidative stress [GO:0034599]; cellular response to UV [GO:0034644]; negative regulation of translational initiation in response to stress [GO:0032057]; PERK-mediated unfolded protein response [GO:0036499]; positive regulation of type B pancreatic cell apoptotic process [GO:2000676]; regulation of translation in response to endoplasmic reticulum stress [GO:0036490]; regulation of translational initiation in response to stress [GO:0043558]; response to endoplasmic reticulum stress [GO:0034976]; response to kainic acid [GO:1904373]; response to manganese-induced endoplasmic reticulum stress [GO:1990737]; stress granule assembly [GO:0034063]; translational initiation [GO:0006413]
|
cytoplasmic stress granule [GO:0010494]; cytosol [GO:0005829]; eukaryotic 48S preinitiation complex [GO:0033290]; eukaryotic translation initiation factor 2 complex [GO:0005850]; extracellular exosome [GO:0070062]; glial limiting end-foot [GO:0097451]; membrane [GO:0016020]; nucleus [GO:0005634]; synapse [GO:0045202]; translation initiation ternary complex [GO:0044207]
|
ribosome binding [GO:0043022]; RNA binding [GO:0003723]; translation initiation factor activity [GO:0003743]
|
PF07541;PF00575;
|
3.30.70.1130;2.40.50.140;
|
EIF-2-alpha family
|
PTM: Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-2/GDP/eIF2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF2 between successive rounds of initiation and leading to global inhibition of translation, while concomitantly initiating the preferential translation of integrated stress response (ISR)-specific mRNAs (PubMed:15207627, PubMed:18032499, PubMed:19131336, PubMed:31048492). Substrate for at least 4 kinases: EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2 (By similarity). Phosphorylated; phosphorylation on Ser-52 by the EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation and UV irradiation (By similarity). {ECO:0000250|UniProtKB:Q6ZWX6, ECO:0000269|PubMed:15207627, ECO:0000269|PubMed:18032499, ECO:0000269|PubMed:19131336, ECO:0000269|PubMed:31048492}.; PTM: (Microbial infection) Phosphorylation by vaccinia virus protein E3 and rotavirus A stabilizes the eIF-2/GDP/eIF2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF2 between successive rounds of initiation and leading to global inhibition of translation. {ECO:0000269|PubMed:15207627, ECO:0000269|PubMed:18032499}.
|
SUBCELLULAR LOCATION: Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q6ZWX6}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P56286}. Note=Colocalizes with NANOS3 in the stress granules. {ECO:0000250|UniProtKB:Q6ZWX6}.
| null | null | null | null | null |
FUNCTION: Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:16289705). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (43S PIC) (PubMed:16289705). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex (PubMed:16289705). In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF2B (PubMed:16289705). EIF2S1/ component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2) in response to stress converts EIF2S1/eIF2-alpha in a global protein synthesis inhibitor, leading to an attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:19131336, PubMed:33384352). {ECO:0000269|PubMed:16289705, ECO:0000269|PubMed:19131336, ECO:0000269|PubMed:33384352}.
|
Homo sapiens (Human)
|
P05200
|
NGF_CHICK
|
MHSVMSMLYYTLIIAFLIGTQAAPKSEDNGPLEYPAEHSLPSTQQSNGQHIAKAAPQTTHGRFAWMPDGTEDLNIAMDQNFFKKKRFRSSRVLFSTQPPPVSRKGQSTGFLSSAVSLNRTARTKRTAHPVLHRGEFSVCDSVSMWVGDKTTATDIKGKEVTVLGEVNINNNVFKQYFFETKCRDPRPVSSGCRGIDAKHWNSYCTTTHTFVKALTMEGKQAAWRFIRIDTACVCVLSRKSGRP
| null | null |
memory [GO:0007613]; modulation of chemical synaptic transmission [GO:0050804]; negative regulation of neuron apoptotic process [GO:0043524]; nerve development [GO:0021675]; nerve growth factor signaling pathway [GO:0038180]; neuron projection morphogenesis [GO:0048812]; peripheral nervous system development [GO:0007422]; positive regulation of collateral sprouting [GO:0048672]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; regulation of neuron differentiation [GO:0045664]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]
|
axon [GO:0030424]; dendrite [GO:0030425]; extracellular space [GO:0005615]; synaptic vesicle [GO:0008021]
|
growth factor activity [GO:0008083]; nerve growth factor receptor binding [GO:0005163]
|
PF00243;
|
2.10.90.10;
|
NGF-beta family
| null |
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades through those receptor tyrosine kinase to regulate neuronal proliferation, differentiation and survival.
|
Gallus gallus (Chicken)
|
P05201
|
AATC_MOUSE
|
MAPPSVFAQVPQAPPVLVFKLTADFRDDPDPRKVNLGVGAYRTDESQPWVLPVVRKVEQKIANDNSLNHEYLPILGLAEFRSCASRLVLGDNSLAIRENRVGGVQSLGGTGALRIGADFLGRWYNGTDNKNTPIYVSSPTWENHNAVFSAAGFKDIRPYCYWDAEKRGLDLQGFLNDLENAPEFSIFVLHACAHNPTGTDPTPEQWKQIAAVMQRRFLFPFFDSAYQGFASGDLEKDAWAIRYFVSEGFELFCAQSFSKNFGLYNERVGNLTVVGKESDSVLRVLSQMEKIVRITWSNPPAQGARIVAATLSDPELFKEWKGNVKTMADRILTMRSELRARLEALKTPGTWSHITEQIGMFSFTGLNPKQVEYLVNEKHIYLLPSGRINMCGLTTKNLDYVATSIHEAVTKIQ
|
2.6.1.1; 2.6.1.3
|
COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
|
2-oxoglutarate metabolic process [GO:0006103]; aspartate biosynthetic process [GO:0006532]; aspartate catabolic process [GO:0006533]; aspartate metabolic process [GO:0006531]; cellular response to insulin stimulus [GO:0032869]; cellular response to mechanical stimulus [GO:0071260]; dicarboxylic acid metabolic process [GO:0043648]; fatty acid homeostasis [GO:0055089]; gluconeogenesis [GO:0006094]; glutamate catabolic process to 2-oxoglutarate [GO:0019551]; glutamate catabolic process to aspartate [GO:0019550]; glutamate metabolic process [GO:0006536]; glycerol biosynthetic process [GO:0006114]; negative regulation of collagen biosynthetic process [GO:0032966]; negative regulation of cytosolic calcium ion concentration [GO:0051481]; negative regulation of mitochondrial depolarization [GO:0051902]; Notch signaling pathway [GO:0007219]; oxaloacetate metabolic process [GO:0006107]; positive regulation of transforming growth factor beta receptor signaling pathway [GO:0030511]; response to glucocorticoid [GO:0051384]; response to transition metal nanoparticle [GO:1990267]; transdifferentiation [GO:0060290]
|
axon terminus [GO:0043679]; cytosol [GO:0005829]
|
carboxylic acid binding [GO:0031406]; L-aspartate:2-oxoglutarate aminotransferase activity [GO:0004069]; L-cysteine transaminase activity [GO:0047801]; phosphatidylserine decarboxylase activity [GO:0004609]; pyridoxal phosphate binding [GO:0030170]
|
PF00155;
|
3.90.1150.10;3.40.640.10;
|
Class-I pyridoxal-phosphate-dependent aminotransferase family
| null |
SUBCELLULAR LOCATION: Cytoplasm.
