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
P00158
CYB_MOUSE
MTNMRKTHPLFKIINHSFIDLPAPSNISSWWNFGSLLGVCLMVQIITGLFLAMHYTSDTMTAFSSVTHICRDVNYGWLIRYMHANGASMFFICLFLHVGRGLYYGSYTFMETWNIGVLLLFAVMATAFMGYVLPWGQMSFWGATVITNLLSAIPYIGTTLVEWIWGGFSVDKATLTRFFAFHFILPFIIAALAIVHLLFLHETGSNNPTGLNSDADKIPFHPYYTIKDILGILIMFLILMTLVLFFPDMLGDPDNYMPANPLNTPPHIKPEWYFLFAYAILRSIPNKLGGVLALILSILILALMPFLHTSKQRSLMFRPITQILYWILVANLLILTWIGGQPVEHPFIIIGQLASISYFSIILILMPISGIIEDKMLKLYP
null
COFACTOR: Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000250|UniProtKB:P00157}; Note=Binds 2 heme b groups non-covalently. {ECO:0000250|UniProtKB:P00157};
animal organ regeneration [GO:0031100]; cellular respiration [GO:0045333]; electron transport coupled proton transport [GO:0015990]; mitochondrial electron transport, ubiquinol to cytochrome c [GO:0006122]; response to cadmium ion [GO:0046686]; response to calcium ion [GO:0051592]; response to cobalamin [GO:0033590]; response to copper ion [GO:0046688]; response to ethanol [GO:0045471]; response to glucagon [GO:0033762]; response to hyperoxia [GO:0055093]; response to hypoxia [GO:0001666]; response to mercury ion [GO:0046689]; response to toxic substance [GO:0009636]; response to xenobiotic stimulus [GO:0009410]
membrane [GO:0016020]; mitochondrial inner membrane [GO:0005743]; mitochondrial respiratory chain complex III [GO:0005750]; mitochondrion [GO:0005739]; protein-containing complex [GO:0032991]
metal ion binding [GO:0046872]; protein-containing complex binding [GO:0044877]; ubiquinol-cytochrome-c reductase activity [GO:0008121]
PF00032;PF00033;
null
Cytochrome b family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:6326133}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P00157}.
null
null
null
null
null
FUNCTION: Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. Contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis. {ECO:0000250|UniProtKB:P00157}.
Mus musculus (Mouse)
P00159
CYB_RAT
MTNIRKSHPLFKIINHSFIDLPAPSNISSWWNFGSLLGVCLMVQILTGLFLAMHYTSDTMTAFSSVTHICRDVNYGWLIRYLHANGASMFFICLFLHVGRGLYYGSYTFLETWNIGIILLFAVMATAFMGYVLPWGQMSFWGATVITNLLSAIPYIGTTLVEWIWGGFSVDKATLTRFFAFHFILPFIIAALAIVHLLFLHETGSNNPTGLNSDADKIPFHPYYTIKDLLGVFMLLLFLMTLVLFFPDLLGDPDNYTPANPLNTPPHIKPEWYFLFAYAILRSIPNKLGGVVALILSILILAFLPFLHTSKQRSLTFRPITQILYWILVANLLILTWIGGQPVEHPFIIIGQLASISYFSIILILMPISGIVEDKMLKWN
null
COFACTOR: Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000250|UniProtKB:P00157}; Note=Binds 2 heme b groups non-covalently. {ECO:0000250|UniProtKB:P00157};
animal organ regeneration [GO:0031100]; electron transport coupled proton transport [GO:0015990]; mitochondrial electron transport, ubiquinol to cytochrome c [GO:0006122]; response to cadmium ion [GO:0046686]; response to calcium ion [GO:0051592]; response to cobalamin [GO:0033590]; response to copper ion [GO:0046688]; response to ethanol [GO:0045471]; response to glucagon [GO:0033762]; response to hormone [GO:0009725]; response to hyperoxia [GO:0055093]; response to hypoxia [GO:0001666]; response to mercury ion [GO:0046689]; response to nutrient [GO:0007584]; response to organic cyclic compound [GO:0014070]; response to organonitrogen compound [GO:0010243]; response to toxic substance [GO:0009636]; response to xenobiotic stimulus [GO:0009410]
membrane [GO:0016020]; mitochondrial inner membrane [GO:0005743]; mitochondrial respiratory chain complex III [GO:0005750]; mitochondrion [GO:0005739]; protein-containing complex [GO:0032991]
metal ion binding [GO:0046872]; protein-containing complex binding [GO:0044877]; ubiquinol-cytochrome-c reductase activity [GO:0008121]
PF00032;PF00033;
null
Cytochrome b family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:6326133}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P00157}.
null
null
null
null
null
FUNCTION: Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. Contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis. {ECO:0000250|UniProtKB:P00157}.
Rattus norvegicus (Rat)
P00163
CYB_YEAST
MAFRKSNVYLSLVNSYIIDSPQPSSINYWWNMGSLLGLCLVIQIVTGIFMAMHYSSNIELAFSSVEHIMRDVHNGYILRYLHANGASFFFMVMFMHMAKGLYYGSYRSPRVTLWNVGVIIFILTIATAFLGYCCVYGQMSHWGATVITNLFSAIPFVGNDIVSWLWGGFSVSNPTIQRFFALHYLVPFIIAAMVIMHLMALHIHGSSNPLGITGNLDRIPMHSYFIFKDLVTVFLFMLILALFVFYSPNTLGHPDNYIPGNPLVTPASIVPEWYLLPFYAILRSIPDKLLGVITMFAAILVLLVLPFTDRSVVRGNTFKVLSKFFFFIFVFNFVLLGQIGACHVEVPYVLMGQIATFIYFAYFLIIVPVISTIENVLFYIGRVNK
7.1.1.8
COFACTOR: Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000269|PubMed:10873857, ECO:0000269|PubMed:11880631, ECO:0000269|PubMed:18390544, ECO:0000269|PubMed:30598554}; Note=Binds 2 heme b groups non-covalently per subunit. {ECO:0000269|PubMed:10873857, ECO:0000269|PubMed:11880631, ECO:0000269|PubMed:18390544, ECO:0000269|PubMed:30598554};
aerobic respiration [GO:0009060]; cellular respiration [GO:0045333]; mitochondrial electron transport, ubiquinol to cytochrome c [GO:0006122]
mitochondrial inner membrane [GO:0005743]; mitochondrial respiratory chain complex III [GO:0005750]; mitochondrion [GO:0005739]
metal ion binding [GO:0046872]; ubiquinol-cytochrome-c reductase activity [GO:0008121]
PF00032;PF00033;
null
Cytochrome b family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:18390544, ECO:0000269|PubMed:30598554, ECO:0000269|PubMed:8031140}; Multi-pass membrane protein {ECO:0000269|PubMed:10873857, ECO:0000269|PubMed:11880631, ECO:0000269|PubMed:18390544, ECO:0000269|PubMed:30598554, ECO:0000269|PubMed:8031140}.
CATALYTIC ACTIVITY: Reaction=a quinol + 2 Fe(III)-[cytochrome c](out) = a quinone + 2 Fe(II)-[cytochrome c](out) + 2 H(+)(out); Xref=Rhea:RHEA:11484, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:132124; EC=7.1.1.8; Evidence={ECO:0000269|PubMed:2551731, ECO:0000269|PubMed:8031140};
null
null
null
null
FUNCTION: Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c (Probable). Cytochrome b is a catalytic core subunit containing 2 b-type hemes BL and BH topographically segregated in the quinone reduction (Qi) and quinol oxidation (Q0) sites on opposite sides of the membrane (PubMed:18390544). {ECO:0000269|PubMed:18390544, ECO:0000305|PubMed:11880631, ECO:0000305|PubMed:2551731, ECO:0000305|PubMed:8031140}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00167
CYB5_HUMAN
MAEQSDEAVKYYTLEEIQKHNHSKSTWLILHHKVYDLTKFLEEHPGGEEVLREQAGGDATENFEDVGHSTDAREMSKTFIIGELHPDDRPKLNKPPETLITTIDSSSSWWTNWVIPAISAVAVALMYRLYMAED
null
null
null
cytosol [GO:0005829]; endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]; membrane [GO:0016020]; mitochondrial outer membrane [GO:0005741]
cytochrome-c oxidase activity [GO:0004129]; enzyme binding [GO:0019899]; heme binding [GO:0020037]; metal ion binding [GO:0046872]
PF00173;
3.10.120.10;
Cytochrome b5 family
null
SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane; Single-pass membrane protein; Cytoplasmic side. Microsome membrane; Single-pass membrane protein; Cytoplasmic side.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm.
null
null
null
null
null
FUNCTION: Cytochrome b5 is a membrane-bound hemoprotein functioning as an electron carrier for several membrane-bound oxygenases.
Homo sapiens (Human)
P00169
CYB5_RABIT
MAAQSDKDVKYYTLEEIKKHNHSKSTWLILHHKVYDLTKFLEEHPGGEEVLREQAGGDATENFEDVGHSTDARELSKTFIIGELHPDDRSKLSKPMETLITTVDSNSSWWTNWVIPAISALIVALMYRLYMADD
null
null
null
cytosol [GO:0005829]; endoplasmic reticulum membrane [GO:0005789]
enzyme binding [GO:0019899]; heme binding [GO:0020037]; metal ion binding [GO:0046872]
PF00173;
3.10.120.10;
Cytochrome b5 family
null
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass membrane protein; Cytoplasmic side. Microsome membrane; Single-pass membrane protein; Cytoplasmic side.
null
null
null
null
null
FUNCTION: Cytochrome b5 is a membrane-bound hemoprotein functioning as an electron carrier for several membrane-bound oxygenases.
Oryctolagus cuniculus (Rabbit)
P00173
CYB5_RAT
MAEQSDKDVKYYTLEEIQKHKDSKSTWVILHHKVYDLTKFLEEHPGGEEVLREQAGGDATENFEDVGHSTDARELSKTYIIGELHPDDRSKIAKPSETLITTVESNSSWWTNWVIPAISALVVALMYRLYMAED
null
null
response to cadmium ion [GO:0046686]
endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]; membrane [GO:0016020]; mitochondrial outer membrane [GO:0005741]
electron transfer activity [GO:0009055]; enzyme binding [GO:0019899]; heme binding [GO:0020037]; metal ion binding [GO:0046872]
PF00173;
3.10.120.10;
Cytochrome b5 family
null
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass membrane protein; Cytoplasmic side. Microsome membrane; Single-pass membrane protein; Cytoplasmic side.
null
null
null
null
null
FUNCTION: Cytochrome b5 is a membrane-bound hemoprotein functioning as an electron carrier for several membrane-bound oxygenases. It is also involved in several steps of the sterol biosynthesis pathway, particularly in the C-6 double bond introduction during the C-6 desaturation.
Rattus norvegicus (Rat)
P00175
CYB2_YEAST
MLKYKPLLKISKNCEAAILRASKTRLNTIRAYGSTVPKSKSFEQDSRKRTQSWTALRVGAILAATSSVAYLNWHNGQIDNEPKLDMNKQKISPAEVAKHNKPDDCWVVINGYVYDLTRFLPNHPGGQDVIKFNAGKDVTAIFEPLHAPNVIDKYIAPEKKLGPLQGSMPPELVCPPYAPGETKEDIARKEQLKSLLPPLDNIINLYDFEYLASQTLTKQAWAYYSSGANDEVTHRENHNAYHRIFFKPKILVDVRKVDISTDMLGSHVDVPFYVSATALCKLGNPLEGEKDVARGCGQGVTKVPQMISTLASCSPEEIIEAAPSDKQIQWYQLYVNSDRKITDDLVKNVEKLGVKALFVTVDAPSLGQREKDMKLKFSNTKAGPKAMKKTNVEESQGASRALSKFIDPSLTWKDIEELKKKTKLPIVIKGVQRTEDVIKAAEIGVSGVVLSNHGGRQLDFSRAPIEVLAETMPILEQRNLKDKLEVFVDGGVRRGTDVLKALCLGAKGVGLGRPFLYANSCYGRNGVEKAIEILRDEIEMSMRLLGVTSIAELKPDLLDLSTLKARTVGVPNDVLYNEVYEGPTLTEFEDA
1.1.2.3
COFACTOR: Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:11914072, ECO:0000269|PubMed:2329585}; COFACTOR: Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000269|PubMed:11914072, ECO:0000269|PubMed:17563122, ECO:0000269|PubMed:2329585}; Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group non-covalently per subunit. {ECO:0000269|PubMed:11914072};
lactate metabolic process [GO:0006089]
cytosol [GO:0005829]; mitochondrial inner membrane [GO:0005743]; mitochondrial intermembrane space [GO:0005758]; mitochondrion [GO:0005739]; nucleus [GO:0005634]; respirasome [GO:0070469]
heme binding [GO:0020037]; L-lactate dehydrogenase (cytochrome) activity [GO:0004460]; metal ion binding [GO:0046872]
PF00173;PF01070;
3.20.20.70;3.10.120.10;
Cytochrome b5 family; FMN-dependent alpha-hydroxy acid dehydrogenase family
null
SUBCELLULAR LOCATION: Mitochondrion intermembrane space {ECO:0000269|PubMed:11502169, ECO:0000269|PubMed:22984289}.
CATALYTIC ACTIVITY: Reaction=(S)-lactate + 2 Fe(III)-[cytochrome c] = 2 Fe(II)-[cytochrome c] + 2 H(+) + pyruvate; Xref=Rhea:RHEA:19909, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.1.2.3; Evidence={ECO:0000269|PubMed:11914072, ECO:0000305|PubMed:3004948, ECO:0000305|PubMed:4593578}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19910; Evidence={ECO:0000269|PubMed:3004948};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.49 mM for (S)-lactate {ECO:0000269|PubMed:11914072}; KM=10 uM for cytochrome c {ECO:0000269|PubMed:11914072}; Note=kcat is 207 sec(-1) with cytochrome c as electron acceptor. kcat is 400 sec(-1) with ferricyanide as electron acceptor. {ECO:0000269|PubMed:11914072};
null
null
null
FUNCTION: Catalyzes the oxidation of (S)-lactate (L-lactate) to pyruvate with subsequent transfer of electrons to cytochrome c (PubMed:11914072). Is involved in the utilization of (S)-lactate as a sole source of carbon for growth (PubMed:3004948). Can also use ferricyanide as an electron acceptor in vitro (PubMed:3004948, PubMed:4593578). {ECO:0000269|PubMed:11914072, ECO:0000269|PubMed:3004948, ECO:0000269|PubMed:4593578}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00176
CP2B1_RAT
MEPTILLLLALLVGFLLLLVRGHPKSRGNFPPGPRPLPLLGNLLQLDRGGLLNSFMQLREKYGDVFTVHLGPRPVVMLCGTDTIKEALVGQAEDFSGRGTIAVIEPIFKEYGVIFANGERWKALRRFSLATMRDFGMGKRSVEERIQEEAQCLVEELRKSQGAPLDPTFLFQCITANIICSIVFGERFDYTDRQFLRLLELFYRTFSLLSSFSSQVFEFFSGFLKYFPGAHRQISKNLQEILDYIGHIVEKHRATLDPSAPRDFIDTYLLRMEKEKSNHHTEFHHENLMISLLSLFFAGTETSSTTLRYGFLLMLKYPHVAEKVQKEIDQVIGSHRLPTLDDRSKMPYTDAVIHEIQRFSDLVPIGVPHRVTKDTMFRGYLLPKNTEVYPILSSALHDPQYFDHPDSFNPEHFLDANGALKKSEAFMPFSTGKRICLGEGIARNELFLFFTTILQNFSVSSHLAPKDIDLTPKESGIGKIPPTYQICFSAR
1.14.14.1
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
epoxygenase P450 pathway [GO:0019373]; response to calcium ion [GO:0051592]; response to insulin [GO:0032868]; response to metal ion [GO:0010038]; response to organic cyclic compound [GO:0014070]; response to sulfur dioxide [GO:0010477]; 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]; mitochondrial inner membrane [GO:0005743]
arachidonic acid epoxygenase activity [GO:0008392]; aromatase activity [GO:0070330]; heme binding [GO:0020037]; Hsp70 protein binding [GO:0030544]; Hsp90 protein binding [GO:0051879]; 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]; steroid hydroxylase activity [GO:0008395]
PF00067;
1.10.630.10;
Cytochrome P450 family
PTM: Phosphorylation is accompanied by a decrease in enzyme activity. {ECO:0000269|PubMed:2583091}.
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein. Mitochondrion inner membrane {ECO:0000305|PubMed:19401463}; Peripheral membrane protein {ECO:0000305|PubMed:19401463}. Note=Post-translationally targeted to mitochondria. Requires the cytosolic chaperones HSP70 and HSP90, for initial targeting to mitochondria, and then requires all three of the receptor proteins in the TOM complex, TOMM70, TOMM20 and TOMM22 for 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;
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)
P00178
CP2B4_RABIT
MEFSLLLLLAFLAGLLLLLFRGHPKAHGRLPPGPSPLPVLGNLLQMDRKGLLRSFLRLREKYGDVFTVYLGSRPVVVLCGTDAIREALVDQAEAFSGRGKIAVVDPIFQGYGVIFANGERWRALRRFSLATMRDFGMGKRSVEERIQEEARCLVEELRKSKGALLDNTLLFHSITSNIICSIVFGKRFDYKDPVFLRLLDLFFQSFSLISSFSSQVFELFPGFLKHFPGTHRQIYRNLQEINTFIGQSVEKHRATLDPSNPRDFIDVYLLRMEKDKSDPSSEFHHQNLILTVLSLFFAGTETTSTTLRYGFLLMLKYPHVTERVQKEIEQVIGSHRPPALDDRAKMPYTDAVIHEIQRLGDLIPFGVPHTVTKDTQFRGYVIPKNTEVFPVLSSALHDPRYFETPNTFNPGHFLDANGALKRNEGFMPFSLGKRICLGEGIARTELFLFFTTILQNFSIASPVPPEDIDLTPRESGVGNVPPSYQIRFLAR
1.14.14.1
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413;
epoxygenase P450 pathway [GO:0019373]; xenobiotic metabolic process [GO:0006805]
endoplasmic reticulum membrane [GO:0005789]
arachidonic acid epoxygenase activity [GO:0008392]; aromatase activity [GO:0070330]; heme binding [GO:0020037]; iron ion binding [GO:0005506]
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. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
Oryctolagus cuniculus (Rabbit)
P00184
CP1A1_MOUSE
MPSMYGLPAFVSATELLLAVTVFCLGFWVVRATRTWVPKGLKTPPGPWGLPFIGHMLTVGKNPHLSLTRLSQQYGDVLQIRIGSTPVVVLSGLNTIKQALVRQGDDFKGRPDLYSFTLITNGKSMTFNPDSGPVWAARRRLAQNALKSFSIASDPTSASSCYLEEHVSKEANYLVSKLQKVMAEVGHFDPYKYLVVSVANVICAICFGQRYDHDDQELLSIVNLSNEFGEVTGSGYPADFIPVLRYLPNSSLDAFKDLNDKFYSFMKKLIKEHYRTFEKGHIRDITDSLIEHCQDRKLDENANVQLSDDKVITIVLDLFGAGFDTVTTAISWSLMYLVTNPRVQRKIQEELDTVIGRDRQPRLSDRPQLPYLEAFILETFRHSSFVPFTIPHSTTRDTSLNGFYIPKGCCVFVNQWQVNHDRELWGDPNEFRPERFLTPSGTLDKRLSEKVTLFGLGKRKCIGETIGRSEVFLFLAILLQQIEFKVSPGEKVDMTPTYGLTLKHARCEHFQVQMRSSGPQHLQA
1.14.14.1; 4.2.1.152
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
9-cis-retinoic acid biosynthetic process [GO:0042904]; amine metabolic process [GO:0009308]; camera-type eye development [GO:0043010]; cellular response to copper ion [GO:0071280]; cellular response to organic cyclic compound [GO:0071407]; coumarin metabolic process [GO:0009804]; dibenzo-p-dioxin catabolic process [GO:0019341]; digestive tract development [GO:0048565]; estrogen metabolic process [GO:0008210]; flavonoid metabolic process [GO:0009812]; hepatocyte differentiation [GO:0070365]; heterocycle metabolic process [GO:0046483]; hormone biosynthetic process [GO:0042446]; hydrogen peroxide biosynthetic process [GO:0050665]; insecticide metabolic process [GO:0017143]; lipid hydroxylation [GO:0002933]; long-chain fatty acid metabolic process [GO:0001676]; maternal process involved in parturition [GO:0060137]; nitric oxide metabolic process [GO:0046209]; porphyrin-containing compound metabolic process [GO:0006778]; positive regulation of G1/S transition of mitotic cell cycle [GO:1900087]; progesterone metabolic process [GO:0042448]; response to 3-methylcholanthrene [GO:1904681]; response to arsenic-containing substance [GO:0046685]; response to food [GO:0032094]; response to herbicide [GO:0009635]; response to hyperoxia [GO:0055093]; response to hypoxia [GO:0001666]; response to immobilization stress [GO:0035902]; response to iron(III) ion [GO:0010041]; response to lipopolysaccharide [GO:0032496]; response to nematode [GO:0009624]; response to toxic substance [GO:0009636]; response to vitamin A [GO:0033189]; retinol metabolic process [GO:0042572]; steroid biosynthetic process [GO:0006694]; tissue remodeling [GO:0048771]; toxin metabolic process [GO:0009404]
endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]; mitochondrial inner membrane [GO:0005743]
17-alpha-hydroxyprogesterone aldolase activity [GO:0047442]; arachidonic acid monooxygenase activity [GO:0008391]; aromatase activity [GO:0070330]; catalytic activity [GO:0003824]; demethylase activity [GO:0032451]; enzyme binding [GO:0019899]; estrogen 16-alpha-hydroxylase activity [GO:0101020]; estrogen 2-hydroxylase activity [GO:0101021]; flavonoid 3'-monooxygenase activity [GO:0016711]; 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]; monooxygenase activity [GO:0004497]; oxidoreductase activity [GO:0016491]; oxidoreductase activity, acting on diphenols and related substances as donors [GO:0016679]; 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]; steroid hydroxylase activity [GO:0008395]; 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};
null
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}.
null
null
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}.
Mus musculus (Mouse)
P00185
CP1A1_RAT
MPSVYGFPAFTSATELLLAVTTFCLGFWVVRVTRTWVPKGLKSPPGPWGLPFIGHVLTLGKNPHLSLTKLSQQYGDVLQIRIGSTPVVVLSGLNTIKQALVKQGDDFKGRPDLYSFTLIANGQSMTFNPDSGPLWAARRRLAQNALKSFSIASDPTLASSCYLEEHVSKEAEYLISKFQKLMAEVGHFDPFKYLVVSVANVICAICFGRRYDHDDQELLSIVNLSNEFGEVTGSGYPADFIPILRYLPNSSLDAFKDLNKKFYSFMKKLIKEHYRTFEKGHIRDITDSLIEHCQDRRLDENANVQLSDDKVITIVFDLFGAGFDTITTAISWSLMYLVTNPRIQRKIQEELDTVIGRDRQPRLSDRPQLPYLEAFILETFRHSSFVPFTIPHSTIRDTSLNGFYIPKGHCVFVNQWQVNHDQELWGDPNEFRPERFLTSSGTLDKHLSEKVILFGLGKRKCIGETIGRLEVFLFLAILLQQMEFNVSPGEKVDMTPAYGLTLKHARCEHFQVQMRSSGPQHLQA
1.14.14.1; 4.2.1.152
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
9-cis-retinoic acid biosynthetic process [GO:0042904]; amine metabolic process [GO:0009308]; camera-type eye development [GO:0043010]; cellular response to copper ion [GO:0071280]; cellular response to organic cyclic compound [GO:0071407]; coumarin metabolic process [GO:0009804]; dibenzo-p-dioxin catabolic process [GO:0019341]; dibenzo-p-dioxin metabolic process [GO:0018894]; digestive tract development [GO:0048565]; estrogen metabolic process [GO:0008210]; fatty acid metabolic process [GO:0006631]; flavonoid metabolic process [GO:0009812]; hepatocyte differentiation [GO:0070365]; heterocycle metabolic process [GO:0046483]; hormone biosynthetic process [GO:0042446]; hydrogen peroxide biosynthetic process [GO:0050665]; insecticide metabolic process [GO:0017143]; lipid hydroxylation [GO:0002933]; liver development [GO:0001889]; long-chain fatty acid metabolic process [GO:0001676]; maternal process involved in parturition [GO:0060137]; nitric oxide metabolic process [GO:0046209]; porphyrin-containing compound metabolic process [GO:0006778]; positive regulation of G1/S transition of mitotic cell cycle [GO:1900087]; progesterone metabolic process [GO:0042448]; response to 3-methylcholanthrene [GO:1904681]; response to arsenic-containing substance [GO:0046685]; response to food [GO:0032094]; response to herbicide [GO:0009635]; response to hyperoxia [GO:0055093]; response to hypoxia [GO:0001666]; response to immobilization stress [GO:0035902]; response to iron(III) ion [GO:0010041]; response to lipopolysaccharide [GO:0032496]; response to nematode [GO:0009624]; response to organic cyclic compound [GO:0014070]; response to organic substance [GO:0010033]; response to toxic substance [GO:0009636]; response to vitamin A [GO:0033189]; response to xenobiotic stimulus [GO:0009410]; retinol metabolic process [GO:0042572]; steroid biosynthetic process [GO:0006694]; steroid metabolic process [GO:0008202]; tissue remodeling [GO:0048771]; toxin metabolic process [GO:0009404]; xenobiotic metabolic process [GO:0006805]
endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]; mitochondrial inner membrane [GO:0005743]
17-alpha-hydroxyprogesterone aldolase activity [GO:0047442]; arachidonic acid monooxygenase activity [GO:0008391]; aromatase activity [GO:0070330]; catalytic activity [GO:0003824]; demethylase activity [GO:0032451]; enzyme binding [GO:0019899]; estrogen 16-alpha-hydroxylase activity [GO:0101020]; estrogen 2-hydroxylase activity [GO:0101021]; flavonoid 3'-monooxygenase activity [GO:0016711]; 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]; monooxygenase activity [GO:0004497]; oxidoreductase activity [GO:0016491]; oxidoreductase activity, acting on diphenols and related substances as donors [GO:0016679]; 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]; steroid hydroxylase activity [GO:0008395]; vitamin D 24-hydroxylase activity [GO:0070576]
PF00067;
1.10.630.10;
Cytochrome P450 family
PTM: Two forms; MT2A (long form) and MT2B (short form); are produced by NH2-terminal proteolytic cleavage. This cleavage activates a cryptic mitochondrial targeting signal.
SUBCELLULAR LOCATION: [Cytochrome P450 1A1]: Cytoplasm {ECO:0000269|PubMed:9348277}.; SUBCELLULAR LOCATION: [Cytochrome P450MT2A]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:9348277}; Peripheral membrane protein {ECO:0000305|PubMed:19401463, ECO:0000305|PubMed:9348277}. Mitochondrion inner membrane {ECO:0000269|PubMed:9348277}; Peripheral membrane protein {ECO:0000305|PubMed:19401463, ECO:0000305|PubMed:9348277}. Microsome membrane {ECO:0000269|PubMed:9348277}; Peripheral membrane protein {ECO:0000305|PubMed:19401463, ECO:0000305|PubMed:9348277}.; SUBCELLULAR LOCATION: [Cytochrome P450MT2B]: Endoplasmic reticulum membrane; Peripheral membrane protein. Mitochondrion inner membrane {ECO:0000305|PubMed:19401463}; Peripheral membrane protein {ECO:0000305|PubMed:19401463, ECO:0000305|PubMed:9348277}. Microsome membrane {ECO:0000269|PubMed:9348277}; Peripheral membrane protein {ECO:0000305|PubMed:19401463, ECO:0000305|PubMed:9348277}.
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:0000269|PubMed:20972997}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49885; Evidence={ECO:0000305|PubMed:20972997}; 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:0000269|PubMed:20972997}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881; Evidence={ECO:0000305|PubMed:20972997}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49876, 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:131969; Evidence={ECO:0000269|PubMed:20972997}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49877; Evidence={ECO:0000305|PubMed:20972997}; 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:20972997}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861; Evidence={ECO:0000305|PubMed:20972997}; 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};
null
PATHWAY: Steroid hormone biosynthesis. {ECO:0000250|UniProtKB:P04798}.; PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000269|PubMed:20972997}.; PATHWAY: Cofactor metabolism; retinol metabolism. {ECO:0000250|UniProtKB:P04798}.
null
null
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 (By similarity). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (By similarity). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:20972997). 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 (By similarity). 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 (By similarity). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (By similarity). {ECO:0000250|UniProtKB:P04798, ECO:0000269|PubMed:20972997}.
Rattus norvegicus (Rat)
P00186
CP1A2_MOUSE
MAFSQYISLAPELLLATAIFCLVFWMVRASRTQVPKGLKNPPGPWGLPFIGHMLTVGKNPHLSLTRLSQQYGDVLQIRIGSTPVVVLSGLNTIKQALVRQGDDFKGRPDLYSFTLITNGKSMTFNPDSGPVWAARRRLAQDALKSFSIASDPTSASSCYLEEHVSKEANHLVSKLQKAMAEVGHFEPVSQVVESVANVIGAMCFGKNFPRKSEEMLNIVNNSKDFVENVTSGNAVDFFPVLRYLPNPALKRFKTFNDNFVLFLQKTVQEHYQDFNKNSIQDITSALFKHSENYKDNGGLIPEEKIVNIVNDIFGAGFDTVTTAITWSILLLVTWPNVQRKIHEELDTVVGRDRQPRLSDRPQLPYLEAFILEIYRYTSFVPFTIPHSTTRDTSLNGFHIPKERCIYINQWQVNHDEKQWKDPFVFRPERFLTNNNSAIDKTQSEKVMLFGLGKRRCIGEIPAKWEVFLFLAILLQHLEFSVPPGVKVDLTPNYGLTMKPGTCEHVQAWPRFSK
1.14.14.1; 4.2.1.152
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
alkaloid metabolic process [GO:0009820]; arachidonic acid metabolic process [GO:0019369]; cellular aromatic compound metabolic process [GO:0006725]; cellular respiration [GO:0045333]; cellular response to cadmium ion [GO:0071276]; cholesterol metabolic process [GO:0008203]; dibenzo-p-dioxin metabolic process [GO:0018894]; estrogen metabolic process [GO:0008210]; hormone biosynthetic process [GO:0042446]; hydrogen peroxide biosynthetic process [GO:0050665]; lung development [GO:0030324]; monoterpenoid metabolic process [GO:0016098]; 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]; toxin metabolic process [GO:0009404]; xenobiotic catabolic process [GO:0042178]; xenobiotic metabolic process [GO:0006805]
endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]
17-alpha-hydroxyprogesterone aldolase activity [GO:0047442]; 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]; hydroperoxy icosatetraenoate dehydratase activity [GO:0106256]; iron ion binding [GO:0005506]; monooxygenase activity [GO:0004497]; nitrite reductase (NO-forming) activity [GO:0050421]; 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]
PF00067;
1.10.630.10;
Cytochrome P450 family
null
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P05177}; Peripheral membrane protein {ECO:0000250|UniProtKB:P05177}. Microsome membrane {ECO:0000250|UniProtKB:P05177}; Peripheral membrane protein {ECO:0000250|UniProtKB:P05177}.
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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47281; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47293; Evidence={ECO:0000250|UniProtKB:P05177}; 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:0000250|UniProtKB:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50257; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42089; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48633; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37948; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48717; Evidence={ECO:0000250|UniProtKB:P05177}; 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:0000250|UniProtKB:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52293; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39760; Evidence={ECO:0000250|UniProtKB:P05177}; 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:0000250|UniProtKB:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52285; Evidence={ECO:0000250|UniProtKB:P05177};
null
PATHWAY: Cofactor metabolism; retinol metabolism. {ECO:0000250|UniProtKB:P05177}.; PATHWAY: Steroid metabolism; cholesterol metabolism. {ECO:0000250|UniProtKB:P05177}.; PATHWAY: Lipid metabolism; arachidonate metabolism. {ECO:0000250|UniProtKB:P05177}.
null
null
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 (NADPH--hemoprotein 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. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. 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. Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer. Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA. May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin. Metabolizes caffeine via N3-demethylation. {ECO:0000250|UniProtKB:P05177}.
Mus musculus (Mouse)
P00187
CP1A2_RABIT
MAMSPAAPLSVTELLLVSAVFCLVFWAVRASRPKVPKGLKRLPGPWGWPLLGHLLTLGKNPHVALARLSRRYGDVFQIRLGSTPVVVLSGLDTIKQALVRQGDDFKGRPDLYSSSFITEGQSMTFSPDSGPVWAARRRLAQDSLKSFSIASNPASSSSCYLEEHVSQEAENLIGRFQELMAAVGRFDPYSQLVVSAARVIGAMCFGRRFPQGSEEMLDVVRNSSKFVETASSGSPVDFFPILRYLPNRPLQRFKDFNQRFLRFLQKTVREHYEDFDRNSIQDITGALFKHSEKNSKANSGLIPQEKIVNLVNDIFGAGFDTITTALSWSLMYLVTNPRRQRKIQEELDAVVGRARQPRLSDRPQLPYLEAFILELFRHTSFVPFTIPHSTTRDTTLNGFHIPKECCIFINQWQINHDPQLWGDPEEFRPERFLTADGAAINKPLSEKVTLFGLGKRRCIGETLARWEVFLFLAILLQRLEFSVPPGVPVDLTPIYGLTMKHPRCEHVQARPRFSDQ
1.14.14.1; 4.2.1.152
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
arachidonic acid metabolic process [GO:0019369]; cholesterol metabolic process [GO:0008203]; estrogen metabolic process [GO:0008210]; hormone biosynthetic process [GO:0042446]; progesterone metabolic process [GO:0042448]; retinol metabolic process [GO:0042572]
endoplasmic reticulum membrane [GO:0005789]
17-alpha-hydroxyprogesterone aldolase activity [GO:0047442]; aromatase activity [GO:0070330]; 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]; steroid 17-alpha-monooxygenase activity [GO:0004508]
PF00067;
1.10.630.10;
Cytochrome P450 family
null
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P05177}; Peripheral membrane protein {ECO:0000250|UniProtKB:P05177}. Microsome membrane {ECO:0000250|UniProtKB:P05177}; Peripheral membrane protein {ECO:0000250|UniProtKB:P05177}.
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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47281; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47293; Evidence={ECO:0000250|UniProtKB:P05177}; 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:0000250|UniProtKB:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50257; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42089; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48633; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37948; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48717; Evidence={ECO:0000250|UniProtKB:P05177}; 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:0000250|UniProtKB:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52293; Evidence={ECO:0000250|UniProtKB:P05177}; 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:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39760; Evidence={ECO:0000250|UniProtKB:P05177}; 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:0000250|UniProtKB:P05177}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52285; Evidence={ECO:0000250|UniProtKB:P05177};
null
PATHWAY: Cofactor metabolism; retinol metabolism. {ECO:0000250|UniProtKB:P05177}.; PATHWAY: Steroid metabolism; cholesterol metabolism. {ECO:0000250|UniProtKB:P05177}.; PATHWAY: Lipid metabolism; arachidonate metabolism. {ECO:0000250|UniProtKB:P05177}.
null
null
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 (NADPH--hemoprotein 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. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. 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. Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer. Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA. May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin. Metabolizes caffeine via N3-demethylation. {ECO:0000250|UniProtKB:P05177}.