|
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-aspartate = L-glutamate + oxaloacetate; Xref=Rhea:RHEA:21824, ChEBI:CHEBI:16452, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:29991; EC=2.6.1.1; Evidence={ECO:0000250|UniProtKB:P13221}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21825; Evidence={ECO:0000250|UniProtKB:P13221}; CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-cysteine = 2-oxo-3-sulfanylpropanoate + L-glutamate; Xref=Rhea:RHEA:17441, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:35235, ChEBI:CHEBI:57678; EC=2.6.1.3; Evidence={ECO:0000250|UniProtKB:P13221}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17442; Evidence={ECO:0000250|UniProtKB:P13221}; CATALYTIC ACTIVITY: Reaction=(2S)-2-aminobutanoate + 2-oxoglutarate = 2-oxobutanoate + L-glutamate; Xref=Rhea:RHEA:70223, ChEBI:CHEBI:16763, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:74359; Evidence={ECO:0000250|UniProtKB:P17174}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70225; Evidence={ECO:0000250|UniProtKB:P17174}; CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + 3-sulfino-L-alanine = 3-sulfinopyruvate + L-glutamate; Xref=Rhea:RHEA:70295, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:61085, ChEBI:CHEBI:140699; Evidence={ECO:0000250|UniProtKB:P13221}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70297; Evidence={ECO:0000250|UniProtKB:P13221};
| null | null | null | null |
FUNCTION: Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain. {ECO:0000250|UniProtKB:P13221}.
|
Mus musculus (Mouse)
|
P05202
|
AATM_MOUSE
|
MALLHSSRILSGMAAAFHPGLAAAASARASSWWTHVEMGPPDPILGVTEAFKRDTNSKKMNLGVGAYRDDNGKPYVLPSVRKAEAQIAAKNLDKEYLPIGGLAEFCKASAELALGENNEVLKSGRFVTVQTISGTGALRVGASFLQRFFKFSRDVFLPKPSWGNHTPIFRDAGMQLQGYRYYDPKTCGFDFSGALEDISKIPEQSVLLLHACAHNPTGVDPRPEQWKEIASVVKKKNLFAFFDMAYQGFASGDGDKDAWAVRHFIEQGINVCLCQSYAKNMGLYGERVGAFTVVCKDAEEAKRVESQLKILIRPLYSNPPLNGARIAATILTSPDLRKQWLQEVKGMADRIISMRTQLVSNLKKEGSSHNWQHITDQIGMFCFTGLKPEQVERLTKEFSVYMTKDGRISVAGVTSGNVGYLAHAIHQVTK
|
2.6.1.1; 2.6.1.7
|
COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000269|PubMed:20977429};
|
2-oxoglutarate metabolic process [GO:0006103]; amino acid metabolic process [GO:0006520]; aspartate biosynthetic process [GO:0006532]; aspartate catabolic process [GO:0006533]; aspartate metabolic process [GO:0006531]; dicarboxylic acid metabolic process [GO:0043648]; fatty acid transport [GO:0015908]; glutamate catabolic process to 2-oxoglutarate [GO:0019551]; glutamate catabolic process to aspartate [GO:0019550]; glutamate metabolic process [GO:0006536]; L-phenylalanine biosynthetic process from chorismate via phenylpyruvate [GO:0033585]; oxaloacetate metabolic process [GO:0006107]; response to ethanol [GO:0045471]
|
cell surface [GO:0009986]; cytosol [GO:0005829]; mitochondrial inner membrane [GO:0005743]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]; myelin sheath [GO:0043209]; perikaryon [GO:0043204]; protein-containing complex [GO:0032991]; sarcolemma [GO:0042383]; T-tubule [GO:0030315]
|
amino acid binding [GO:0016597]; carboxylic acid binding [GO:0031406]; enzyme binding [GO:0019899]; identical protein binding [GO:0042802]; kynurenine-oxoglutarate transaminase activity [GO:0016212]; L-aspartate:2-oxoglutarate aminotransferase activity [GO:0004069]; L-tyrosine:2-oxoglutarate aminotransferase activity [GO:0004838]; phospholipid binding [GO:0005543]; pyridoxal phosphate binding [GO:0030170]
|
PF00155;
|
3.90.1150.10;3.40.640.10;
|
Class-I pyridoxal-phosphate-dependent aminotransferase family
|
PTM: Acetylation of Lys-296, Lys-345 and Lys-363 is observed in liver mitochondria from fasted mice but not from fed mice.
|
SUBCELLULAR LOCATION: Mitochondrion matrix. Cell membrane {ECO:0000269|PubMed:7878064}.
|
CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-aspartate = L-glutamate + oxaloacetate; Xref=Rhea:RHEA:21824, ChEBI:CHEBI:16452, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:29991; EC=2.6.1.1; Evidence={ECO:0000250|UniProtKB:P00507}; CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-kynurenine = H2O + kynurenate + L-glutamate; Xref=Rhea:RHEA:65560, ChEBI:CHEBI:15377, ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:57959, ChEBI:CHEBI:58454; EC=2.6.1.7; Evidence={ECO:0000250|UniProtKB:P00507};
| null | null | null | null |
FUNCTION: Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular NAD(H) redox balance. Is important for metabolite exchange between mitochondria and cytosol, and for amino acid metabolism. Facilitates cellular uptake of long-chain free fatty acids. {ECO:0000269|PubMed:20977429, ECO:0000269|PubMed:7878064}.
|
Mus musculus (Mouse)
|
P05204
|
HMGN2_HUMAN
|
MPKRKAEGDAKGDKAKVKDEPQRRSARLSAKPAPPKPEPKPKKAPAKKGEKVPKGKKGKADAGKEGNNPAENGDAKTDQAQKAEGAGDAK
| null | null |
antimicrobial humoral immune response mediated by antimicrobial peptide [GO:0061844]; chromatin organization [GO:0006325]; killing of cells of another organism [GO:0031640]
|
chromatin [GO:0000785]; cytoplasm [GO:0005737]; extracellular space [GO:0005615]; nucleus [GO:0005634]
|
chromatin binding [GO:0003682]; nucleosomal DNA binding [GO:0031492]; RNA binding [GO:0003723]
|
PF01101;
| null |
HMGN family
|
PTM: Phosphorylation favors cytoplasmic localization. {ECO:0000269|PubMed:10739259}.
|
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10739259}. Cytoplasm {ECO:0000269|PubMed:10739259}. Note=Cytoplasmic enrichment upon phosphorylation.
| null | null | null | null | null |
FUNCTION: Binds to the inner side of the nucleosomal DNA thus altering the interaction between the DNA and the histone octamer. May be involved in the process which maintains transcribable genes in a unique chromatin conformation (By similarity). {ECO:0000250}.