Oryctolagus cuniculus (Rabbit)
P00189
CP11A_BOVIN
MLARGLPLRSALVKACPPILSTVGEGWGHHRVGTGEGAGISTKTPRPYSEIPSPGDNGWLNLYHFWREKGSQRIHFRHIENFQKYGPIYREKLGNLESVYIIHPEDVAHLFKFEGSYPERYDIPPWLAYHRYYQKPIGVLFKKSGTWKKDRVVLNTEVMAPEAIKNFIPLLNPVSQDFVSLLHKRIKQQGSGKFVGDIKEDLFHFAFESITNVMFGERLGMLEETVNPEAQKFIDAVYKMFHTSVPLLNVPPELYRLFRTKTWRDHVAAWDTIFNKAEKYTEIFYQDLRRKTEFRNYPGILYCLLKSEKMLLEDVKANITEMLAGGVNTTSMTLQWHLYEMARSLNVQEMLREEVLNARRQAEGDISKMLQMVPLLKASIKETLRLHPISVTLQRYPESDLVLQDYLIPAKTLVQVAIYAMGRDPAFFSSPDKFDPTRWLSKDKDLIHFRNLGFGWGVRQCVGRRIAELEMTLFLIHILENFKVEMQHIGDVDTIFNLILTPDKPIFLVFRPFNQDPPQA
1.14.15.6
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269|PubMed:21159775};
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]; vitamin D metabolic process [GO:0042359]
mitochondrial inner membrane [GO:0005743]; 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:11412116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35740; Evidence={ECO:0000305|PubMed:11412116}; 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:11412116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34336; Evidence={ECO:0000305|PubMed:11412116}; 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:11412116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34340; Evidence={ECO:0000305|PubMed:11412116}; 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:11412116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34344; Evidence={ECO:0000305|PubMed:11412116};
null
PATHWAY: Lipid metabolism; C21-steroid hormone metabolism. {ECO:0000269|PubMed:11412116}.; PATHWAY: Steroid metabolism; cholesterol metabolism. {ECO:0000269|PubMed:11412116}.
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:11412116). 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:11412116). 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:11412116). {ECO:0000269|PubMed:11412116}.
Bos taurus (Bovine)
P00191
CP21A_BOVIN
MVLAGLLLLLTLLAGAHLLWGRWKLRNLHLPPLVPGFLHLLQPNLPIHLLSLTQKLGPVYRLRLGLQEVVVLNSKRTIEEAMIRKWVDFAGRPQIPSYKLVSQRCQDISLGDYSLLWKAHKKLTRSALLLGTRSSMEPWVDQLTQEFCERMRVQAGAPVTIQKEFSLLTCSIICYLTFGNKEDTLVHAFHDCVQDLMKTWDHWSIQILDMVPFLRFFPNPGLWRLKQAIENRDHMVEKQLTRHKESMVAGQWRDMTDYMLQGVGRQRVEEGPGQLLEGHVHMSVVDLFIGGTETTASTLSWAVAFLLHHPEIQRRLQEELDRELGPGASCSRVTYKDRARLPLLNATIAEVLRLRPVVPLALPHRTTRPSSIFGYDIPEGMVVIPNLQGAHLDETVWEQPHEFRPDRFLEPGANPSALAFGCGARVCLGESLARLELFVVLLRLLQAFTLLPPPVGALPSLQPDPYCGVNLKVQPFQVRLQPRGVEAGAWESASAQ
1.14.14.16
COFACTOR: Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000269|PubMed:22262854};
glucocorticoid biosynthetic process [GO:0006704]; hormone biosynthetic process [GO:0042446]; progesterone metabolic process [GO:0042448]; steroid biosynthetic process [GO:0006694]; steroid metabolic process [GO:0008202]
endoplasmic reticulum membrane [GO:0005789]
17-alpha-hydroxyprogesterone aldolase activity [GO:0047442]; 17-hydroxyprogesterone 21-hydroxylase activity [GO:0103069]; heme binding [GO:0020037]; iron ion binding [GO:0005506]; progesterone 21-hydroxylase activity [GO:0106309]; steroid 17-alpha-monooxygenase activity [GO:0004508]; steroid 21-monooxygenase activity [GO:0004509]; steroid binding [GO:0005496]; steroid hydroxylase activity [GO:0008395]
PF00067;
1.10.630.10;
Cytochrome P450 family
null
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P08686}; Peripheral membrane protein {ECO:0000250|UniProtKB:P08686}. Microsome membrane {ECO:0000250|UniProtKB:P08686}; Peripheral membrane protein {ECO:0000250|UniProtKB:P08686}.
CATALYTIC ACTIVITY: Reaction=O2 + progesterone + reduced [NADPH--hemoprotein reductase] = 21-hydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50304, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16973, ChEBI:CHEBI:17026, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.16; Evidence={ECO:0000269|PubMed:22262854, ECO:0000269|PubMed:25855791}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50305; Evidence={ECO:0000305|PubMed:22262854, ECO:0000305|PubMed:25855791}; CATALYTIC ACTIVITY: Reaction=17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein reductase] = 11-deoxycortisol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50308, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17252, ChEBI:CHEBI:28324, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.16; Evidence={ECO:0000269|PubMed:22262854, ECO:0000269|PubMed:25855791}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50309; Evidence={ECO:0000305|PubMed:22262854, ECO:0000305|PubMed:25855791};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.5 uM for progesterone {ECO:0000269|PubMed:25855791}; KM=0.44 uM for 17alpha-hydroxyprogesterone {ECO:0000269|PubMed:25855791};
null
null
null
FUNCTION: A cytochrome P450 monooxygenase that plays a major role in adrenal steroidogenesis. Catalyzes the hydroxylation at C-21 of progesterone and 17alpha-hydroxyprogesterone to respectively form 11-deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in the biosynthetic pathway of mineralocorticoids and glucocorticoids (PubMed:22262854, PubMed:25855791). 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:22262854, PubMed:25855791). {ECO:0000269|PubMed:22262854, ECO:0000269|PubMed:25855791}.
Bos taurus (Bovine)
P00257
ADX_BOVIN
MAARLLRVASAALGDTAGRWRLLARPRAGAGGLRGSRGPGLGGGAVATRTLSVSGRAQSSSEDKITVHFINRDGETLTTKGKIGDSLLDVVVQNNLDIDGFGACEGTLACSTCHLIFEQHIFEKLEAITDEENDMLDLAYGLTDRSRLGCQICLTKAMDNMTVRVPDAVSDARESIDMGMNSSKIE
null
COFACTOR: Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135; Note=Binds 1 [2Fe-2S] cluster.;
cholesterol metabolic process [GO:0008203]; electron transport chain [GO:0022900]; hormone biosynthetic process [GO:0042446]; P450-containing electron transport chain [GO:0140647]; respiratory electron transport chain [GO:0022904]; steroid biosynthetic process [GO:0006694]
mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
2 iron, 2 sulfur cluster binding [GO:0051537]; electron transfer activity [GO:0009055]; metal ion binding [GO:0046872]; protein homodimerization activity [GO:0042803]
PF00111;
3.10.20.30;
Adrenodoxin/putidaredoxin family
null
SUBCELLULAR LOCATION: Mitochondrion matrix.
null
null
null
null
null
FUNCTION: Essential for the synthesis of various steroid hormones. Participates in the reduction of mitochondrial cytochrome P450 for steroidogenesis. Transfers electrons from adrenodoxin reductase to CYP11A1, a cytochrome P450 that catalyzes cholesterol side-chain cleavage to produce pregnenolone, the precursor of most steroid hormones. Does not form a ternary complex with adrenodoxin reductase and CYP11A1 but shuttles between the two enzymes to transfer electrons. {ECO:0000269|PubMed:6766943}.
Bos taurus (Bovine)
P00282
AZUR_PSEAE
MLRKLAAVSLLSLLSAPLLAAECSVDIQGNDQMQFNTNAITVDKSCKQFTVNLSHPGNLPKNVMGHNWVLSTAADMQGVVTDGMASGLDKDYLKPDDSRVIAHTKLIGSGEKDSVTFDVSKLKEGEQYMFFCTFPGHSALMKGTLTLK
null
null
null
periplasmic space [GO:0042597]
copper ion binding [GO:0005507]; electron transfer activity [GO:0009055]; identical protein binding [GO:0042802]; transition metal ion binding [GO:0046914]; zinc ion binding [GO:0008270]
PF00127;
2.60.40.420;
null
null
SUBCELLULAR LOCATION: Periplasm.
null
null
null
null
null
FUNCTION: Transfers electrons from cytochrome c551 to cytochrome oxidase.
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
P00325
ADH1B_HUMAN
MSTAGKVIKCKAAVLWEVKKPFSIEDVEVAPPKAYEVRIKMVAVGICHTDDHVVSGNLVTPLPVILGHEAAGIVESVGEGVTTVKPGDKVIPLFTPQCGKCRVCKNPESNYCLKNDLGNPRGTLQDGTRRFTCRGKPIHHFLGTSTFSQYTVVDENAVAKIDAASPLEKVCLIGCGFSTGYGSAVNVAKVTPGSTCAVFGLGGVGLSAVMGCKAAGAARIIAVDINKDKFAKAKELGATECINPQDYKKPIQEVLKEMTDGGVDFSFEVIGRLDTMMASLLCCHEACGTSVIVGVPPASQNLSINPMLLLTGRTWKGAVYGGFKSKEGIPKLVADFMAKKFSLDALITHVLPFEKINEGFDLLHSGKSIRTVLTF
1.1.1.105
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 2 Zn(2+) ions per subunit.;
ethanol oxidation [GO:0006069]; retinoic acid metabolic process [GO:0042573]; retinoid metabolic process [GO:0001523]; retinol metabolic process [GO:0042572]
cytosol [GO:0005829]; nucleoplasm [GO:0005654]; plasma membrane [GO:0005886]
alcohol dehydrogenase activity, zinc-dependent [GO:0004024]; NAD-retinol dehydrogenase activity [GO:0004745]; zinc ion binding [GO:0008270]
PF08240;PF00107;
3.90.180.10;3.40.50.720;
Zinc-containing alcohol dehydrogenase family
null
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=all-trans-retinol + NAD(+) = all-trans-retinal + H(+) + NADH; Xref=Rhea:RHEA:21284, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.105; Evidence={ECO:0000269|PubMed:16787387}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21285; Evidence={ECO:0000305|PubMed:16787387}; CATALYTIC ACTIVITY: Reaction=all-trans-4-hydroxyretinol + NAD(+) = all-trans-4-hydroxyretinal + H(+) + NADH; Xref=Rhea:RHEA:55936, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:132259, ChEBI:CHEBI:139346; Evidence={ECO:0000269|PubMed:15369820}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55937; Evidence={ECO:0000305|PubMed:15369820}; CATALYTIC ACTIVITY: Reaction=all-trans-4-oxoretinol + NAD(+) = all-trans-4-oxoretinal + H(+) + NADH; Xref=Rhea:RHEA:60632, ChEBI:CHEBI:15378, ChEBI:CHEBI:44597, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:139347; Evidence={ECO:0000269|PubMed:15369820};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=4 uM for all-trans-4-hydroxyretinol (in allele ADH1B*1) {ECO:0000269|PubMed:15369820}; KM=25 uM for all-trans-4-oxoretinal (in allele ADH1B*1) {ECO:0000269|PubMed:15369820}; KM=11 uM for all-trans-4-hydroxyretinol (in allele ADH1B*2) {ECO:0000269|PubMed:15369820}; KM=27 uM for all-trans-4-oxoretinal (in allele ADH1B*2) {ECO:0000269|PubMed:15369820}; KM=24 uM for all-trans-3,4-didehydroretinol(in allele ADH1B*2) {ECO:0000269|PubMed:15369820}; KM=25 uM for all-trans-3,4-didehydroretinal(in allele ADH1B*2) {ECO:0000269|PubMed:15369820}; KM=0.4 uM for all-trans-retinaldehyde (in allele ADH1B*2) {ECO:0000269|PubMed:16787387}; KM=0.3 uM for all-trans-retinol (in allele ADH1B*2) {ECO:0000269|PubMed:16787387};
null
null
null
FUNCTION: Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism (PubMed:15369820, PubMed:16787387). In vitro can also catalyze the NADH-dependent reduction of all-trans-retinal and its derivatives such as all-trans-4-oxoretinal (PubMed:15369820, PubMed:16787387). Catalyzes in the oxidative direction with higher efficiency (PubMed:16787387). Has the same affinity for all-trans-4-hydroxyretinol and all-trans-4-oxoretinal (PubMed:15369820). {ECO:0000269|PubMed:15369820, ECO:0000269|PubMed:16787387}.
Homo sapiens (Human)
P00326
ADH1G_HUMAN
MSTAGKVIKCKAAVLWELKKPFSIEEVEVAPPKAHEVRIKMVAAGICRSDEHVVSGNLVTPLPVILGHEAAGIVESVGEGVTTVKPGDKVIPLFTPQCGKCRICKNPESNYCLKNDLGNPRGTLQDGTRRFTCSGKPIHHFVGVSTFSQYTVVDENAVAKIDAASPLEKVCLIGCGFSTGYGSAVKVAKVTPGSTCAVFGLGGVGLSVVMGCKAAGAARIIAVDINKDKFAKAKELGATECINPQDYKKPIQEVLKEMTDGGVDFSFEVIGRLDTMMASLLCCHEACGTSVIVGVPPDSQNLSINPMLLLTGRTWKGAIFGGFKSKESVPKLVADFMAKKFSLDALITNILPFEKINEGFDLLRSGKSIRTVLTF
1.1.1.1
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:11274460, ECO:0000269|PubMed:15449945}; Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:11274460, ECO:0000269|PubMed:15449945};
ethanol oxidation [GO:0006069]; retinoic acid metabolic process [GO:0042573]; retinol metabolic process [GO:0042572]
cytosol [GO:0005829]; nucleoplasm [GO:0005654]; plasma membrane [GO:0005886]
alcohol dehydrogenase (NAD+) activity [GO:0004022]; alcohol dehydrogenase activity, zinc-dependent [GO:0004024]; NAD-retinol dehydrogenase activity [GO:0004745]; zinc ion binding [GO:0008270]
PF08240;PF00107;
3.90.180.10;3.40.50.720;
Zinc-containing alcohol dehydrogenase family
null
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=a primary alcohol + NAD(+) = an aldehyde + H(+) + NADH; Xref=Rhea:RHEA:10736, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734, ChEBI:CHEBI:17478, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000269|PubMed:6391957}; CATALYTIC ACTIVITY: Reaction=ethanol + NAD(+) = acetaldehyde + H(+) + NADH; Xref=Rhea:RHEA:25290, ChEBI:CHEBI:15343, ChEBI:CHEBI:15378, ChEBI:CHEBI:16236, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000269|PubMed:6391957}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25291; Evidence={ECO:0000305|PubMed:6391957};
null
null
null
null
FUNCTION: Alcohol dehydrogenase. Exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism. {ECO:0000269|PubMed:6391957}.
Homo sapiens (Human)
P00329
ADH1_MOUSE
MSTAGKVIKCKAAVLWELHKPFTIEDIEVAPPKAHEVRIKMVATGVCRSDDHVVSGTLVTPLPAVLGHEGAGIVESVGEGVTCVKPGDKVIPLFSPQCGECRICKHPESNFCSRSDLLMPRGTLREGTSRFSCKGKQIHNFISTSTFSQYTVVDDIAVAKIDGASPLDKVCLIGCGFSTGYGSAVKVAKVTPGSTCAVFGLGGVGLSVIIGCKAAGAARIIAVDINKDKFAKAKELGATECINPQDYSKPIQEVLQEMTDGGVDFSFEVIGRLDTMTSALLSCHAACGVSVVVGVPPNAQNLSMNPMLLLLGRTWKGAIFGGFKSKDSVPKLVADFMAKKFPLDPLITHVLPFEKINEAFDLLRSGKSIRTVLTF
1.1.1.1
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 2 Zn(2+) ions per subunit.;
acetaldehyde biosynthetic process [GO:0046186]; animal organ regeneration [GO:0031100]; behavioral response to ethanol [GO:0048149]; ethanol catabolic process [GO:0006068]; ethanol oxidation [GO:0006069]; response to progesterone [GO:0032570]; response to retinoic acid [GO:0032526]; response to steroid hormone [GO:0048545]; response to testosterone [GO:0033574]; retinoic acid metabolic process [GO:0042573]; retinoid metabolic process [GO:0001523]; retinol metabolic process [GO:0042572]
cytosol [GO:0005829]; mitochondrion [GO:0005739]
alcohol dehydrogenase (NAD+) activity [GO:0004022]; alcohol dehydrogenase activity, zinc-dependent [GO:0004024]; ethanol binding [GO:0035276]; identical protein binding [GO:0042802]; NAD binding [GO:0051287]; NAD-retinol dehydrogenase activity [GO:0004745]; organic cyclic compound binding [GO:0097159]; zinc ion binding [GO:0008270]
PF08240;PF00107;
3.90.180.10;3.40.50.720;
Zinc-containing alcohol dehydrogenase family, Class-I subfamily
null
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=a primary alcohol + NAD(+) = an aldehyde + H(+) + NADH; Xref=Rhea:RHEA:10736, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734, ChEBI:CHEBI:17478, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; CATALYTIC ACTIVITY: Reaction=a secondary alcohol + NAD(+) = a ketone + H(+) + NADH; Xref=Rhea:RHEA:10740, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087, ChEBI:CHEBI:35681, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1;
null
null
null
null
null
Mus musculus (Mouse)
P00330
ADH1_YEAST
MSIPETQKGVIFYESHGKLEYKDIPVPKPKANELLINVKYSGVCHTDLHAWHGDWPLPVKLPLVGGHEGAGVVVGMGENVKGWKIGDYAGIKWLNGSCMACEYCELGNESNCPHADLSGYTHDGSFQQYATADAVQAAHIPQGTDLAQVAPILCAGITVYKALKSANLMAGHWVAISGAAGGLGSLAVQYAKAMGYRVLGIDGGEGKEELFRSIGGEVFIDFTKEKDIVGAVLKATDGGAHGVINVSVSEAAIEASTRYVRANGTTVLVGMPAGAKCCSDVFNQVVKSISIVGSYVGNRADTREALDFFARGLVKSPIKVVGLSTLPEIYEKMEKGQIVGRYVVDTSK
1.1.1.1; 1.1.1.54; 1.1.1.78
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:25157460, ECO:0000269|PubMed:26743849}; Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:25157460, ECO:0000269|PubMed:26743849};
amino acid catabolic process to alcohol via Ehrlich pathway [GO:0000947]; glycolytic fermentation to ethanol [GO:0019655]; NADH oxidation [GO:0006116]
cytoplasm [GO:0005737]; plasma membrane [GO:0005886]
alcohol dehydrogenase (NAD+) activity [GO:0004022]; allyl-alcohol dehydrogenase activity [GO:0047655]; butanol dehydrogenase activity [GO:1990362]; identical protein binding [GO:0042802]; melatonin binding [GO:1904408]; methylglyoxal reductase (NADH-dependent) activity [GO:0019170]; octanol dehydrogenase activity [GO:0004552]; zinc ion binding [GO:0008270]
PF08240;PF00107;
3.90.180.10;3.40.50.720;
Zinc-containing alcohol dehydrogenase family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:2937632}.
CATALYTIC ACTIVITY: Reaction=a primary alcohol + NAD(+) = an aldehyde + H(+) + NADH; Xref=Rhea:RHEA:10736, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734, ChEBI:CHEBI:17478, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000305|PubMed:12702265}; CATALYTIC ACTIVITY: Reaction=a secondary alcohol + NAD(+) = a ketone + H(+) + NADH; Xref=Rhea:RHEA:10740, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087, ChEBI:CHEBI:35681, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000269|PubMed:6985717, ECO:0000305|PubMed:12702265}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10741; Evidence={ECO:0000305|PubMed:6985717}; CATALYTIC ACTIVITY: Reaction=ethanol + NAD(+) = acetaldehyde + H(+) + NADH; Xref=Rhea:RHEA:25290, ChEBI:CHEBI:15343, ChEBI:CHEBI:15378, ChEBI:CHEBI:16236, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000269|PubMed:241323, ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908, ECO:0000269|PubMed:6985717}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25291; Evidence={ECO:0000269|PubMed:241323, ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25292; Evidence={ECO:0000269|PubMed:241323, ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908, ECO:0000269|PubMed:6985717}; CATALYTIC ACTIVITY: Reaction=allyl alcohol + NADP(+) = acrolein + H(+) + NADPH; Xref=Rhea:RHEA:12168, ChEBI:CHEBI:15368, ChEBI:CHEBI:15378, ChEBI:CHEBI:16605, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.54; Evidence={ECO:0000305|PubMed:6985717}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12169; Evidence={ECO:0000305|PubMed:6985717}; CATALYTIC ACTIVITY: Reaction=1-propanol + NAD(+) = H(+) + NADH + propanal; Xref=Rhea:RHEA:50704, ChEBI:CHEBI:15378, ChEBI:CHEBI:17153, ChEBI:CHEBI:28831, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:170911, ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50705; Evidence={ECO:0000269|PubMed:170911, ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908}; CATALYTIC ACTIVITY: Reaction=butan-1-ol + NAD(+) = butanal + H(+) + NADH; Xref=Rhea:RHEA:33199, ChEBI:CHEBI:15378, ChEBI:CHEBI:15743, ChEBI:CHEBI:28885, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:170911, ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33200; Evidence={ECO:0000269|PubMed:170911, ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:33201; Evidence={ECO:0000269|PubMed:241323, ECO:0000269|PubMed:4352908}; CATALYTIC ACTIVITY: Reaction=hexan-1-ol + NAD(+) = H(+) + hexanal + NADH; Xref=Rhea:RHEA:60972, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:87393, ChEBI:CHEBI:88528; Evidence={ECO:0000269|PubMed:3546317}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60973; Evidence={ECO:0000269|PubMed:3546317}; CATALYTIC ACTIVITY: Reaction=(R)-lactaldehyde + NAD(+) = H(+) + methylglyoxal + NADH; Xref=Rhea:RHEA:24528, ChEBI:CHEBI:15378, ChEBI:CHEBI:17158, ChEBI:CHEBI:17167, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.78; Evidence={ECO:0000269|PubMed:12722185}; CATALYTIC ACTIVITY: Reaction=NAD(+) + octan-1-ol = H(+) + NADH + octanal; Xref=Rhea:RHEA:24620, ChEBI:CHEBI:15378, ChEBI:CHEBI:16188, ChEBI:CHEBI:17935, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:8463307}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24621; Evidence={ECO:0000269|PubMed:8463307}; CATALYTIC ACTIVITY: Reaction=butan-2-ol + NAD(+) = butan-2-one + H(+) + NADH; Xref=Rhea:RHEA:64560, ChEBI:CHEBI:15378, ChEBI:CHEBI:28398, ChEBI:CHEBI:35687, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:8463307}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64561; Evidence={ECO:0000269|PubMed:8463307}; CATALYTIC ACTIVITY: Reaction=NAD(+) + propan-2-ol = acetone + H(+) + NADH; Xref=Rhea:RHEA:41984, ChEBI:CHEBI:15347, ChEBI:CHEBI:15378, ChEBI:CHEBI:17824, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:170911, ECO:0000269|PubMed:4352908, ECO:0000269|PubMed:8463307}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41985; Evidence={ECO:0000269|PubMed:170911, ECO:0000269|PubMed:4352908, ECO:0000269|PubMed:8463307}; CATALYTIC ACTIVITY: Reaction=isobutanol + NAD(+) = 2-methylpropanal + H(+) + NADH; Xref=Rhea:RHEA:64692, ChEBI:CHEBI:15378, ChEBI:CHEBI:46645, ChEBI:CHEBI:48943, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:8463307}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64693; Evidence={ECO:0000269|PubMed:8463307};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=160 uM for NAD(+) {ECO:0000269|PubMed:2201405, ECO:0000269|PubMed:3546317}; KM=21 mM for ethanol {ECO:0000269|PubMed:2201405, ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908}; KM=0.74 mM for acetaldehyde {ECO:0000269|PubMed:2201405, ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908}; KM=94 uM for NADH {ECO:0000269|PubMed:2201405, ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908}; KM=27 mM for 1-propanol {ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908}; KM=55 mM for butan-1-ol {ECO:0000269|PubMed:3546317, ECO:0000269|PubMed:4352908}; KM=27.5 mM for butanal {ECO:0000269|PubMed:4352908}; KM=37 mM for pentan-1-ol {ECO:0000269|PubMed:3546317}; KM=9.5 mM for hexan-1-ol {ECO:0000269|PubMed:3546317}; KM=7.8 mM for heptan-1-ol {ECO:0000269|PubMed:8463307}; KM=5.3 mM for octan-1-ol {ECO:0000269|PubMed:8463307}; KM=1.7 mM for nonan-1-ol {ECO:0000269|PubMed:8463307}; KM=190 mM for 2-propanol {ECO:0000269|PubMed:4352908, ECO:0000269|PubMed:8463307}; KM=61 mM for (R)-2-butanol {ECO:0000269|PubMed:8463307}; KM=55 mM for (S)-2-butanol {ECO:0000269|PubMed:8463307}; KM=25 mM for isobutanol {ECO:0000269|PubMed:8463307};
null
null
null
FUNCTION: Preferentially fermentative isozyme that reduces acetaldehyde to ethanol during the fermentation of glucose. Major enzyme required for the conversion of acetaldehyde to ethanol (Probable) (PubMed:22094012). Plays a key role in the carbohydrate metabolism through the regeneration of NAD(+) from glycolytic NADH (Probable). In the reverse reaction, preferentially catalyzes the conversion of primary unbranched alcohols to their corresponding aldehydes. Also shows activity toward secondary alcohols (Probable). Most active with ethanol, and its activity decreases as the size of the alcohol is increased (PubMed:8463307). {ECO:0000269|PubMed:22094012, ECO:0000269|PubMed:8463307, ECO:0000305|PubMed:12702265}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00331
ADH2_YEAST
MSIPETQKAIIFYESNGKLEHKDIPVPKPKPNELLINVKYSGVCHTDLHAWHGDWPLPTKLPLVGGHEGAGVVVGMGENVKGWKIGDYAGIKWLNGSCMACEYCELGNESNCPHADLSGYTHDGSFQEYATADAVQAAHIPQGTDLAEVAPILCAGITVYKALKSANLRAGHWAAISGAAGGLGSLAVQYAKAMGYRVLGIDGGPGKEELFTSLGGEVFIDFTKEKDIVSAVVKATNGGAHGIINVSVSEAAIEASTRYCRANGTVVLVGLPAGAKCSSDVFNHVVKSISIVGSYVGNRADTREALDFFARGLVKSPIKVVGLSSLPEIYEKMEKGQIAGRYVVDTSK
1.1.1.1
COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:P00330}; Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P00330};
amino acid catabolic process to alcohol via Ehrlich pathway [GO:0000947]; ethanol metabolic process [GO:0006067]; NADH oxidation [GO:0006116]
cytoplasm [GO:0005737]
alcohol dehydrogenase (NAD+) activity [GO:0004022]; butanol dehydrogenase activity [GO:1990362]; zinc ion binding [GO:0008270]
PF08240;PF00107;
3.90.180.10;3.40.50.720;
Zinc-containing alcohol dehydrogenase family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:2937632}.
CATALYTIC ACTIVITY: Reaction=a primary alcohol + NAD(+) = an aldehyde + H(+) + NADH; Xref=Rhea:RHEA:10736, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734, ChEBI:CHEBI:17478, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000305|PubMed:12702265}; CATALYTIC ACTIVITY: Reaction=a secondary alcohol + NAD(+) = a ketone + H(+) + NADH; Xref=Rhea:RHEA:10740, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087, ChEBI:CHEBI:35681, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000305|PubMed:12702265}; CATALYTIC ACTIVITY: Reaction=ethanol + NAD(+) = acetaldehyde + H(+) + NADH; Xref=Rhea:RHEA:25290, ChEBI:CHEBI:15343, ChEBI:CHEBI:15378, ChEBI:CHEBI:16236, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000269|PubMed:3546317}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25291; Evidence={ECO:0000269|PubMed:3546317}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25292; Evidence={ECO:0000269|PubMed:3546317}; CATALYTIC ACTIVITY: Reaction=butan-1-ol + NAD(+) = butanal + H(+) + NADH; Xref=Rhea:RHEA:33199, ChEBI:CHEBI:15378, ChEBI:CHEBI:15743, ChEBI:CHEBI:28885, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:3546317}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33200; Evidence={ECO:0000269|PubMed:3546317}; CATALYTIC ACTIVITY: Reaction=hexan-1-ol + NAD(+) = H(+) + hexanal + NADH; Xref=Rhea:RHEA:60972, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:87393, ChEBI:CHEBI:88528; Evidence={ECO:0000269|PubMed:3546317}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60973; Evidence={ECO:0000269|PubMed:3546317};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=110 uM for NAD(+) {ECO:0000269|PubMed:3546317}; KM=0.81 mM for ethanol {ECO:0000269|PubMed:3546317}; KM=0.09 mM for acetaldehyde {ECO:0000269|PubMed:3546317}; KM=50 uM for NADH {ECO:0000269|PubMed:3546317}; KM=2.6 mM for propanol {ECO:0000269|PubMed:3546317}; KM=2.9 mM for butanol {ECO:0000269|PubMed:3546317}; KM=3.8 mM for pentanol {ECO:0000269|PubMed:3546317}; KM=1.4 mM for hexanol {ECO:0000269|PubMed:3546317};
null
null
null
FUNCTION: Preferentially oxidative, glucose-repressed isozyme that catalyzes the conversion of ethanol to acetaldehyde. Main enzyme involved in ethanol consumption. Acts on a variety of primary unbranched aliphatic alcohols (Probable) (PubMed:3546317). Also produces ethanol from glucose, albeit less than ADH1 (PubMed:22094012). {ECO:0000269|PubMed:22094012, ECO:0000269|PubMed:3546317, ECO:0000305|PubMed:12702265}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00334
ADH_DROME
MSFTLTNKNVIFVAGLGGIGLDTSKELLKRDLKNLVILDRIENPAAIAELKAINPKVTVTFYPYDVTVPIAETTKLLKTIFAQLKTVDVLINGAGILDDHQIERTIAVNYTGLVNTTTAILDFWDKRKGGPGGIICNIGSVTGFNAIYQVPVYSGTKAAVVNFTSSLAKLAPITGVTAYTVNPGITRTTLVHKFNSWLDVEPQVAEKLLAHPTQPSLACAENFVKAIELNQNGAIWKLDLGTLEAIQWTKHWDSGI
1.1.1.1
null
acetaldehyde metabolic process [GO:0006117]; alcohol catabolic process [GO:0046164]; alcohol metabolic process [GO:0006066]; behavioral response to ethanol [GO:0048149]; ethanol metabolic process [GO:0006067]; ethanol oxidation [GO:0006069]; NADH metabolic process [GO:0006734]
cytosol [GO:0005829]
acetaldehyde dehydrogenase (acetylating) activity [GO:0008774]; alcohol dehydrogenase (NAD+) activity [GO:0004022]; protein homodimerization activity [GO:0042803]
PF00106;
3.40.50.720;
Short-chain dehydrogenases/reductases (SDR) family
null
null
CATALYTIC ACTIVITY: Reaction=a primary alcohol + NAD(+) = an aldehyde + H(+) + NADH; Xref=Rhea:RHEA:10736, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734, ChEBI:CHEBI:17478, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10001}; CATALYTIC ACTIVITY: Reaction=a secondary alcohol + NAD(+) = a ketone + H(+) + NADH; Xref=Rhea:RHEA:10740, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087, ChEBI:CHEBI:35681, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10001};
null
null
null
null
null
Drosophila melanogaster (Fruit fly)
P00338
LDHA_HUMAN
MATLKDQLIYNLLKEEQTPQNKITVVGVGAVGMACAISILMKDLADELALVDVIEDKLKGEMMDLQHGSLFLRTPKIVSGKDYNVTANSKLVIITAGARQQEGESRLNLVQRNVNIFKFIIPNVVKYSPNCKLLIVSNPVDILTYVAWKISGFPKNRVIGSGCNLDSARFRYLMGERLGVHPLSCHGWVLGEHGDSSVPVWSGMNVAGVSLKTLHPDLGTDKDKEQWKEVHKQVVESAYEVIKLKGYTSWAIGLSVADLAESIMKNLRRVHPVSTMIKGLYGIKDDVFLSVPCILGQNGISDLVKVTLTSEEEARLKKSADTLWGIQKELQF
1.1.1.27
null
glycolytic process [GO:0006096]; lactate metabolic process [GO:0006089]; pyruvate metabolic process [GO:0006090]; substantia nigra development [GO:0021762]
cytosol [GO:0005829]; extracellular exosome [GO:0070062]; membrane [GO:0016020]; mitochondrion [GO:0005739]; nucleus [GO:0005634]; oxidoreductase complex [GO:1990204]
cadherin binding [GO:0045296]; identical protein binding [GO:0042802]; L-lactate dehydrogenase activity [GO:0004459]
PF02866;PF00056;
3.90.110.10;3.40.50.720;
LDH/MDH superfamily, LDH family
PTM: ISGylated. {ECO:0000269|PubMed:16139798}.
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate; Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27; Evidence={ECO:0000269|PubMed:11276087}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23445; Evidence={ECO:0000269|PubMed:11276087}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23446; Evidence={ECO:0000269|PubMed:11276087};
null
PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1. {ECO:0000305|PubMed:11276087}.
null
null
FUNCTION: Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:11276087}.
Homo sapiens (Human)
P00339
LDHA_PIG
MATLKDQLIHNLLKEEHVPHNKITVVGVGAVGMACAISILMKELADEIALVDVMEDKLKGEMMDLQHGSLFLRTPKIVSGKDYNVTANSRLVVITAGARQQEGESRLNLVQRNVNIFKFIIPNIVKYSPNCKLLVVSNPVDILTYVAWKISGFPKNRVIGSGCNLDSARFRYLMGERLGVHPLSCHGWILGEHGDSSVPVWSGVNVAGVSLKNLHPELGTDADKEHWKAVHKQVVDSAYEVIKLKGYTSWAIGLSVADLAESIMKNLRRVHPISTMIKGLYGIKEDVFLSVPCILGQNGISDVVKVTLTPEEEAHLKKSADTLWGIQKELQF
1.1.1.27
null
lactate metabolic process [GO:0006089]; pyruvate metabolic process [GO:0006090]
mitochondrion [GO:0005739]; oxidoreductase complex [GO:1990204]
identical protein binding [GO:0042802]; L-lactate dehydrogenase activity [GO:0004459]
PF02866;PF00056;
3.90.110.10;3.40.50.720;
LDH/MDH superfamily, LDH family
PTM: ISGylated. {ECO:0000250|UniProtKB:P00338}.
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate; Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27; Evidence={ECO:0000250|UniProtKB:P00338}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23445; Evidence={ECO:0000250|UniProtKB:P00338}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23446; Evidence={ECO:0000250|UniProtKB:P00338};
null
PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1. {ECO:0000250|UniProtKB:P00338}.
null
null
FUNCTION: Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000250|UniProtKB:P00338}.
Sus scrofa (Pig)
P00341
LDHA_SQUAC
MATLKDKLIGHLATSQEPRSYNKITVVGVGAVGMACAISILMKDLADEVALVDVMEDKLKGEMMDLQHGSLFLHTAKIVSGKDYSVSAGSKLVVITAGARQQEGESRLNLVQRNVNIFKFIIPDIVKHSPDCIILVVSNPVDVLTYVAWKLSGLPMHRIIGSGCNLDSARFRYLMGERLGVHSSSCHGWVIGEHGDSSVPVWSGMNVAGVSLKELHPELGTDKDKENWKKLHKDVVDSAYEVIKLKGYTSWAIGLSVADLAETIMKNLCRVHPVSTMVKDFYGIKNDVFLSLPCVLDNHGISNIVKMKLKPDEEQQLQKSATTLWDIQKDLKF
1.1.1.27
null
lactate metabolic process [GO:0006089]; pyruvate metabolic process [GO:0006090]
cytoplasm [GO:0005737]
L-lactate dehydrogenase activity [GO:0004459]
PF02866;PF00056;
3.90.110.10;3.40.50.720;
LDH/MDH superfamily, LDH family
null
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate; Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27; Evidence={ECO:0000250|UniProtKB:P00338}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23445; Evidence={ECO:0000250|UniProtKB:P00338}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23446; Evidence={ECO:0000250|UniProtKB:P00338};
null
PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1. {ECO:0000250|UniProtKB:P00338}.
null
null
FUNCTION: Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000250|UniProtKB:P00338}.
Squalus acanthias (Spiny dogfish)
P00342
LDHC_MOUSE
MSTVKEQLIQNLVPEDKLSRCKITVVGVGNVGMACAISILLKGLADELALVDADTNKLRGEALDLLHGSLFLSTPKIVFGKDYNVSANSKLVIITAGARMVSGETRLDLLQRNVAIMKAIVPGIVQNSPDCKIIIVTNPVDILTYVVWKISGFPVGRVIGSGCNLDSARFRYLIGEKLGVNPTSCHGWVLGEHGDSSVPIWSGVNVAGVTLKSLNPAIGTDSDKEHWKNVHKQVVEGGYEVLNMKGYTSWAIGLSVTDLARSILKNLKRVHPVTTLVKGFHGIKEEVFLSIPCVLGQSGITDFVKVNMTAEEEGLLKKSADTLWNMQKDLQL
1.1.1.27
null
ATP biosynthetic process [GO:0006754]; flagellated sperm motility [GO:0030317]; lactate biosynthetic process from pyruvate [GO:0019244]; lactate metabolic process [GO:0006089]; lactate oxidation [GO:0019516]; pyruvate catabolic process [GO:0042867]; pyruvate metabolic process [GO:0006090]
cilium [GO:0005929]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; mitochondrion [GO:0005739]; motile cilium [GO:0031514]
L-lactate dehydrogenase activity [GO:0004459]
PF02866;PF00056;
3.90.110.10;3.40.50.720;
LDH/MDH superfamily, LDH family
null
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate; Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27;
null
PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1.
null
null
FUNCTION: Possible role in sperm motility. {ECO:0000250}.
Mus musculus (Mouse)
P00343
LDH_LACCA
MASITDKDHQKVILVGDGAVGSSYAYAMVLQGIAQEIGIVDIFKDKTKGDAIDLSNALPFTSPKKIYSAEYSDAKDADLVVITAGAPQKPGETRLDLVNKNLKILKSIVDPIVDSGFNGIFLVAANPVDILTYATWKLSGFPKNRVVGSGTSLDTARFRQSIAEMVNVDARSVHAYIMGEHGDTEFPVWSHANIGGVTIAEWVKAHPEIKEDKLVKMFEDVRDAAYEIIKLKGATFYGIATALARISKAILNDENAVLPLSVYMDGQYGLNDIYIGTPAVINRNGIQNILEIPLTDHEEESMQKSASQLKKVLTDAFAKNDIETRQ
1.1.1.27
null
glycolytic process [GO:0006096]; lactate metabolic process [GO:0006089]
cytoplasm [GO:0005737]
L-lactate dehydrogenase activity [GO:0004459]
PF02866;PF00056;
3.90.110.10;3.40.50.720;
LDH/MDH superfamily, LDH family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00488}.
CATALYTIC ACTIVITY: Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate; Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27; Evidence={ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000269|PubMed:14601, ECO:0000269|PubMed:7766183, ECO:0000305|PubMed:19787773};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.45 mM for pyruvate (at pH 4.8) {ECO:0000269|PubMed:14601}; KM=0.71 mM for pyruvate (at pH 5.5) {ECO:0000269|PubMed:14601}; KM=3 mM for pyruvate (at pH 6.2) {ECO:0000269|PubMed:14601}; KM=12 mM for pyruvate (at pH 7) {ECO:0000269|PubMed:14601}; Vmax=2500 umol/min/mg enzyme with pyruvate as substrate (at pH 6.2) {ECO:0000269|PubMed:14601}; Vmax=2400 umol/min/mg enzyme with pyruvate as substrate (at pH 7) {ECO:0000269|PubMed:14601}; Vmax=2000 umol/min/mg enzyme with pyruvate as substrate (at pH 5.5) {ECO:0000269|PubMed:14601}; Vmax=1900 umol/min/mg enzyme with pyruvate as substrate (at pH 4.8) {ECO:0000269|PubMed:14601};
PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00488}.
null
BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Thermostable up to 50 degrees Celsius. Thermostabilized in the presence of both fructose 1,6-bisphosphate (FBP) and Mn(2+) ions. {ECO:0000269|PubMed:14601, ECO:0000269|PubMed:7766183};
FUNCTION: Catalyzes the conversion of lactate to pyruvate. {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000269|PubMed:14601, ECO:0000269|PubMed:19787773, ECO:0000269|PubMed:7766183, ECO:0000305|PubMed:1768113}.
Lacticaseibacillus casei (Lactobacillus casei)
P00344
LDH_GEOSE
MKNNGGARVVVIGAGFVGASYVFALMNQGIADEIVLIDANESKAIGDAMDFNHGKVFAPKPVDIWHGDYDDCRDADLVVICAGANQKPGETRLDLVDKNIAIFRSIVESVMASGFQGLFLVATNPVDILTYATWKFSGLPHERVIGSGTILDTARFRFLLGEYFSVAPQNVHAYIIGEHGDTELPVWSQAYIGVMPIRKLVESKGEEAQKDLERIFVNVRDAAYQIIEKKGATYYGIAMGLARVTRAILHNENAILTVSAYLDGLYGERDVYIGVPAVINRNGIREVIEIELNDDEKNRFHHSAATLKSVLARAFTR
1.1.1.27
null
glycolytic process [GO:0006096]; lactate metabolic process [GO:0006089]
cytoplasm [GO:0005737]
L-lactate dehydrogenase activity [GO:0004459]; NAD binding [GO:0051287]
PF02866;PF00056;
3.90.110.10;3.40.50.720;
LDH/MDH superfamily, LDH family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00488}.
CATALYTIC ACTIVITY: Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate; Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27; Evidence={ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000305|PubMed:3580377};
null
PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00488}.
null
null
FUNCTION: Catalyzes the conversion of lactate to pyruvate. {ECO:0000255|HAMAP-Rule:MF_00488, ECO:0000269|PubMed:3580377, ECO:0000269|Ref.5}.
Geobacillus stearothermophilus (Bacillus stearothermophilus)
P00346
MDHM_PIG
MLSALARPAGAALRRSFSTSXQNNAKVAVLGASGGIGQPLSLLLKNSPLVSRLTLYDIAHTPGVAADLSHIETRATVKGYLGPEQLPDCLKGCDVVVIPAGVPRKPGMTRDDLFNTNATIVATLTAACAQHCPDAMICIISNPVNSTIPITAEVFKKHGVYNPNKIFGVTTLDIVRANAFVAELKGLDPARVSVPVIGGHAGKTIIPLISQCTPKVDFPQDQLSTLTGRIQEAGTEVVKAKAGAGSATLSMAYAGARFVFSLVDAMNGKEGVVECSFVKSQETDCPYFSTPLLLGKKGIEKNLGIGKISPFEEKMIAEAIPELKASIKKGEEFVKNMK
1.1.1.37
null
aerobic respiration [GO:0009060]; malate metabolic process [GO:0006108]; tricarboxylic acid cycle [GO:0006099]
cytoplasm [GO:0005737]; cytosol [GO:0005829]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
L-malate dehydrogenase activity [GO:0030060]; protein homodimerization activity [GO:0042803]; protein-folding chaperone binding [GO:0051087]
PF02866;PF00056;
3.90.110.10;3.40.50.720;
LDH/MDH superfamily, MDH type 1 family
PTM: Acetylation is enhanced after treatment either with trichostin A (TCA) or with nicotinamide (NAM) with the appearance of tri- and tetraacetylations. Glucose also increases acetylation. {ECO:0000250|UniProtKB:P40926}.
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250|UniProtKB:P04636}.
CATALYTIC ACTIVITY: Reaction=(S)-malate + NAD(+) = H(+) + NADH + oxaloacetate; Xref=Rhea:RHEA:21432, ChEBI:CHEBI:15378, ChEBI:CHEBI:15589, ChEBI:CHEBI:16452, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.37; Evidence={ECO:0000255|PROSITE-ProRule:PRU10004};
null
null
null
null
null
Sus scrofa (Pig)
P00347
HMDH_CRIGR
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSSDIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTGLNEALPFFLLLIDLSRASALAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIGVGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFARVLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTTEHSKVSLGLDEDVSKRIEPSVSLWQFYLSKMISMDIEQVVTLSLAFLLAVKYIFFEQAETESTLSLKNPITSPVVTPKKAPDNCCRREPLLVRRSEKLSSVEEEPGVSQDRKVEVIKPLVVETESASRATFVLGASGTSPPVAARTQELEIELPSEPRPNEECLQILESAEKGAKFLSDAEIIQLVNAKHIPAYKLETLMETHERGVSIRRQLLSTKLPEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGVAGPLCLDGKEYQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRACDSAEVKAWLETPEGFAVIKDAFDSTSRFARLQKLHVTMAGRNLYIRFQSKTGDAMGMNMISKGTEKALLKLQEFFPEMQILAVSGNYCTDKKPAAINWIEGRGKTVVCEAVIPAKVVREVLKTTTEAMIDVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAALAAGHLVRSHMVHNRSKINLQDLQGTCTKKSA
1.1.1.34
null
cholesterol biosynthetic process [GO:0006695]; coenzyme A metabolic process [GO:0015936]; ergosterol biosynthetic process [GO:0006696]; isoprenoid biosynthetic process [GO:0008299]; long-term synaptic potentiation [GO:0060291]; negative regulation of amyloid-beta clearance [GO:1900222]; negative regulation of protein catabolic process [GO:0042177]; negative regulation of protein secretion [GO:0050709]; regulation of ERK1 and ERK2 cascade [GO:0070372]; visual learning [GO:0008542]
endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; peroxisomal membrane [GO:0005778]
coenzyme A binding [GO:0120225]; GTPase regulator activity [GO:0030695]; hydroxymethylglutaryl-CoA reductase (NADPH) activity [GO:0004420]; NADPH binding [GO:0070402]
PF00368;PF12349;
1.10.3270.10;3.30.70.420;
HMG-CoA reductase family
PTM: N-glycosylated. Glycosylated with high mannose chains including Man(6)(GlcNAc)(2), Man(7)(GlcNAc)(2) and Man(8)(GlcNAc)(2) (PubMed:6580634). Deglycosylated by NGLY1 on release from the endoplasmic reticulum (ER) in a sterol-mediated manner (By similarity). {ECO:0000250|UniProtKB:P04035, ECO:0000269|PubMed:6580634}.; PTM: Undergoes sterol-mediated ubiquitination and ER-associated degradation (ERAD) (PubMed:14563840, PubMed:15247208, PubMed:17090658, PubMed:29374057). Accumulation of sterols in the endoplasmic reticulum (ER) membrane, triggers binding of the reductase to the ER membrane protein INSIG1 or INSIG2 (PubMed:14563840, PubMed:17090658). The INSIG1 binding leads to the recruitment of the ubiquitin ligase, AMFR/gp78, RNF139 or RNF145, initiating ubiquitination of the reductase (PubMed:14563840, PubMed:29374057). The ubiquitinated reductase is then extracted from the ER membrane and delivered to cytosolic 26S proteosomes by a mechanism probably mediated by the ATPase Valosin-containing protein VCP/p97 (PubMed:14563840). The INSIG2-binding leads to the recruitment of the ubiquitin ligase RNF139, initiating ubiquitination of the reductase (By similarity). Lys-248 is the main site of ubiquitination (PubMed:14563840, PubMed:15247208). Ubiquitination is enhanced by the presence of a geranylgeranylated protein (By similarity). {ECO:0000250|UniProtKB:P04035, ECO:0000269|PubMed:14563840, ECO:0000269|PubMed:15247208, ECO:0000269|PubMed:17090658, ECO:0000269|PubMed:29374057}.; PTM: Phosphorylated. Phosphorylation at Ser-871 reduces the catalytic activity. {ECO:0000269|PubMed:8415689}.
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:6546784}; Multi-pass membrane protein {ECO:0000269|PubMed:1374417}. Peroxisome membrane {ECO:0000250|UniProtKB:P04035}; Multi-pass membrane protein {ECO:0000269|PubMed:1374417}.
CATALYTIC ACTIVITY: Reaction=(R)-mevalonate + CoA + 2 NADP(+) = (3S)-hydroxy-3-methylglutaryl-CoA + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:15989, ChEBI:CHEBI:15378, ChEBI:CHEBI:36464, ChEBI:CHEBI:43074, ChEBI:CHEBI:57287, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.34; Evidence={ECO:0000250|UniProtKB:P04035}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15991; Evidence={ECO:0000250|UniProtKB:P04035};
null
PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
null
null
FUNCTION: Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis. {ECO:0000250|UniProtKB:P04035}.
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
P00348
HCDH_PIG
MAFATRQLVRSLSSSSTAAASAKKILVKHVTVIGGGLMGAGIAQVAAATGHTVVLVDQTEDILAKSKKGIEESLRKVAKKKFAENPKAGDEFVEKTLSSISTSTDAASVVHSTDLVVEAIVENLKVKSELFKRLDKFAAEHTIFASNTSSLQITSLANATTRQDRFAGLHFFNPVPLMKLVEVVKTPMTSQKTLESLVDFSKTLGKHPVSCKDTPGFIVNRLLVPYLIEAVRLYERGDASKEDIDTAMKLGAGYPMGPFELLDYVGLDTTKFIIDGWHEMDSQNPLFQPSPAMNKLVAENKFGKKTGEGFYKYK
1.1.1.35
null
fatty acid beta-oxidation [GO:0006635]; regulation of insulin secretion [GO:0050796]
mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
3-hydroxyacyl-CoA dehydrogenase activity [GO:0003857]; identical protein binding [GO:0042802]; NAD+ binding [GO:0070403]
PF00725;PF02737;
3.40.50.720;
3-hydroxyacyl-CoA dehydrogenase family
PTM: Succinylation at Lys-81, adjacent to a coenzyme A binding site. Desuccinylated by SIRT5. {ECO:0000250|UniProtKB:Q61425}.
SUBCELLULAR LOCATION: Mitochondrion matrix.
CATALYTIC ACTIVITY: Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35; Evidence={ECO:0000269|PubMed:9593854}; CATALYTIC ACTIVITY: Reaction=(3S)-3-hydroxybutanoyl-CoA + NAD(+) = acetoacetyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:30799, ChEBI:CHEBI:15378, ChEBI:CHEBI:57286, ChEBI:CHEBI:57316, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:2817332}; CATALYTIC ACTIVITY: Reaction=(3S)-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:31187, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62548, ChEBI:CHEBI:62616; Evidence={ECO:0000269|PubMed:2817332}; CATALYTIC ACTIVITY: Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378, ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62613; Evidence={ECO:0000269|PubMed:2817332};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=7.2 uM for (3S)-hydroxybutanoyl-CoA {ECO:0000269|PubMed:2817332}; KM=2.9 uM for (3S)-hydroxydecanoyl-CoA {ECO:0000269|PubMed:2817332}; KM=3 uM for (3S)-hydroxyhexadecanoyl-CoA {ECO:0000269|PubMed:2817332};
PATHWAY: Lipid metabolism; fatty acid beta-oxidation. {ECO:0000305}.
null
null
FUNCTION: Mitochondrial fatty acid beta-oxidation enzyme that catalyzes the third step of the beta-oxidation cycle for medium and short-chain 3-hydroxy fatty acyl-CoAs (C4 to C10) (PubMed:2817332, PubMed:9593854). Plays a role in the control of insulin secretion by inhibiting the activation of glutamate dehydrogenase 1 (GLUD1), an enzyme that has an important role in regulating amino acid-induced insulin secretion (By similarity). {ECO:0000250|UniProtKB:Q61425, ECO:0000269|PubMed:2817332, ECO:0000269|PubMed:9593854}.
Sus scrofa (Pig)
P00349
6PGD_SHEEP
MAQADIALIGLAVMGQNLILNMNDHGFVVCAFNRTVSKVDDFLANEAKGTKVLGAHSLEEMVSKLKKPRRIILLVKAGQAVDNFIEKLVPLLDIGDIIIDGGNSEYRDTMRRCRDLKDKGILFVGSGVSGGEDGARYGPSLMPGGNKEAWPHIKAIFQGIAAKVGTGEPCCDWVGDDGAGHFVKMVHNGIEYGDMQLICEAYHLMKDVLGLGHKEMAKAFEEWNKTELDSFLIEITASILKFQDADGKHLLPKIRDSAGQKGTGKWTAISALEYGVPVTLIGEAVFARCLSSLKDERIQASKKLKGPQNIPFEGDKKSFLEDIRKALYASKIISYAQGFMLLRQAATEFGWTLNYGGIALMWRGGCIIRSVFLGKIKDAFDRNPGLQNLLLDDFFKSAVENCQDSWRRAISTGVQAGIPMPCFTTALSFYDGYRHAMLPANLIQAQRDYFGAHTYELLAKPGQFIHTNWTGHGGSVSSSSYNA
1.1.1.44
null
D-gluconate catabolic process [GO:0046177]; pentose-phosphate shunt [GO:0006098]; pentose-phosphate shunt, oxidative branch [GO:0009051]
cytosol [GO:0005829]
NADP binding [GO:0050661]; phosphogluconate 2-dehydrogenase activity [GO:0008114]; phosphogluconate dehydrogenase (decarboxylating) activity [GO:0004616]
PF00393;PF03446;
1.20.5.320;3.40.50.720;
6-phosphogluconate dehydrogenase family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CATALYTIC ACTIVITY: Reaction=6-phospho-D-gluconate + NADP(+) = CO2 + D-ribulose 5-phosphate + NADPH; Xref=Rhea:RHEA:10116, ChEBI:CHEBI:16526, ChEBI:CHEBI:57783, ChEBI:CHEBI:58121, ChEBI:CHEBI:58349, ChEBI:CHEBI:58759; EC=1.1.1.44;
null
PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 3/3.
null
null
FUNCTION: Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.
Ovis aries (Sheep)
P00350
6PGD_ECOLI
MSKQQIGVVGMAVMGRNLALNIESRGYTVSIFNRSREKTEEVIAENPGKKLVPYYTVKEFVESLETPRRILLMVKAGAGTDAAIDSLKPYLDKGDIIIDGGNTFFQDTIRRNRELSAEGFNFIGTGVSGGEEGALKGPSIMPGGQKEAYELVAPILTKIAAVAEDGEPCVTYIGADGAGHYVKMVHNGIEYGDMQLIAEAYSLLKGGLNLTNEELAQTFTEWNNGELSSYLIDITKDIFTKKDEDGNYLVDVILDEAANKGTGKWTSQSALDLGEPLSLITESVFARYISSLKDQRVAASKVLSGPQAQPAGDKAEFIEKVRRALYLGKIVSYAQGFSQLRAASEEYNWDLNYGEIAKIFRAGCIIRAQFLQKITDAYAENPQIANLLLAPYFKQIADDYQQALRDVVAYAVQNGIPVPTFSAAVAYYDSYRAAVLPANLIQAQRDYFGAHTYKRIDKEGVFHTEWLD
1.1.1.44
null
D-gluconate catabolic process [GO:0046177]; pentose-phosphate shunt [GO:0006098]; pentose-phosphate shunt, oxidative branch [GO:0009051]
cytosol [GO:0005829]
guanosine tetraphosphate binding [GO:0097216]; identical protein binding [GO:0042802]; NADP binding [GO:0050661]; phosphogluconate 2-dehydrogenase activity [GO:0008114]; phosphogluconate dehydrogenase (decarboxylating) activity [GO:0004616]; protein homodimerization activity [GO:0042803]
PF00393;PF03446;
1.20.5.320;3.40.50.720;
6-phosphogluconate dehydrogenase family
null
null
CATALYTIC ACTIVITY: Reaction=6-phospho-D-gluconate + NADP(+) = CO2 + D-ribulose 5-phosphate + NADPH; Xref=Rhea:RHEA:10116, ChEBI:CHEBI:16526, ChEBI:CHEBI:57783, ChEBI:CHEBI:58121, ChEBI:CHEBI:58349, ChEBI:CHEBI:58759; EC=1.1.1.44; Evidence={ECO:0000269|PubMed:19686854};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=49 uM for NADP {ECO:0000269|PubMed:19686854}; KM=93 uM for 6-phospho-D-gluconate {ECO:0000269|PubMed:19686854};
PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 3/3. {ECO:0000305|PubMed:19686854}.
null
null
FUNCTION: Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH. {ECO:0000269|PubMed:19686854}.
Escherichia coli (strain K12)
P00352
AL1A1_HUMAN
MSSSGTPDLPVLLTDLKIQYTKIFINNEWHDSVSGKKFPVFNPATEEELCQVEEGDKEDVDKAVKAARQAFQIGSPWRTMDASERGRLLYKLADLIERDRLLLATMESMNGGKLYSNAYLNDLAGCIKTLRYCAGWADKIQGRTIPIDGNFFTYTRHEPIGVCGQIIPWNFPLVMLIWKIGPALSCGNTVVVKPAEQTPLTALHVASLIKEAGFPPGVVNIVPGYGPTAGAAISSHMDIDKVAFTGSTEVGKLIKEAAGKSNLKRVTLELGGKSPCIVLADADLDNAVEFAHHGVFYHQGQCCIAASRIFVEESIYDEFVRRSVERAKKYILGNPLTPGVTQGPQIDKEQYDKILDLIESGKKEGAKLECGGGPWGNKGYFVQPTVFSNVTDEMRIAKEEIFGPVQQIMKFKSLDDVIKRANNTFYGLSAGVFTKDIDKAITISSALQAGTVWVNCYGVVSAQCPFGGFKMSGNGRELGEYGFHEYTEVKTVTVKISQKNS
1.2.1.19; 1.2.1.28; 1.2.1.3; 1.2.1.36
null
cellular aldehyde metabolic process [GO:0006081]; cellular detoxification of aldehyde [GO:0110095]; fructosamine catabolic process [GO:0030392]; gamma-aminobutyric acid biosynthetic process [GO:0009449]; maintenance of lens transparency [GO:0036438]; negative regulation of cold-induced thermogenesis [GO:0120163]; retinoid metabolic process [GO:0001523]; retinol metabolic process [GO:0042572]
axon [GO:0030424]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular exosome [GO:0070062]; synapse [GO:0045202]
3-deoxyglucosone dehydrogenase activity [GO:0106373]; aldehyde dehydrogenase (NAD+) activity [GO:0004029]; aminobutyraldehyde dehydrogenase activity [GO:0019145]; androgen binding [GO:0005497]; benzaldehyde dehydrogenase (NAD+) activity [GO:0018479]; glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity [GO:0043878]; GTPase activator activity [GO:0005096]; NAD binding [GO:0051287]; retinal dehydrogenase activity [GO:0001758]
PF00171;
null
Aldehyde dehydrogenase family
PTM: The N-terminus is blocked most probably by acetylation. {ECO:0000250|UniProtKB:P15437}.
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12941160}. Cell projection, axon {ECO:0000250|UniProtKB:P24549}.
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; Evidence={ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:15623782, ECO:0000269|PubMed:17175089, ECO:0000269|PubMed:19296407}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16186; Evidence={ECO:0000305|PubMed:19296407}; CATALYTIC ACTIVITY: Reaction=all-trans-retinal + H2O + NAD(+) = all-trans-retinoate + 2 H(+) + NADH; Xref=Rhea:RHEA:42080, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17898, ChEBI:CHEBI:35291, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.36; Evidence={ECO:0000250|UniProtKB:P51647}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42081; Evidence={ECO:0000250|UniProtKB:P51647}; CATALYTIC ACTIVITY: Reaction=9-cis-retinal + H2O + NAD(+) = 9-cis-retinoate + 2 H(+) + NADH; Xref=Rhea:RHEA:42084, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78273, ChEBI:CHEBI:78630; Evidence={ECO:0000250|UniProtKB:P51647}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42085; Evidence={ECO:0000250|UniProtKB:P51647}; CATALYTIC ACTIVITY: Reaction=11-cis-retinal + H2O + NAD(+) = 11-cis-retinoate + 2 H(+) + NADH; Xref=Rhea:RHEA:47132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16066, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:87435; Evidence={ECO:0000250|UniProtKB:P51647}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47133; Evidence={ECO:0000250|UniProtKB:P51647}; CATALYTIC ACTIVITY: Reaction=13-cis-retinal + H2O + NAD(+) = 13-cis-retinoate + 2 H(+) + NADH; Xref=Rhea:RHEA:67332, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:45487, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:169952; Evidence={ECO:0000250|UniProtKB:Q8HYE4}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67333; Evidence={ECO:0000250|UniProtKB:Q8HYE4}; CATALYTIC ACTIVITY: Reaction=3-deoxyglucosone + H2O + NAD(+) = 2-dehydro-3-deoxy-D-gluconate + 2 H(+) + NADH; Xref=Rhea:RHEA:67244, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:57990, ChEBI:CHEBI:60777; Evidence={ECO:0000269|PubMed:17175089}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67245; Evidence={ECO:0000305|PubMed:17175089}; CATALYTIC ACTIVITY: Reaction=(E)-4-hydroxynon-2-enal + H2O + NAD(+) = (E)-4-hydroxynon-2-enoate + 2 H(+) + NADH; Xref=Rhea:RHEA:67248, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58968, ChEBI:CHEBI:142920; Evidence={ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:15623782, ECO:0000269|PubMed:19296407}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67249; Evidence={ECO:0000269|PubMed:15623782}; CATALYTIC ACTIVITY: Reaction=H2O + malonaldehyde + NAD(+) = 3-oxopropanoate + 2 H(+) + NADH; Xref=Rhea:RHEA:67252, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33190, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:566274; Evidence={ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:19296407}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67253; Evidence={ECO:0000305|PubMed:19296407}; CATALYTIC ACTIVITY: Reaction=H2O + hexanal + NAD(+) = 2 H(+) + hexanoate + NADH; Xref=Rhea:RHEA:67276, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17120, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:88528; Evidence={ECO:0000269|PubMed:12941160}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67277; Evidence={ECO:0000305|PubMed:12941160}; CATALYTIC ACTIVITY: Reaction=H2O + NAD(+) + propanal = 2 H(+) + NADH + propanoate; Xref=Rhea:RHEA:67256, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17153, ChEBI:CHEBI:17272, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:19296407}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67257; Evidence={ECO:0000305|PubMed:19296407}; CATALYTIC ACTIVITY: Reaction=acetaldehyde + H2O + NAD(+) = acetate + 2 H(+) + NADH; Xref=Rhea:RHEA:25294, ChEBI:CHEBI:15343, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.3; Evidence={ECO:0000269|PubMed:19296407}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25295; Evidence={ECO:0000305|PubMed:19296407}; CATALYTIC ACTIVITY: Reaction=benzaldehyde + H2O + NAD(+) = benzoate + 2 H(+) + NADH; Xref=Rhea:RHEA:11840, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16150, ChEBI:CHEBI:17169, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.28; Evidence={ECO:0000269|PubMed:17175089, ECO:0000269|PubMed:19296407}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11841; Evidence={ECO:0000305|PubMed:19296407}; CATALYTIC ACTIVITY: Reaction=4-aminobutanal + H2O + NAD(+) = 4-aminobutanoate + 2 H(+) + NADH; Xref=Rhea:RHEA:19105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58264, ChEBI:CHEBI:59888; EC=1.2.1.19; Evidence={ECO:0000250|UniProtKB:P24549}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19106; Evidence={ECO:0000250|UniProtKB:P24549};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=59.4 uM for NAD (at pH 8.0) {ECO:0000269|PubMed:19296407}; KM=85 uM for NAD (at pH 7.1 and 30 degrees Celsius) {ECO:0000269|PubMed:17175089}; KM=2 uM for benzaldehyde (at pH 7.1 and 30 degrees Celsius) {ECO:0000269|PubMed:17175089}; KM=4.8 uM for (E)-4-hydroxynon-2-enal (at pH 8.0) {ECO:0000269|PubMed:19296407}; KM=17.9 uM for (E)-4-hydroxynon-2-enal (at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12941160}; KM=114.4 uM for malonaldehyde (at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12941160}; KM=3.5 uM for malonaldehyde (at pH 8.0) {ECO:0000269|PubMed:19296407}; KM=95 uM for 3-deoxyglucosone (at pH 7.1 and 30 degrees Celsius) {ECO:0000269|PubMed:17175089}; KM=238.2 uM for acetaldehyde (at pH 8.0) {ECO:0000269|PubMed:19296407}; KM=121.4 uM for propanal (at pH 8.0) {ECO:0000269|PubMed:19296407}; KM=137.2 uM for propanal (at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12941160}; KM=15 uM for propanal (at pH 7.5) {ECO:0000269|PubMed:25450233}; KM=13.4 uM for hexanal (at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12941160}; KM=142.2 uM for benzaldehyde (at pH 8.0) {ECO:0000269|PubMed:19296407}; KM=177.1 uM for trans-2-heptenal (at pH 8.0) {ECO:0000269|PubMed:19296407}; Vmax=254.6 nmol/min/mg enzyme with (E)-4-hydroxynon-2-enal (at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12941160}; Vmax=135 nmol/min/mg enzyme with (E)-4-hydroxynon-2-enal (at pH 8.0) {ECO:0000269|PubMed:19296407}; Vmax=564.9 nmol/min/mg enzyme with malonaldehyde (at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12941160}; Vmax=381.6 nmol/min/mg enzyme with malonaldehyde (at pH 8.0) {ECO:0000269|PubMed:19296407}; Vmax=45 nmol/min/mg enzyme with 3-deoxyglucosone (at pH 7.1 and 30 degrees Celsius) {ECO:0000269|PubMed:17175089}; Vmax=631.4 nmol/min/mg enzyme with acetaldehyde (at pH 8.0) {ECO:0000269|PubMed:19296407}; Vmax=747.3 nmol/min/mg enzyme with propanal (at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12941160}; Vmax=445.3 nmol/min/mg enzyme with propanal (at pH 8.0) {ECO:0000269|PubMed:19296407}; Vmax=707.1 nmol/min/mg enzyme with hexanal (at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:12941160}; Vmax=750.3 nmol/min/mg enzyme with benzaldehyde (at pH 8.0) {ECO:0000269|PubMed:19296407}; Vmax=72 nmol/min/mg enzyme with benzaldehyde (at pH 7.1 and 30 degrees Celsius) {ECO:0000269|PubMed:17175089}; Vmax=155.8 nmol/min/mg enzyme with trans-2-heptenal (at pH 8.0) {ECO:0000269|PubMed:19296407};
PATHWAY: Cofactor metabolism; retinol metabolism. {ECO:0000250|UniProtKB:P51647}.
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.1-9 for the 3-deoxyglucosone dehydrogenase activity. {ECO:0000269|PubMed:17175089};
null
FUNCTION: Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:19296407, PubMed:25450233, PubMed:26373694). Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid (By similarity). This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic (By similarity). Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification (PubMed:12941160, PubMed:15623782, PubMed:19296407). Functions also downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins (PubMed:17175089). Has also an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission (By similarity). {ECO:0000250|UniProtKB:P24549, ECO:0000269|PubMed:12941160, ECO:0000269|PubMed:15623782, ECO:0000269|PubMed:17175089, ECO:0000269|PubMed:19296407, ECO:0000269|PubMed:25450233, ECO:0000269|PubMed:26373694}.
Homo sapiens (Human)
P00355
G3P_PIG
MVKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLHYMVYMFQYDSTHGKFHGTVKAENGKLVINGKAITIFQERDPANIKWGDAGATYVVESTGVFTTMEKAGAHLKGGAKRVIISAPSADAPMFVMGVNHEKYDNSLKIVSNASCTTNCLAPLAKVIHDHFGIVEGLMTTVHAITATQKTVDGPSGKLWRDGRGAAQNIIPASTGAAKAVGKVIPELNGKLTGMAFRVPTPNVSVVDLTCRLEKPAKYDDIKKVVKQASEGPLKGILGYTEDQVVSCDFNSDTHSSTFDAGAGIALNDHFVKLISWYDNEFGYSNRVVDLMVHMASKE
1.2.1.12; 2.6.99.-
null
glucose metabolic process [GO:0006006]; glycolytic process [GO:0006096]; innate immune response [GO:0045087]; microtubule cytoskeleton organization [GO:0000226]; neuron apoptotic process [GO:0051402]; peptidyl-cysteine S-trans-nitrosylation [GO:0035606]; positive regulation of canonical NF-kappaB signal transduction [GO:0043123]; positive regulation of type I interferon production [GO:0032481]; protein stabilization [GO:0050821]; regulation of translation [GO:0006417]
cytoplasm [GO:0005737]; cytosol [GO:0005829]; GAIT complex [GO:0097452]; microtubule cytoskeleton [GO:0015630]; nucleus [GO:0005634]
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity [GO:0004365]; microtubule binding [GO:0008017]; NAD binding [GO:0051287]; NADP binding [GO:0050661]; peptidyl-cysteine S-nitrosylase activity [GO:0035605]
PF02800;PF00044;
3.40.50.720;
Glyceraldehyde-3-phosphate dehydrogenase family
PTM: ISGylated. {ECO:0000250|UniProtKB:P04406}.; PTM: S-nitrosylation of Cys-150 leads to interaction with SIAH1, followed by translocation to the nucleus S-nitrosylation of Cys-245 is induced by interferon-gamma and LDL(ox) implicating the iNOS-S100A8/9 transnitrosylase complex and seems to prevent interaction with phosphorylated RPL13A and to interfere with GAIT complex activity (By similarity). {ECO:0000250|UniProtKB:P04406, ECO:0000250|UniProtKB:P04797}.; PTM: Sulfhydration at Cys-150 increases catalytic activity. {ECO:0000250|UniProtKB:P16858}.; PTM: Oxidative stress can promote the formation of high molecular weight disulfide-linked GAPDH aggregates, through a process called nucleocytoplasmic coagulation. {ECO:0000250|UniProtKB:P04406}.
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P04797}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P04797}. Nucleus {ECO:0000250|UniProtKB:P04797}. Note=Translocates to the nucleus following S-nitrosylation and interaction with SIAH1, which contains a nuclear localization signal. Colocalizes with CHP1 to small punctate structures along the microtubules tracks. {ECO:0000250|UniProtKB:P04797}.
CATALYTIC ACTIVITY: Reaction=D-glyceraldehyde 3-phosphate + NAD(+) + phosphate = (2R)-3-phospho-glyceroyl phosphate + H(+) + NADH; Xref=Rhea:RHEA:10300, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57540, ChEBI:CHEBI:57604, ChEBI:CHEBI:57945, ChEBI:CHEBI:59776; EC=1.2.1.12; Evidence={ECO:0000250|UniProtKB:P04406, ECO:0000255|PROSITE-ProRule:PRU10009}; CATALYTIC ACTIVITY: Reaction=L-cysteinyl-[protein] + S-nitroso-L-cysteinyl-[GAPDH] = L-cysteinyl-[GAPDH] + S-nitroso-L-cysteinyl-[protein]; Xref=Rhea:RHEA:66684, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:17089, Rhea:RHEA-COMP:17090, Rhea:RHEA-COMP:17091, ChEBI:CHEBI:29950, ChEBI:CHEBI:149494; Evidence={ECO:0000250|UniProtKB:P04797}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66685; Evidence={ECO:0000250|UniProtKB:P04797};
null
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.
null
null
FUNCTION: Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (By similarity). Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (By similarity). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04406, ECO:0000250|UniProtKB:P04797}.