|
Homo sapiens (Human)
|
P05205
|
HP1_DROME
|
MGKKIDNPESSAKVSDAEEEEEEYAVEKIIDRRVRKGKVEYYLKWKGYPETENTWEPENNLDCQDLIQQYEASRKDEEKSAASKKDRPSSSAKAKETQGRASSSTSTASKRKSEEPTAPSGNKSKRTTDAEQDTIPVSGSTGFDRGLEAEKILGASDNNGRLTFLIQFKGVDQAEMVPSSVANEKIPRMVIHFYEERLSWYSDNED
| null | null |
chromatin organization [GO:0006325]; chromosome organization [GO:0051276]; heterochromatin formation [GO:0031507]; mitotic cell cycle [GO:0000278]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of gene expression [GO:0010629]; negative regulation of transcription by RNA polymerase II [GO:0000122]; pericentric heterochromatin formation [GO:0031508]; positive regulation of DNA methylation-dependent heterochromatin formation [GO:0090309]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of FACT complex assembly [GO:1905646]; positive regulation of transcription by RNA polymerase II [GO:0045944]; protein localization to euchromatin [GO:1905632]; regulation of DNA-templated transcription [GO:0006355]; regulation of protein localization to chromatin [GO:1905634]; telomere maintenance [GO:0000723]
|
chromocenter [GO:0010369]; chromosome [GO:0005694]; chromosome, centromeric region [GO:0000775]; chromosome, telomeric region [GO:0000781]; condensed chromosome [GO:0000793]; condensed chromosome, centromeric region [GO:0000779]; euchromatin [GO:0000791]; heterochromatin [GO:0000792]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; pericentric heterochromatin [GO:0005721]; polytene chromosome [GO:0005700]; polytene chromosome chromocenter [GO:0005701]; polytene chromosome puff [GO:0005703]
|
chromatin binding [GO:0003682]; histone binding [GO:0042393]; Hsp70 protein binding [GO:0030544]; methylated histone binding [GO:0035064]; mRNA binding [GO:0003729]; protein-containing complex binding [GO:0044877]; protein-macromolecule adaptor activity [GO:0030674]; rDNA binding [GO:0000182]; RNA binding [GO:0003723]; RNA polymerase binding [GO:0070063]; RNA polymerase II C-terminal domain binding [GO:0099122]; satellite DNA binding [GO:0003696]
|
PF00385;PF01393;
|
2.40.50.40;
| null | null |
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17875665, ECO:0000269|PubMed:19181850, ECO:0000269|PubMed:20679394, ECO:0000269|PubMed:26110638, ECO:0000269|PubMed:26389589, ECO:0000269|PubMed:9378752}. Nucleus, nucleoplasm {ECO:0000269|PubMed:9378752}. Chromosome {ECO:0000269|PubMed:12826664, ECO:0000269|PubMed:17875665, ECO:0000269|PubMed:19181850, ECO:0000269|PubMed:20679394, ECO:0000269|PubMed:26110638, ECO:0000269|PubMed:26389589, ECO:0000269|PubMed:9378752}. Chromosome, telomere {ECO:0000269|PubMed:12826664, ECO:0000269|PubMed:19181850, ECO:0000269|PubMed:19240120, ECO:0000269|PubMed:20679394, ECO:0000269|PubMed:26110638}. Note=Colocalizes with Arp6 on pericentric heterochromatin (PubMed:12826664, PubMed:9378752). Telomere localization is not dependent on peo/pendolino, ver/verrocchio or moi/modigliani (PubMed:19181850, PubMed:19240120, PubMed:20679394, PubMed:26110638). {ECO:0000269|PubMed:12826664, ECO:0000269|PubMed:19181850, ECO:0000269|PubMed:19240120, ECO:0000269|PubMed:20679394, ECO:0000269|PubMed:26110638, ECO:0000269|PubMed:9378752}.
| null | null | null | null | null |
FUNCTION: Structural component of heterochromatin, involved in gene repression and the modification of position-effect-variegation. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. Stabilizes chromatin-associated RNAs probably by binding to them and thereby preventing their degradation (PubMed:26389589). Associates with, and may be a part of, the HipHop-HOAP complex that recruits the MTV complex to form the terminin telomere-capping complex, which binds to chromosome ends in a sequence-independent manner and prevents telomere fusion (PubMed:12510197, PubMed:20057353). Telomere capping is independent of the origin recognition complex (ORC) (PubMed:12510197). {ECO:0000269|PubMed:11566886, ECO:0000269|PubMed:11859155, ECO:0000269|PubMed:12510197, ECO:0000269|PubMed:20057353, ECO:0000269|PubMed:26389589}.
|
Drosophila melanogaster (Fruit fly)
|
P05207
|
KAP2_PIG
|
SGSQDLEPSSGLVTDAIADSESEDDEDLDVPIPSRFDRRVSVCAETYNPDEEEEDTDPRVIHPKTDQQRCRLQEACKDILLFKNLDQEQLSQVLDAMFERTVKVDEHVIDQRDDGDNFYVIERGTYDILVTKDNQTRSVGQYDNHGSFGELALMY
| null | null |
negative regulation of cAMP-dependent protein kinase activity [GO:2000480]; positive regulation of meiotic cell cycle process involved in oocyte maturation [GO:1904146]; regulation of meiotic cell cycle process involved in oocyte maturation [GO:1903538]
|
cAMP-dependent protein kinase complex [GO:0005952]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; germinal vesicle [GO:0042585]; plasma membrane [GO:0005886]
|
cAMP binding [GO:0030552]; cAMP-dependent protein kinase inhibitor activity [GO:0004862]; protein kinase A catalytic subunit binding [GO:0034236]
| null |
2.60.120.10;
|
CAMP-dependent kinase regulatory chain family
|
PTM: Phosphorylated by the activated catalytic chain. {ECO:0000269|PubMed:225318}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}. Note=Colocalizes with PJA2 in the cytoplasm and the cell membrane. {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.
|
Sus scrofa (Pig)
|
P05208
|
CEL2A_MOUSE
|
MIRTLLLSALVAGALSCGYPTYEVEDDVSRVVGGQEATPNTWPWQVSLQVLSSGRWRHNCGGSLVANNWVLTAAHCLSNYQTYRVLLGAHSLSNPGAGSAAVQVSKLVVHQRWNSQNVGNGYDIALIKLASPVTLSKNIQTACLPPAGTILPRNYVCYVTGWGLLQTNGNSPDTLRQGRLLVVDYATCSSASWWGSSVKSSMVCAGGDGVTSSCNGDSGGPLNCRASNGQWQVHGIVSFGSSLGCNYPRKPSVFTRVSNYIDWINSVMARN
|
3.4.21.71
| null |
insulin catabolic process [GO:1901143]; proteolysis [GO:0006508]; regulation of insulin secretion [GO:0050796]; regulation of platelet aggregation [GO:0090330]; response to insulin [GO:0032868]
|
collagen-containing extracellular matrix [GO:0062023]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; keratohyalin granule [GO:0036457]
|
endopeptidase activity [GO:0004175]; serine hydrolase activity [GO:0017171]; serine-type endopeptidase activity [GO:0004252]
|
PF00089;
|
2.40.10.10;
|
Peptidase S1 family, Elastase subfamily
| null |
SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:31358993}.
|
CATALYTIC ACTIVITY: Reaction=Preferential cleavage: Leu-|-Xaa, Met-|-Xaa and Phe-|-Xaa. Hydrolyzes elastin.; EC=3.4.21.71; Evidence={ECO:0000305|PubMed:31358993};
| null | null | null | null |
FUNCTION: Elastase that enhances insulin signaling and might have a physiologic role in cellular glucose metabolism. Circulates in plasma and reduces platelet hyperactivation, triggers both insulin secretion and degradation, and increases insulin sensitivity. {ECO:0000269|PubMed:31358993}.