Sus scrofa (Pig)
P00356
G3P_CHICK
MVKVGVNGFGRIGRLVTRAAVLSGKVQVVAINDPFIDLNYMVYMFKYDSTHGHFKGTVKAENGKLVINGHAITIFQERDPSNIKWADAGAEYVVESTGVFTTMEKAGAHLKGGAKRVIISAPSADAPMFVMGVNHEKYDKSLKIVSNASCTTNCLAPLAKVIHDNFGIVEGLMTTVHAITATQKTVDGPSGKLWRDGRGAAQNIIPASTGAAKAVGKVIPELNGKLTGMAFRVPTPNVSVVDLTCRLEKPAKYDDIKRVVKAAADGPLKGILGYTEDQVVSCDFNGDSHSSTFDAGAGIALNDHFVKLVSWYDNEFGYSNRVVDLMVHMASKE
1.2.1.12; 2.6.99.-
null
antimicrobial humoral immune response mediated by antimicrobial peptide [GO:0061844]; cellular response to type II interferon [GO:0071346]; defense response to fungus [GO:0050832]; gluconeogenesis [GO:0006094]; glycolytic process [GO:0006096]; killing by host of symbiont cells [GO:0051873]; microtubule cytoskeleton organization [GO:0000226]; negative regulation of apoptotic process [GO:0043066]; negative regulation of translation [GO:0017148]; neuron apoptotic process [GO:0051402]; nuclear membrane fusion [GO:0000740]; peptidyl-cysteine S-trans-nitrosylation [GO:0035606]; positive regulation of canonical NF-kappaB signal transduction [GO:0043123]; positive regulation of type I interferon production [GO:0032481]; protein stabilization [GO:0050821]
cytoplasm [GO:0005737]; cytosol [GO:0005829]; GAIT complex [GO:0097452]; lipid droplet [GO:0005811]; membrane [GO:0016020]; microtubule cytoskeleton [GO:0015630]; nuclear membrane [GO:0031965]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; ribonucleoprotein complex [GO:1990904]
aspartic-type endopeptidase inhibitor activity [GO:0019828]; disordered domain specific binding [GO:0097718]; glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity [GO:0004365]; identical protein binding [GO:0042802]; microtubule binding [GO:0008017]; NAD binding [GO:0051287]; NADP binding [GO:0050661]; peptidyl-cysteine S-nitrosylase activity [GO:0035605]
PF02800;PF00044;
3.40.50.720;
Glyceraldehyde-3-phosphate dehydrogenase family
PTM: S-nitrosylation of Cys-150 leads to translocation to the nucleus. {ECO:0000250|UniProtKB:P04797}.
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P04797}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P04797}. Nucleus {ECO:0000250|UniProtKB:P04797}.
CATALYTIC ACTIVITY: Reaction=D-glyceraldehyde 3-phosphate + NAD(+) + phosphate = (2R)-3-phospho-glyceroyl phosphate + H(+) + NADH; Xref=Rhea:RHEA:10300, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57540, ChEBI:CHEBI:57604, ChEBI:CHEBI:57945, ChEBI:CHEBI:59776; EC=1.2.1.12; Evidence={ECO:0000250|UniProtKB:P04406, ECO:0000255|PROSITE-ProRule:PRU10009}; CATALYTIC ACTIVITY: Reaction=L-cysteinyl-[protein] + S-nitroso-L-cysteinyl-[GAPDH] = L-cysteinyl-[GAPDH] + S-nitroso-L-cysteinyl-[protein]; Xref=Rhea:RHEA:66684, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:17089, Rhea:RHEA-COMP:17090, Rhea:RHEA-COMP:17091, ChEBI:CHEBI:29950, ChEBI:CHEBI:149494; Evidence={ECO:0000250|UniProtKB:P04797}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66685; Evidence={ECO:0000250|UniProtKB:P04797};
null
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.
null
null
FUNCTION: Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (By similarity). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04406, ECO:0000250|UniProtKB:P04797}.
Gallus gallus (Chicken)
P00357
G3P_HOMAM
SKIGINGFGRIGRLVLRAALSCGAQVVAVNDPFIALEYMVYMFKYDSTHGVFKGEVKMEDGALVVDGKKITVFNEMKPENIPWSKAGAEYIVESTGVFTTIEKASAHFKGGAKKVVISAPSADAPMFVCGVNLEKYSKDMTVVSNASCTTNCLAPVAKVLHENFEIVEGLMTTVHAVTATQKTVDGPSAKDWRGGRGAAQNIIPSSTGAAKAVGKVIPELDGKLTGMAFRVPTPDVSVVDLTVRLGKECSYDDIKAAMKTASEGPLQGFLGYTEDDVVSSDFIGDNRSSIFDAKAGIQLSKTFVKVVSWYDNEFGYSQRVIDLLKHMQKVDSA
1.2.1.12
null
glucose metabolic process [GO:0006006]; glycolytic process [GO:0006096]
cytoplasm [GO:0005737]
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity [GO:0004365]; NAD binding [GO:0051287]; NADP binding [GO:0050661]
PF02800;PF00044;
3.40.50.720;
Glyceraldehyde-3-phosphate dehydrogenase family
null
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=D-glyceraldehyde 3-phosphate + NAD(+) + phosphate = (2R)-3-phospho-glyceroyl phosphate + H(+) + NADH; Xref=Rhea:RHEA:10300, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57540, ChEBI:CHEBI:57604, ChEBI:CHEBI:57945, ChEBI:CHEBI:59776; EC=1.2.1.12; Evidence={ECO:0000255|PROSITE-ProRule:PRU10009};
null
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.
null
null
null
Homarus americanus (American lobster)
P00358
G3P2_YEAST
MVRVAINGFGRIGRLVMRIALQRKNVEVVALNDPFISNDYSAYMFKYDSTHGRYAGEVSHDDKHIIVDGHKIATFQERDPANLPWASLNIDIAIDSTGVFKELDTAQKHIDAGAKKVVITAPSSTAPMFVMGVNEEKYTSDLKIVSNASCTTNCLAPLAKVINDAFGIEEGLMTTVHSMTATQKTVDGPSHKDWRGGRTASGNIIPSSTGAAKAVGKVLPELQGKLTGMAFRVPTVDVSVVDLTVKLNKETTYDEIKKVVKAAAEGKLKGVLGYTEDAVVSSDFLGDSNSSIFDAAAGIQLSPKFVKLVSWYDNEYGYSTRVVDLVEHVAKA
1.2.1.12
null
apoptotic process [GO:0006915]; gluconeogenesis [GO:0006094]; glycolytic process [GO:0006096]; reactive oxygen species metabolic process [GO:0072593]
cytoplasm [GO:0005737]; cytosol [GO:0005829]; fungal-type cell wall [GO:0009277]; lipid droplet [GO:0005811]; mitochondrion [GO:0005739]; nucleus [GO:0005634]; plasma membrane [GO:0005886]
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity [GO:0004365]; melatonin binding [GO:1904408]; NAD binding [GO:0051287]; NADP binding [GO:0050661]; promoter-specific chromatin binding [GO:1990841]
PF02800;PF00044;
3.40.50.720;
Glyceraldehyde-3-phosphate dehydrogenase family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P00360}.
CATALYTIC ACTIVITY: Reaction=D-glyceraldehyde 3-phosphate + NAD(+) + phosphate = (2R)-3-phospho-glyceroyl phosphate + H(+) + NADH; Xref=Rhea:RHEA:10300, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57540, ChEBI:CHEBI:57604, ChEBI:CHEBI:57945, ChEBI:CHEBI:59776; EC=1.2.1.12; Evidence={ECO:0000269|PubMed:3905788}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10301; Evidence={ECO:0000269|PubMed:3905788}; CATALYTIC ACTIVITY: Reaction=H2O + NADH = (6R)-NADHX; Xref=Rhea:RHEA:57360, ChEBI:CHEBI:15377, ChEBI:CHEBI:57945, ChEBI:CHEBI:64075; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57361; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; CATALYTIC ACTIVITY: Reaction=H2O + NADH = (6S)-NADHX; Xref=Rhea:RHEA:57364, ChEBI:CHEBI:15377, ChEBI:CHEBI:57945, ChEBI:CHEBI:64074; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57365; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; CATALYTIC ACTIVITY: Reaction=H2O + NADPH = (6R)-NADPHX; Xref=Rhea:RHEA:57368, ChEBI:CHEBI:15377, ChEBI:CHEBI:57783, ChEBI:CHEBI:64077; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57369; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; CATALYTIC ACTIVITY: Reaction=H2O + NADPH = (6S)-NADPHX; Xref=Rhea:RHEA:57372, ChEBI:CHEBI:15377, ChEBI:CHEBI:57783, ChEBI:CHEBI:64076; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57373; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.37 uM for NAD(+) {ECO:0000303|PubMed:3905788};
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5. {ECO:0000269|PubMed:3905788}.
null
null
FUNCTION: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) involved in glycolysis and gluconeogenesis (PubMed:2999100). Catalyzes the reaction of glyceraldehyde-3-phosphate to 1,3 bis-phosphoglycerate (PubMed:3905788). The contribution of the TDH1, TDH2, and TDH3 to the total glyceraldehyde-3-phosphate dehydrogenase activity is 10-15, 25-30, and 50-60%, respectively (PubMed:3905788). {ECO:0000269|PubMed:2999100, ECO:0000269|PubMed:3905788}.; FUNCTION: As a side activity, catalyzes the hydration of the nicotinamide ring of NADH or NADPH at the C6 position to give the corresponding hydrates, NADHX and NADPHX, which exist as R and S epimers, that cannot act as electron donors or acceptors and inhibit several dehydrogenases, making them toxic. {ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00359
G3P3_YEAST
MVRVAINGFGRIGRLVMRIALSRPNVEVVALNDPFITNDYAAYMFKYDSTHGRYAGEVSHDDKHIIVDGKKIATYQERDPANLPWGSSNVDIAIDSTGVFKELDTAQKHIDAGAKKVVITAPSSTAPMFVMGVNEEKYTSDLKIVSNASCTTNCLAPLAKVINDAFGIEEGLMTTVHSLTATQKTVDGPSHKDWRGGRTASGNIIPSSTGAAKAVGKVLPELQGKLTGMAFRVPTVDVSVVDLTVKLNKETTYDEIKKVVKAAAEGKLKGVLGYTEDAVVSSDFLGDSHSSIFDASAGIQLSPKFVKLVSWYDNEYGYSTRVVDLVEHVAKA
1.2.1.12
null
apoptotic process [GO:0006915]; gluconeogenesis [GO:0006094]; glycolytic process [GO:0006096]; heme transport [GO:0015886]; reactive oxygen species metabolic process [GO:0072593]
cytoplasm [GO:0005737]; cytosol [GO:0005829]; fungal-type cell wall [GO:0009277]; lipid droplet [GO:0005811]; mitochondrion [GO:0005739]; nucleus [GO:0005634]; plasma membrane [GO:0005886]
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity [GO:0004365]; melatonin binding [GO:1904408]; NAD binding [GO:0051287]; NADP binding [GO:0050661]; RNA binding [GO:0003723]
PF02800;PF00044;
3.40.50.720;
Glyceraldehyde-3-phosphate dehydrogenase family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11502169}. Mitochondrion {ECO:0000269|PubMed:16823961}.
CATALYTIC ACTIVITY: Reaction=D-glyceraldehyde 3-phosphate + NAD(+) + phosphate = (2R)-3-phospho-glyceroyl phosphate + H(+) + NADH; Xref=Rhea:RHEA:10300, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57540, ChEBI:CHEBI:57604, ChEBI:CHEBI:57945, ChEBI:CHEBI:59776; EC=1.2.1.12; Evidence={ECO:0000269|PubMed:3905788}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10301; Evidence={ECO:0000269|PubMed:3905788}; CATALYTIC ACTIVITY: Reaction=H2O + NADH = (6R)-NADHX; Xref=Rhea:RHEA:57360, ChEBI:CHEBI:15377, ChEBI:CHEBI:57945, ChEBI:CHEBI:64075; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57361; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; CATALYTIC ACTIVITY: Reaction=H2O + NADH = (6S)-NADHX; Xref=Rhea:RHEA:57364, ChEBI:CHEBI:15377, ChEBI:CHEBI:57945, ChEBI:CHEBI:64074; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57365; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; CATALYTIC ACTIVITY: Reaction=H2O + NADPH = (6R)-NADPHX; Xref=Rhea:RHEA:57368, ChEBI:CHEBI:15377, ChEBI:CHEBI:57783, ChEBI:CHEBI:64077; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57369; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; CATALYTIC ACTIVITY: Reaction=H2O + NADPH = (6S)-NADPHX; Xref=Rhea:RHEA:57372, ChEBI:CHEBI:15377, ChEBI:CHEBI:57783, ChEBI:CHEBI:64076; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57373; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.32 uM for NAD(+) {ECO:0000303|PubMed:3905788};
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5. {ECO:0000269|PubMed:3905788}.
null
null
FUNCTION: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) involved in glycolysis and gluconeogenesis (PubMed:2999100). Catalyzes the reaction of glyceraldehyde-3-phosphate to 1,3 bis-phosphoglycerate (PubMed:3905788). The contribution of the TDH1, TDH2, and TDH3 to the total glyceraldehyde-3-phosphate dehydrogenase activity is 10-15, 25-30, and 50-60%, respectively (PubMed:3905788). {ECO:0000269|PubMed:2999100, ECO:0000269|PubMed:3905788}.; FUNCTION: As a side activity, catalyzes the hydration of the nicotinamide ring of NADH or NADPH at the C6 position to give the corresponding hydrates, NADHX and NADPHX, which exist as R and S epimers, that cannot act as electron donors or acceptors and inhibit several dehydrogenases, making them toxic. {ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00360
G3P1_YEAST
MIRIAINGFGRIGRLVLRLALQRKDIEVVAVNDPFISNDYAAYMVKYDSTHGRYKGTVSHDDKHIIIDGVKIATYQERDPANLPWGSLKIDVAVDSTGVFKELDTAQKHIDAGAKKVVITAPSSSAPMFVVGVNHTKYTPDKKIVSNASCTTNCLAPLAKVINDAFGIEEGLMTTVHSMTATQKTVDGPSHKDWRGGRTASGNIIPSSTGAAKAVGKVLPELQGKLTGMAFRVPTVDVSVVDLTVKLEKEATYDQIKKAVKAAAEGPMKGVLGYTEDAVVSSDFLGDTHASIFDASAGIQLSPKFVKLISWYDNEYGYSARVVDLIEYVAKA
1.2.1.12
null
gluconeogenesis [GO:0006094]; glycolytic process [GO:0006096]
cytosol [GO:0005829]; fungal-type cell wall [GO:0009277]; lipid droplet [GO:0005811]; mitochondrion [GO:0005739]; plasma membrane [GO:0005886]
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity [GO:0004365]; melatonin binding [GO:1904408]; NAD binding [GO:0051287]; NADP binding [GO:0050661]
PF02800;PF00044;
3.40.50.720;
Glyceraldehyde-3-phosphate dehydrogenase family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11502169}.
CATALYTIC ACTIVITY: Reaction=D-glyceraldehyde 3-phosphate + NAD(+) + phosphate = (2R)-3-phospho-glyceroyl phosphate + H(+) + NADH; Xref=Rhea:RHEA:10300, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57540, ChEBI:CHEBI:57604, ChEBI:CHEBI:57945, ChEBI:CHEBI:59776; EC=1.2.1.12; Evidence={ECO:0000269|PubMed:3905788}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10301; Evidence={ECO:0000269|PubMed:3905788}; CATALYTIC ACTIVITY: Reaction=H2O + NADH = (6R)-NADHX; Xref=Rhea:RHEA:57360, ChEBI:CHEBI:15377, ChEBI:CHEBI:57945, ChEBI:CHEBI:64075; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57361; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; CATALYTIC ACTIVITY: Reaction=H2O + NADH = (6S)-NADHX; Xref=Rhea:RHEA:57364, ChEBI:CHEBI:15377, ChEBI:CHEBI:57945, ChEBI:CHEBI:64074; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57365; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; CATALYTIC ACTIVITY: Reaction=H2O + NADPH = (6R)-NADPHX; Xref=Rhea:RHEA:57368, ChEBI:CHEBI:15377, ChEBI:CHEBI:57783, ChEBI:CHEBI:64077; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57369; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; CATALYTIC ACTIVITY: Reaction=H2O + NADPH = (6S)-NADPHX; Xref=Rhea:RHEA:57372, ChEBI:CHEBI:15377, ChEBI:CHEBI:57783, ChEBI:CHEBI:64076; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57373; Evidence={ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815};
null
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5. {ECO:0000269|PubMed:3905788}.
null
null
FUNCTION: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) involved in glycolysis and gluconeogenesis (PubMed:2999100). Catalyzes the reaction of glyceraldehyde-3-phosphate to 1,3 bis-phosphoglycerate (PubMed:3905788). The contribution of the TDH1, TDH2, and TDH3 to the total glyceraldehyde-3-phosphate dehydrogenase activity is 10-15, 25-30, and 50-60%, respectively (PubMed:3905788). May be involved in a process other than glycolysis because it is synthesized by cells in stationary phase (PubMed:7875559). {ECO:0000269|PubMed:2999100, ECO:0000269|PubMed:3905788, ECO:0000269|PubMed:7875559}.; FUNCTION: As a side activity, catalyzes the hydration of the nicotinamide ring of NADH or NADPH at the C6 position to give the corresponding hydrates, NADHX and NADPHX, which exist as R and S epimers, that cannot act as electron donors or acceptors and inhibit several dehydrogenases, making them toxic. {ECO:0000269|PubMed:13174589, ECO:0000269|PubMed:4371815}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00362
G3P_GEOSE
MAVKVGINGFGRIGRNVFRAALKNPDIEVVAVNDLTDANTLAHLLKYDSVHGRLDAEVSVNGNNLVVNGKEIIVKAERDPENLAWGEIGVDIVVESTGRFTKREDAAKHLEAGAKKVIISAPAKNEDITIVMGVNQDKYDPKAHHVISNASCTTNCLAPFAKVLHEQFGIVRGMMTTVHSYTNDQRILDLPHKDLRRARAAAESIIPTTTGAAKAVALVLPELKGKLNGMAMRVPTPNVSVVDLVAELEKEVTVEEVNAALKAAAEGELKGILAYSEEPLVSRDYNGSTVSSTIDALSTMVIDGKMVKVVSWYDNETGYSHRVVDLAAYIASKGL
1.2.1.12
null
glucose metabolic process [GO:0006006]; glycolytic process [GO:0006096]
cytoplasm [GO:0005737]
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity [GO:0004365]; NAD binding [GO:0051287]; NADP binding [GO:0050661]
PF02800;PF00044;
3.40.50.720;
Glyceraldehyde-3-phosphate dehydrogenase family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:9175858}.
CATALYTIC ACTIVITY: Reaction=D-glyceraldehyde 3-phosphate + NAD(+) + phosphate = (2R)-3-phospho-glyceroyl phosphate + H(+) + NADH; Xref=Rhea:RHEA:10300, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57540, ChEBI:CHEBI:57604, ChEBI:CHEBI:57945, ChEBI:CHEBI:59776; EC=1.2.1.12; Evidence={ECO:0000250|UniProtKB:P09124};
null
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5. {ECO:0000305}.
null
null
FUNCTION: Catalyzes the oxidative phosphorylation of glyceraldehyde 3-phosphate (G3P) to 1,3-bisphosphoglycerate (BPG) using the cofactor NAD. The first reaction step involves the formation of a hemiacetal intermediate between G3P and a cysteine residue, and this hemiacetal intermediate is then oxidized to a thioester, with concomitant reduction of NAD to NADH. The reduced NADH is then exchanged with the second NAD, and the thioester is attacked by a nucleophilic inorganic phosphate to produce BPG. {ECO:0000269|PubMed:12569100, ECO:0000269|PubMed:18480053}.
Geobacillus stearothermophilus (Bacillus stearothermophilus)
P00363
FRDA_ECOLI
MQTFQADLAIVGAGGAGLRAAIAAAQANPNAKIALISKVYPMRSHTVAAEGGSAAVAQDHDSFEYHFHDTVAGGDWLCEQDVVDYFVHHCPTEMTQLELWGCPWSRRPDGSVNVRRFGGMKIERTWFAADKTGFHMLHTLFQTSLQFPQIQRFDEHFVLDILVDDGHVRGLVAMNMMEGTLVQIRANAVVMATGGAGRVYRYNTNGGIVTGDGMGMALSHGVPLRDMEFVQYHPTGLPGSGILMTEGCRGEGGILVNKNGYRYLQDYGMGPETPLGEPKNKYMELGPRDKVSQAFWHEWRKGNTISTPRGDVVYLDLRHLGEKKLHERLPFICELAKAYVGVDPVKEPIPVRPTAHYTMGGIETDQNCETRIKGLFAVGECSSVGLHGANRLGSNSLAELVVFGRLAGEQATERAATAGNGNEAAIEAQAAGVEQRLKDLVNQDGGENWAKIRDEMGLAMEEGCGIYRTPELMQKTIDKLAELQERFKRVRITDTSSVFNTDLLYTIELGHGLNVAECMAHSAMARKESRGAHQRLDEGCTERDDVNFLKHTLAFRDADGTTRLEYSDVKITTLPPAKRVYGGEADAADKAEAANKKEKANG
1.3.5.1
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD covalently per subunit (PubMed:10373108, PubMed:24374335, PubMed:26644464). Flavinylated by SdhE, about 5% flavinylation occurs in the absence of SdhE (PubMed:24374335, PubMed:26644464). {ECO:0000269|PubMed:10373108, ECO:0000269|PubMed:24374335, ECO:0000269|PubMed:26644464};
anaerobic electron transport chain [GO:0019645]; anaerobic respiration [GO:0009061]; bacterial-type flagellum assembly [GO:0044780]; DNA damage response [GO:0006974]; fermentation [GO:0006113]
cytosol [GO:0005829]; membrane [GO:0016020]; plasma membrane [GO:0005886]; plasma membrane fumarate reductase complex [GO:0045284]
electron transfer activity [GO:0009055]; FAD binding [GO:0071949]; flavin adenine dinucleotide binding [GO:0050660]; succinate dehydrogenase (quinone) activity [GO:0008177]; succinate dehydrogenase activity [GO:0000104]
PF00890;PF02910;
3.50.50.60;1.20.58.100;4.10.80.40;3.90.700.10;
FAD-dependent oxidoreductase 2 family, FRD/SDH subfamily
null
SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305|PubMed:10373108, ECO:0000305|PubMed:20484676}; Peripheral membrane protein {ECO:0000305|PubMed:10373108}; Cytoplasmic side {ECO:0000305|PubMed:10373108}.
CATALYTIC ACTIVITY: Reaction=a quinone + succinate = a quinol + fumarate; Xref=Rhea:RHEA:40523, ChEBI:CHEBI:24646, ChEBI:CHEBI:29806, ChEBI:CHEBI:30031, ChEBI:CHEBI:132124; EC=1.3.5.1; Evidence={ECO:0000269|PubMed:11850430}; CATALYTIC ACTIVITY: Reaction=a menaquinone + succinate = a menaquinol + fumarate; Xref=Rhea:RHEA:27834, Rhea:RHEA-COMP:9537, Rhea:RHEA-COMP:9539, ChEBI:CHEBI:16374, ChEBI:CHEBI:18151, ChEBI:CHEBI:29806, ChEBI:CHEBI:30031; EC=1.3.5.1; Evidence={ECO:0000305|PubMed:10373108};
null
null
null
null
FUNCTION: Two distinct, membrane-bound, FAD-containing enzymes are responsible for the catalysis of fumarate and succinate interconversion; fumarate reductase is used during anaerobic growth, and succinate dehydrogenase is used during aerobic growth. The QFR enzyme complex binds 2 quinones in or near the membrane; 1 near the [3Fe-4S] cluster (QP is proximal to the [3Fe-4S] cluster, on the cytoplasmic side of the membrane) while QD (the distal cluster) is on the other side of the membrane. It is not clear if both of the quinol-binding sites are functionally relevant (PubMed:10373108, PubMed:11850430). {ECO:0000269|PubMed:10373108, ECO:0000269|PubMed:11850430, ECO:0000269|PubMed:24374335}.
Escherichia coli (strain K12)
P00366
DHE3_BOVIN
MYRYLGEALLLSRAGPAALGSASADSAALLGWARGQPAAAPQPGLVPPARRHYSEAAADREDDPNFFKMVEGFFDRGASIVEDKLVEDLKTRETEEQKRNRVRSILRIIKPCNHVLSLSFPIRRDDGSWEVIEGYRAQHSQHRTPCKGGIRYSTDVSVDEVKALASLMTYKCAVVDVPFGGAKAGVKINPKNYTDNELEKITRRFTMELAKKGFIGPGVDVPAPDMSTGEREMSWIADTYASTIGHYDINAHACVTGKPISQGGIHGRISATGRGVFHGIENFINEASYMSILGMTPGFGDKTFVVQGFGNVGLHSMRYLHRFGAKCITVGESDGSIWNPDGIDPKELEDFKLQHGTILGFPKAKIYEGSILEVDCDILIPAASEKQLTKSNAPRVKAKIIAEGANGPTTPEADKIFLERNIMVIPDLYLNAGGVTVSYFEWLNNLNHVSYGRLTFKYERDSNYHLLMSVQESLERKFGKHGGTIPIVPTAEFQDRISGASEKDIVHSGLAYTMERSARQIMRTAMKYNLGLDLRTAAYVNAIEKVFRVYNEAGVTFT
1.4.1.3
null
glutamate catabolic process [GO:0006538]; glutamine metabolic process [GO:0006541]; tricarboxylic acid metabolic process [GO:0072350]
endoplasmic reticulum [GO:0005783]; mitochondrial inner membrane [GO:0005743]; mitochondrion [GO:0005739]
ATP binding [GO:0005524]; glutamate dehydrogenase (NAD+) activity [GO:0004352]; glutamate dehydrogenase (NADP+) activity [GO:0004354]; glutamate dehydrogenase [NAD(P)+] activity [GO:0004353]; GTP binding [GO:0005525]; identical protein binding [GO:0042802]
PF00208;PF02812;
1.10.287.140;3.40.50.10860;3.40.50.720;
Glu/Leu/Phe/Val dehydrogenases family
PTM: ADP-ribosylated by SIRT4, leading to inactivate glutamate dehydrogenase activity. Stoichiometry shows that ADP-ribosylation occurs in one subunit per catalytically active homohexamer. {ECO:0000250|UniProtKB:P00367}.
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P00367}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P00367}. Note=Mostly translocates into the mitochondria, only a small amount of the protein localizes to the endoplasmic reticulum. {ECO:0000250|UniProtKB:P00367}.
CATALYTIC ACTIVITY: Reaction=H2O + L-glutamate + NAD(+) = 2-oxoglutarate + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:15133, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.4.1.3; Evidence={ECO:0000269|PubMed:14659072, ECO:0000269|PubMed:4365183}; CATALYTIC ACTIVITY: Reaction=H2O + L-glutamate + NADP(+) = 2-oxoglutarate + H(+) + NADPH + NH4(+); Xref=Rhea:RHEA:11612, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.4.1.3; Evidence={ECO:0000250|UniProtKB:P00367};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.1 mM for NAD(+) {ECO:0000269|PubMed:14659072}; Vmax=100 umol/min/mg enzyme with NAD(+)as substrate {ECO:0000269|PubMed:14659072};
null
null
null
FUNCTION: Mitochondrial glutamate dehydrogenase that converts L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle (PubMed:14659072, PubMed:4365183). Plays a role in insulin homeostasis (By similarity). May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity). {ECO:0000250|UniProtKB:P00367, ECO:0000250|UniProtKB:P10860, ECO:0000269|PubMed:14659072, ECO:0000269|PubMed:4365183}.
Bos taurus (Bovine)
P00367
DHE3_HUMAN
MYRYLGEALLLSRAGPAALGSASADSAALLGWARGQPAAAPQPGLALAARRHYSEAVADREDDPNFFKMVEGFFDRGASIVEDKLVEDLRTRESEEQKRNRVRGILRIIKPCNHVLSLSFPIRRDDGSWEVIEGYRAQHSQHRTPCKGGIRYSTDVSVDEVKALASLMTYKCAVVDVPFGGAKAGVKINPKNYTDNELEKITRRFTMELAKKGFIGPGIDVPAPDMSTGEREMSWIADTYASTIGHYDINAHACVTGKPISQGGIHGRISATGRGVFHGIENFINEASYMSILGMTPGFGDKTFVVQGFGNVGLHSMRYLHRFGAKCIAVGESDGSIWNPDGIDPKELEDFKLQHGSILGFPKAKPYEGSILEADCDILIPAASEKQLTKSNAPRVKAKIIAEGANGPTTPEADKIFLERNIMVIPDLYLNAGGVTVSYFEWLKNLNHVSYGRLTFKYERDSNYHLLMSVQESLERKFGKHGGTIPIVPTAEFQDRISGASEKDIVHSGLAYTMERSARQIMRTAMKYNLGLDLRTAAYVNAIEKVFKVYNEAGVTFT
1.4.1.3
null
glutamate biosynthetic process [GO:0006537]; glutamate catabolic process [GO:0006538]; glutamine metabolic process [GO:0006541]; positive regulation of insulin secretion [GO:0032024]; substantia nigra development [GO:0021762]; tricarboxylic acid metabolic process [GO:0072350]
cytoplasm [GO:0005737]; endoplasmic reticulum [GO:0005783]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
ADP binding [GO:0043531]; ATP binding [GO:0005524]; glutamate dehydrogenase (NAD+) activity [GO:0004352]; glutamate dehydrogenase (NADP+) activity [GO:0004354]; glutamate dehydrogenase [NAD(P)+] activity [GO:0004353]; GTP binding [GO:0005525]; leucine binding [GO:0070728]; NAD+ binding [GO:0070403]; protein homodimerization activity [GO:0042803]
PF00208;PF02812;
1.10.287.140;3.40.50.10860;3.40.50.720;
Glu/Leu/Phe/Val dehydrogenases family
PTM: ADP-ribosylated by SIRT4, leading to inactivate glutamate dehydrogenase activity (PubMed:16959573). Stoichiometry shows that ADP-ribosylation occurs in one subunit per catalytically active homohexamer (PubMed:16023112). {ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573}.
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:19448744}. Endoplasmic reticulum {ECO:0000269|PubMed:19448744}. Note=Mostly translocates into the mitochondria, only a small amount of the protein localizes to the endoplasmic reticulum. {ECO:0000269|PubMed:19448744}.
CATALYTIC ACTIVITY: Reaction=H2O + L-glutamate + NAD(+) = 2-oxoglutarate + H(+) + NADH + NH4(+); Xref=Rhea:RHEA:15133, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.4.1.3; Evidence={ECO:0000269|PubMed:11254391, ECO:0000269|PubMed:11903050, ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573}; CATALYTIC ACTIVITY: Reaction=H2O + L-glutamate + NADP(+) = 2-oxoglutarate + H(+) + NADPH + NH4(+); Xref=Rhea:RHEA:11612, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.4.1.3; Evidence={ECO:0000269|PubMed:11032875};
null
null
null
null
FUNCTION: Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle (PubMed:11032875, PubMed:11254391, PubMed:16023112, PubMed:16959573). Plays a role in insulin homeostasis (PubMed:11297618, PubMed:9571255). May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity). {ECO:0000250|UniProtKB:P10860, ECO:0000269|PubMed:11032875, ECO:0000269|PubMed:11254391, ECO:0000269|PubMed:11297618, ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573, ECO:0000269|PubMed:9571255}.
Homo sapiens (Human)
P00370
DHE4_ECOLI
MDQTYSLESFLNHVQKRDPNQTEFAQAVREVMTTLWPFLEQNPKYRQMSLLERLVEPERVIQFRVVWVDDRNQIQVNRAWRVQFSSAIGPYKGGMRFHPSVNLSILKFLGFEQTFKNALTTLPMGGGKGGSDFDPKGKSEGEVMRFCQALMTELYRHLGADTDVPAGDIGVGGREVGFMAGMMKKLSNNTACVFTGKGLSFGGSLIRPEATGYGLVYFTEAMLKRHGMGFEGMRVSVSGSGNVAQYAIEKAMEFGARVITASDSSGTVVDESGFTKEKLARLIEIKASRDGRVADYAKEFGLVYLEGQQPWSLPVDIALPCATQNELDVDAAHQLIANGVKAVAEGANMPTTIEATELFQQAGVLFAPGKAANAGGVATSGLEMAQNAARLGWKAEKVDARLHHIMLDIHHACVEHGGEGEQTNYVQGANIAGFVKVADAMLAQGVI
1.4.1.4
null
glutamate biosynthetic process [GO:0006537]; glutamate metabolic process [GO:0006536]
cytoplasm [GO:0005737]; cytosol [GO:0005829]; glutamate dehydrogenase complex [GO:1990148]
glutamate dehydrogenase (NADP+) activity [GO:0004354]; guanosine tetraphosphate binding [GO:0097216]; identical protein binding [GO:0042802]
PF00208;PF02812;
1.10.285.10;3.40.50.10860;3.40.50.720;
Glu/Leu/Phe/Val dehydrogenases family
null
null
CATALYTIC ACTIVITY: Reaction=H2O + L-glutamate + NADP(+) = 2-oxoglutarate + H(+) + NADPH + NH4(+); Xref=Rhea:RHEA:11612, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.4.1.4; Evidence={ECO:0000269|PubMed:235298, ECO:0000269|PubMed:241744};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=40 uM for NADPH {ECO:0000269|PubMed:241744}; KM=42 uM for NADP {ECO:0000269|PubMed:241744}; KM=640 uM for 2-oxoglutarate {ECO:0000269|PubMed:241744}; KM=1100 uM for ammonia {ECO:0000269|PubMed:241744};
null
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8 and 9 for the reductive amination and for the oxidative deamination, respectively. {ECO:0000269|PubMed:235298};
BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: The enzyme remains active when heat treated or when left at room temperature for several months but is inactivated by freezing. {ECO:0000269|PubMed:241744};
FUNCTION: Catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate and ammonia. {ECO:0000269|PubMed:235298, ECO:0000269|PubMed:241744}.
Escherichia coli (strain K12)
P00371
OXDA_PIG
MRVVVIGAGVIGLSTALCIHERYHSVLQPLDVKVYADRFTPFTTTDVAAGLWQPYTSEPSNPQEANWNQQTFNYLLSHIGSPNAANMGLTPVSGYNLFREAVPDPYWKDMVLGFRKLTPRELDMFPDYRYGWFNTSLILEGRKYLQWLTERLTERGVKFFLRKVESFEEVARGGADVIINCTGVWAGVLQPDPLLQPGRGQIIKVDAPWLKNFIITHDLERGIYNSPYIIPGLQAVTLGGTFQVGNWNEINNIQDHNTIWEGCCRLEPTLKDAKIVGEYTGFRPVRPQVRLEREQLRFGSSNTEVIHNYGHGGYGLTIHWGCALEVAKLFGKVLEERNLLTMPPSHL
1.4.3.3
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:10876160, ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:24644036, ECO:0000269|PubMed:6120171, ECO:0000269|PubMed:8755502, ECO:0000269|PubMed:9153426, ECO:0000269|PubMed:9399588};
D-alanine catabolic process [GO:0055130]; D-amino acid catabolic process [GO:0019478]; D-serine catabolic process [GO:0036088]; digestion [GO:0007586]; dopamine biosynthetic process [GO:0042416]; neutrophil-mediated killing of gram-negative bacterium [GO:0070945]; proline catabolic process [GO:0006562]
cytoplasm [GO:0005737]; peroxisomal matrix [GO:0005782]; peroxisome [GO:0005777]; presynaptic active zone [GO:0048786]
D-amino-acid oxidase activity [GO:0003884]; FAD binding [GO:0071949]
PF01266;
3.30.9.10;3.40.50.720;
DAMOX/DASOX family
PTM: Phosphorylated in the cerebellum; probably not by PRKACA, PRKCA or PRKCE. {ECO:0000250|UniProtKB:P14920}.; PTM: May be S-nitrosylated, which partially inactivates the enzyme. {ECO:0000250|UniProtKB:P14920}.