|
Mus musculus (Mouse)
|
P05213
|
TBA1B_MOUSE
|
MRECISIHVGQAGVQIGNACWELYCLEHGIQPDGQMPSDKTIGGGDDSFNTFFSETGAGKHVPRAVFVDLEPTVIDEVRTGTYRQLFHPEQLITGKEDAANNYARGHYTIGKEIIDLVLDRIRKLADQCTGLQGFLVFHSFGGGTGSGFTSLLMERLSVDYGKKSKLEFSIYPAPQVSTAVVEPYNSILTTHTTLEHSDCAFMVDNEAIYDICRRNLDIERPTYTNLNRLISQIVSSITASLRFDGALNVDLTEFQTNLVPYPRIHFPLATYAPVISAEKAYHEQLSVAEITNACFEPANQMVKCDPRHGKYMACCLLYRGDVVPKDVNAAIATIKTKRSIQFVDWCPTGFKVGINYQPPTVVPGGDLAKVQRAVCMLSNTTAIAEAWARLDHKFDLMYAKRAFVHWYVGEGMEEGEFSEAREDMAALEKDYEEVGVDSVEGEGEEEGEEY
|
3.6.5.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P68363};
|
cellular response to interleukin-4 [GO:0071353]; microtubule cytoskeleton organization [GO:0000226]; mitotic cell cycle [GO:0000278]
|
cytoplasm [GO:0005737]; cytoplasmic microtubule [GO:0005881]; cytosol [GO:0005829]; membrane raft [GO:0045121]; microtubule [GO:0005874]; myelin sheath [GO:0043209]
|
double-stranded RNA binding [GO:0003725]; GTP binding [GO:0005525]; GTPase activity [GO:0003924]; metal ion binding [GO:0046872]; structural constituent of cytoskeleton [GO:0005200]; ubiquitin protein ligase binding [GO:0031625]
|
PF00091;PF03953;
|
1.10.287.600;3.30.1330.20;3.40.50.1440;
|
Tubulin family
|
PTM: Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192). {ECO:0000269|PubMed:19524510, ECO:0000269|PubMed:23897886, ECO:0000269|PubMed:33414192}.; PTM: Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843, PubMed:1967194). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886). {ECO:0000250|UniProtKB:Q71U36, ECO:0000269|PubMed:15890843, ECO:0000269|PubMed:1967194, ECO:0000269|PubMed:23897886}.; PTM: Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly. {ECO:0000269|PubMed:16954346, ECO:0000269|PubMed:19564401}.; PTM: Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability. {ECO:0000250|UniProtKB:P68363}.; PTM: Nitration of Tyr-451 is irreversible and interferes with normal dynein intracellular distribution. {ECO:0000250|UniProtKB:Q71U36}.; PTM: Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (MATCAP, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively. {ECO:0000269|PubMed:16954346, ECO:0000269|PubMed:19564401, ECO:0000269|PubMed:26446751, ECO:0000269|PubMed:27102488, ECO:0000269|PubMed:29146868}.; PTM: [Tubulin alpha-1B chain]: Tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 and DCTN1 (PubMed:16954346, PubMed:19564401). Tyrosination regulates the initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules. In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport (By similarity). {ECO:0000250|UniProtKB:Q71U36, ECO:0000269|PubMed:16954346, ECO:0000269|PubMed:19564401}.; PTM: [Detyrosinated tubulin alpha-1B chain]: Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis: detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator (By similarity). Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle (PubMed:26446751). In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction: detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules and mechanical resistance to contraction (PubMed:27102488). {ECO:0000250|UniProtKB:P68363, ECO:0000269|PubMed:26446751, ECO:0000269|PubMed:27102488}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
|
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:P68363}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000250|UniProtKB:P68363};
| null | null | null | null |
FUNCTION: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. {ECO:0000250|UniProtKB:P68363}.
|
Mus musculus (Mouse)
|
P05214
|
TBA3_MOUSE
|
MRECISIHVGQAGVQIGNACWELYCLEHGIQPDGQMPSDKTIGGGDDSFNTFFSETGAGKHVPRAVFVDLEPTVVDEVRTGTYRQLFHPEQLITGKEDAANNYARGHYTIGKEIVDLVLDRIRKLADLCTGLQGFLIFHSFGGGTGSGFASLLMERLSVDYGKKSKLEFAIYPAPQVSTAVVEPYNSILTTHTTLEHSDCAFMVDNEAIYDICRRNLDIERPTYTNLNRLIGQIVSSITASLRFDGALNVDLTEFQTNLVPYPRIHFPLATYAPVISAEKAYHEQLSVAEITNACFEPANQMVKCDPRHGKYMACCMLYRGDVVPKDVNAAIATIKTKRTIQFVDWCPTGFKVGINYQPPTVVPGGDLAKVQRAVCMLSNTTAIAEAWARLDHKFDLMYAKRAFVHWYVGEGMEEGEFSEAREDLAALEKDYEEVGVDSVEAEAEEGEEY
|
3.6.5.-
|
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P68363};
|
male germ-line stem cell population maintenance [GO:0036098]; microtubule cytoskeleton organization [GO:0000226]; mitotic cell cycle [GO:0000278]
|
ciliary basal body [GO:0036064]; cilium [GO:0005929]; cytoplasm [GO:0005737]; microtubule [GO:0005874]
|
GTP binding [GO:0005525]; hydrolase activity [GO:0016787]; metal ion binding [GO:0046872]; structural constituent of cytoskeleton [GO:0005200]
|
PF00091;PF03953;
|
1.10.287.600;3.30.1330.20;3.40.50.1440;
|
Tubulin family
|
PTM: Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192). {ECO:0000269|PubMed:19524510, ECO:0000269|PubMed:23897886, ECO:0000269|PubMed:33414192}.; PTM: Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886). {ECO:0000250|UniProtKB:Q71U36, ECO:0000269|PubMed:15890843, ECO:0000269|PubMed:23897886}.; PTM: Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly. {ECO:0000250|UniProtKB:Q71U36}.; PTM: Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability. {ECO:0000250|UniProtKB:P68363}.; PTM: Nitration of Tyr-450 is irreversible and interferes with normal dynein intracellular distribution. {ECO:0000250|UniProtKB:Q71U36}.; PTM: Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (MATCAP, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively. {ECO:0000269|PubMed:16954346, ECO:0000269|PubMed:19564401, ECO:0000269|PubMed:26446751, ECO:0000269|PubMed:27102488, ECO:0000269|PubMed:29146868}.; PTM: [Tubulin alpha-3 chain]: Tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 and DCTN1 (PubMed:16954346, PubMed:19564401). Tyrosination regulates the initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules. In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport (By similarity). {ECO:0000250|UniProtKB:Q71U36, ECO:0000269|PubMed:16954346, ECO:0000269|PubMed:19564401}.; PTM: [Detyrosinated tubulin alpha-3 chain]: Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis: detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator (By similarity). Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle (PubMed:26446751). In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction: detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules and mechanical resistance to contraction (PubMed:27102488). {ECO:0000250|UniProtKB:Q6PEY2, ECO:0000269|PubMed:26446751, ECO:0000269|PubMed:27102488}.
|
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
|
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:P68363}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000250|UniProtKB:P68363};
| null | null | null | null |
FUNCTION: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
|
Mus musculus (Mouse)
|
P05219
|
TBB_SCHPO
|
MREIVHIQAGQCGNQVGAAFWSTIADEHGLDSAGIYHGTSEAQHERLNVYFNEAAGGKYVPRAVLVDLEPGTMDAVKSGKFGNLFRPDNIIYGQSGAGNIWAKGHYTEGAELADAVLDVVRREAEACDALQGFQLTHSLGGGTGSGMGTLLLSKIREEYPDRMMATFSVAPAPKSSDTVVEPYNATLSMHQLVENSDETFCIDNEALSSIFANTLKIKSPSYDDLNHLVSAVMAGVTTSFRFPGELNSDLRKLAVNMVPFPRLHFFMVGFAPLAAIGSSSFQAVSVPELTQQMFDANNMMVAADPRHGRYLTVAALFRGKVSMKEVDEQIRSVQTKNSAYFVEWIPDNVLKAVCSVPPKDLKMSATFIGNSTSIQEIFRRLGDQFSAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVSEYQQYQEAGIDEGDEDYEIEEEKEPLEY
| null |
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P68363};
|
cytoplasmic microtubule organization [GO:0031122]; intracellular distribution of mitochondria [GO:0048312]; microtubule cytoskeleton organization [GO:0000226]; mitotic cell cycle [GO:0000278]; mitotic spindle elongation [GO:0000022]; mitotic spindle pole body duplication [GO:1903087]; nuclear migration by microtubule mediated pushing forces [GO:0098863]; response to antibiotic [GO:0046677]
|
astral microtubule [GO:0000235]; cytoplasm [GO:0005737]; cytoplasmic microtubule [GO:0005881]; cytosol [GO:0005829]; microtubule [GO:0005874]; nucleus [GO:0005634]; spindle microtubule [GO:0005876]
|
GTP binding [GO:0005525]; GTPase activity [GO:0003924]; metal ion binding [GO:0046872]; structural constituent of cytoskeleton [GO:0005200]
|
PF00091;PF03953;
|
1.10.287.600;3.30.1330.20;3.40.50.1440;
|
Tubulin family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
| null | null | null | null | null |
FUNCTION: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
|
Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)
|
P05221
|
NUPL_XENLA
|
MASTVSNTSKLEKPVSLIWGCELNEQDKTFEFKVEDDEEKCEHQLALRTVCLGDKAKDEFNIVEIVTQEEGAEKSVPIATLKPSILPMATMVGIELTPPVTFRLKAGSGPLYISGQHVAMEEDYSWAEEEDEGEAEGEEEEEEEEDQESPPKAVKRPAATKKAGQAKKKKLDKEDESSEEDSPTKKGKGAGRGRKPAAKK
| null | null |
chromatin remodeling [GO:0006338]; positive regulation of DNA replication [GO:0045740]; sperm DNA decondensation [GO:0035041]
|
cytoplasm [GO:0005737]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]
|
histone binding [GO:0042393]; histone chaperone activity [GO:0140713]; importin-alpha family protein binding [GO:0061676]; nucleosome binding [GO:0031491]; RNA binding [GO:0003723]
|
PF03066;
|
2.60.120.340;
|
Nucleoplasmin family
|
PTM: Activated by phosphorylation of multiple serine/threonine residues, along both core and tail domains. The level of phosphorylation gradually increases during egg maturation, reaching an average of 7-10 phosphates per monomer, so that at the time of fertilization the activity of the protein is maximum. {ECO:0000269|PubMed:17510054, ECO:0000269|PubMed:19055325}.; PTM: Methylated by prmt5, yielding both monomethylated and symmetrically dimethylated Arg-192. {ECO:0000269|PubMed:22009756}.
|
SUBCELLULAR LOCATION: Nucleus.
| null | null | null | null |
BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Thermostable.;
|
FUNCTION: Acts as a chaperone for histones, such as histone H2A-H2B, and thus regulates the assembly of nucleosome cores (PubMed:11684019, PubMed:19055325). Involved in chromatin remodeling, especially during fertilization and early embryonic development (By similarity). May be involved in sperm chromatin decondensation during fertilization (PubMed:17510054). {ECO:0000250|UniProtKB:Q86SE8, ECO:0000269|PubMed:11684019, ECO:0000269|PubMed:17510054, ECO:0000269|PubMed:19055325}.
|
Xenopus laevis (African clawed frog)
|
P05230
|
FGF1_HUMAN
|
MAEGEITTFTALTEKFNLPPGNYKKPKLLYCSNGGHFLRILPDGTVDGTRDRSDQHIQLQLSAESVGEVYIKSTETGQYLAMDTDGLLYGSQTPNEECLFLERLEENHYNTYISKKHAEKNWFVGLKKNGSCKRGPRTHYGQKAILFLPLPVSSD
| null | null |
activation of protein kinase B activity [GO:0032148]; anatomical structure morphogenesis [GO:0009653]; angiogenesis [GO:0001525]; animal organ morphogenesis [GO:0009887]; branch elongation involved in ureteric bud branching [GO:0060681]; cell differentiation [GO:0030154]; cellular response to heat [GO:0034605]; epithelial cell proliferation [GO:0050673]; fibroblast growth factor receptor signaling pathway [GO:0008543]; lung development [GO:0030324]; mesonephric epithelium development [GO:0072163]; organ induction [GO:0001759]; positive regulation of angiogenesis [GO:0045766]; positive regulation of cell division [GO:0051781]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cholesterol biosynthetic process [GO:0045542]; positive regulation of endothelial cell migration [GO:0010595]; positive regulation of epithelial cell proliferation [GO:0050679]; 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 intracellular signal transduction [GO:1902533]; positive regulation of MAP kinase activity [GO:0043406]; positive regulation of sprouting angiogenesis [GO:1903672]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of endothelial cell chemotaxis to fibroblast growth factor [GO:2000544]; regulation of endothelial tube morphogenesis [GO:1901509]; signal transduction [GO:0007165]; wound healing [GO:0042060]
|
cell cortex [GO:0005938]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular matrix [GO:0031012]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]
|
fibroblast growth factor receptor binding [GO:0005104]; growth factor activity [GO:0008083]; heparin binding [GO:0008201]; Hsp70 protein binding [GO:0030544]; integrin binding [GO:0005178]; S100 protein binding [GO:0044548]
|
PF00167;
|
2.80.10.50;
|
Heparin-binding growth factors family
|
PTM: In the nucleus, phosphorylated by PKC/PRKCD. {ECO:0000269|PubMed:22321063}.
|
SUBCELLULAR LOCATION: Secreted. Cytoplasm. Cytoplasm, cell cortex. Cytoplasm, cytosol. Nucleus. Note=Lacks a cleavable signal sequence. Within the cytoplasm, it is transported to the cell membrane and then secreted by a non-classical pathway that requires Cu(2+) ions and S100A13. Secreted in a complex with SYT1 (By similarity). Binding of exogenous FGF1 to FGFR facilitates endocytosis followed by translocation of FGF1 across endosomal membrane into the cytosol. Nuclear import from the cytosol requires the classical nuclear import machinery, involving proteins KPNA1 and KPNB1, as well as LRRC59. {ECO:0000250}.
| null | null | null | null | null |
FUNCTION: Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as a potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:18441324, PubMed:20422052). Can induce angiogenesis (PubMed:23469107). {ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:20145243, ECO:0000269|PubMed:20422052, ECO:0000269|PubMed:23469107, ECO:0000269|PubMed:8663044}.
|
Homo sapiens (Human)
|
P05231
|
IL6_HUMAN
|
MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYILDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLLEFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQAQNQWLQDMTTHLILRSFKEFLQSSLRALRQM
| null | null |
acute-phase response [GO:0006953]; cellular response to hydrogen peroxide [GO:0070301]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to virus [GO:0098586]; cytokine-mediated signaling pathway [GO:0019221]; defense response to Gram-negative bacterium [GO:0050829]; defense response to Gram-positive bacterium [GO:0050830]; defense response to virus [GO:0051607]; endocrine pancreas development [GO:0031018]; germinal center B cell differentiation [GO:0002314]; glucagon secretion [GO:0070091]; glucose homeostasis [GO:0042593]; hepatic immune response [GO:0002384]; hepatocyte proliferation [GO:0072574]; humoral immune response [GO:0006959]; inflammatory response [GO:0006954]; inflammatory response to wounding [GO:0090594]; interleukin-6-mediated signaling pathway [GO:0070102]; liver regeneration [GO:0097421]; maintenance of blood-brain barrier [GO:0035633]; monocyte chemotaxis [GO:0002548]; negative regulation of apoptotic process [GO:0043066]; negative regulation of bone resorption [GO:0045779]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of chemokine production [GO:0032682]; negative regulation of collagen biosynthetic process [GO:0032966]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of interleukin-1-mediated signaling pathway [GO:2000660]; negative regulation of lipid storage [GO:0010888]; negative regulation of neurogenesis [GO:0050768]; negative regulation of primary miRNA processing [GO:2000635]; neuron cellular homeostasis [GO:0070050]; neuron projection development [GO:0031175]; neutrophil apoptotic process [GO:0001781]; neutrophil mediated immunity [GO:0002446]; platelet activation [GO:0030168]; positive regulation of acute inflammatory response [GO:0002675]; positive regulation of apoptotic DNA fragmentation [GO:1902512]; positive regulation of apoptotic process [GO:0043065]; positive regulation of B cell activation [GO:0050871]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of chemokine production [GO:0032722]; positive regulation of cytokine production involved in inflammatory response [GO:1900017]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of epithelial to mesenchymal transition [GO:0010718]; positive regulation of extracellular matrix disassembly [GO:0090091]; positive regulation of gene expression [GO:0010628]; positive regulation of glial cell proliferation [GO:0060252]; positive regulation of immunoglobulin production [GO:0002639]; positive regulation of interleukin-1 beta production [GO:0032731]; positive regulation of interleukin-10 production [GO:0032733]; positive regulation of interleukin-17 production [GO:0032740]; positive regulation of interleukin-21 production [GO:0032745]; positive regulation of interleukin-6 production [GO:0032755]; positive regulation of interleukin-8 production [GO:0032757]; positive regulation of leukocyte adhesion to vascular endothelial cell [GO:1904996]; positive regulation of leukocyte chemotaxis [GO:0002690]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of neuroinflammatory response [GO:0150078]; positive regulation of osteoblast differentiation [GO:0045669]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of platelet aggregation [GO:1901731]; positive regulation of receptor signaling pathway via JAK-STAT [GO:0046427]; positive regulation of receptor signaling pathway via STAT [GO:1904894]; positive regulation of smooth muscle cell proliferation [GO:0048661]; positive regulation of T cell proliferation [GO:0042102]; positive regulation of T-helper 2 cell cytokine production [GO:2000553]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of translation [GO:0045727]; positive regulation of tumor necrosis factor production [GO:0032760]; positive regulation of type B pancreatic cell apoptotic process [GO:2000676]; positive regulation of tyrosine phosphorylation of STAT protein [GO:0042531]; positive regulation of vascular endothelial growth factor production [GO:0010575]; regulation of angiogenesis [GO:0045765]; regulation of astrocyte activation [GO:0061888]; regulation of glucagon secretion [GO:0070092]; regulation of insulin secretion [GO:0050796]; regulation of microglial cell activation [GO:1903978]; regulation of neuroinflammatory response [GO:0150077]; regulation of vascular endothelial growth factor production [GO:0010574]; response to activity [GO:0014823]; response to glucocorticoid [GO:0051384]; response to peptidoglycan [GO:0032494]; T follicular helper cell differentiation [GO:0061470]; T-helper 17 cell lineage commitment [GO:0072540]; vascular endothelial growth factor production [GO:0010573]
|
endoplasmic reticulum lumen [GO:0005788]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; interleukin-6 receptor complex [GO:0005896]
|
cytokine activity [GO:0005125]; growth factor activity [GO:0008083]; interleukin-6 receptor binding [GO:0005138]
|
PF00489;
|
1.20.1250.10;
|
IL-6 superfamily
|
PTM: N- and O-glycosylated. {ECO:0000269|PubMed:1883960}.