SUBCELLULAR LOCATION: Peroxisome matrix {ECO:0000269|PubMed:33725110}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P14920}. Presynaptic active zone {ECO:0000250|UniProtKB:O35078}. Secreted {ECO:0000250|UniProtKB:P18894}. Note=Transiently present in the cytosol before being delivered to the peroxisomes (By similarity). In the cerebellum, a fraction of protein localizes to the presynaptic active zone, where its activity is regulated by protein BSN (By similarity). Secreted into the lumen of the small intestine (By similarity). {ECO:0000250|UniProtKB:O35078, ECO:0000250|UniProtKB:P14920, ECO:0000250|UniProtKB:P18894}.
CATALYTIC ACTIVITY: Reaction=a D-alpha-amino acid + H2O + O2 = a 2-oxocarboxylate + H2O2 + NH4(+); Xref=Rhea:RHEA:21816, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:35179, ChEBI:CHEBI:59871; EC=1.4.3.3; Evidence={ECO:0000269|PubMed:10876160, ECO:0000269|PubMed:15058991, ECO:0000269|PubMed:1673125, ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:17469229, ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:24492954, ECO:0000269|PubMed:24644036, ECO:0000269|PubMed:28592826, ECO:0000269|PubMed:2904274, ECO:0000269|PubMed:30333894, ECO:0000269|PubMed:6120171, ECO:0000269|PubMed:6129252, ECO:0000305|PubMed:27648606}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21817; Evidence={ECO:0000269|PubMed:10876160, ECO:0000269|PubMed:15058991, ECO:0000269|PubMed:1673125, ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:17469229, ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:24492954, ECO:0000269|PubMed:24644036, ECO:0000269|PubMed:28592826, ECO:0000269|PubMed:2904274, ECO:0000269|PubMed:30333894, ECO:0000269|PubMed:6120171, ECO:0000269|PubMed:6129252, ECO:0000305|PubMed:27648606}; CATALYTIC ACTIVITY: Reaction=D-alanine + H2O + O2 = H2O2 + NH4(+) + pyruvate; Xref=Rhea:RHEA:22688, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:57416; Evidence={ECO:0000269|PubMed:15058991, ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:17469229, ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:28592826, ECO:0000269|PubMed:2904274}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22689; Evidence={ECO:0000269|PubMed:15058991, ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:17469229, ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:28592826, ECO:0000269|PubMed:2904274}; CATALYTIC ACTIVITY: Reaction=D-cysteine + H2O + O2 = 2-oxo-3-sulfanylpropanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:78791, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:35236, ChEBI:CHEBI:57678; Evidence={ECO:0000250|UniProtKB:P14920}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78792; Evidence={ECO:0000250|UniProtKB:P14920}; CATALYTIC ACTIVITY: Reaction=D-dopa + H2O + O2 = 3-(3,4-dihydroxyphenyl)pyruvate + H2O2 + NH4(+); Xref=Rhea:RHEA:70971, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:29055, ChEBI:CHEBI:149689; Evidence={ECO:0000250|UniProtKB:P14920}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70972; Evidence={ECO:0000250|UniProtKB:P14920}; CATALYTIC ACTIVITY: Reaction=D-leucine + H2O + O2 = 4-methyl-2-oxopentanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:78211, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17865, ChEBI:CHEBI:28938, ChEBI:CHEBI:143079; Evidence={ECO:0000269|PubMed:28592826}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78212; Evidence={ECO:0000269|PubMed:28592826}; CATALYTIC ACTIVITY: Reaction=D-lysine + H2O + O2 = 6-amino-2-oxohexanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:37583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:32557, ChEBI:CHEBI:58183; EC=1.4.3.3; Evidence={ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:28592826}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37584; Evidence={ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:28592826}; CATALYTIC ACTIVITY: Reaction=D-methionine + H2O + O2 = 4-methylsulfanyl-2-oxobutanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:78207, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:16723, ChEBI:CHEBI:28938, ChEBI:CHEBI:57932; Evidence={ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:24492954, ECO:0000269|PubMed:28592826}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78208; Evidence={ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:24492954, ECO:0000269|PubMed:28592826}; CATALYTIC ACTIVITY: Reaction=D-phenylalanine + H2O + O2 = 3-phenylpyruvate + H2O2 + NH4(+); Xref=Rhea:RHEA:70963, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:18005, ChEBI:CHEBI:28938, ChEBI:CHEBI:57981; Evidence={ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:24644036, ECO:0000269|PubMed:28592826}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70964; Evidence={ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:24644036, ECO:0000269|PubMed:28592826}; CATALYTIC ACTIVITY: Reaction=D-proline + O2 = 1-pyrroline-2-carboxylate + H2O2; Xref=Rhea:RHEA:78259, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:39785, ChEBI:CHEBI:57726; Evidence={ECO:0000269|PubMed:10876160, ECO:0000269|PubMed:28592826}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78260; Evidence={ECO:0000269|PubMed:10876160, ECO:0000269|PubMed:28592826}; CATALYTIC ACTIVITY: Reaction=D-serine + H2O + O2 = 3-hydroxypyruvate + H2O2 + NH4(+); Xref=Rhea:RHEA:70951, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17180, ChEBI:CHEBI:28938, ChEBI:CHEBI:35247; Evidence={ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:28592826}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70952; Evidence={ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:28592826}; CATALYTIC ACTIVITY: Reaction=D-tryptophan + H2O + O2 = H2O2 + indole-3-pyruvate + NH4(+); Xref=Rhea:RHEA:78247, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17640, ChEBI:CHEBI:28938, ChEBI:CHEBI:57719; Evidence={ECO:0000269|PubMed:28592826}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78248; Evidence={ECO:0000269|PubMed:28592826}; CATALYTIC ACTIVITY: Reaction=D-valine + H2O + O2 = 3-methyl-2-oxobutanoate + H2O2 + NH4(+); Xref=Rhea:RHEA:78203, ChEBI:CHEBI:11851, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:74338; Evidence={ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:28592826}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78204; Evidence={ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:28592826};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=13 mM for D-arginine (at 25 degrees Celsius and at pH 8.3) {ECO:0000269|PubMed:16751595}; KM=10 mM for D-lysine (at 25 degrees Celsius and at pH 8.3) {ECO:0000269|PubMed:16751595}; KM=0.65 mM for D-methionine (at 25 degrees Celsius and at pH 8.3) {ECO:0000269|PubMed:16751595}; KM=0.19 mM for D-methionine (at 30 degrees Celsius and at pH 7.6) {ECO:0000269|PubMed:24492954}; KM=1.4 mM for D-phenylalanine (at 25 degrees Celsius and at pH 8.3) {ECO:0000269|PubMed:16751595}; KM=0.56 mM for D-proline (at 25 degrees Celsius and at pH 8.3) {ECO:0000269|PubMed:16751595}; KM=0.38 mM for D-proline (at 37 degrees Celsius and at pH 7.5) {ECO:0000269|PubMed:28592826}; KM=0.33 mM for D-proline (at 37 degrees Celsius and at pH 8) {ECO:0000269|PubMed:28592826}; KM=0.85 mM for D-proline (at 37 degrees Celsius and at pH 8.5) {ECO:0000269|PubMed:28592826}; KM=0.63 mM for D-valine (at 25 degrees Celsius and at pH 8.3) {ECO:0000269|PubMed:16751595}; KM=0.77 mM for D-alanine (at 25 degrees Celsius and at pH 8.3) {ECO:0000269|PubMed:16751595}; KM=2.56 mM for D-alanine (at 25 degrees Celsius and at pH 8.3) {ECO:0000269|PubMed:2904274}; KM=1.7 mM for D-alanine (at 25 degrees Celsius and at pH 8.5) {ECO:0000269|PubMed:15058991}; KM=30.5 mM for D-alanine (at 37 degrees Celsius and at pH 7) {ECO:0000269|PubMed:28592826}; KM=38.2 mM for D-alanine (at 37 degrees Celsius and at pH 9.8) {ECO:0000269|PubMed:28592826}; KM=3.3 mM for D-serine (at 25 degrees Celsius and at pH 8.3) {ECO:0000269|PubMed:16751595}; KM=2.3 mM for cephalosporin C (CPC) (at 25 degrees Celsius and at pH 8.5) {ECO:0000269|PubMed:15058991}; KM=252 mM for L-proline (at 37 degrees Celsius and at pH 7.5) {ECO:0000269|PubMed:28592826}; KM=20 mM for L-proline (at 37 degrees Celsius and at pH 8) {ECO:0000269|PubMed:28592826}; KM=1800 mM for L-proline (at 37 degrees Celsius and at pH 8.5) {ECO:0000269|PubMed:28592826}; KM=362 mM for L-alanine (at 37 degrees Celsius and at pH 7) {ECO:0000269|PubMed:28592826}; KM=43.11 mM for L-alanine (at 37 degrees Celsius and at pH 9.8) {ECO:0000269|PubMed:28592826}; KM=45 mM for L-aspartate (at 37 degrees Celsius and at pH 8) {ECO:0000269|PubMed:28592826}; KM=43 mM for D-aspartate (at 37 degrees Celsius and at pH 8) {ECO:0000269|PubMed:28592826}; KM=0.09 mM for oxygen (at 30 degrees Celsius and at pH 7.6) {ECO:0000269|PubMed:24492954}; Note=kcat is 3.5 sec(-1) with D-arginine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:16751595). kcat is 0.8 sec(-1) with D-lysine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:16751595). kcat is 6.8 sec(-1) with D-methionine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:16751595). kcat is 16.7 sec(-1) with D-phenylalanine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:16751595). kcat is 10.3 sec(-1) with D-proline as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:16751595). kcat is 50.2 sec(-1) with D-proline as substrate (at 37 degrees Celsius and at pH 7.5) (PubMed:28592826). kcat is 107.3 sec(-1) with D-proline as substrate (at 37 degrees Celsius and at pH 8) (PubMed:28592826). kcat is 43.3 sec(-1) with D-proline as substrate (at 37 degrees Celsius and at pH 8.5) (PubMed:28592826). kcat is 2.5 sec(-1) with D-valine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:16751595). kcat is 6.5 sec(-1) with D-alanine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:16751595). kcat is 7.3 sec(-1) with D-alanine as substrate (at 25 degrees Celsius and at pH 8.5) (PubMed:15058991). kcat is 151.2 sec(-1) with D-alanine as substrate (at 37 degrees Celsius and at pH 7) (PubMed:28592826). kcat is 133.3 sec(-1) with D-alanine as substrate (at 37 degrees Celsius and at pH 9.8) (PubMed:28592826). kcat is 3 sec(-1) with D-serine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:16751595). kcat is 0.65 sec(-1) with cephalosporin C (CPC) as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:15058991). kcat is 0.7 sec(-1) with L-proline as substrate (at 37 degrees Celsius and at pH 7.5) (PubMed:28592826). kcat is 6.71 sec(-1) with L-proline as substrate (at 37 degrees Celsius and at pH 8) (PubMed:28592826). kcat is 0.4 sec(-1) with L-proline as substrate (at 37 degrees Celsius and at pH 8.5) (PubMed:28592826). kcat is 0.09 sec(-1) with L-alanine as substrate (at 37 degrees Celsius and at pH 7) (PubMed:28592826). kcat is 9.4 sec(-1) with L-alanine as substrate (at 37 degrees Celsius and at pH 9.8) (PubMed:28592826). kcat is 0.89 sec(-1) with L-aspartate as substrate (at 37 degrees Celsius and at pH 8) (PubMed:28592826). kcat is 0.95 sec(-1) with D-aspartate as substrate (at 37 degrees Celsius and at pH 8) (PubMed:28592826). {ECO:0000269|PubMed:15058991, ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:28592826};
null
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is around 9-10. {ECO:0000269|PubMed:15058991};
null
FUNCTION: Catalyzes the oxidative deamination of D-amino acids with broad substrate specificity (PubMed:10876160, PubMed:16751595, PubMed:17469229, PubMed:20603179, PubMed:24492954, PubMed:24644036, PubMed:28592826, PubMed:2904274, PubMed:30333894). Required to catabolize D-amino acids synthesized endogenously, of gastrointestinal bacterial origin or obtained from the diet, and to use these as nutrients (By similarity). Regulates the level of D-amino acid neurotransmitters in the brain, such as D-serine, a co-agonist of N-methyl D-aspartate (NMDA) receptors, and may modulate synaptic transmission (By similarity). Catalyzes the first step of the racemization of D-DOPA to L-DOPA, for possible use in an alternative dopamine biosynthesis pathway (By similarity). Also catalyzes the first step of the chiral inversion of N(gamma)-nitro-D-arginine methyl ester (D-NNA) to its L-enantiomer L-NNA that acts as a nitric oxide synthase inhibitor (By similarity). The hydrogen peroxide produced in the reaction provides protection against microbial infection; it contributes to the oxidative killing activity of phagocytic leukocytes and protects against bacterial colonization of the small intestine (PubMed:22271930, PubMed:25425233, PubMed:27670111). Enzyme secreted into the lumen of the intestine may not be catalytically active and could instead be proteolytically cleaved into peptides with antimicrobial activity (By similarity). The hydrogen peroxide produced in the reaction may also play a role in promoting cellular senescence in response to DNA damage (By similarity). Could act as a detoxifying agent which removes D-amino acids accumulated during aging (By similarity). {ECO:0000250|UniProtKB:P14920, ECO:0000250|UniProtKB:P18894, ECO:0000269|PubMed:10876160, ECO:0000269|PubMed:16751595, ECO:0000269|PubMed:17469229, ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:22271930, ECO:0000269|PubMed:24492954, ECO:0000269|PubMed:24644036, ECO:0000269|PubMed:25425233, ECO:0000269|PubMed:27670111, ECO:0000269|PubMed:28592826, ECO:0000269|PubMed:2904274, ECO:0000269|PubMed:30333894}.
Sus scrofa (Pig)
P00372
DHML_METEA
MLGKSQFDDLFEKMSRKVAGHTSRRGFIGRVGTAVAGVALVPLLPVDRRGRVSRANAAESAGDPRGKWKPQDNDVQSCDYWRHCSIDGNICDCSGGSLTSCPPGTKLASSSWVASCYNPTDKQSYLISYRDCCGANVSGRCACLNTEGELPVYRPEFGNDIIWCFGAEDDAMTYHCTISPIVGKAS
1.4.9.1
COFACTOR: Name=tryptophan tryptophylquinone residue; Xref=ChEBI:CHEBI:20251; Note=Uses a protein-derived tryptophan tryptophylquinone (TTQ) cofactor.;
amine metabolic process [GO:0009308]
outer membrane-bounded periplasmic space [GO:0030288]
amine dehydrogenase activity [GO:0030058]; methylamine dehydrogenase (amicyanin) activity [GO:0052876]
PF02975;
2.60.30.10;
Aromatic amine dehydrogenase light chain family
PTM: Predicted to be exported by the Tat system. The position of the signal peptide cleavage has been experimentally proven.; PTM: Tryptophan tryptophylquinone (TTQ) is formed by oxidation of the indole ring of a tryptophan to form tryptophylquinone followed by covalent cross-linking with another tryptophan residue.
SUBCELLULAR LOCATION: Periplasm.
CATALYTIC ACTIVITY: Reaction=H2O + methylamine + 2 oxidized [amicyanin] = formaldehyde + 2 H(+) + NH4(+) + 2 reduced [amicyanin]; Xref=Rhea:RHEA:30207, Rhea:RHEA-COMP:11100, Rhea:RHEA-COMP:11101, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16842, ChEBI:CHEBI:28938, ChEBI:CHEBI:29036, ChEBI:CHEBI:49552, ChEBI:CHEBI:59338; EC=1.4.9.1;
null
PATHWAY: One-carbon metabolism; methylamine degradation; formaldehyde from methylamine: step 1/1.
null
null
FUNCTION: Methylamine dehydrogenase carries out the oxidation of methylamine. Electrons are passed from methylamine dehydrogenase to amicyanin.
Methylorubrum extorquens (strain ATCC 14718 / DSM 1338 / JCM 2805 / NCIMB 9133 / AM1) (Methylobacterium extorquens)
P00374
DYR_HUMAN
MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND
1.5.1.3
null
axon regeneration [GO:0031103]; dihydrofolate metabolic process [GO:0046452]; folic acid metabolic process [GO:0046655]; glycine biosynthetic process [GO:0006545]; negative regulation of translation [GO:0017148]; one-carbon metabolic process [GO:0006730]; positive regulation of nitric-oxide synthase activity [GO:0051000]; regulation of removal of superoxide radicals [GO:2000121]; response to methotrexate [GO:0031427]; tetrahydrobiopterin biosynthetic process [GO:0006729]; tetrahydrofolate biosynthetic process [GO:0046654]; tetrahydrofolate metabolic process [GO:0046653]
cytosol [GO:0005829]; mitochondrion [GO:0005739]
dihydrofolate reductase activity [GO:0004146]; folic acid binding [GO:0005542]; mRNA binding [GO:0003729]; mRNA regulatory element binding translation repressor activity [GO:0000900]; NADP binding [GO:0050661]; NADPH binding [GO:0070402]; sequence-specific mRNA binding [GO:1990825]
PF00186;
3.40.430.10;
Dihydrofolate reductase family
null
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P00375}. Cytoplasm {ECO:0000250|UniProtKB:P00375}.
CATALYTIC ACTIVITY: Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378, ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.5.1.3; Evidence={ECO:0000255|PROSITE-ProRule:PRU00660, ECO:0000269|PubMed:12096917, ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:17569517, ECO:0000269|PubMed:19196009, ECO:0000269|PubMed:19478082, ECO:0000269|PubMed:21876184, ECO:0000269|PubMed:9719595};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.7 uM for dihydrofolate {ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:19196009, ECO:0000269|PubMed:21876184}; KM=4 uM for NADPH {ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:19196009, ECO:0000269|PubMed:21876184};
PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
null
null
FUNCTION: Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2. {ECO:0000269|PubMed:12096917, ECO:0000269|PubMed:21876188}.
Homo sapiens (Human)
P00375
DYR_MOUSE
MVRPLNCIVAVSQNMGIGKNGDLPWPPLRNEFKYFQRMTTTSSVEGKQNLVIMGRKTWFSIPEKNRPLKDRINIVLSRELKEPPRGAHFLAKSLDDALRLIEQPELASKVDMVWIVGGSSVYQEAMNQPGHLRLFVTRIMQEFESDTFFPEIDLGKYKLLPEYPGVLSEVQEEKGIKYKFEVYEKKD
1.5.1.3
null
axon regeneration [GO:0031103]; dihydrofolate metabolic process [GO:0046452]; folic acid metabolic process [GO:0046655]; glycine biosynthetic process [GO:0006545]; positive regulation of nitric-oxide synthase activity [GO:0051000]; regulation of removal of superoxide radicals [GO:2000121]; response to methotrexate [GO:0031427]; response to nicotine [GO:0035094]; tetrahydrobiopterin biosynthetic process [GO:0006729]; tetrahydrofolate biosynthetic process [GO:0046654]; tetrahydrofolate interconversion [GO:0035999]; tetrahydrofolate metabolic process [GO:0046653]
cytoplasm [GO:0005737]; cytosol [GO:0005829]; mitochondrion [GO:0005739]; nucleus [GO:0005634]
dihydrofolate reductase activity [GO:0004146]; dihydrofolic acid binding [GO:0051871]; mRNA binding [GO:0003729]; NADP binding [GO:0050661]
PF00186;
3.40.430.10;
Dihydrofolate reductase family
null
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:25980602}. Cytoplasm {ECO:0000269|PubMed:25980602}.
CATALYTIC ACTIVITY: Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378, ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.5.1.3; Evidence={ECO:0000255|PROSITE-ProRule:PRU00660, ECO:0000269|PubMed:19748785, ECO:0000269|PubMed:25980602};
null
PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
null
null
FUNCTION: Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway (PubMed:25980602). Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (PubMed:25980602). Binds its own mRNA. {ECO:0000250|UniProtKB:P00374, ECO:0000269|PubMed:25980602}.
Mus musculus (Mouse)
P00381
DYR_LACCA
MTAFLWAQDRDGLIGKDGHLPWHLPDDLHYFRAQTVGKIMVVGRRTYESFPKRPLPERTNVVLTHQEDYQAQGAVVVHDVAAVFAYAKQHPDQELVIAGGAQIFTAFKDDVDTLLVTRLAGSFEGDTKMIPLNWDDFTKVSSRTVEDTNPALTHTYEVWQKKA
1.5.1.3
null
dihydrofolate metabolic process [GO:0046452]; folic acid metabolic process [GO:0046655]; glycine biosynthetic process [GO:0006545]; one-carbon metabolic process [GO:0006730]; response to antibiotic [GO:0046677]; response to methotrexate [GO:0031427]; tetrahydrofolate biosynthetic process [GO:0046654]
cytosol [GO:0005829]
dihydrofolate reductase activity [GO:0004146]; NADP binding [GO:0050661]
PF00186;
3.40.430.10;
Dihydrofolate reductase family
null
null
CATALYTIC ACTIVITY: Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378, ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.5.1.3; Evidence={ECO:0000255|PROSITE-ProRule:PRU00660};
null
PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
null
null
FUNCTION: Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
Lacticaseibacillus casei (Lactobacillus casei)
P00383
DYR21_ECOLX
MERSSNEVSNPVAGNFVFPSNATFGMGDRVRKKSGAAWQGQIVGWYCTNLTPEGYAVESEAHPGSVQIYPVAALERIN
1.5.1.3
null
one-carbon metabolic process [GO:0006730]; response to antibiotic [GO:0046677]; response to methotrexate [GO:0031427]; response to xenobiotic stimulus [GO:0009410]; tetrahydrofolate biosynthetic process [GO:0046654]
null
dihydrofolate reductase activity [GO:0004146]
PF06442;
2.30.30.60;
null
null
null
CATALYTIC ACTIVITY: Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378, ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.5.1.3;
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=5.8 uM for dihydrofolate {ECO:0000269|PubMed:11560482}; KM=3 uM for NADPH {ECO:0000269|PubMed:11560482};
PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
null
null
FUNCTION: Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
Escherichia coli
P00387
NB5R3_HUMAN
MGAQLSTLGHMVLFPVWFLYSLLMKLFQRSTPAITLESPDIKYPLRLIDREIISHDTRRFRFALPSPQHILGLPVGQHIYLSARIDGNLVVRPYTPISSDDDKGFVDLVIKVYFKDTHPKFPAGGKMSQYLESMQIGDTIEFRGPSGLLVYQGKGKFAIRPDKKSNPIIRTVKSVGMIAGGTGITPMLQVIRAIMKDPDDHTVCHLLFANQTEKDILLRPELEELRNKHSARFKLWYTLDRAPEAWDYGQGFVNEEMIRDHLPPPEEEPLVLMCGPPPMIQYACLPNLDHVGHPTERCFVF
1.6.2.2
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:15953014, ECO:0000269|PubMed:1898726};
blood circulation [GO:0008015]; cholesterol biosynthetic process [GO:0006695]; nitric oxide biosynthetic process [GO:0006809]
azurophil granule lumen [GO:0035578]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; extracellular region [GO:0005576]; hemoglobin complex [GO:0005833]; lipid droplet [GO:0005811]; membrane [GO:0016020]; mitochondrial membrane [GO:0031966]; mitochondrial outer membrane [GO:0005741]; mitochondrion [GO:0005739]; nitric-oxide synthase complex [GO:1903958]
ADP binding [GO:0043531]; AMP binding [GO:0016208]; cytochrome-b5 reductase activity, acting on NAD(P)H [GO:0004128]; FAD binding [GO:0071949]; NAD binding [GO:0051287]
PF00970;PF00175;
3.40.50.80;2.40.30.10;
Flavoprotein pyridine nucleotide cytochrome reductase family
null
SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:9639531}; Lipid-anchor {ECO:0000250|UniProtKB:P20070}; Cytoplasmic side {ECO:0000250|UniProtKB:P20070}. Mitochondrion outer membrane {ECO:0000305|PubMed:9639531}; Lipid-anchor {ECO:0000250|UniProtKB:P20070}; Cytoplasmic side {ECO:0000250|UniProtKB:P20070}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:9639531}.
CATALYTIC ACTIVITY: Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] + H(+) + NAD(+); Xref=Rhea:RHEA:46680, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.6.2.2; Evidence={ECO:0000269|PubMed:10807796, ECO:0000269|PubMed:1400360, ECO:0000269|PubMed:15953014, ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:2019583, ECO:0000269|PubMed:8119939, ECO:0000269|PubMed:9639531}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46681; Evidence={ECO:0000305|PubMed:10807796, ECO:0000305|PubMed:15953014, ECO:0000305|PubMed:1898726, ECO:0000305|PubMed:2019583, ECO:0000305|PubMed:8119939}; CATALYTIC ACTIVITY: [Isoform 2]: Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] + H(+) + NAD(+); Xref=Rhea:RHEA:46680, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.6.2.2; Evidence={ECO:0000269|PubMed:9639531}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46681; Evidence={ECO:0000305|PubMed:9639531};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.5 uM for NADH {ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:8119939}; KM=0.6 uM for NADH {ECO:0000269|PubMed:1400360}; KM=6.6 uM for 2 Fe(III)-[cytochrome b5] {ECO:0000269|PubMed:1400360, ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:8119939}; KM=8.6 uM for 2 Fe(III)-[cytochrome b5] {ECO:0000269|PubMed:2019583}; Note=kcat is 896 sec(-1). {ECO:0000269|PubMed:15953014, ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:8119939};
null
null
null
FUNCTION: Catalyzes the reduction of two molecules of cytochrome b5 using NADH as the electron donor. {ECO:0000269|PubMed:10807796, ECO:0000269|PubMed:1400360, ECO:0000269|PubMed:15953014, ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:2019583, ECO:0000269|PubMed:8119939, ECO:0000269|PubMed:9639531}.
Homo sapiens (Human)
P00388
NCPR_RAT
MGDSHEDTSATMPEAVAEEVSLFSTTDMVLFSLIVGVLTYWFIFRKKKEEIPEFSKIQTTAPPVKESSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMSADPEEYDLADLSSLPEIDKSLVVFCMATYGEGDPTDNAQDFYDWLQETDVDLTGVKFAVFGLGNKTYEHFNAMGKYVDQRLEQLGAQRIFELGLGDDDGNLEEDFITWREQFWPAVCEFFGVEATGEESSIRQYELVVHEDMDVAKVYTGEMGRLKSYENQKPPFDAKNPFLAAVTANRKLNQGTERHLMHLELDISDSKIRYESGDHVAVYPANDSALVNQIGEILGADLDVIMSLNNLDEESNKKHPFPCPTTYRTALTYYLDITNPPRTNVLYELAQYASEPSEQEHLHKMASSSGEGKELYLSWVVEARRHILAILQDYPSLRPPIDHLCELLPRLQARYYSIASSSKVHPNSVHICAVAVEYEAKSGRVNKGVATSWLRAKEPAGENGGRALVPMFVRKSQFRLPFKSTTPVIMVGPGTGIAPFMGFIQERAWLREQGKEVGETLLYYGCRRSDEDYLYREELARFHKDGALTQLNVAFSREQAHKVYVQHLLKRDREHLWKLIHEGGAHIYVCGDARNMAKDVQNTFYDIVAEFGPMEHTQAVDYVKKLMTKGRYSLDVWS
1.6.2.4
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000255|HAMAP-Rule:MF_03212, ECO:0000269|PubMed:9237990}; Note=Binds 1 FAD per monomer. {ECO:0000255|HAMAP-Rule:MF_03212, ECO:0000269|PubMed:9237990}; COFACTOR: Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000255|HAMAP-Rule:MF_03212, ECO:0000269|PubMed:9237990}; Note=Binds 1 FMN per monomer. {ECO:0000255|HAMAP-Rule:MF_03212, ECO:0000269|PubMed:9237990};
carnitine metabolic process [GO:0009437]; cellular organofluorine metabolic process [GO:0090346]; cellular response to follicle-stimulating hormone stimulus [GO:0071372]; cellular response to gonadotropin stimulus [GO:0071371]; cellular response to peptide hormone stimulus [GO:0071375]; demethylation [GO:0070988]; electron transport chain [GO:0022900]; fatty acid oxidation [GO:0019395]; flavonoid metabolic process [GO:0009812]; negative regulation of apoptotic process [GO:0043066]; nitrate catabolic process [GO:0043602]; nitric oxide catabolic process [GO:0046210]; positive regulation of cholesterol biosynthetic process [GO:0045542]; positive regulation of chondrocyte differentiation [GO:0032332]; positive regulation of smoothened signaling pathway [GO:0045880]; positive regulation of steroid hormone biosynthetic process [GO:0090031]; regulation of cholesterol metabolic process [GO:0090181]; regulation of growth plate cartilage chondrocyte proliferation [GO:0003420]; response to dexamethasone [GO:0071548]; response to hormone [GO:0009725]; response to nutrient [GO:0007584]; response to xenobiotic stimulus [GO:0009410]
cytosol [GO:0005829]; endoplasmic reticulum membrane [GO:0005789]; intracellular membrane-bounded organelle [GO:0043231]
cytochrome-b5 reductase activity, acting on NAD(P)H [GO:0004128]; electron transfer activity [GO:0009055]; enzyme binding [GO:0019899]; flavin adenine dinucleotide binding [GO:0050660]; FMN binding [GO:0010181]; hydrolase activity [GO:0016787]; iron-cytochrome-c reductase activity [GO:0047726]; NADP binding [GO:0050661]; NADPH-hemoprotein reductase activity [GO:0003958]; nitric oxide dioxygenase NAD(P)H activity [GO:0008941]; oxidoreductase activity [GO:0016491]
PF00667;PF00258;PF00175;
3.40.50.360;3.40.50.80;2.40.30.10;
NADPH--cytochrome P450 reductase family; Flavodoxin family; Flavoprotein pyridine nucleotide cytochrome reductase family
null
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000255|HAMAP-Rule:MF_03212}; Single-pass membrane protein {ECO:0000255|HAMAP-Rule:MF_03212}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_03212}.
CATALYTIC ACTIVITY: Reaction=NADPH + 2 oxidized [cytochrome P450] = H(+) + NADP(+) + 2 reduced [cytochrome P450]; Xref=Rhea:RHEA:24040, Rhea:RHEA-COMP:14627, Rhea:RHEA-COMP:14628, ChEBI:CHEBI:15378, ChEBI:CHEBI:55376, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:60344; EC=1.6.2.4; Evidence={ECO:0000255|HAMAP-Rule:MF_03212};
null
null
null
null
FUNCTION: This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5. {ECO:0000255|HAMAP-Rule:MF_03212}.
Rattus norvegicus (Rat)
P00390
GSHR_HUMAN
MALLPRALSAGAGPSWRRAARAFRGFLLLLPEPAALTRALSRAMACRQEPQPQGPPPAAGAVASYDYLVIGGGSGGLASARRAAELGARAAVVESHKLGGTCVNVGCVPKKVMWNTAVHSEFMHDHADYGFPSCEGKFNWRVIKEKRDAYVSRLNAIYQNNLTKSHIEIIRGHAAFTSDPKPTIEVSGKKYTAPHILIATGGMPSTPHESQIPGASLGITSDGFFQLEELPGRSVIVGAGYIAVEMAGILSALGSKTSLMIRHDKVLRSFDSMISTNCTEELENAGVEVLKFSQVKEVKKTLSGLEVSMVTAVPGRLPVMTMIPDVDCLLWAIGRVPNTKDLSLNKLGIQTDDKGHIIVDEFQNTNVKGIYAVGDVCGKALLTPVAIAAGRKLAHRLFEYKEDSKLDYNNIPTVVFSHPPIGTVGLTEDEAIHKYGIENVKTYSTSFTPMYHAVTKRKTKCVMKMVCANKEEKVVGIHMQGLGCDEMLQGFAVAVKMGATKADFDNTVAIHPTSSEELVTLR
1.8.1.7
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD per subunit.;
cell redox homeostasis [GO:0045454]; cellular response to oxidative stress [GO:0034599]; glutathione metabolic process [GO:0006749]
cytosol [GO:0005829]; external side of plasma membrane [GO:0009897]; extracellular exosome [GO:0070062]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
electron transfer activity [GO:0009055]; flavin adenine dinucleotide binding [GO:0050660]; glutathione-disulfide reductase (NADP) activity [GO:0004362]; NADP binding [GO:0050661]
PF07992;PF02852;
3.30.390.30;3.50.50.60;
Class-I pyridine nucleotide-disulfide oxidoreductase family
null
SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion.; SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=2 glutathione + NADP(+) = glutathione disulfide + H(+) + NADPH; Xref=Rhea:RHEA:11740, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:58349; EC=1.8.1.7; Evidence={ECO:0000269|PubMed:17185460};
null
null
null
null
FUNCTION: Maintains high levels of reduced glutathione in the cytosol.
Homo sapiens (Human)
P00392
MERA_PSEAI
MTHLKITGMTCDSCAAHVKEALEKVPGVQSALVSYPKGTAQLAIVPGTSPDALTAAVAGLGYKATLADAPLADNRVGLLDKVRGWMAAAEKHSGNEPPVQVAVIGSGGAAMAAALKAVEQGAQVTLIERGTIGGTCVNVGCVPSKIMIRAAHIAHLRRESPFDGGIAATVPTIDRSKLLAQQQARVDELRHAKYEGILGGNPAITVVHGEARFKDDQSLTVRLNEGGERVVMFDRCLVATGASPAVPPIPGLKESPYWTSTEALASDTIPERLAVIGSSVVALELAQAFARLGSKVTVLARNTLFFREDPAIGEAVTAAFRAEGIEVLEHTQASQVAHMDGEFVLTTTHGELRADKLLVATGRTPNTRSLALDAAGVTVNAQGAIVIDQGMRTSNPNIYAAGDCTDQPQFVYVAAAAGTRAAINMTGGDAALDLTAMPAVVFTDPQVATVGYSEAEAHHDGIETDSRTLTLDNVPRALANFDTRGFIKLVIEEGSHRLIGVQAVAPEAGELIQTAALAIRNRMTVQELADQLFPYLTMVEGLKLAAQTFNKDVKQLSCCAG
1.16.1.1
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:6412751}; Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:6412751};
detoxification of mercury ion [GO:0050787]
null
flavin adenine dinucleotide binding [GO:0050660]; mercury (II) reductase activity [GO:0016152]; mercury ion binding [GO:0045340]; NADP binding [GO:0050661]; oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor [GO:0016668]
PF00403;PF07992;PF02852;
3.30.390.30;3.30.70.100;3.50.50.60;
Class-I pyridine nucleotide-disulfide oxidoreductase family
null
null
CATALYTIC ACTIVITY: Reaction=H(+) + Hg + NADP(+) = Hg(2+) + NADPH; Xref=Rhea:RHEA:23856, ChEBI:CHEBI:15378, ChEBI:CHEBI:16170, ChEBI:CHEBI:16793, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.16.1.1; Evidence={ECO:0000269|PubMed:6412751};
null
null
null
null
FUNCTION: Resistance to Hg(2+) in bacteria appears to be governed by a specialized system which includes mercuric reductase. MerA protein is responsible for volatilizing mercury as Hg(0). Plays a pivotal role in mercury resistance under thiol-depleted conditions and cell protection (PubMed:16114877). Protects cells under thiol-depleted conditions (PubMed:16114877). {ECO:0000269|PubMed:16114877, ECO:0000269|PubMed:6412751}.