|
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11080265}.
| null | null | null | null | null |
FUNCTION: Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable). {ECO:0000305|PubMed:30995492}.; FUNCTION: IL6 is a potent inducer of the acute phase response. Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology. In the innate immune response, is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury (Probable). In the adaptive immune response, is required for the differentiation of B cells into immunoglobulin-secreting cells. Plays a major role in the differentiation of CD4(+) T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Required to drive naive CD4(+) T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells (By similarity). {ECO:0000250|UniProtKB:P08505, ECO:0000305|PubMed:30995492}.; FUNCTION: Acts as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability (PubMed:12794819, PubMed:17075861). Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF (PubMed:12794819). Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance (PubMed:20823453). 'Trans-signaling' in central nervous system also regulates energy and glucose homeostasis (By similarity). Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand (By similarity). Also acts as a myokine (Probable). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection (PubMed:15124018). Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity). {ECO:0000250|UniProtKB:P08505, ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:15124018, ECO:0000269|PubMed:17075861, ECO:0000269|PubMed:20823453, ECO:0000305|PubMed:30995492}.
|
Homo sapiens (Human)
|
P05300
|
LAMP1_CHICK
|
MGGAARAVLLGFLQASSSFDVRDSTGKVCIIANLTVAFSVEYKSSGQKQFAHFFLPQNATSQSHSSCGEGNTSHPILALSFGAGHLISLNFSKTLDKYQVEELTFHYNLSDETLFPNATEGKVMVATQKSVIQARIGTEYRCINSKYVRMKHVNITFSNVTLEAYPTNDTFSANKTECREDMVSTTTVAPTTPKHATSQVPTTSPAPTAAPSSPAVGKYNVTGANGTCVLASMGLQLNITYVKKDEKMGLDLLNFIPHNTSASGMCESTSAFLNLAFEKTKITFHFVLNASSEKFFLQGVNVSTTLPSEAKAPTFEASNDSMSESRATVGNSYKCSAEENFQVTDKALVNVFNVQVQAFKVDGDKFGAMEECQLDENNMLIPIIVGAALAGLVLIVLIAYLIGRKRSHAGYQTI
| null | null |
establishment of protein localization to organelle [GO:0072594]; lysosomal lumen acidification [GO:0007042]
|
cytolytic granule membrane [GO:0101004]; endosome membrane [GO:0010008]; late endosome membrane [GO:0031902]; lysosomal membrane [GO:0005765]; membrane [GO:0016020]; plasma membrane [GO:0005886]
|
ion channel inhibitor activity [GO:0008200]
|
PF01299;PF21222;
|
2.40.160.110;
|
LAMP family
| null |
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:2871029, ECO:0000269|PubMed:3107839}; Single-pass type I membrane protein {ECO:0000255}. Endosome membrane {ECO:0000269|PubMed:2871029, ECO:0000269|PubMed:3107839}; Single-pass type I membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000250|UniProtKB:P11279}; Single-pass type I membrane protein {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:2871029, ECO:0000269|PubMed:3107839}; Single-pass type I membrane protein {ECO:0000255}. Cytolytic granule membrane {ECO:0000250|UniProtKB:P11279}; Single-pass type I membrane protein {ECO:0000255}. Note=This protein shuttles between lysosomes, endosomes, and the plasma membrane (PubMed:2871029, PubMed:3107839). Colocalizes with OSBPL1A at the late endosome (PubMed:3107839). {ECO:0000269|PubMed:2871029, ECO:0000269|PubMed:3107839}.
| null | null | null | null | null |
FUNCTION: Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis. {ECO:0000250|UniProtKB:P11279}.; FUNCTION: (Microbial infection) Plays an essential role in efficient replication and spread of Marek's disease virus, by facilitating viral cell-to-cell spread. {ECO:0000269|PubMed:32999035}.
|
Gallus gallus (Chicken)
|
P05305
|
EDN1_HUMAN
|
MDYLLMIFSLLFVACQGAPETAVLGAELSAVGENGGEKPTPSPPWRLRRSKRCSCSSLMDKECVYFCHLDIIWVNTPEHVVPYGLGSPRSKRALENLLPTKATDRENRCQCASQKDKKCWNFCQAGKELRAEDIMEKDWNNHKKGKDCSKLGKKCIYQQLVRGRKIRRSSEEHLRQTRSETMRNSVKSSFHDPKLKGKPSRERYVTHNRAHW
| null | null |
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway [GO:0007193]; artery smooth muscle contraction [GO:0014824]; axon extension [GO:0048675]; axonogenesis involved in innervation [GO:0060385]; body fluid secretion [GO:0007589]; branching involved in blood vessel morphogenesis [GO:0001569]; calcium ion transmembrane transport [GO:0070588]; calcium-mediated signaling [GO:0019722]; canonical Wnt signaling pathway [GO:0060070]; cardiac neural crest cell migration involved in outflow tract morphogenesis [GO:0003253]; cartilage development [GO:0051216]; cell surface receptor signaling pathway [GO:0007166]; cell-cell signaling [GO:0007267]; cellular response to calcium ion [GO:0071277]; cellular response to fatty acid [GO:0071398]; cellular response to follicle-stimulating hormone stimulus [GO:0071372]; cellular response to glucocorticoid stimulus [GO:0071385]; cellular response to human chorionic gonadotropin stimulus [GO:0044751]; cellular response to hydrogen peroxide [GO:0070301]; cellular response to hypoxia [GO:0071456]; cellular response to interleukin-1 [GO:0071347]; cellular response to luteinizing hormone stimulus [GO:0071373]; cellular response to mineralocorticoid stimulus [GO:0071389]; cellular response to organic substance [GO:0071310]; cellular response to transforming growth factor beta stimulus [GO:0071560]; cellular response to tumor necrosis factor [GO:0071356]; cellular response to type II interferon [GO:0071346]; cellular response to xenobiotic stimulus [GO:0071466]; dorsal/ventral pattern formation [GO:0009953]; embryonic heart tube development [GO:0035050]; endothelin receptor signaling pathway [GO:0086100]; endothelin receptor signaling pathway involved in heart process [GO:0086101]; epithelial fluid transport [GO:0042045]; ERK1 and ERK2 cascade [GO:0070371]; G protein-coupled receptor signaling pathway [GO:0007186]; glomerular endothelium development [GO:0072011]; glomerular filtration [GO:0003094]; histamine secretion [GO:0001821]; in utero embryonic development [GO:0001701]; intracellular calcium ion homeostasis [GO:0006874]; leukocyte activation [GO:0045321]; maternal process involved in parturition [GO:0060137]; meiotic cell cycle process involved in oocyte maturation [GO:1903537]; membrane depolarization [GO:0051899]; middle ear morphogenesis [GO:0042474]; mitochondrion organization [GO:0007005]; negative regulation of blood coagulation [GO:0030195]; negative regulation of gene expression [GO:0010629]; negative regulation of hormone secretion [GO:0046888]; negative regulation of nitric-oxide synthase biosynthetic process [GO:0051771]; negative regulation of protein metabolic process [GO:0051248]; negative regulation of smooth muscle cell apoptotic process [GO:0034392]; negative regulation of transcription by RNA polymerase II [GO:0000122]; neural crest cell fate commitment [GO:0014034]; nitric oxide transport [GO:0030185]; noradrenergic neuron differentiation [GO:0003357]; peptide hormone secretion [GO:0030072]; pharyngeal arch artery morphogenesis [GO:0061626]; phosphatidylinositol 3-kinase/protein kinase B signal transduction [GO:0043491]; phospholipase C-activating G protein-coupled receptor signaling pathway [GO:0007200]; phospholipase D-activating G protein-coupled receptor signaling pathway [GO:0031583]; podocyte differentiation [GO:0072112]; positive regulation of artery morphogenesis [GO:1905653]; positive regulation of calcium-mediated signaling [GO:0050850]; positive regulation of canonical NF-kappaB signal transduction [GO:0043123]; positive regulation of cardiac muscle hypertrophy [GO:0010613]; positive regulation of cation channel activity [GO:2001259]; positive regulation of cell growth involved in cardiac muscle cell development [GO:0061051]; positive regulation of cell migration [GO:0030335]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cell size [GO:0045793]; positive regulation of chemokine-mediated signaling pathway [GO:0070101]; positive regulation of cytosolic calcium ion concentration [GO:0007204]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of endothelial cell migration [GO:0010595]; positive regulation of heart rate [GO:0010460]; positive regulation of hormone secretion [GO:0046887]; positive regulation of JUN kinase activity [GO:0043507]; positive regulation of MAP kinase activity [GO:0043406]; positive regulation of mitotic nuclear division [GO:0045840]; positive regulation of neutrophil chemotaxis [GO:0090023]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; positive regulation of non-canonical NF-kappaB signal transduction [GO:1901224]; positive regulation of odontogenesis [GO:0042482]; positive regulation of prostaglandin secretion [GO:0032308]; positive regulation of prostaglandin-endoperoxide synthase activity [GO:0060585]; positive regulation of protein localization to nucleus [GO:1900182]; positive regulation of renal sodium excretion [GO:0035815]; positive regulation of sarcomere organization [GO:0060298]; positive regulation of signaling receptor activity [GO:2000273]; positive regulation of smooth muscle cell proliferation [GO:0048661]; positive regulation of smooth muscle contraction [GO:0045987]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of urine volume [GO:0035810]; positive regulation of vascular associated smooth muscle cell proliferation [GO:1904707]; prostaglandin biosynthetic process [GO:0001516]; protein kinase A signaling [GO:0010737]; protein kinase C deactivation [GO:0042313]; protein kinase C-activating G protein-coupled receptor signaling pathway [GO:0007205]; regulation of glucose transmembrane transport [GO:0010827]; regulation of pH [GO:0006885]; regulation of systemic arterial blood pressure by endothelin [GO:0003100]; regulation of vasoconstriction [GO:0019229]; renal sodium ion absorption [GO:0070294]; respiratory gaseous exchange by respiratory system [GO:0007585]; response to activity [GO:0014823]; response to amino acid [GO:0043200]; response to amphetamine [GO:0001975]; response to dexamethasone [GO:0071548]; response to leptin [GO:0044321]; response to lipopolysaccharide [GO:0032496]; response to muscle stretch [GO:0035994]; response to nicotine [GO:0035094]; response to ozone [GO:0010193]; response to prostaglandin F [GO:0034696]; response to salt [GO:1902074]; response to testosterone [GO:0033574]; rhythmic excitation [GO:0043179]; semaphorin-plexin signaling pathway involved in axon guidance [GO:1902287]; superoxide anion generation [GO:0042554]; sympathetic neuron axon guidance [GO:0097492]; thyroid gland development [GO:0030878]; transcription by RNA polymerase II [GO:0006366]; vasoconstriction [GO:0042310]; vein smooth muscle contraction [GO:0014826]
|
basal part of cell [GO:0045178]; cytoplasm [GO:0005737]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; rough endoplasmic reticulum lumen [GO:0048237]; transport vesicle [GO:0030133]; Weibel-Palade body [GO:0033093]
|
cytokine activity [GO:0005125]; endothelin A receptor binding [GO:0031707]; endothelin B receptor binding [GO:0031708]; hormone activity [GO:0005179]
|
PF00322;
| null |
Endothelin/sarafotoxin family
| null |
SUBCELLULAR LOCATION: Secreted.
| null | null | null | null | null |
FUNCTION: Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and RHOA cascade in glomerular mesangial cells (PubMed:19086031). Also binds the DEAR/FBXW7-AS1 receptor (PubMed:17446437). Promotes mesenteric arterial wall remodeling via activation of ROCK signaling and subsequent colocalization of NFATC3 with F-actin filaments (By similarity). NFATC3 then translocates to the nucleus where it subsequently promotes the transcription of the smooth muscle hypertrophy and differentiation marker ACTA2 (By similarity). {ECO:0000250|UniProtKB:P09558, ECO:0000250|UniProtKB:P22387, ECO:0000269|PubMed:17446437, ECO:0000269|PubMed:19086031}.
|
Homo sapiens (Human)
|
P05307
|
PDIA1_BOVIN
|
MLRRALLCLALTALFRAGAGAPDEEDHVLVLHKGNFDEALAAHKYLLVEFYAPWCGHCKALAPEYAKAAGKLKAEGSEIRLAKVDATEESDLAQQYGVRGYPTIKFFKNGDTASPKEYTAGREADDIVNWLKKRTGPAASTLSDGAAAEALVESSEVAVIGFFKDMESDSAKQFFLAAEVIDDIPFGITSNSDVFSKYQLDKDGVVLFKKFDEGRNNFEGEVTKEKLLDFIKHNQLPLVIEFTEQTAPKIFGGEIKTHILLFLPKSVSDYEGKLSNFKKAAESFKGKILFIFIDSDHTDNQRILEFFGLKKEECPAVRLITLEEEMTKYKPESDELTAEKITEFCHRFLEGKIKPHLMSQELPDDWDKQPVKVLVGKNFEEVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANEVEAVKVHSFPTLKFFPASADRTVIDYNGERTLDGFKKFLESGGQDGAGDDDDLEDLEEAEEPDLEEDDDQKAVKDEL
|
5.3.4.1
| null |
peptidyl-proline hydroxylation to 4-hydroxy-L-proline [GO:0018401]; protein folding [GO:0006457]; response to endoplasmic reticulum stress [GO:0034976]
|
endoplasmic reticulum [GO:0005783]; endoplasmic reticulum lumen [GO:0005788]; external side of plasma membrane [GO:0009897]; melanosome [GO:0042470]
|
procollagen-proline 4-dioxygenase activity [GO:0004656]; protein disulfide isomerase activity [GO:0003756]; protein heterodimerization activity [GO:0046982]
|
PF00085;PF13848;
|
3.40.30.10;
|
Protein disulfide isomerase family
|
PTM: Phosphorylation of Ser-359 by FAM20C is induced by endoplasmic reticulum stress and results in a functional switch from oxidoreductase to molecular chaperone. It also promotes interaction with ERN1. {ECO:0000250|UniProtKB:P07237}.