Pseudomonas aeruginosa
P00393
NDH_ECOLI
MTTPLKKIVIVGGGAGGLEMATQLGHKLGRKKKAKITLVDRNHSHLWKPLLHEVATGSLDEGVDALSYLAHARNHGFQFQLGSVIDIDREAKTITIAELRDEKGELLVPERKIAYDTLVMALGSTSNDFNTPGVKENCIFLDNPHQARRFHQEMLNLFLKYSANLGANGKVNIAIVGGGATGVELSAELHNAVKQLHSYGYKGLTNEALNVTLVEAGERILPALPPRISAAAHNELTKLGVRVLTQTMVTSADEGGLHTKDGEYIEADLMVWAAGIKAPDFLKDIGGLETNRINQLVVEPTLQTTRDPDIYAIGDCASCPRPEGGFVPPRAQAAHQMATCAMNNILAQMNGKPLKNYQYKDHGSLVSLSNFSTVGSLMGNLTRGSMMIEGRIARFVYISLYRMHQIALHGYFKTGLMMLVGSINRVIRPRLKLH
1.16.1.-; 1.6.5.9
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:2679883, ECO:0000269|PubMed:6362717, ECO:0000269|PubMed:6784762, ECO:0000269|PubMed:7009604, ECO:0000269|PubMed:7020757}; Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:6362717};
aerobic electron transport chain [GO:0019646]; aerobic respiration [GO:0009060]; anaerobic respiration [GO:0009061]; copper ion homeostasis [GO:0055070]; NADH oxidation [GO:0006116]
NADH dehydrogenase complex [GO:0030964]; plasma membrane [GO:0005886]
flavin adenine dinucleotide binding [GO:0050660]; NADH dehydrogenase (ubiquinone) activity [GO:0008137]
PF07992;
3.50.50.100;
NADH dehydrogenase family
null
SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:10664466, ECO:0000269|PubMed:2679883, ECO:0000269|PubMed:6362717, ECO:0000269|PubMed:6784762, ECO:0000269|PubMed:7009604, ECO:0000269|PubMed:7020757}; Peripheral membrane protein {ECO:0000269|PubMed:10664466, ECO:0000305|PubMed:12176061}; Cytoplasmic side {ECO:0000305|PubMed:12176061}. Note=Membrane-bound (PubMed:10664466). Interaction with the membrane is probably mediated by amphipathic helices and electrostatic interactions (PubMed:15581635). Copurifies with phospholipids (PubMed:6362717, PubMed:7020757). {ECO:0000269|PubMed:10664466, ECO:0000269|PubMed:15581635, ECO:0000269|PubMed:6362717, ECO:0000269|PubMed:7020757}.
CATALYTIC ACTIVITY: Reaction=a quinone + H(+) + NADH = a quinol + NAD(+); Xref=Rhea:RHEA:46160, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:132124; EC=1.6.5.9; Evidence={ECO:0000269|PubMed:10664466, ECO:0000269|PubMed:2679883, ECO:0000269|PubMed:6362717, ECO:0000269|PubMed:6784762, ECO:0000269|PubMed:7009604, ECO:0000269|PubMed:7020757}; CATALYTIC ACTIVITY: Reaction=a ubiquinone + H(+) + NADH = a ubiquinol + NAD(+); Xref=Rhea:RHEA:23152, Rhea:RHEA-COMP:9565, Rhea:RHEA-COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:10664466, ECO:0000269|PubMed:2679883, ECO:0000269|PubMed:6362717, ECO:0000269|PubMed:6784762, ECO:0000269|PubMed:7009604, ECO:0000269|PubMed:7020757}; CATALYTIC ACTIVITY: Reaction=H(+) + NADH + ubiquinone-8 = NAD(+) + ubiquinol-8; Xref=Rhea:RHEA:29107, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:61682, ChEBI:CHEBI:61683; Evidence={ECO:0000269|PubMed:7020757}; CATALYTIC ACTIVITY: Reaction=2 Cu(2+) + NADH = 2 Cu(+) + H(+) + NAD(+); Xref=Rhea:RHEA:66848, ChEBI:CHEBI:15378, ChEBI:CHEBI:29036, ChEBI:CHEBI:49552, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:10510271}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66849; Evidence={ECO:0000269|PubMed:10510271};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=50 uM for NADH (for NADH:quinone oxidoreductase activity) {ECO:0000269|PubMed:7009604}; KM=6.1 uM for NADH (for cupric reductase activity, in the presence of FAD) {ECO:0000269|PubMed:10510271}; KM=6.9 uM for NADH (for cupric reductase activity, in the presence of duroquinone) {ECO:0000269|PubMed:10510271}; KM=34 uM for NADH (for NADH:quinone oxidoreductase activity) {ECO:0000269|PubMed:10664466}; KM=5.9 uM for ubiquinone-1 {ECO:0000269|PubMed:10664466}; KM=2.3 uM for ubiquinone-2 {ECO:0000269|PubMed:10664466}; KM=40 uM for ubiquinone-3 (for NADH:quinone oxidoreductase activity) {ECO:0000269|PubMed:7009604}; KM=32 uM for duroquinone (for cupric reductase activity) {ECO:0000269|PubMed:10510271}; KM=18.7 uM for decylbenzoquinone {ECO:0000269|PubMed:10664466}; KM=1.8 uM for idebenone {ECO:0000269|PubMed:10664466}; KM=20 uM for dichlorophenolindophenol {ECO:0000269|PubMed:10664466}; KM=12 uM for decylbenzoquinone (for NADH:quinone oxidoreductase activity) {ECO:0000269|PubMed:7009604}; KM=0.022 nM for Cu(2+) (in the presence of FAD) {ECO:0000269|PubMed:10510271}; KM=0.032 nM for Cu(2+) (in the presence of duroquinone) {ECO:0000269|PubMed:10510271}; KM=102 uM for FAD (for cupric reductase activity) {ECO:0000269|PubMed:10510271}; Vmax=106 mmol/min/mg enzyme with NADH as substrate {ECO:0000269|PubMed:10664466}; Vmax=106 mmol/min/mg enzyme with ubiquinone-1 as substrate {ECO:0000269|PubMed:10664466}; Vmax=190 mmol/min/mg enzyme with ubiquinone-2 as substrate {ECO:0000269|PubMed:10664466}; Vmax=191 mmol/min/mg enzyme with decylbenzoquinone as substrate {ECO:0000269|PubMed:10664466}; Vmax=107 mmol/min/mg enzyme with idebenone as substrate {ECO:0000269|PubMed:10664466}; Vmax=19.5 mmol/min/mg enzyme with dichlorophenolindophenol as substrate {ECO:0000269|PubMed:10664466}; Vmax=8.8 umol/min/mg enzyme (for cupric reductase activity, in the presence of FAD) {ECO:0000269|PubMed:10510271}; Vmax=21.1 umol/min/mg enzyme (for cupric reductase activity, in the presence of duroquinone) {ECO:0000269|PubMed:10510271};
null
null
null
FUNCTION: Alternative, nonproton pumping NADH:quinone oxidoreductase that delivers electrons to the respiratory chain by oxidation of NADH and reduction of quinones (PubMed:10664466, PubMed:2679883, PubMed:3122832, PubMed:6362717, PubMed:6784762, PubMed:7009604, PubMed:7020757). Utilizes NADH exclusively, and electron flow from NADH to ubiquinone does not generate an electrochemical gradient (PubMed:2679883, PubMed:3122832). {ECO:0000269|PubMed:10664466, ECO:0000269|PubMed:2679883, ECO:0000269|PubMed:3122832, ECO:0000269|PubMed:6362717, ECO:0000269|PubMed:6784762, ECO:0000269|PubMed:7009604, ECO:0000269|PubMed:7020757}.; FUNCTION: It may also contribute to copper homeostasis and bacterial oxidative protection (PubMed:10510271, PubMed:16759635, PubMed:21390523, PubMed:7487066). Shows cupric reductase activity, and catalyzes the reduction of Cu(2+) to Cu(+) with NADH as electron donor (PubMed:10510271). Exhibits Cu(2+) reductase activity in the presence of either FAD or quinone, but is unable to reduce Fe(3+) (PubMed:10510271). Contains thiolate-bound copper (PubMed:12176061). {ECO:0000269|PubMed:10510271, ECO:0000269|PubMed:12176061, ECO:0000269|PubMed:16759635, ECO:0000269|PubMed:21390523, ECO:0000269|PubMed:7487066}.
Escherichia coli (strain K12)
P00395
COX1_HUMAN
MFADRWLFSTNHKDIGTLYLLFGAWAGVLGTALSLLIRAELGQPGNLLGNDHIYNVIVTAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLLLLLASAMVEAGAGTGWTVYPPLAGNYSHPGASVDLTIFSLHLAGVSSILGAINFITTIINMKPPAMTQYQTPLFVWSVLITAVLLLLSLPVLAAGITMLLTDRNLNTTFFDPAGGGDPILYQHLFWFFGHPEVYILILPGFGMISHIVTYYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVDTRAYFTSATMIIAIPTGVKVFSWLATLHGSNMKWSAAVLWALGFIFLFTVGGLTGIVLANSSLDIVLHDTYYVVAHFHYVLSMGAVFAIMGGFIHWFPLFSGYTLDQTYAKIHFTIMFIGVNLTFFPQHFLGLSGMPRRYSDYPDAYTTWNILSSVGSFISLTAVMLMIFMIWEAFASKRKVLMVEEPSMNLEWLYGCPPPYHTFEEPVYMKS
7.1.1.9
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269|PubMed:30030519}; Note=Binds 2 heme A groups non-covalently per subunit. {ECO:0000269|PubMed:30030519}; COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000269|PubMed:30030519}; Note=Binds a copper B center. {ECO:0000269|PubMed:30030519};
cellular respiration [GO:0045333]; cerebellum development [GO:0021549]; electron transport coupled proton transport [GO:0015990]; mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]; response to copper ion [GO:0046688]; response to electrical stimulus [GO:0051602]; response to hypoxia [GO:0001666]; response to oxidative stress [GO:0006979]
mitochondrial inner membrane [GO:0005743]; mitochondrial membrane [GO:0031966]; mitochondrial respiratory chain complex III [GO:0005750]; mitochondrial respiratory chain complex IV [GO:0005751]; respiratory chain complex IV [GO:0045277]
cytochrome-c oxidase activity [GO:0004129]; heme binding [GO:0020037]; metal ion binding [GO:0046872]
PF00115;
1.20.210.10;
Heme-copper respiratory oxidase family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:30030519}; Multi-pass membrane protein {ECO:0000269|PubMed:30030519}.
CATALYTIC ACTIVITY: Reaction=4 Fe(II)-[cytochrome c] + 8 H(+)(in) + O2 = 4 Fe(III)-[cytochrome c] + 4 H(+)(out) + 2 H2O; Xref=Rhea:RHEA:11436, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=7.1.1.9; Evidence={ECO:0000250|UniProtKB:P00401}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437; Evidence={ECO:0000250|UniProtKB:P00401};
null
PATHWAY: Energy metabolism; oxidative phosphorylation. {ECO:0000250|UniProtKB:P00401}.
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:P00401}.
Homo sapiens (Human)
P00396
COX1_BOVIN
MFINRWLFSTNHKDIGTLYLLFGAWAGMVGTALSLLIRAELGQPGTLLGDDQIYNVVVTAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSFLLLLASSMVEAGAGTGWTVYPPLAGNLAHAGASVDLTIFSLHLAGVSSILGAINFITTIINMKPPAMSQYQTPLFVWSVMITAVLLLLSLPVLAAGITMLLTDRNLNTTFFDPAGGGDPILYQHLFWFFGHPEVYILILPGFGMISHIVTYYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVDTRAYFTSATMIIAIPTGVKVFSWLATLHGGNIKWSPAMMWALGFIFLFTVGGLTGIVLANSSLDIVLHDTYYVVAHFHYVLSMGAVFAIMGGFVHWFPLFSGYTLNDTWAKIHFAIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTMWNTISSMGSFISLTAVMLMVFIIWEAFASKREVLTVDLTTTNLEWLNGCPPPYHTFEEPTYVNLK
7.1.1.9
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269|PubMed:20385840, ECO:0000269|PubMed:2165784, ECO:0000269|PubMed:8638158}; Note=Binds 2 heme A groups non-covalently per subunit. {ECO:0000269|PubMed:20385840, ECO:0000269|PubMed:2165784, ECO:0000269|PubMed:8638158}; COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000269|PubMed:20385840, ECO:0000269|PubMed:2165784, ECO:0000269|PubMed:8638158}; Note=Binds a copper B center. {ECO:0000269|PubMed:20385840, ECO:0000269|PubMed:2165784, ECO:0000269|PubMed:8638158};
electron transport coupled proton transport [GO:0015990]; mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]
mitochondrial respiratory chain complex IV [GO:0005751]; respiratory chain complex IV [GO:0045277]
cytochrome-c oxidase activity [GO:0004129]; heme binding [GO:0020037]; metal ion binding [GO:0046872]
PF00115;
1.20.210.10;
Heme-copper respiratory oxidase family
PTM: His-240 and Tyr-244 are involved in the formation of a copper-coordinated covalent cross-link at the active site of the catalytic subunit I.
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:27605664, ECO:0000269|PubMed:31533957}; Multi-pass membrane protein {ECO:0000269|PubMed:27605664, ECO:0000269|PubMed:31533957}.
CATALYTIC ACTIVITY: Reaction=4 Fe(II)-[cytochrome c] + 8 H(+)(in) + O2 = 4 Fe(III)-[cytochrome c] + 4 H(+)(out) + 2 H2O; Xref=Rhea:RHEA:11436, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=7.1.1.9; Evidence={ECO:0000250|UniProtKB:P00401}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437; Evidence={ECO:0000250|UniProtKB:P00401};
null
PATHWAY: Energy metabolism; oxidative phosphorylation. {ECO:0000250|UniProtKB:P00401}.
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:P00401}.
Bos taurus (Bovine)
P00397
COX1_MOUSE
MFINRWLFSTNHKDIGTLYLLFGAWAGMVGTALSILIRAELGQPGALLGDDQIYNVIVTAHAFVMIFFMVMPMMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSFLLLLASSMVEAGAGTGWTVYPPLAGNLAHAGASVDLTIFSLHLAGVSSILGAINFITTIINMKPPAMTQYQTPLFVWSVLITAVLLLLSLPVLAAGITMLLTDRNLNTTFFDPAGGGDPILYQHLFWFFGHPEVYILILPGFGIISHVVTYYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGLDVDTRAYFTSATMIIAIPTGVKVFSWLATLHGGNIKWSPAMLWALGFIFLFTVGGLTGIVLSNSSLDIVLHDTYYVVAHFHYVLSMGAVFAIMAGFVHWFPLFSGFTLDDTWAKAHFAIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTTWNTVSSMGSFISLTAVLIMIFMIWEAFASKREVMSVSYASTNLEWLHGCPPPYHTFEEPTYVKVK
7.1.1.9
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250|UniProtKB:P00396}; Note=Binds 2 heme A groups non-covalently per subunit. {ECO:0000250|UniProtKB:P00396}; COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000250|UniProtKB:P00396}; Note=Binds a copper B center. {ECO:0000250|UniProtKB:P00396};
cerebellum development [GO:0021549]; electron transport coupled proton transport [GO:0015990]; mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]; response to copper ion [GO:0046688]; response to electrical stimulus [GO:0051602]; response to hypoxia [GO:0001666]; response to oxidative stress [GO:0006979]
mitochondrial inner membrane [GO:0005743]; mitochondrial respiratory chain complex III [GO:0005750]; mitochondrial respiratory chain complex IV [GO:0005751]; mitochondrion [GO:0005739]; respiratory chain complex IV [GO:0045277]
cytochrome-c oxidase activity [GO:0004129]; heme binding [GO:0020037]; metal ion binding [GO:0046872]
PF00115;
1.20.210.10;
Heme-copper respiratory oxidase family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000250|UniProtKB:P00396}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P00396}.
CATALYTIC ACTIVITY: Reaction=4 Fe(II)-[cytochrome c] + 8 H(+)(in) + O2 = 4 Fe(III)-[cytochrome c] + 4 H(+)(out) + 2 H2O; Xref=Rhea:RHEA:11436, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=7.1.1.9; Evidence={ECO:0000250|UniProtKB:P00401}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437; Evidence={ECO:0000250|UniProtKB:P00401};
null
PATHWAY: Energy metabolism; oxidative phosphorylation. {ECO:0000250|UniProtKB:P00401}.
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:P00401}.
Mus musculus (Mouse)
P00401
COX1_YEAST
MVQRWLYSTNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSQYLHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFGNYLLPLMIGATDTAFPRINNIAFWVLPMGLVCLVTSTLVESGAGTGWTVYPPLSSIQAHSGPSVDLAIFALHLTSISSLLGAINFIVTTLNMRTNGMTMHKLPLFVWSIFITAFLLLLSLPVLSAGITMLLLDRNFNTSFFEVSGGGDPILYEHLFWFFGHPEVYILIIPGFGIISHVVSTYSKKPVFGEISMVYAMASIGLLGFLVWSHHMYIVGLDADTRAYFTSATMIIAIPTGIKIFSWLATIHGGSIRLATPMLYAIAFLFLFTMGGLTGVALANASLDVAFHDTYYVVGHFHYVLSMGAIFSLFAGYYYWSPQILGLNYNEKLAQIQFWLIFIGANVIFFPMHFLGINGMPRRIPDYPDAFAGWNYVASIGSFIATLSLFLFIYILYDQLVNGLNNKVNNKSVIYNKAPDFVESNTIFNLNTVKSSSIEFLLTSPPAVHSFNTPAVQS
7.1.1.9
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269|PubMed:30598554, ECO:0000269|PubMed:30598556}; Note=Binds 2 heme A groups non-covalently per subunit. {ECO:0000269|PubMed:30598554, ECO:0000269|PubMed:30598556}; COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Note=Binds a copper B center. {ECO:0000269|PubMed:30598554, ECO:0000269|PubMed:30598556};
aerobic respiration [GO:0009060]; cellular respiration [GO:0045333]; electron transport coupled proton transport [GO:0015990]; mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]
mitochondrial membrane [GO:0031966]; mitochondrial respiratory chain complex IV [GO:0005751]; mitochondrion [GO:0005739]
cytochrome-c oxidase activity [GO:0004129]; heme binding [GO:0020037]; metal ion binding [GO:0046872]
PF00115;
1.20.210.10;
Heme-copper respiratory oxidase family
PTM: The N-terminus is blocked. {ECO:0000269|PubMed:7851399}.
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:30598554}; Multi-pass membrane protein {ECO:0000269|PubMed:30598554}.
CATALYTIC ACTIVITY: Reaction=4 Fe(II)-[cytochrome c] + 8 H(+)(in) + O2 = 4 Fe(III)-[cytochrome c] + 4 H(+)(out) + 2 H2O; Xref=Rhea:RHEA:11436, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=7.1.1.9; Evidence={ECO:0000269|PubMed:30598554}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437; Evidence={ECO:0000269|PubMed:30598554};
null
PATHWAY: Energy metabolism; oxidative phosphorylation.
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of COX2 and heme A of COX1 to the active site in COX1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix (Probable). COX1 is a catalytic core subunit containing heme A and the active site BNC with heme A3 and the copper atom CU(B) (PubMed:30598554). {ECO:0000269|PubMed:30598554, ECO:0000305|PubMed:30598554}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00403
COX2_HUMAN
MAHAAQVGLQDATSPIMEELITFHDHALMIIFLICFLVLYALFLTLTTKLTNTNISDAQEMETVWTILPAIILVLIALPSLRILYMTDEVNDPSLTIKSIGHQWYWTYEYTDYGGLIFNSYMLPPLFLEPGDLRLLDVDNRVVLPIEAPIRMMITSQDVLHSWAVPTLGLKTDAIPGRLNQTTFTATRPGVYYGQCSEICGANHSFMPIVLELIPLKIFEMGPVFTL
7.1.1.9
COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000269|PubMed:30030519}; Note=Binds a dinuclear copper A center per subunit. {ECO:0000269|PubMed:30030519};
ATP synthesis coupled electron transport [GO:0042773]; cellular respiration [GO:0045333]; lactation [GO:0007595]; mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]; response to hypoxia [GO:0001666]
membrane [GO:0016020]; mitochondrial inner membrane [GO:0005743]; mitochondrial membrane [GO:0031966]; mitochondrial respiratory chain complex IV [GO:0005751]; mitochondrion [GO:0005739]; respiratory chain complex IV [GO:0045277]
copper ion binding [GO:0005507]; cytochrome-c oxidase activity [GO:0004129]
PF00116;PF02790;
1.10.287.90;2.60.40.420;
Cytochrome c oxidase subunit 2 family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:30030519}; Multi-pass membrane protein {ECO:0000269|PubMed:30030519}.
CATALYTIC ACTIVITY: Reaction=4 Fe(II)-[cytochrome c] + 8 H(+)(in) + O2 = 4 Fe(III)-[cytochrome c] + 4 H(+)(out) + 2 H2O; Xref=Rhea:RHEA:11436, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=7.1.1.9; Evidence={ECO:0000250|UniProtKB:P00410}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437; Evidence={ECO:0000250|UniProtKB:P00410};
null
null
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:P00410}.
Homo sapiens (Human)
P00410
COX2_YEAST
MLDLLRLQLTTFIMNDVPTPYACYFQDSATPNQEGILELHDNIMFYLLVILGLVSWMLYTIVMTYSKNPIAYKYIKHGQTIEVIWTIFPAVILLIIAFPSFILLYLCDEVISPAMTIKAIGYQWYWKYEYSDFINDSGETVEFESYVIPDELLEEGQLRLLDTDTSMVVPVDTHIRFVVTAADVIHDFAIPSLGIKVDATPGRLNQVSALIQREGVFYGACSELCGTGHANMPIKIEAVSLPKFLEWLNEQ
7.1.1.9
COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000269|PubMed:30598554, ECO:0000269|PubMed:30598556}; Note=Binds a dinuclear copper A center per subunit. {ECO:0000269|PubMed:30598554, ECO:0000269|PubMed:30598556};
aerobic respiration [GO:0009060]; ATP synthesis coupled electron transport [GO:0042773]; mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]
mitochondrial inner membrane [GO:0005743]; mitochondrial respiratory chain complex IV [GO:0005751]; mitochondrion [GO:0005739]
copper ion binding [GO:0005507]; cytochrome-c oxidase activity [GO:0004129]
PF00116;PF02790;
1.10.287.90;2.60.40.420;
Cytochrome c oxidase subunit 2 family
PTM: The N-terminal sequence of COX2 is processed by IMP1.
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:30598554}; Multi-pass membrane protein {ECO:0000269|PubMed:30598554}.
CATALYTIC ACTIVITY: Reaction=4 Fe(II)-[cytochrome c] + 8 H(+)(in) + O2 = 4 Fe(III)-[cytochrome c] + 4 H(+)(out) + 2 H2O; Xref=Rhea:RHEA:11436, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=7.1.1.9; Evidence={ECO:0000269|PubMed:30598554}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437; Evidence={ECO:0000269|PubMed:30598554};
null
null
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of COX2 and heme A of COX1 to the active site in COX1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix (Probable). COX2 is a catalytic core subunit which transfers the electrons from cytochrome c via its dinuclear copper A center (CU(A)) to the BNC of the COX1 (PubMed:30598554). {ECO:0000269|PubMed:30598554, ECO:0000305|PubMed:30598554}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00414
COX3_HUMAN
MTHQSHAYHMVKPSPWPLTGALSALLMTSGLAMWFHFHSMTLLMLGLLTNTLTMYQWWRDVTRESTYQGHHTPPVQKGLRYGMILFITSEVFFFAGFFWAFYHSSLAPTPQLGGHWPPTGITPLNPLEVPLLNTSVLLASGVSITWAHHSLMENNRNQMIQALLITILLGLYFTLLQASEYFESPFTISDGIYGSTFFVATGFHGLHVIIGSTFLTICFIRQLMFHFTSKHHFGFEAAAWYWHFVDVVWLFLYVSIYWWGS
7.1.1.9
null
cellular respiration [GO:0045333]; mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]; respiratory chain complex IV assembly [GO:0008535]
mitochondrial inner membrane [GO:0005743]; mitochondrial membrane [GO:0031966]; mitochondrial respiratory chain complex IV [GO:0005751]; respiratory chain complex IV [GO:0045277]
cytochrome-c oxidase activity [GO:0004129]
PF00510;
1.10.287.70;1.20.120.80;
Cytochrome c oxidase subunit 3 family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:30030519}; Multi-pass membrane protein {ECO:0000269|PubMed:30030519}.
CATALYTIC ACTIVITY: Reaction=4 Fe(II)-[cytochrome c] + 8 H(+)(in) + O2 = 4 Fe(III)-[cytochrome c] + 4 H(+)(out) + 2 H2O; Xref=Rhea:RHEA:11436, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=7.1.1.9; Evidence={ECO:0000250|UniProtKB:P00420}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437; Evidence={ECO:0000250|UniProtKB:P00420};
null
null
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:P00420}.
Homo sapiens (Human)
P00420
COX3_YEAST
MTHLERSRHQQHPFHMVMPSPWPIVVSFALLSLALSTALTMHGYIGNMNMVYLALFVLLTSSILWFRDIVAEATYLGDHTMAVRKGINLGFLMFVLSEVLIFAGLFWAYFHSAMSPDVTLGACWPPVGIEAVQPTELPLLNTIILLSSGATVTYSHHALIAGNRNKALSGLLITFWLIVIFVTCQYIEYTNAAFTISDGVYGSVFYAGTGLHFLHMVMLAAMLGVNYWRMRNYHLTAGHHVGYETTIIYTHVLDVIWLFLYVVFYWWGV
7.1.1.9
null
aerobic respiration [GO:0009060]; cellular respiration [GO:0045333]; mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]
mitochondrial membrane [GO:0031966]; mitochondrial respiratory chain complex IV [GO:0005751]; mitochondrion [GO:0005739]
cytochrome-c oxidase activity [GO:0004129]
PF00510;
1.10.287.70;1.20.120.80;
Cytochrome c oxidase subunit 3 family
PTM: The N-terminus is blocked. {ECO:0000269|PubMed:7851399}.
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:30598554}; Multi-pass membrane protein {ECO:0000269|PubMed:30598554}.
CATALYTIC ACTIVITY: Reaction=4 Fe(II)-[cytochrome c] + 8 H(+)(in) + O2 = 4 Fe(III)-[cytochrome c] + 4 H(+)(out) + 2 H2O; Xref=Rhea:RHEA:11436, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=7.1.1.9; Evidence={ECO:0000269|PubMed:30598554}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11437; Evidence={ECO:0000269|PubMed:30598554};
null
null
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of COX2 and heme A of COX1 to the active site in COX1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix (Probable). COX3 is a catalytic core subunit (PubMed:30598554). {ECO:0000269|PubMed:30598554, ECO:0000305|PubMed:30598554}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00423
COX41_BOVIN
MLATRVFSLIGRRAISTSVCVRAHGSVVKSEDYALPSYVDRRDYPLPDVAHVKNLSASQKALKEKEKASWSSLSIDEKVELYRLKFKESFAEMNRSTNEWKTVVGAAMFFIGFTALLLIWEKHYVYGPIPHTFEEEWVAKQTKRMLDMKVAPIQGFSAKWDYDKNEWKK
null
null
mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]
mitochondrial respiratory chain complex IV [GO:0005751]; respiratory chain complex IV [GO:0045277]
cytochrome-c oxidase activity [GO:0004129]
PF02936;
1.10.442.10;
Cytochrome c oxidase IV family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:27605664, ECO:0000269|PubMed:31533957}; Single-pass membrane protein {ECO:0000269|PubMed:27605664, ECO:0000269|PubMed:31533957}.
null
null
PATHWAY: Energy metabolism; oxidative phosphorylation. {ECO:0000250|UniProtKB:P00424}.
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:P00424}.
Bos taurus (Bovine)
P00424
COX5A_YEAST
MLRNTFTRAGGLSRITSVRFAQTHALSNAAVMDLQSRWENMPSTEQQDIVSKLSERQKLPWAQLTEPEKQAVWYISYGEWGPRRPVLNKGDSSFIAKGVAAGLLFSVGLFAVVRMAGGQDAKTMNKEWQLKSDEYLKSKNANPWGGYSQVQSK
null
null
mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]; proton transmembrane transport [GO:1902600]
mitochondrial inner membrane [GO:0005743]; mitochondrial intermembrane space [GO:0005758]; mitochondrial respiratory chain complex IV [GO:0005751]; mitochondrion [GO:0005739]
oxidoreductase activity [GO:0016491]
PF02936;
1.10.442.10;
Cytochrome c oxidase IV family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:30598554}; Single-pass membrane protein {ECO:0000269|PubMed:30598554}.
null
null
PATHWAY: Energy metabolism; oxidative phosphorylation.
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of COX2 and heme A of COX1 to the active site in COX1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000305|PubMed:30598554}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00429
CX6B1_BOVIN
MAEDIQAKIKNYQTAPFDSRFPNQNQTRNCWQNYLDFHRCEKAMTAKGGDVSVCEWYRRVYKSLCPISWVSTWDDRRAEGTFPGKI
null
null
oxidative phosphorylation [GO:0006119]
mitochondrial inner membrane [GO:0005743]; mitochondrion [GO:0005739]; respiratory chain complex IV [GO:0045277]
null
PF02297;
1.10.10.140;
Cytochrome c oxidase subunit 6B family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:27605664, ECO:0000269|PubMed:31533957}; Peripheral membrane protein {ECO:0000269|PubMed:27605664, ECO:0000269|PubMed:31533957}; Intermembrane side {ECO:0000269|PubMed:27605664, ECO:0000269|PubMed:31533957}.
null
null
PATHWAY: Energy metabolism; oxidative phosphorylation. {ECO:0000250|UniProtKB:Q01519}.
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:Q01519}.
Bos taurus (Bovine)
P00430
COX7C_BOVIN
MLGQSIRRFTTSVVRRSHYEEGPGKNIPFSVENKWRLLAMMTLFFGSGFAAPFFIVRHQLLKK
null
null
mitochondrial electron transport, cytochrome c to oxygen [GO:0006123]
mitochondrial respiratory chain complex IV [GO:0005751]; respiratory chain complex IV [GO:0045277]
null
PF02935;
4.10.49.10;
Cytochrome c oxidase VIIc family
null
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:27605664, ECO:0000269|PubMed:31533957}; Single-pass membrane protein {ECO:0000269|PubMed:27605664, ECO:0000269|PubMed:31533957}.
null
null
PATHWAY: Energy metabolism; oxidative phosphorylation. {ECO:0000250|UniProtKB:P04039}.
null
null
FUNCTION: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. {ECO:0000250|UniProtKB:P04039}.
Bos taurus (Bovine)
P00431
CCPR_YEAST
MTTAVRLLPSLGRTAHKRSLYLFSAAAAAAAAATFAYSQSQKRSSSSPGGGSNHGWNNWGKAAALASTTPLVHVASVEKGRSYEDFQKVYNAIALKLREDDEYDNYIGYGPVLVRLAWHTSGTWDKHDNTGGSYGGTYRFKKEFNDPSNAGLQNGFKFLEPIHKEFPWISSGDLFSLGGVTAVQEMQGPKIPWRCGRVDTPEDTTPDNGRLPDADKDADYVRTFFQRLNMNDREVVALMGAHALGKTHLKNSGYEGPWGAANNVFTNEFYLNLLNEDWKLEKNDANNEQWDSKSGYMMLPTDYSLIQDPKYLSIVKEYANDQDKFFKDFSKAFEKLLENGITFPKDAPSPFIFKTLEEQGL
1.11.1.5
COFACTOR: Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000269|PubMed:10722697, ECO:0000269|PubMed:11170452, ECO:0000269|PubMed:2169873, ECO:0000269|PubMed:6092361, ECO:0000269|PubMed:8384877, ECO:0000269|PubMed:8673607}; Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit. {ECO:0000269|PubMed:10722697, ECO:0000269|PubMed:11170452, ECO:0000269|PubMed:2169873, ECO:0000269|PubMed:6092361, ECO:0000269|PubMed:8384877, ECO:0000269|PubMed:8673607};
cellular response to oxidative stress [GO:0034599]; hydrogen peroxide catabolic process [GO:0042744]; response to reactive oxygen species [GO:0000302]
mitochondrial intermembrane space [GO:0005758]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
cytochrome-c peroxidase activity [GO:0004130]; heme binding [GO:0020037]; metal ion binding [GO:0046872]; peroxidase activity [GO:0004601]
PF00141;
1.10.520.10;1.10.420.10;
Peroxidase family, Cytochrome c peroxidase subfamily
PTM: CCP1 precursor is processed by the rhomboid protease PCP1, which cleaves the N-terminal hydrophobic transit peptide (PubMed:12774122, PubMed:17245427). The m-AAA protease (composed of YTA12/RCA1 and YTA10/AFG3) is required for CCP1 maturation: m-AAA protease promotes membrane dislocation of the CCP1 transmembrane segment within the transit peptide to ensure the correct positioning of CCP1 within the membrane bilayer, allowing intramembrane cleavage by PCP1 (PubMed:17245427). {ECO:0000269|PubMed:12774122, ECO:0000269|PubMed:17245427}.
SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane space {ECO:0000269|PubMed:22984289}.
CATALYTIC ACTIVITY: Reaction=2 Fe(II)-[cytochrome c] + 2 H(+) + H2O2 = 2 Fe(III)-[cytochrome c] + 2 H2O; Xref=Rhea:RHEA:16581, Rhea:RHEA-COMP:10350, Rhea:RHEA-COMP:14399, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.11.1.5; Evidence={ECO:0000269|PubMed:2851317};
null
null
null
null
FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems. {ECO:0000269|PubMed:2851317}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00432
CATA_BOVIN
MADNRDPASDQMKHWKEQRAAQKPDVLTTGGGNPVGDKLNSLTVGPRGPLLVQDVVFTDEMAHFDRERIPERVVHAKGAGAFGYFEVTHDITRYSKAKVFEHIGKRTPIAVRFSTVAGESGSADTVRDPRGFAVKFYTEDGNWDLVGNNTPIFFIRDALLFPSFIHSQKRNPQTHLKDPDMVWDFWSLRPESLHQVSFLFSDRGIPDGHRHMNGYGSHTFKLVNANGEAVYCKFHYKTDQGIKNLSVEDAARLAHEDPDYGLRDLFNAIATGNYPSWTLYIQVMTFSEAEIFPFNPFDLTKVWPHGDYPLIPVGKLVLNRNPVNYFAEVEQLAFDPSNMPPGIEPSPDKMLQGRLFAYPDTHRHRLGPNYLQIPVNCPYRARVANYQRDGPMCMMDNQGGAPNYYPNSFSAPEHQPSALEHRTHFSGDVQRFNSANDDNVTQVRTFYLKVLNEEQRKRLCENIAGHLKDAQLFIQKKAVKNFSDVHPEYGSRIQALLDKYNEEKPKNAVHTYVQHGSHLSAREKANL
1.11.1.6
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269|PubMed:10417406}; COFACTOR: Name=NADP(+); Xref=ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:10417406};
cellular detoxification of hydrogen peroxide [GO:0061692]; hydrogen peroxide catabolic process [GO:0042744]; positive regulation of cell division [GO:0051781]; response to hydrogen peroxide [GO:0042542]
catalase complex [GO:0062151]; cytoplasm [GO:0005737]; mitochondrion [GO:0005739]; peroxisome [GO:0005777]
catalase activity [GO:0004096]; enzyme binding [GO:0019899]; heme binding [GO:0020037]; metal ion binding [GO:0046872]
PF00199;PF06628;
2.40.180.10;
Catalase family
null
SUBCELLULAR LOCATION: Peroxisome matrix {ECO:0000269|PubMed:7082009}.
CATALYTIC ACTIVITY: Reaction=2 H2O2 = 2 H2O + O2; Xref=Rhea:RHEA:20309, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240; EC=1.11.1.6; Evidence={ECO:0000255|PROSITE-ProRule:PRU10013, ECO:0000269|PubMed:10691967};
null
null
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7. {ECO:0000269|PubMed:10691967};
null
FUNCTION: Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide (PubMed:10691967). Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells (PubMed:10691967). {ECO:0000269|PubMed:10691967}.