|
SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000250|UniProtKB:P07237}. Endoplasmic reticulum lumen {ECO:0000250|UniProtKB:P07237}. Melanosome {ECO:0000250|UniProtKB:P07237}. Cell membrane {ECO:0000250|UniProtKB:P09103}; Peripheral membrane protein {ECO:0000305}. Note=Highly abundant. In some cell types, seems to be also secreted or associated with the plasma membrane, where it undergoes constant shedding and replacement from intracellular sources. Localizes near CD4-enriched regions on lymphoid cell surfaces. Colocalizes with MTTP in the endoplasmic reticulum. {ECO:0000250|UniProtKB:P07237}.
|
CATALYTIC ACTIVITY: Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.; EC=5.3.4.1; Evidence={ECO:0000250|UniProtKB:P07237};
| null | null | null | null |
FUNCTION: This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration. {ECO:0000250|UniProtKB:P07237}.
|
Bos taurus (Bovine)
|
P05317
|
RLA0_YEAST
|
MGGIREKKAEYFAKLREYLEEYKSLFVVGVDNVSSQQMHEVRKELRGRAVVLMGKNTMVRRAIRGFLSDLPDFEKLLPFVKGNVGFVFTNEPLTEIKNVIVSNRVAAPARAGAVAPEDIWVRAVNTGMEPGKTSFFQALGVPTKIARGTIEIVSDVKVVDAGNKVGQSEASLLNLLNISPFTFGLTVVQVYDNGQVFPSSILDITDEELVSHFVSAVSTIASISLAIGYPTLPSVGHTLINNYKDLLAVAIAASYHYPEIEDLVDRIENPEKYAAAAPAATSAASGDAAPAEEAAAEEEEESDDDMGFGLFD
| null | null |
cytoplasmic translation [GO:0002181]; ribosomal large subunit assembly [GO:0000027]
|
90S preribosome [GO:0030686]; cytoplasm [GO:0005737]; cytosolic large ribosomal subunit [GO:0022625]
|
large ribosomal subunit rRNA binding [GO:0070180]; structural constituent of ribosome [GO:0003735]
|
PF00428;PF00466;PF17777;
|
3.30.70.1730;3.90.105.20;
|
Universal ribosomal protein uL10 family
| null |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22096102}.
| null | null | null | null | null |
FUNCTION: Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. uL10 forms part of the P stalk that participates in recruiting G proteins to the ribosome. {ECO:0000305|PubMed:22096102}.
|
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
|
P05318
|
RLA1_YEAST
|
MSTESALSYAALILADSEIEISSEKLLTLTNAANVPVENIWADIFAKALDGQNLKDLLVNFSAGAAAPAGVAGGVAGGEAGEAEAEKEEEEAKEESDDDMGFGLFD
| null | null |
cytoplasmic translation [GO:0002181]; translational elongation [GO:0006414]
|
cytosolic large ribosomal subunit [GO:0022625]
|
protein kinase activator activity [GO:0030295]; ribonucleoprotein complex binding [GO:0043021]; structural constituent of ribosome [GO:0003735]
|
PF00428;
|
1.10.10.1410;
|
Eukaryotic ribosomal protein P1/P2 family
|
PTM: N-terminally acetylated by acetyltransferase NatA. {ECO:0000269|PubMed:10601260, ECO:0000269|PubMed:8476850}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:22096102}.
| null | null | null | null | null |
FUNCTION: Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. {ECO:0000305|PubMed:22096102}.
|
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
|
P05319
|
RLA2_YEAST
|
MKYLAAYLLLNAAGNTPDATKIKAILESVGIEIEDEKVSSVLSALEGKSVDELITEGNEKLAAVPAAGPASAGGAAAASGDAAAEEEKEEEAAEESDDDMGFGLFD
| null | null |
cytoplasmic translation [GO:0002181]; cytoplasmic translational elongation [GO:0002182]
|
cytosolic large ribosomal subunit [GO:0022625]
|
protein kinase activator activity [GO:0030295]; structural constituent of ribosome [GO:0003735]
|
PF00428;
|
1.10.10.1410;
|
Eukaryotic ribosomal protein P1/P2 family
|
PTM: Phosphorylation is not involved in the interaction of the acidic P proteins with the ribosome, however it is suggested to affect the ribosome activity and to participate in a possible ribosome regulatory mechanism.; PTM: The N-terminus is not modified. {ECO:0000269|PubMed:8476850}.
|
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:22096102}.
| null | null | null | null | null |
FUNCTION: Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. {ECO:0000305|PubMed:22096102}.
|
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
|
P05326
|
IPNA_EMENI
|
MGSVSKANVPKIDVSPLFGDDQAAKMRVAQQIDAASRDTGFFYAVNHGINVQRLSQKTKEFHMSITPEEKWDLAIRAYNKEHQDQVRAGYYLSIPGKKAVESFCYLNPNFTPDHPRIQAKTPTHEVNVWPDETKHPGFQDFAEQYYWDVFGLSSALLKGYALALGKEENFFARHFKPDDTLASVVLIRYPYLDPYPEAAIKTAADGTKLSFEWHEDVSLITVLYQSNVQNLQVETAAGYQDIEADDTGYLINCGSYMAHLTNNYYKAPIHRVKWVNAERQSLPFFVNLGYDSVIDPFDPREPNGKSDREPLSYGDYLQNGLVSLINKNGQT
|
1.21.3.1
|
COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|PROSITE-ProRule:PRU00805, ECO:0000269|PubMed:10537113, ECO:0000269|PubMed:7791906, ECO:0000269|PubMed:9194566}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-ProRule:PRU00805, ECO:0000269|PubMed:10537113, ECO:0000269|PubMed:7791906, ECO:0000269|PubMed:9194566};
|
penicillin biosynthetic process [GO:0042318]
|
cytosol [GO:0005829]
|
iron ion binding [GO:0005506]; isopenicillin-N synthase activity [GO:0016216]; L-ascorbic acid binding [GO:0031418]
|
PF03171;PF14226;
| null |
Iron/ascorbate-dependent oxidoreductase family
| null |
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P08703}.
|
CATALYTIC ACTIVITY: Reaction=N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine + O2 = 2 H2O + isopenicillin N; Xref=Rhea:RHEA:22428, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:58399, ChEBI:CHEBI:58572; EC=1.21.3.1; Evidence={ECO:0000269|PubMed:11755401, ECO:0000269|PubMed:28703303, ECO:0000269|PubMed:3319778}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22429; Evidence={ECO:0000269|PubMed:11755401, ECO:0000269|PubMed:28703303, ECO:0000269|PubMed:3319778};
| null |
PATHWAY: Antibiotic biosynthesis; penicillin G biosynthesis; penicillin G from L-alpha-aminoadipate and L-cysteine and L-valine: step 2/3. {ECO:0000269|PubMed:3319778}.
| null | null |
FUNCTION: Isopenicillin N synthase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic (PubMed:11755401, PubMed:3319778). IpnA catalyzes the cyclization of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) to form isopenicillin N (IPN) that contains the beta-lactam nucleus (PubMed:11755401, PubMed:28703303, PubMed:3319778). The penicillin biosynthesis occurs via 3 enzymatic steps, the first corresponding to the production of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) by the NRPS acvA. The tripeptide ACV is then cyclized to isopenicillin N (IPN) by the isopenicillin N synthase ipnA that forms the beta-lactam nucleus. Finally, the alpha-aminoadipyl side chain is exchanged for phenylacetic acid by the isopenicillin N acyltransferase penDE to yield penicillin in the peroxisomal matrix (By similarity). {ECO:0000250|UniProtKB:P08703, ECO:0000269|PubMed:11755401, ECO:0000269|PubMed:28703303, ECO:0000269|PubMed:3319778}.
|
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans)
|
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