Bos taurus (Bovine)
P00433
PER1A_ARMRU
MHFSSSSTLFTCITLIPLVCLILHASLSDAQLTPTFYDNSCPNVSNIVRDTIVNELRSDPRIAASILRLHFHDCFVNGCDASILLDNTTSFRTEKDAFGNANSARGFPVIDRMKAAVESACPRTVSCADLLTIAAQQSVTLAGGPSWRVPLGRRDSLQAFLDLANANLPAPFFTLPQLKDSFRNVGLNRSSDLVALSGGHTFGKNQCRFIMDRLYNFSNTGLPDPTLNTTYLQTLRGLCPLNGNLSALVDFDLRTPTIFDNKYYVNLEEQKGLIQSDQELFSSPNATDTIPLVRSFANSTQTFFNAFVEAMDRMGNITPLTGTQGQIRLNCRVVNSNSLLHDMVEVVDFVSSM
1.11.1.7
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Note=Binds 2 calcium ions per subunit.; COFACTOR: Name=heme b; Xref=ChEBI:CHEBI:60344; Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.;
hydrogen peroxide catabolic process [GO:0042744]; response to oxidative stress [GO:0006979]
extracellular region [GO:0005576]; vacuole [GO:0005773]
heme binding [GO:0020037]; lactoperoxidase activity [GO:0140825]; metal ion binding [GO:0046872]
PF00141;
1.10.520.10;1.10.420.10;
Peroxidase family, Classical plant (class III) peroxidase subfamily
null
SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Vacuole {ECO:0000305}. Note=Carboxy-terminal extension appears to target the protein to vacuoles.
CATALYTIC ACTIVITY: Reaction=2 a phenolic donor + H2O2 = 2 a phenolic radical donor + 2 H2O; Xref=Rhea:RHEA:56136, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:139520, ChEBI:CHEBI:139521; EC=1.11.1.7;
null
null
null
null
FUNCTION: Removal of H(2)O(2), oxidation of toxic reductants, biosynthesis and degradation of lignin, suberization, auxin catabolism, response to environmental stresses such as wounding, pathogen attack and oxidative stress. These functions might be dependent on each isozyme/isoform in each plant tissue.
Armoracia rusticana (Horseradish) (Armoracia laphatifolia)
P00434
PERP7_BRARR
QLTTNFYSTSCPNLLSTVKSGVKSAVSSQPRMGASILRLFFHDCFVNGCDGSILLDDTSSFTGEQNAGPNRNSARGFTVINDIKSAVEKACPGVVSCADILAIAARDSVVQLGGPNWNVKVGRRDAKTASQAAANSNIPAPSMSLSQLISSFSAVGLSTRDMVALSGAHTIGQSRCVNFRARVYNETNINAAFATLRQRSCPRAAGSGDANLAPLDINSATSFDNSYFKNLMAQRGLLHSDQVLFNGGSTDSIVRGYSNSPSSFNSDFAAAMIKMGDISPLTGSSGEIRKVCGKTN
1.11.1.7
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Note=Binds 2 calcium ions per subunit.; COFACTOR: Name=heme b; Xref=ChEBI:CHEBI:60344; Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.;
hydrogen peroxide catabolic process [GO:0042744]; response to oxidative stress [GO:0006979]
null
heme binding [GO:0020037]; lactoperoxidase activity [GO:0140825]; metal ion binding [GO:0046872]
PF00141;
1.10.520.10;1.10.420.10;
Peroxidase family, Classical plant (class III) peroxidase subfamily
null
null
CATALYTIC ACTIVITY: Reaction=2 a phenolic donor + H2O2 = 2 a phenolic radical donor + 2 H2O; Xref=Rhea:RHEA:56136, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:139520, ChEBI:CHEBI:139521; EC=1.11.1.7;
null
null
null
null
FUNCTION: Removal of H(2)O(2), oxidation of toxic reductants, biosynthesis and degradation of lignin, suberization, auxin catabolism, response to environmental stresses such as wounding, pathogen attack and oxidative stress. These functions might be dependent on each isozyme/isoform in each plant tissue.
Brassica rapa subsp. rapa (Turnip)
P00435
GPX1_BOVIN
MCAAQRSAAALAAAAPRTVYAFSARPLAGGEPFNLSSLRGKVLLIENVASLUGTTVRDYTQMNDLQRRLGPRGLVVLGFPCNQFGHQENAKNEEILNCLKYVRPGGGFEPNFMLFEKCEVNGEKAHPLFAFLREVLPTPSDDATALMTDPKFITWSPVCRNDVSWNFEKFLVGPDGVPVRRYSRRFLTIDIEPDIETLLSQGASA
1.11.1.12; 1.11.1.9
null
arachidonic acid metabolic process [GO:0019369]; glutathione metabolic process [GO:0006749]; hydrogen peroxide catabolic process [GO:0042744]; lipoxygenase pathway [GO:0019372]; positive regulation of supramolecular fiber organization [GO:1902905]; response to hydrogen peroxide [GO:0042542]; response to selenium ion [GO:0010269]
cytosol [GO:0005829]; mitochondrion [GO:0005739]
glutathione peroxidase activity [GO:0004602]; phospholipid-hydroperoxide glutathione peroxidase activity [GO:0047066]
PF00255;
3.40.30.10;
Glutathione peroxidase family
PTM: During periods of oxidative stress, Sec-52 may react with a superoxide radical, irreversibly lose hydroselenide and be converted to dehydroalanine. {ECO:0000250|UniProtKB:P11352}.
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P11352}. Mitochondrion {ECO:0000250|UniProtKB:P11352}.
CATALYTIC ACTIVITY: Reaction=2 glutathione + H2O2 = glutathione disulfide + 2 H2O; Xref=Rhea:RHEA:16833, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297; EC=1.11.1.9; Evidence={ECO:0000250|UniProtKB:P11352}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16834; Evidence={ECO:0000250|UniProtKB:P11352}; CATALYTIC ACTIVITY: Reaction=a hydroperoxy polyunsaturated fatty acid + 2 glutathione = a hydroxy polyunsaturated fatty acid + glutathione disulfide + H2O; Xref=Rhea:RHEA:19057, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:131871, ChEBI:CHEBI:134019; EC=1.11.1.12; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19058; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=2 glutathione + tert-butyl hydroperoxide = glutathione disulfide + H2O + tert-butanol; Xref=Rhea:RHEA:69412, ChEBI:CHEBI:15377, ChEBI:CHEBI:45895, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:64090; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69413; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=cumene hydroperoxide + 2 glutathione = 2-phenylpropan-2-ol + glutathione disulfide + H2O; Xref=Rhea:RHEA:69651, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:78673, ChEBI:CHEBI:131607; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69652; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione = (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:48888, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90850; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48889; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=(9S)-hydroperoxy-(10E,12Z)-octadecadienoate + 2 glutathione = (9S)-hydroxy-(10E,12Z)-octadecadienoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:76687, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:60955, ChEBI:CHEBI:77852; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76688; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + 2 glutathione = (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:48620, ChEBI:CHEBI:15377, ChEBI:CHEBI:57450, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90632; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48621; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + 2 glutathione = (12S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:50708, ChEBI:CHEBI:15377, ChEBI:CHEBI:57444, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90680; Evidence={ECO:0000250|UniProtKB:P11352}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50709; Evidence={ECO:0000250|UniProtKB:P11352}; CATALYTIC ACTIVITY: Reaction=(12R)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + 2 glutathione = (12R)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:76691, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:75230, ChEBI:CHEBI:83343; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76692; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + 2 glutathione = (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:76695, ChEBI:CHEBI:15377, ChEBI:CHEBI:57409, ChEBI:CHEBI:57446, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76696; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z,17Z)-eicosapentaenoate + 2 glutathione = (5S)-hydroxy-(6E,8Z,11Z,14Z,17Z)-eicosapentaenoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:76699, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:195399, ChEBI:CHEBI:195400; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76700; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + 2 glutathione = (15S)-hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:76707, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:132087, ChEBI:CHEBI:194369; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76708; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=(15S)-hydroperoxy-(11Z,13E)-eicosadienoate + 2 glutathione = (15S)-hydroxy-(11Z,13E)-eicosadienoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:76711, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:144832, ChEBI:CHEBI:195402; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76712; Evidence={ECO:0000250|UniProtKB:P07203}; CATALYTIC ACTIVITY: Reaction=(17S)-hydroperoxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate + 2 glutathione = (17S)-hydroxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:76715, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:133795, ChEBI:CHEBI:195403; Evidence={ECO:0000250|UniProtKB:P07203}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76716; Evidence={ECO:0000250|UniProtKB:P07203};
null
null
null
null
FUNCTION: Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis. Can reduce small soluble hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl hydroperoxide, as well as several fatty acid-derived hydroperoxides. In platelets catalyzes the reduction of 12-hydroperoxyeicosatetraenoic acid, the primary product of the arachidonate 12-lipoxygenase pathway. {ECO:0000250|UniProtKB:P11352}.
Bos taurus (Bovine)
P00438
PHHY_PSEFL
MKTQVAIIGAGPSGLLLGQLLHKAGIDNVILERQTPDYVLGRIRAGVLEQGMVDLLREAGVDRRMARDGLVHEGVEIAFAGQRRRIDLKRLSGGKTVTVYGQTEVTRDLMEAREACGATTVYQAAEVRLHDLQGERPYVTFERDGERLRLDCDYIAGCDGFHGISRQSIPAERLKVFERVYPFGWLGLLADTPPVSHELIYANHPRGFALCSQRSATRSRYYVQVPLTEKVEDWSDERFWTELKARLPAEVAEKLVTGPSLEKSIAPLRSFVVEPMQHGRLFLAGDAAHIVPPTGAKGLNLAASDVSTLYRLLLKAYREGRGELLERYSAICLRRIWKAERFSWWMTSVLHRFPDTDAFSQRIQQTELEYYLGSEAGLATIAENYVGLPYEEIE
1.14.13.2
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:10025942, ECO:0000269|PubMed:10493859, ECO:0000269|PubMed:1409567, ECO:0000269|PubMed:1459126, ECO:0000269|PubMed:2819062, ECO:0000269|PubMed:3351945, ECO:0000269|PubMed:7628466, ECO:0000269|PubMed:9578477, ECO:0000269|PubMed:9694855}; Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:10025942, ECO:0000269|PubMed:10493859, ECO:0000269|PubMed:2819062, ECO:0000269|PubMed:3351945, ECO:0000269|PubMed:7628466, ECO:0000269|PubMed:9578477, ECO:0000269|PubMed:9694855};
benzoate catabolic process via hydroxylation [GO:0043640]
null
4-hydroxybenzoate 3-monooxygenase [NADPH] activity [GO:0106356]; 4-hydroxybenzoate 3-monooxygenase activity [GO:0018659]; FAD binding [GO:0071949]; flavin adenine dinucleotide binding [GO:0050660]
PF01494;
3.30.9.10;3.50.50.60;
Aromatic-ring hydroxylase family
null
null
CATALYTIC ACTIVITY: Reaction=4-hydroxybenzoate + H(+) + NADPH + O2 = 3,4-dihydroxybenzoate + H2O + NADP(+); Xref=Rhea:RHEA:19477, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17879, ChEBI:CHEBI:36241, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.2; Evidence={ECO:0000269|PubMed:10025942, ECO:0000269|PubMed:10493859, ECO:0000269|PubMed:1459126, ECO:0000269|PubMed:7628466, ECO:0000269|PubMed:7756982, ECO:0000269|PubMed:9578477, ECO:0000269|PubMed:9694855};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=15 uM for p-OHB {ECO:0000269|PubMed:9578477}; KM=15 uM for p-OHB (at pH 6) {ECO:0000269|PubMed:10025942, ECO:0000269|PubMed:10493859}; KM=20 uM for p-OHB {ECO:0000269|PubMed:7756982, ECO:0000269|PubMed:9694855}; KM=25 uM for p-OHB (at 25 degrees Celsius) {ECO:0000269|PubMed:1459126}; KM=30 uM for NADPH {ECO:0000269|PubMed:9694855}; KM=30 uM for p-OHB (at 6 degrees Celsius) {ECO:0000269|PubMed:1459126}; KM=34 uM for NADPH (at pH 6) {ECO:0000269|PubMed:10025942, ECO:0000269|PubMed:10493859}; KM=40 uM for NADPH (at 6 degrees Celsius) {ECO:0000269|PubMed:1459126}; KM=50 uM for NADPH (at 25 degrees Celsius) {ECO:0000269|PubMed:1459126}; KM=50 uM for NADPH {ECO:0000269|PubMed:9578477}; KM=70 uM for NADPH {ECO:0000269|PubMed:7756982}; Note=kcat is 55 sec(-1) for hydroxylase activity (PubMed:9578477, PubMed:9694855). kcat is 55 sec(-1) for hydroxylase activity (at 25 degrees Celsius) (PubMed:1459126). kcat is 55 sec(-1) for hydroxylase activity (at pH 8) (PubMed:10025942, PubMed:10493859). kcat is 9 sec(-1) for hydroxylase activity (at 6 degrees Celsius) (PubMed:1459126). {ECO:0000269|PubMed:10025942, ECO:0000269|PubMed:10493859, ECO:0000269|PubMed:1459126, ECO:0000269|PubMed:7756982, ECO:0000269|PubMed:9578477, ECO:0000269|PubMed:9694855};
PATHWAY: Aromatic compound metabolism; benzoate degradation via hydroxylation; 3,4-dihydroxybenzoate from benzoate: step 2/2. {ECO:0000305}.
null
null
FUNCTION: Catalyzes the incorporation of an atom of dioxygen into p-hydroxybenzoate (p-OHB) to form 3,4-dihydroxybenzoate (3,4DOHB). The reaction occurs in two parts: reduction of the flavin adenine dinucleotide (FAD) in the enzyme by reduced nicotinamide adenine dinucleotide phosphate (NADPH) in response to binding p-hydroxybenzoate to the enzyme and oxidation of reduced FAD with oxygen to form a hydroperoxide, which then oxygenates p-hydroxybenzoate. {ECO:0000269|PubMed:10025942, ECO:0000269|PubMed:10493859, ECO:0000269|PubMed:1459126, ECO:0000269|PubMed:2819062, ECO:0000269|PubMed:3351945, ECO:0000269|PubMed:7520279, ECO:0000269|PubMed:7628466, ECO:0000269|PubMed:7756982, ECO:0000269|PubMed:9578477, ECO:0000269|PubMed:9694855}.
Pseudomonas fluorescens
P00439
PH4H_HUMAN
MSTAVLENPGLGRKLSDFGQETSYIEDNCNQNGAISLIFSLKEEVGALAKVLRLFEENDVNLTHIESRPSRLKKDEYEFFTHLDKRSLPALTNIIKILRHDIGATVHELSRDKKKDTVPWFPRTIQELDRFANQILSYGAELDADHPGFKDPVYRARRKQFADIAYNYRHGQPIPRVEYMEEEKKTWGTVFKTLKSLYKTHACYEYNHIFPLLEKYCGFHEDNIPQLEDVSQFLQTCTGFRLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFAQFSQEIGLASLGAPDEYIEKLATIYWFTVEFGLCKQGDSIKAYGAGLLSSFGELQYCLSEKPKLLPLELEKTAIQNYTVTEFQPLYYVAESFNDAKEKVRNFAATIPRPFSVRYDPYTQRIEVLDNTQQLKILADSINSEIGILCSALQKIK
1.14.16.1
COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250|UniProtKB:P04176};
amino acid biosynthetic process [GO:0008652]; catecholamine biosynthetic process [GO:0042423]; L-phenylalanine catabolic process [GO:0006559]; tyrosine biosynthetic process [GO:0006571]
cytosol [GO:0005829]
iron ion binding [GO:0005506]; phenylalanine 4-monooxygenase activity [GO:0004505]
PF01842;PF00351;
1.10.800.10;
Biopterin-dependent aromatic amino acid hydroxylase family
PTM: Phosphorylation at Ser-16 increases basal activity and facilitates activation by the substrate phenylalanine. {ECO:0000269|PubMed:12185072}.
null
CATALYTIC ACTIVITY: Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-phenylalanine + O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tyrosine; Xref=Rhea:RHEA:20273, ChEBI:CHEBI:15379, ChEBI:CHEBI:15642, ChEBI:CHEBI:58095, ChEBI:CHEBI:58315, ChEBI:CHEBI:59560; EC=1.14.16.1; Evidence={ECO:0000269|PubMed:18460651, ECO:0000269|PubMed:18835579};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=150 uM for L-phenylalanine {ECO:0000269|PubMed:18835579}; KM=154 uM for L-phenylalanine (at 25 degrees Celsius) {ECO:0000269|PubMed:18460651}; KM=30 uM for tetrahydrobiopterin (BH(4)) {ECO:0000269|PubMed:18835579}; KM=36 uM for tetrahydrobiopterin (BH(4)) (at 25 degrees Celsius) {ECO:0000269|PubMed:18460651}; Vmax=3500 nmol/min/mg enzyme towards L-phenylalanine (at 25 degrees Celsius) {ECO:0000269|PubMed:18460651}; Vmax=3600 nmol/min/mg enzyme towards tetrahydrobiopterin (BH(4)) (at 25 degrees Celsius) {ECO:0000269|PubMed:18460651}; Vmax=3640 nmol/min/mg enzyme towards L-phenylalanine (preincubated with L-Phe) {ECO:0000269|PubMed:18835579}; Vmax=1230 nmol/min/mg enzyme towards L-phenylalanine (preincubated with BH(4)) {ECO:0000269|PubMed:18835579};
PATHWAY: Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 1/6.
null
BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 50 degrees Celsius. {ECO:0000269|PubMed:18835579};
FUNCTION: Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine. {ECO:0000269|PubMed:18460651, ECO:0000269|PubMed:18835579}.
Homo sapiens (Human)
P00440
TYRO_NEUCR
MSTDIKFAITGVPTPPSSNGAVPLRRELRDLQQNYPEQFNLYLLGLRDFQGLDEAKLDSYYQVAGIHGMPFKPWAGVPSDTDWSQPGSSGFGGYCTHSSILFITWHRPYLALYEQALYASVQAVAQKFPVEGGLRAKYVAAAKDFRAPYFDWASQPPKGTLAFPESLSSRTIQVVDVDGKTKSINNPLHRFTFHPVNPSPGDFSAAWSRYPSTVRYPNRLTGASRDERIAPILANELASLRNNVSLLLLSYKDFDAFSYNRWDPNTNPGDFGSLEDVHNEIHDRTGGNGHMSSLEVSAFDPLFWLHHVNVDRLWSIWQDLNPNSFMTPRPAPYSTFVAQEGESQSKSTPLEPFWDKSAANFWTSEQVKDSITFGYAYPETQKWKYSSVKEYQAAIRKSVTALYGSNVFANFVENVADRTPALKKPQATGEESKSTVSAAAAHAVELSGAKKVAEKVHNVFQHAEEKAQKPVVPVKDTKAESSTAAGMMIGLSIKRPSKLTASPGPIPESLKYLAPDGKYTDWIVNVRAQKHGLGQSFRVIVFLGEFNPDPETWDDEFNCVGRVSVLGRSAETQCGKCRKDNANGLIVSGTVPLTSALLQDIVGGELQSLKPEDVIPHLRANLKWKVALFNGDEYNLEEVPDLKVSVASTEVTIDEEGLPHYSRQYTVYPEITEGKPCGHGPEDHI
1.14.18.1
COFACTOR: Name=Cu(2+); Xref=ChEBI:CHEBI:29036; Evidence={ECO:0000250|UniProtKB:Q9ZP19}; Note=Binds 2 copper ions per subunit. {ECO:0000250|UniProtKB:Q9ZP19};
melanin biosynthetic process [GO:0042438]
null
metal ion binding [GO:0046872]; tyrosinase activity [GO:0004503]
PF18132;PF00264;
2.60.310.20;1.10.1280.10;
Tyrosinase family
null
null
CATALYTIC ACTIVITY: Reaction=2 L-dopa + O2 = 2 H2O + 2 L-dopaquinone; Xref=Rhea:RHEA:34287, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57504, ChEBI:CHEBI:57924; EC=1.14.18.1; CATALYTIC ACTIVITY: Reaction=L-tyrosine + O2 = H2O + L-dopaquinone; Xref=Rhea:RHEA:18117, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57924, ChEBI:CHEBI:58315; EC=1.14.18.1;
null
null
null
null
FUNCTION: This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.
Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
P00441
SODC_HUMAN
MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVVHEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ
1.15.1.1
COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000269|PubMed:17888947}; Note=Binds 1 copper ion per subunit. {ECO:0000269|PubMed:17888947}; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:17888947}; Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:17888947};
action potential initiation [GO:0099610]; anterograde axonal transport [GO:0008089]; apoptotic process [GO:0006915]; auditory receptor cell stereocilium organization [GO:0060088]; determination of adult lifespan [GO:0008340]; ectopic germ cell programmed cell death [GO:0035234]; embryo implantation [GO:0007566]; gene expression [GO:0010467]; glutathione metabolic process [GO:0006749]; heart contraction [GO:0060047]; hydrogen peroxide biosynthetic process [GO:0050665]; intracellular iron ion homeostasis [GO:0006879]; locomotory behavior [GO:0007626]; muscle cell cellular homeostasis [GO:0046716]; myeloid cell homeostasis [GO:0002262]; negative regulation of cholesterol biosynthetic process [GO:0045541]; negative regulation of developmental process [GO:0051093]; negative regulation of inflammatory response [GO:0050728]; negative regulation of neuron apoptotic process [GO:0043524]; negative regulation of reproductive process [GO:2000242]; neurofilament cytoskeleton organization [GO:0060052]; neuronal action potential [GO:0019228]; ovarian follicle development [GO:0001541]; peripheral nervous system myelin maintenance [GO:0032287]; placenta development [GO:0001890]; positive regulation of apoptotic process [GO:0043065]; positive regulation of catalytic activity [GO:0043085]; positive regulation of cytokine production [GO:0001819]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway [GO:1902177]; positive regulation of phagocytosis [GO:0050766]; positive regulation of superoxide anion generation [GO:0032930]; reactive oxygen species metabolic process [GO:0072593]; regulation of blood pressure [GO:0008217]; regulation of GTPase activity [GO:0043087]; regulation of mitochondrial membrane potential [GO:0051881]; regulation of multicellular organism growth [GO:0040014]; regulation of organ growth [GO:0046620]; regulation of protein kinase activity [GO:0045859]; regulation of T cell differentiation in thymus [GO:0033081]; relaxation of vascular associated smooth muscle [GO:0060087]; removal of superoxide radicals [GO:0019430]; response to axon injury [GO:0048678]; response to ethanol [GO:0045471]; response to heat [GO:0009408]; response to hydrogen peroxide [GO:0042542]; response to organic substance [GO:0010033]; response to superoxide [GO:0000303]; response to xenobiotic stimulus [GO:0009410]; retina homeostasis [GO:0001895]; retrograde axonal transport [GO:0008090]; sensory perception of sound [GO:0007605]; spermatogenesis [GO:0007283]; superoxide anion generation [GO:0042554]; superoxide metabolic process [GO:0006801]; thymus development [GO:0048538]; transmission of nerve impulse [GO:0019226]
axon cytoplasm [GO:1904115]; cytoplasm [GO:0005737]; cytoplasmic vesicle [GO:0031410]; cytosol [GO:0005829]; dendrite cytoplasm [GO:0032839]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; mitochondrial intermembrane space [GO:0005758]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]; neuronal cell body [GO:0043025]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; peroxisome [GO:0005777]; protein-containing complex [GO:0032991]
copper ion binding [GO:0005507]; identical protein binding [GO:0042802]; protein phosphatase 2B binding [GO:0030346]; protein-folding chaperone binding [GO:0051087]; small GTPase binding [GO:0031267]; superoxide dismutase activity [GO:0004784]; zinc ion binding [GO:0008270]
PF00080;
2.60.40.200;
Cu-Zn superoxide dismutase family
PTM: Unlike wild-type protein, the pathogenic variants ALS1 Arg-38, Arg-47, Arg-86 and Ala-94 are polyubiquitinated by RNF19A leading to their proteasomal degradation. The pathogenic variants ALS1 Arg-86 and Ala-94 are ubiquitinated by MARCH5 leading to their proteasomal degradation. {ECO:0000269|PubMed:12145308, ECO:0000269|PubMed:19741096}.; PTM: The ditryptophan cross-link at Trp-33 is responsible for the non-disulfide-linked homodimerization. Such modification might only occur in extreme conditions and additional experimental evidence is required. {ECO:0000269|PubMed:20600836}.; PTM: Palmitoylation helps nuclear targeting and decreases catalytic activity. {ECO:0000269|PubMed:22496122}.; PTM: Succinylation, adjacent to copper catalytic site, probably inhibits activity. Desuccinylation by SIRT5 enhances activity. {ECO:0000269|PubMed:24140062}.
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19741096}. Nucleus {ECO:0000269|PubMed:22496122}. Note=Predominantly cytoplasmic; the pathogenic variants ALS1 Arg-86 and Ala-94 gradually aggregates and accumulates in mitochondria. {ECO:0000269|PubMed:19741096}.
CATALYTIC ACTIVITY: Reaction=2 H(+) + 2 superoxide = H2O2 + O2; Xref=Rhea:RHEA:20696, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:18421; EC=1.15.1.1; Evidence={ECO:0000269|PubMed:24140062};
null
null
null
null
FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems. {ECO:0000269|PubMed:24140062}.
Homo sapiens (Human)
P00442
SODC_BOVIN
MATKAVCVLKGDGPVQGTIHFEAKGDTVVVTGSITGLTEGDHGFHVHQFGDNTQGCTSAGPHFNPLSKKHGGPKDEERHVGDLGNVTADKNGVAIVDIVDPLISLSGEYSIIGRTMVVHEKPDDLGRGGNEESTKTGNAGSRLACGVIGIAK
1.15.1.1
COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Note=Binds 1 copper ion per subunit.; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
auditory receptor cell stereocilium organization [GO:0060088]; embryo implantation [GO:0007566]; glutathione metabolic process [GO:0006749]; heart contraction [GO:0060047]; hydrogen peroxide biosynthetic process [GO:0050665]; intracellular iron ion homeostasis [GO:0006879]; locomotory behavior [GO:0007626]; muscle cell cellular homeostasis [GO:0046716]; myeloid cell homeostasis [GO:0002262]; negative regulation of cholesterol biosynthetic process [GO:0045541]; negative regulation of neuron apoptotic process [GO:0043524]; neurofilament cytoskeleton organization [GO:0060052]; ovarian follicle development [GO:0001541]; peripheral nervous system myelin maintenance [GO:0032287]; positive regulation of catalytic activity [GO:0043085]; positive regulation of cytokine production [GO:0001819]; positive regulation of MAPK cascade [GO:0043410]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; protein polyubiquitination [GO:0000209]; reactive oxygen species metabolic process [GO:0072593]; regulation of blood pressure [GO:0008217]; regulation of mitochondrial membrane potential [GO:0051881]; regulation of multicellular organism growth [GO:0040014]; regulation of protein kinase activity [GO:0045859]; relaxation of vascular associated smooth muscle [GO:0060087]; removal of superoxide radicals [GO:0019430]; response to axon injury [GO:0048678]; response to ethanol [GO:0045471]; response to heat [GO:0009408]; response to hydrogen peroxide [GO:0042542]; response to organic substance [GO:0010033]; response to superoxide [GO:0000303]; retina homeostasis [GO:0001895]; sensory perception of sound [GO:0007605]; spermatogenesis [GO:0007283]; superoxide metabolic process [GO:0006801]; transmission of nerve impulse [GO:0019226]
cytoplasm [GO:0005737]; cytoplasmic vesicle [GO:0031410]; cytosol [GO:0005829]; dendrite cytoplasm [GO:0032839]; mitochondrion [GO:0005739]; neuronal cell body [GO:0043025]; nucleus [GO:0005634]; peroxisome [GO:0005777]; protein-containing complex [GO:0032991]
copper ion binding [GO:0005507]; protein homodimerization activity [GO:0042803]; protein phosphatase 2B binding [GO:0030346]; protein-folding chaperone binding [GO:0051087]; superoxide dismutase activity [GO:0004784]; ubiquitin-protein transferase activity [GO:0004842]; zinc ion binding [GO:0008270]
PF00080;
2.60.40.200;
Cu-Zn superoxide dismutase family
PTM: Palmitoylation helps nuclear targeting and decreases catalytic activity. {ECO:0000250}.; PTM: Succinylation, adjacent to copper catalytic site, probably inhibits activity. Desuccinylation by SIRT5 enhances activity. {ECO:0000250|UniProtKB:P00441}.
SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000250}.
CATALYTIC ACTIVITY: Reaction=2 H(+) + 2 superoxide = H2O2 + O2; Xref=Rhea:RHEA:20696, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:18421; EC=1.15.1.1; Evidence={ECO:0000269|PubMed:518876};
null
null
null
null
FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems. {ECO:0000269|PubMed:518876}.
Bos taurus (Bovine)
P00443
SODC_HORSE
MALKAVCVLKGDGPVHGVIHFEQQQEGGPVVLKGFIEGLTKGDHGFHVHEFGDNTQGCTTAGAHFNPLSKKHGGPKDEERHVGDLGNVTADENGKADVDMKDSVISLSGKHSIIGRTMVVHEKQDDLGKGGNEESTKTGNAGSRLACGVIGIAP
1.15.1.1
COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000250}; Note=Binds 1 copper ion per subunit. {ECO:0000250}; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 1 zinc ion per subunit. {ECO:0000250};
reactive oxygen species metabolic process [GO:0072593]; removal of superoxide radicals [GO:0019430]
cytosol [GO:0005829]; mitochondrion [GO:0005739]; nucleus [GO:0005634]; peroxisome [GO:0005777]
copper ion binding [GO:0005507]; superoxide dismutase activity [GO:0004784]
PF00080;
2.60.40.200;
Cu-Zn superoxide dismutase family
PTM: Palmitoylation helps nuclear targeting and decreases catalytic activity. {ECO:0000250}.; PTM: Succinylation, adjacent to copper catalytic site, probably inhibits activity. Desuccinylation by SIRT5 enhances activity. {ECO:0000250|UniProtKB:P00441}.
SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000250}.
CATALYTIC ACTIVITY: Reaction=2 H(+) + 2 superoxide = H2O2 + O2; Xref=Rhea:RHEA:20696, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:18421; EC=1.15.1.1;
null
null
null
null
FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Equus caballus (Horse)
P00445
SODC_YEAST
MVQAVAVLKGDAGVSGVVKFEQASESEPTTVSYEIAGNSPNAERGFHIHEFGDATNGCVSAGPHFNPFKKTHGAPTDEVRHVGDMGNVKTDENGVAKGSFKDSLIKLIGPTSVVGRSVVIHAGQDDLGKGDTEESLKTGNAGPRPACGVIGLTN
1.15.1.1
COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000269|PubMed:10026301, ECO:0000269|PubMed:8652572}; Note=Binds 1 copper ion per subunit. {ECO:0000269|PubMed:10026301, ECO:0000269|PubMed:8652572}; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:10026301, ECO:0000269|PubMed:11524675}; Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:10026301, ECO:0000269|PubMed:11524675};
fungal-type cell wall organization [GO:0031505]; intracellular copper ion homeostasis [GO:0006878]; intracellular zinc ion homeostasis [GO:0006882]; negative regulation of cellular respiration [GO:1901856]; positive regulation of transcription by RNA polymerase II [GO:0045944]; protein maturation by copper ion transfer [GO:0015680]; protein stabilization [GO:0050821]; removal of superoxide radicals [GO:0019430]; superoxide metabolic process [GO:0006801]
cytosol [GO:0005829]; mitochondrial intermembrane space [GO:0005758]; mitochondrion [GO:0005739]; nucleus [GO:0005634]; peroxisome [GO:0005777]; superoxide dismutase complex [GO:1902693]
copper ion binding [GO:0005507]; superoxide dismutase activity [GO:0004784]
PF00080;
2.60.40.200;
Cu-Zn superoxide dismutase family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11500508}. Mitochondrion intermembrane space {ECO:0000269|PubMed:11500508, ECO:0000269|PubMed:22984289}. Note=A small percentage (around 1-5 percent) localizes to the mitochondrial intermembrane space. {ECO:0000269|PubMed:11500508}.
CATALYTIC ACTIVITY: Reaction=2 H(+) + 2 superoxide = H2O2 + O2; Xref=Rhea:RHEA:20696, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:18421; EC=1.15.1.1; Evidence={ECO:0000250|UniProtKB:P85978};
null
null
null
null
FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems. {ECO:0000250|UniProtKB:P00442}.
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
P00446
SODC_PHOLE
MNKAKTLLFTALAFGLSHQALAQDLTVKMTDLQTGKPVGTIELSQNKYGVVFTPELADLTPGMHGFHIHQNGSCASSEKDGKVVLGGAAGGHYDPEHTNKHGFPWTDDNHKGDLPALFVSANGLATNPVLAPRLTLKELKGHAIMIHAGGDNHSDMPKALGGGGARVACGVIQ
1.15.1.1
COFACTOR: Name=Cu cation; Xref=ChEBI:CHEBI:23378; Note=Binds 1 copper ion per subunit.; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
null
extracellular space [GO:0005615]; periplasmic space [GO:0042597]
copper ion binding [GO:0005507]; superoxide dismutase activity [GO:0004784]
PF00080;
2.60.40.200;
Cu-Zn superoxide dismutase family
null
SUBCELLULAR LOCATION: Periplasm.
CATALYTIC ACTIVITY: Reaction=2 H(+) + 2 superoxide = H2O2 + O2; Xref=Rhea:RHEA:20696, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:18421; EC=1.15.1.1;
null
null
null
null
FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Photobacterium leiognathi
P00448
SODM_ECOLI
MSYTLPSLPYAYDALEPHFDKQTMEIHHTKHHQTYVNNANAALESLPEFANLPVEELITKLDQLPADKKTVLRNNAGGHANHSLFWKGLKKGTTLQGDLKAAIERDFGSVDNFKAEFEKAAASRFGSGWAWLVLKGDKLAVVSTANQDSPLMGEAISGASGFPIMGLDVWEHAYYLKFQNRRPDYIKEFWNVVNWDEAAARFAAKK
1.15.1.1
COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Note=Binds 1 Mn(2+) ion per subunit.;
cellular response to selenium ion [GO:0071291]; removal of superoxide radicals [GO:0019430]; response to acidic pH [GO:0010447]; response to heat [GO:0009408]; response to oxidative stress [GO:0006979]; superoxide metabolic process [GO:0006801]
cytoplasm [GO:0005737]; cytosol [GO:0005829]
antioxidant activity [GO:0016209]; DNA binding [GO:0003677]; manganese ion binding [GO:0030145]; metal ion binding [GO:0046872]; protein homodimerization activity [GO:0042803]; superoxide dismutase activity [GO:0004784]
PF02777;PF00081;
1.10.287.990;3.55.40.20;
Iron/manganese superoxide dismutase family
null
null
CATALYTIC ACTIVITY: Reaction=2 H(+) + 2 superoxide = H2O2 + O2; Xref=Rhea:RHEA:20696, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:18421; EC=1.15.1.1;
null
null
null
null
FUNCTION: Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.
Escherichia coli (strain K12)
P00450
CERU_HUMAN
MKILILGIFLFLCSTPAWAKEKHYYIGIIETTWDYASDHGEKKLISVDTEHSNIYLQNGPDRIGRLYKKALYLQYTDETFRTTIEKPVWLGFLGPIIKAETGDKVYVHLKNLASRPYTFHSHGITYYKEHEGAIYPDNTTDFQRADDKVYPGEQYTYMLLATEEQSPGEGDGNCVTRIYHSHIDAPKDIASGLIGPLIICKKDSLDKEKEKHIDREFVVMFSVVDENFSWYLEDNIKTYCSEPEKVDKDNEDFQESNRMYSVNGYTFGSLPGLSMCAEDRVKWYLFGMGNEVDVHAAFFHGQALTNKNYRIDTINLFPATLFDAYMVAQNPGEWMLSCQNLNHLKAGLQAFFQVQECNKSSSKDNIRGKHVRHYYIAAEEIIWNYAPSGIDIFTKENLTAPGSDSAVFFEQGTTRIGGSYKKLVYREYTDASFTNRKERGPEEEHLGILGPVIWAEVGDTIRVTFHNKGAYPLSIEPIGVRFNKNNEGTYYSPNYNPQSRSVPPSASHVAPTETFTYEWTVPKEVGPTNADPVCLAKMYYSAVEPTKDIFTGLIGPMKICKKGSLHANGRQKDVDKEFYLFPTVFDENESLLLEDNIRMFTTAPDQVDKEDEDFQESNKMHSMNGFMYGNQPGLTMCKGDSVVWYLFSAGNEADVHGIYFSGNTYLWRGERRDTANLFPQTSLTLHMWPDTEGTFNVECLTTDHYTGGMKQKYTVNQCRRQSEDSTFYLGERTYYIAAVEVEWDYSPQREWEKELHHLQEQNVSNAFLDKGEFYIGSKYKKVVYRQYTDSTFRVPVERKAEEEHLGILGPQLHADVGDKVKIIFKNMATRPYSIHAHGVQTESSTVTPTLPGETLTYVWKIPERSGAGTEDSACIPWAYYSTVDQVKDLYSGLIGPLIVCRRPYLKVFNPRRKLEFALLFLVFDENESWYLDDNIKTYSDHPEKVNKDDEEFIESNKMHAINGRMFGNLQGLTMHVGDEVNWYLMGMGNEIDLHTVHFHGHSFQYKHRGVYSSDVFDIFPGTYQTLEMFPRTPGIWLLHCHVTDHIHAGMETTYTVLQNEDTKSG
1.11.1.27; 1.11.1.9; 1.16.3.1; 1.16.3.4
COFACTOR: Name=Cu(2+); Xref=ChEBI:CHEBI:29036; Evidence={ECO:0000269|PubMed:17242517, ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29}; Note=Binds 6 Cu(2+) cations per monomer. {ECO:0000269|PubMed:17242517, ECO:0000269|PubMed:23843990, ECO:0000269|Ref.29};
copper ion transport [GO:0006825]; intracellular copper ion homeostasis [GO:0006878]; intracellular iron ion homeostasis [GO:0006879]; iron ion transport [GO:0006826]
blood microparticle [GO:0072562]; endoplasmic reticulum lumen [GO:0005788]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; lysosomal membrane [GO:0005765]; plasma membrane [GO:0005886]
copper ion binding [GO:0005507]; ferroxidase activity [GO:0004322]; glutathione peroxidase activity [GO:0004602]; oxidoreductase activity [GO:0016491]; oxidoreductase activity, acting on metal ions, oxygen as acceptor [GO:0016724]; phospholipid-hydroperoxide glutathione peroxidase activity [GO:0047066]; protein-folding chaperone binding [GO:0051087]; signaling receptor activity [GO:0038023]
PF00394;PF07731;PF07732;
2.60.40.420;
Multicopper oxidase family
null
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16150804}. Note=Colocalizes with GCP1 in secretory intracellular compartments. {ECO:0000250|UniProtKB:P13635}.
CATALYTIC ACTIVITY: Reaction=4 Fe(2+) + 4 H(+) + O2 = 4 Fe(3+) + 2 H2O; Xref=Rhea:RHEA:11148, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.16.3.1; Evidence={ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:16150804, ECO:0000269|PubMed:29183916, ECO:0000269|PubMed:5912351}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11150; Evidence={ECO:0000269|PubMed:16150804, ECO:0000269|PubMed:29183916}; CATALYTIC ACTIVITY: Reaction=4 Cu(+) + 4 H(+) + O2 = 4 Cu(2+) + 2 H2O; Xref=Rhea:RHEA:30083, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:29036, ChEBI:CHEBI:49552; EC=1.16.3.4; Evidence={ECO:0000269|PubMed:14623105}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30084; Evidence={ECO:0000305|PubMed:14623105}; CATALYTIC ACTIVITY: Reaction=a hydroperoxide + 2 glutathione = an alcohol + glutathione disulfide + H2O; Xref=Rhea:RHEA:62632, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879, ChEBI:CHEBI:35924, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297; EC=1.11.1.27; Evidence={ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:10508415}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62633; Evidence={ECO:0000305|PubMed:10508415}; CATALYTIC ACTIVITY: Reaction=2 H2O + 4 nitric oxide + O2 = 4 H(+) + 4 nitrite; Xref=Rhea:RHEA:78539, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16301, ChEBI:CHEBI:16480; Evidence={ECO:0000269|PubMed:29183916}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78540; Evidence={ECO:0000305|PubMed:29183916}; CATALYTIC ACTIVITY: Reaction=2 glutathione + H2O2 = glutathione disulfide + 2 H2O; Xref=Rhea:RHEA:16833, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297; EC=1.11.1.9; Evidence={ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:10508415}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16834; Evidence={ECO:0000305|PubMed:10508415};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=36.8 uM for Cu(+) {ECO:0000269|PubMed:14623105}; KM=8.3 uM for Fe(2+) {ECO:0000269|PubMed:14623105}; KM=1.57 mM for glutathione {ECO:0000269|PubMed:10508415}; KM=0.63 mM for tert-butyl hydroperoxide {ECO:0000269|PubMed:10508415}; KM=0.87 mM for glutathione {ECO:0000269|PubMed:10508415}; Vmax=156 nmol/min/mg enzyme (in presence of 5 mM tert-butyl hydroperoxide) {ECO:0000269|PubMed:10508415}; Vmax=49 nmol/min/mg enzyme (in presence of 5 mM H2O2) {ECO:0000269|PubMed:10508415}; Note=kcat is 22.5 min(-1) and 30.3 min(-1) with Cu(+) and Fe(2+) as substrates, respectively. {ECO:0000269|PubMed:14623105};
null
null
null
FUNCTION: Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane (PubMed:16150804). Copper ions provide a large number of enzymatic activites. Oxidizes highly toxic ferrous ions to the ferric state for further incorporation onto apo-transferrins, catalyzes Cu(+) oxidation and promotes the oxidation of biogenic amines such as norepinephrin and serotonin (PubMed:14623105, PubMed:4643313, PubMed:5912351). Provides Cu(2+) ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1 (By similarity). Has glutathione peroxidase-like activity, can remove both hydrogen peroxide and lipid hydroperoxide in the presence of thiols (PubMed:10481051). Also shows NO-oxidase and NO2 synthase activities that determine endocrine NO homeostasis (PubMed:16906150). {ECO:0000250|UniProtKB:P13635, ECO:0000269|PubMed:10481051, ECO:0000269|PubMed:14623105, ECO:0000269|PubMed:16150804, ECO:0000269|PubMed:16906150, ECO:0000269|PubMed:4643313, ECO:0000269|PubMed:5912351}.
Homo sapiens (Human)
P00451
FA8_HUMAN
MQIELSTCFFLCLLRFCFSATRRYYLGAVELSWDYMQSDLGELPVDARFPPRVPKSFPFNTSVVYKKTLFVEFTDHLFNIAKPRPPWMGLLGPTIQAEVYDTVVITLKNMASHPVSLHAVGVSYWKASEGAEYDDQTSQREKEDDKVFPGGSHTYVWQVLKENGPMASDPLCLTYSYLSHVDLVKDLNSGLIGALLVCREGSLAKEKTQTLHKFILLFAVFDEGKSWHSETKNSLMQDRDAASARAWPKMHTVNGYVNRSLPGLIGCHRKSVYWHVIGMGTTPEVHSIFLEGHTFLVRNHRQASLEISPITFLTAQTLLMDLGQFLLFCHISSHQHDGMEAYVKVDSCPEEPQLRMKNNEEAEDYDDDLTDSEMDVVRFDDDNSPSFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLAPDDRSYKSQYLNNGPQRIGRKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTLLIIFKNQASRPYNIYPHGITDVRPLYSRRLPKGVKHLKDFPILPGEIFKYKWTVTVEDGPTKSDPRCLTRYYSSFVNMERDLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDENRSWYLTENIQRFLPNPAGVQLEDPEFQASNIMHSINGYVFDSLQLSVCLHEVAYWYILSIGAQTDFLSVFFSGYTFKHKMVYEDTLTLFPFSGETVFMSMENPGLWILGCHNSDFRNRGMTALLKVSSCDKNTGDYYEDSYEDISAYLLSKNNAIEPRSFSQNSRHPSTRQKQFNATTIPENDIEKTDPWFAHRTPMPKIQNVSSSDLLMLLRQSPTPHGLSLSDLQEAKYETFSDDPSPGAIDSNNSLSEMTHFRPQLHHSGDMVFTPESGLQLRLNEKLGTTAATELKKLDFKVSSTSNNLISTIPSDNLAAGTDNTSSLGPPSMPVHYDSQLDTTLFGKKSSPLTESGGPLSLSEENNDSKLLESGLMNSQESSWGKNVSSTESGRLFKGKRAHGPALLTKDNALFKVSISLLKTNKTSNNSATNRKTHIDGPSLLIENSPSVWQNILESDTEFKKVTPLIHDRMLMDKNATALRLNHMSNKTTSSKNMEMVQQKKEGPIPPDAQNPDMSFFKMLFLPESARWIQRTHGKNSLNSGQGPSPKQLVSLGPEKSVEGQNFLSEKNKVVVGKGEFTKDVGLKEMVFPSSRNLFLTNLDNLHENNTHNQEKKIQEEIEKKETLIQENVVLPQIHTVTGTKNFMKNLFLLSTRQNVEGSYDGAYAPVLQDFRSLNDSTNRTKKHTAHFSKKGEEENLEGLGNQTKQIVEKYACTTRISPNTSQQNFVTQRSKRALKQFRLPLEETELEKRIIVDDTSTQWSKNMKHLTPSTLTQIDYNEKEKGAITQSPLSDCLTRSHSIPQANRSPLPIAKVSSFPSIRPIYLTRVLFQDNSSHLPAASYRKKDSGVQESSHFLQGAKKNNLSLAILTLEMTGDQREVGSLGTSATNSVTYKKVENTVLPKPDLPKTSGKVELLPKVHIYQKDLFPTETSNGSPGHLDLVEGSLLQGTEGAIKWNEANRPGKVPFLRVATESSAKTPSKLLDPLAWDNHYGTQIPKEEWKSQEKSPEKTAFKKKDTILSLNACESNHAIAAINEGQNKPEIEVTWAKQGRTERLCSQNPPVLKRHQREITRTTLQSDQEEIDYDDTISVEMKKEDFDIYDEDENQSPRSFQKKTRHYFIAAVERLWDYGMSSSPHVLRNRAQSGSVPQFKKVVFQEFTDGSFTQPLYRGELNEHLGLLGPYIRAEVEDNIMVTFRNQASRPYSFYSSLISYEEDQRQGAEPRKNFVKPNETKTYFWKVQHHMAPTKDEFDCKAWAYFSDVDLEKDVHSGLIGPLLVCHTNTLNPAHGRQVTVQEFALFFTIFDETKSWYFTENMERNCRAPCNIQMEDPTFKENYRFHAINGYIMDTLPGLVMAQDQRIRWYLLSMGSNENIHSIHFSGHVFTVRKKEEYKMALYNLYPGVFETVEMLPSKAGIWRVECLIGEHLHAGMSTLFLVYSNKCQTPLGMASGHIRDFQITASGQYGQWAPKLARLHYSGSINAWSTKEPFSWIKVDLLAPMIIHGIKTQGARQKFSSLYISQFIIMYSLDGKKWQTYRGNSTGTLMVFFGNVDSSGIKHNIFNPPIIARYIRLHPTHYSIRSTLRMELMGCDLNSCSMPLGMESKAISDAQITASSYFTNMFATWSPSKARLHLQGRSNAWRPQVNNPKEWLQVDFQKTMKVTGVTTQGVKSLLTSMYVKEFLISSSQDGHQWTLFFQNGKVKVFQGNQDSFTPVVNSLDPPLLTRYLRIHPQSWVHQIALRMEVLGCEAQDLY
null
null
acute-phase response [GO:0006953]; blood coagulation [GO:0007596]; blood coagulation, intrinsic pathway [GO:0007597]
COPII-coated ER to Golgi transport vesicle [GO:0030134]; endoplasmic reticulum lumen [GO:0005788]; endoplasmic reticulum-Golgi intermediate compartment membrane [GO:0033116]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; Golgi lumen [GO:0005796]; plasma membrane [GO:0005886]; platelet alpha granule lumen [GO:0031093]
copper ion binding [GO:0005507]; oxidoreductase activity [GO:0016491]; signaling receptor activity [GO:0038023]
PF07731;PF07732;PF00754;
2.60.40.420;2.60.120.260;
Multicopper oxidase family
PTM: Sulfation on Tyr-1699 is essential for binding vWF. {ECO:0000269|PubMed:10368977, ECO:0000269|PubMed:1554716, ECO:0000269|PubMed:1898735}.; PTM: Proteolytically cleaved by cathepsin CTSG to produce a partially activated form. {ECO:0000269|PubMed:18217133}.
SUBCELLULAR LOCATION: Secreted, extracellular space.
null
null
null
null
null
FUNCTION: Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa.
Homo sapiens (Human)
P00452
RIR1_ECOLI
MNQNLLVTKRDGSTERINLDKIHRVLDWAAEGLHNVSISQVELRSHIQFYDGIKTSDIHETIIKAAADLISRDAPDYQYLAARLAIFHLRKKAYGQFEPPALYDHVVKMVEMGKYDNHLLEDYTEEEFKQMDTFIDHDRDMTFSYAAVKQLEGKYLVQNRVTGEIYESAQFLYILVAACLFSNYPRETRLQYVKRFYDAVSTFKISLPTPIMSGVRTPTRQFSSCVLIECGDSLDSINATSSAIVKYVSQRAGIGINAGRIRALGSPIRGGEAFHTGCIPFYKHFQTAVKSCSQGGVRGGAATLFYPMWHLEVESLLVLKNNRGVEGNRVRHMDYGVQINKLMYTRLLKGEDITLFSPSDVPGLYDAFFADQEEFERLYTKYEKDDSIRKQRVKAVELFSLMMQERASTGRIYIQNVDHCNTHSPFDPAIAPVRQSNLCLEIALPTKPLNDVNDENGEIALCTLSAFNLGAINNLDELEELAILAVRALDALLDYQDYPIPAAKRGAMGRRTLGIGVINFAYYLAKHGKRYSDGSANNLTHKTFEAIQYYLLKASNELAKEQGACPWFNETTYAKGILPIDTYKKDLDTIANEPLHYDWEALRESIKTHGLRNSTLSALMPSETSSQISNATNGIEPPRGYVSIKASKDGILRQVVPDYEHLHDAYELLWEMPGNDGYLQLVGIMQKFIDQSISANTNYDPSRFPSGKVPMQQLLKDLLTAYKFGVKTLYYQNTRDGAEDAQDDLVPSIQDDGCESGACKI
1.17.4.1
null
2'-deoxyribonucleotide biosynthetic process [GO:0009265]; deoxyribonucleotide biosynthetic process [GO:0009263]; DNA replication [GO:0006260]; nucleobase-containing small molecule interconversion [GO:0015949]; ribonucleoside diphosphate metabolic process [GO:0009185]
cytosol [GO:0005829]; ribonucleoside-diphosphate reductase complex [GO:0005971]
ATP binding [GO:0005524]; identical protein binding [GO:0042802]; protein folding chaperone [GO:0044183]; ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor [GO:0004748]
PF03477;PF02867;PF00317;
1.10.1650.20;3.20.70.20;
Ribonucleoside diphosphate reductase large chain family
PTM: Binding of the substrate occurs primarily when the active-site cysteines are reduced.
null
CATALYTIC ACTIVITY: Reaction=[thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'-diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'-diphosphate; Xref=Rhea:RHEA:23252, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57930, ChEBI:CHEBI:73316; EC=1.17.4.1;
null
null
null
null
FUNCTION: Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R1 contains the binding sites for both substrates and allosteric effectors and carries out the actual reduction of the ribonucleotide. It also provides redox-active cysteines.
Escherichia coli (strain K12)
P00455
FENR_SPIOL
MTTAVTAAVSFPSTKTTSLSARSSSVISPDKISYKKVPLYYRNVSATGKMGPIRAQIASDVEAPPPAPAKVEKHSKKMEEGITVNKFKPKTPYVGRCLLNTKITGDDAPGETWHMVFSHEGEIPYREGQSVGVIPDGEDKNGKPHKLRLYSIASSALGDFGDAKSVSLCVKRLIYTNDAGETIKGVCSNFLCDLKPGAEVKLTGPVGKEMLMPKDPNATIIMLGTGTGIAPFRSFLWKMFFEKHDDYKFNGLAWLFLGVPTSSSLLYKEEFEKMKEKAPDNFRLDFAVSREQTNEKGEKMYIQTRMAQYAVELWEMLKKDNTYFYMCGLKGMEKGIDDIMVSLAAAEGIDWIEYKRQLKKAEQWNVEVY
1.18.1.2
COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692;
electron transport chain [GO:0022900]; photosynthesis [GO:0015979]
chloroplast stroma [GO:0009570]; chloroplast thylakoid membrane protein complex [GO:0098807]
ferredoxin-NADP+ reductase activity [GO:0004324]; NADPH dehydrogenase activity [GO:0003959]
PF00175;
3.40.50.80;2.40.30.10;
Ferredoxin--NADP reductase type 1 family
null
SUBCELLULAR LOCATION: Plastid, chloroplast stroma. Plastid, chloroplast thylakoid membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Stromal side {ECO:0000305}. Note=In the vicinity of the photosystem I in the non-stacked and fringe portion of the membrane.
CATALYTIC ACTIVITY: Reaction=H(+) + NADP(+) + 2 reduced [2Fe-2S]-[ferredoxin] = NADPH + 2 oxidized [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:20125, Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001, ChEBI:CHEBI:15378, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.18.1.2;
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=35 uM for NADPH {ECO:0000269|PubMed:1986412};
PATHWAY: Energy metabolism; photosynthesis.
null
null
FUNCTION: May play a key role in regulating the relative amounts of cyclic and non-cyclic electron flow to meet the demands of the plant for ATP and reducing power.
Spinacia oleracea (Spinach)
P00459
NIFH1_AZOVI
MAMRQCAIYGKGGIGKSTTTQNLVAALAEMGKKVMIVGCDPKADSTRLILHSKAQNTIMEMAAEAGTVEDLELEDVLKAGYGGVKCVESGGPEPGVGCAGRGVITAINFLEEEGAYEDDLDFVFYDVLGDVVCGGFAMPIRENKAQEIYIVCSGEMMAMYAANNISKGIVKYANSGSVRLGGLICNSRNTDREDELIIALANKLGTQMIHFVPRDNVVQRAEIRRMTVIEYDPKAKQADEYRALARKVVDNKLLVIPNPITMDELEELLMEFGIMEVEDESIVGKTAEEV
1.18.6.1
COFACTOR: Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Note=Binds 1 [4Fe-4S] cluster per dimer.;
nitrogen fixation [GO:0009399]
null
4 iron, 4 sulfur cluster binding [GO:0051539]; ATP binding [GO:0005524]; carbonyl sulfide nitrogenase activity [GO:0018697]; metal ion binding [GO:0046872]; nitrogenase activity [GO:0016163]
PF00142;
3.40.50.300;
NifH/BchL/ChlL family
PTM: The reversible ADP-ribosylation of Arg-101 inactivates the nitrogenase reductase and regulates nitrogenase activity. {ECO:0000250}.
null
CATALYTIC ACTIVITY: Reaction=16 ATP + 16 H2O + N2 + 8 reduced [2Fe-2S]-[ferredoxin] = 16 ADP + 6 H(+) + H2 + 2 NH4(+) + 8 oxidized [2Fe-2S]-[ferredoxin] + 16 phosphate; Xref=Rhea:RHEA:21448, Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17997, ChEBI:CHEBI:18276, ChEBI:CHEBI:28938, ChEBI:CHEBI:30616, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=1.18.6.1;
null
null
null
null
FUNCTION: The key enzymatic reactions in nitrogen fixation are catalyzed by the nitrogenase complex, which has 2 components: the iron protein (component 2) and a component 1 which is either a molybdenum-iron protein, a vanadium-iron, or an iron-iron protein.
Azotobacter vinelandii
P00480
OTC_HUMAN
MLFNLRILLNNAAFRNGHNFMVRNFRCGQPLQNKVQLKGRDLLTLKNFTGEEIKYMLWLSADLKFRIKQKGEYLPLLQGKSLGMIFEKRSTRTRLSTETGFALLGGHPCFLTTQDIHLGVNESLTDTARVLSSMADAVLARVYKQSDLDTLAKEASIPIINGLSDLYHPIQILADYLTLQEHYSSLKGLTLSWIGDGNNILHSIMMSAAKFGMHLQAATPKGYEPDASVTKLAEQYAKENGTKLLLTNDPLEAAHGGNVLITDTWISMGQEEEKKKRLQAFQGYQVTMKTAKVAASDWTFLHCLPRKPEEVDDEVFYSPRSLVFPEAENRKWTIMAVMVSLLTDYSPQLQKPKF
2.1.3.3
null
ammonium homeostasis [GO:0097272]; arginine biosynthetic process via ornithine [GO:0042450]; citrulline biosynthetic process [GO:0019240]; liver development [GO:0001889]; midgut development [GO:0007494]; monoatomic anion homeostasis [GO:0055081]; ornithine catabolic process [GO:0006593]; response to biotin [GO:0070781]; response to insulin [GO:0032868]; response to xenobiotic stimulus [GO:0009410]; response to zinc ion [GO:0010043]; urea cycle [GO:0000050]
mitochondrial inner membrane [GO:0005743]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
amino acid binding [GO:0016597]; identical protein binding [GO:0042802]; ornithine carbamoyltransferase activity [GO:0004585]; phosphate ion binding [GO:0042301]; phospholipid binding [GO:0005543]
PF00185;PF02729;
3.40.50.1370;
Aspartate/ornithine carbamoyltransferase superfamily, OTCase family
PTM: Acetylation at Lys-88 negatively regulates ornithine carbamoyltransferase activity in response to nutrient signals. {ECO:0000269|PubMed:19318352}.
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:3895227}.
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; Evidence={ECO:0000269|PubMed:2556444, ECO:0000269|PubMed:6372096, ECO:0000269|PubMed:8112735}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19515; Evidence={ECO:0000305|PubMed:6372096};
null
PATHWAY: Nitrogen metabolism; urea cycle; L-citrulline from L-ornithine and carbamoyl phosphate: step 1/1. {ECO:0000269|PubMed:2556444}.
null
null
FUNCTION: Catalyzes the second step of the urea cycle, the condensation of carbamoyl phosphate with L-ornithine to form L-citrulline (PubMed:2556444, PubMed:6372096, PubMed:8112735). The urea cycle ensures the detoxification of ammonia by converting it to urea for excretion (PubMed:2556444). {ECO:0000269|PubMed:2556444, ECO:0000269|PubMed:6372096, ECO:0000269|PubMed:8112735}.
Homo sapiens (Human)
P00481
OTC_RAT
MLSNLRILLNKAALRKAHTSMVRNFRYGKPVQSQVQLKGRDLLTLKNFTGEEIQYMLWLSADLKFRIKQKGEYLPLLQGKSLGMIFEKRSTRTRLSTETGFALLGGHPSFLTTQDIHLGVNESLTDTARVLSSMTDAVLARVYKQSDLDILAKEATIPIVNGLSDLYHPIQILADYLTLQEHYGSLKGLTLSWIGDGNNILHSIMMSAAKFGMHLQAATPKGYEPDPNIVKLAEQYAKENGTRLSMTNDPLEAARGGNVLITDTWISMGQEDEKKKRLQAFQGYQVTMKTAKVAASDWTFLHCLPRKPEEVDDEVFYSPRSLVFPEAENRKWTIMAVMVSLLTDYSPVLQKPKF
2.1.3.3
null
ammonium homeostasis [GO:0097272]; arginine biosynthetic process via ornithine [GO:0042450]; citrulline biosynthetic process [GO:0019240]; liver development [GO:0001889]; midgut development [GO:0007494]; monoatomic anion homeostasis [GO:0055081]; ornithine catabolic process [GO:0006593]; ornithine metabolic process [GO:0006591]; response to biotin [GO:0070781]; response to insulin [GO:0032868]; response to nutrient levels [GO:0031667]; response to xenobiotic stimulus [GO:0009410]; response to zinc ion [GO:0010043]; urea cycle [GO:0000050]
mitochondrial inner membrane [GO:0005743]; mitochondrial matrix [GO:0005759]; mitochondrion [GO:0005739]
amino acid binding [GO:0016597]; identical protein binding [GO:0042802]; ornithine carbamoyltransferase activity [GO:0004585]; phosphate ion binding [GO:0042301]; phospholipid binding [GO:0005543]
PF00185;PF02729;
3.40.50.1370;
Aspartate/ornithine carbamoyltransferase superfamily, OTCase family
PTM: Acetylation at Lys-88 negatively regulates ornithine carbamoyltransferase activity in response to nutrient signals. {ECO:0000250|UniProtKB:P00480}.
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250|UniProtKB:P00480}.
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; Evidence={ECO:0000269|PubMed:2290837}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19515; Evidence={ECO:0000305|PubMed:2290837};
null
PATHWAY: Nitrogen metabolism; urea cycle; L-citrulline from L-ornithine and carbamoyl phosphate: step 1/1. {ECO:0000305|PubMed:2290837}.
null
null
FUNCTION: Catalyzes the second step of the urea cycle, the condensation of carbamoyl phosphate with L-ornithine to form L-citrulline (PubMed:2290837). The urea cycle ensures the detoxification of ammonia by converting it to urea for excretion (PubMed:2290837). {ECO:0000269|PubMed:2290837}.
Rattus norvegicus (Rat)
P00488
F13A_HUMAN
MSETSRTAFGGRRAVPPNNSNAAEDDLPTVELQGVVPRGVNLQEFLNVTSVHLFKERWDTNKVDHHTDKYENNKLIVRRGQSFYVQIDFSRPYDPRRDLFRVEYVIGRYPQENKGTYIPVPIVSELQSGKWGAKIVMREDRSVRLSIQSSPKCIVGKFRMYVAVWTPYGVLRTSRNPETDTYILFNPWCEDDAVYLDNEKEREEYVLNDIGVIFYGEVNDIKTRSWSYGQFEDGILDTCLYVMDRAQMDLSGRGNPIKVSRVGSAMVNAKDDEGVLVGSWDNIYAYGVPPSAWTGSVDILLEYRSSENPVRYGQCWVFAGVFNTFLRCLGIPARIVTNYFSAHDNDANLQMDIFLEEDGNVNSKLTKDSVWNYHCWNEAWMTRPDLPVGFGGWQAVDSTPQENSDGMYRCGPASVQAIKHGHVCFQFDAPFVFAEVNSDLIYITAKKDGTHVVENVDATHIGKLIVTKQIGGDGMMDITDTYKFQEGQEEERLALETALMYGAKKPLNTEGVMKSRSNVDMDFEVENAVLGKDFKLSITFRNNSHNRYTITAYLSANITFYTGVPKAEFKKETFDVTLEPLSFKKEAVLIQAGEYMGQLLEQASLHFFVTARINETRDVLAKQKSTVLTIPEIIIKVRGTQVVGSDMTVTVEFTNPLKETLRNVWVHLDGPGVTRPMKKMFREIRPNSTVQWEEVCRPWVSGHRKLIASMSSDSLRHVYGELDVQIQRRPSM
2.3.2.13
COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:9988734}; Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:9988734};
blood coagulation [GO:0007596]; blood coagulation, fibrin clot formation [GO:0072378]; peptide cross-linking [GO:0018149]
blood microparticle [GO:0072562]; collagen-containing extracellular matrix [GO:0062023]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; platelet alpha granule lumen [GO:0031093]; transferase complex [GO:1990234]
metal ion binding [GO:0046872]; protein-glutamine gamma-glutamyltransferase activity [GO:0003810]
PF00927;PF01841;PF00868;
2.60.40.10;3.90.260.10;
Transglutaminase superfamily, Transglutaminase family
PTM: The activation peptide is released by thrombin.
SUBCELLULAR LOCATION: Cytoplasm. Secreted {ECO:0000269|PubMed:4405643}. Note=Secreted into the blood plasma. Cytoplasmic in most tissues, but also secreted in the blood plasma.
CATALYTIC ACTIVITY: Reaction=L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L-lysyl-N(6)-5-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:54816, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:14005, ChEBI:CHEBI:28938, ChEBI:CHEBI:29969, ChEBI:CHEBI:30011, ChEBI:CHEBI:138370; EC=2.3.2.13; Evidence={ECO:0000255|PROSITE-ProRule:PRU10024, ECO:0000269|PubMed:27363989};
null
null
null
null
FUNCTION: Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. Also cross-link alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin. {ECO:0000269|PubMed:27363989}.
Homo sapiens (Human)
P00489
PYGM_RABIT
MSRPLSDQEKRKQISVRGLAGVENVTELKKNFNRHLHFTLVKDRNVATPRDYYFALAHTVRDHLVGRWIRTQQHYYEKDPKRIYYLSLEFYMGRTLQNTMVNLALENACDEATYQLGLDMEELEEIEEDAGLGNGGLGRLAACFLDSMATLGLAAYGYGIRYEFGIFNQKICGGWQMEEADDWLRYGNPWEKARPEFTLPVHFYGRVEHTSQGAKWVDTQVVLAMPYDTPVPGYRNNVVNTMRLWSAKAPNDFNLKDFNVGGYIQAVLDRNLAENISRVLYPNDNFFEGKELRLKQEYFVVAATLQDIIRRFKSSKFGCRDPVRTNFDAFPDKVAIQLNDTHPSLAIPELMRVLVDLERLDWDKAWEVTVKTCAYTNHTVLPEALERWPVHLLETLLPRHLQIIYEINQRFLNRVAAAFPGDVDRLRRMSLVEEGAVKRINMAHLCIAGSHAVNGVARIHSEILKKTIFKDFYELEPHKFQNKTNGITPRRWLVLCNPGLAEIIAERIGEEYISDLDQLRKLLSYVDDEAFIRDVAKVKQENKLKFAAYLEREYKVHINPNSLFDVQVKRIHEYKRQLLNCLHVITLYNRIKKEPNKFVVPRTVMIGGKAAPGYHMAKMIIKLITAIGDVVNHDPVVGDRLRVIFLENYRVSLAEKVIPAADLSEQISTAGTEASGTGNMKFMLNGALTIGTMDGANVEMAEEAGEENFFIFGMRVEDVDRLDQRGYNAQEYYDRIPELRQIIEQLSSGFFSPKQPDLFKDIVNMLMHHDRFKVFADYEEYVKCQERVSALYKNPREWTRMVIRNIATSGKFSSDRTIAQYAREIWGVEPSRQRLPAPDEKIP
2.4.1.1
COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000269|PubMed:7500360, ECO:0000269|PubMed:8976550, ECO:0007744|PDB:2PRI, ECO:0007744|PDB:2SKC, ECO:0007744|PDB:2SKD, ECO:0007744|PDB:2SKE};
glycogen catabolic process [GO:0005980]
skeletal muscle myofibril [GO:0098723]
glycogen phosphorylase activity [GO:0008184]; linear malto-oligosaccharide phosphorylase activity [GO:0102250]; nucleotide binding [GO:0000166]; pyridoxal phosphate binding [GO:0030170]; SHG alpha-glucan phosphorylase activity [GO:0102499]
PF00343;
3.40.50.2000;
Glycogen phosphorylase family
PTM: Phosphorylation of Ser-15 converts phosphorylase B (unphosphorylated) to phosphorylase A. {ECO:0000250|UniProtKB:P11217}.
null
CATALYTIC ACTIVITY: Reaction=[(1->4)-alpha-D-glucosyl](n) + phosphate = [(1->4)-alpha-D-glucosyl](n-1) + alpha-D-glucose 1-phosphate; Xref=Rhea:RHEA:41732, Rhea:RHEA-COMP:9584, Rhea:RHEA-COMP:9586, ChEBI:CHEBI:15444, ChEBI:CHEBI:43474, ChEBI:CHEBI:58601; EC=2.4.1.1; Evidence={ECO:0000250|UniProtKB:P11217}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41733; Evidence={ECO:0000250|UniProtKB:P11217};
null
null
null
null
FUNCTION: Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis. {ECO:0000250|UniProtKB:P11217}.
Oryctolagus cuniculus (Rabbit)
P00490
PHSM_ECOLI
MSQPIFNDKQFQEALSRQWQRYGLNSAAEMTPRQWWLAVSEALAEMLRAQPFAKPVANQRHVNYISMEFLIGRLTGNNLLNLGWYQDVQDSLKAYDINLTDLLEEEIDPALGNGGLGRLAACFLDSMATVGQSATGYGLNYQYGLFRQSFVDGKQVEAPDDWHRSNYPWFRHNEALDVQVGIGGKVTKDGRWEPEFTITGQAWDLPVVGYRNGVAQPLRLWQATHAHPFDLTKFNDGDFLRAEQQGINAEKLTKVLYPNDNHTAGKKLRLMQQYFQCACSVADILRRHHLAGRKLHELADYEVIQLNDTHPTIAIPELLRVLIDEHQMSWDDAWAITSKTFAYTNHTLMPEALERWDVKLVKGLLPRHMQIINEINTRFKTLVEKTWPGDEKVWAKLAVVHDKQVHMANLCVVGGFAVNGVAALHSDLVVKDLFPEYHQLWPNKFHNVTNGITPRRWIKQCNPALAALLDKSLQKEWANDLDQLINLEKFADDAKFRQQYREIKQANKVRLAEFVKVRTGIEINPQAIFDIQIKRLHEYKRQHLNLLHILALYKEIRENPQADRVPRVFLFGAKAAPGYYLAKNIIFAINKVADVINNDPLVGDKLKVVFLPDYCVSAAEKLIPAADISEQISTAGKEASGTGNMKLALNGALTVGTLDGANVEIAEKVGEENIFIFGHTVEQVKAILAKGYDPVKWRKKDKVLDAVLKELESGKYSDGDKHAFDQMLHSIGKQGGDPYLVMADFAAYVEAQKQVDVLYRDQEAWTRAAILNTARCGMFSSDRSIRDYQARIWQAKR
2.4.1.1
COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
alpha-glucan catabolic process [GO:0030980]; glycogen catabolic process [GO:0005980]
cytoplasm [GO:0005737]; cytosol [GO:0005829]
glycogen phosphorylase activity [GO:0008184]; linear malto-oligosaccharide phosphorylase activity [GO:0102250]; maltodextrin phosphorylase activity [GO:0031220]; protein homodimerization activity [GO:0042803]; pyridoxal phosphate binding [GO:0030170]; SHG alpha-glucan phosphorylase activity [GO:0102499]
PF00343;
3.40.50.2000;
Glycogen phosphorylase family
null
null
CATALYTIC ACTIVITY: Reaction=[(1->4)-alpha-D-glucosyl](n) + phosphate = [(1->4)-alpha-D-glucosyl](n-1) + alpha-D-glucose 1-phosphate; Xref=Rhea:RHEA:41732, Rhea:RHEA-COMP:9584, Rhea:RHEA-COMP:9586, ChEBI:CHEBI:15444, ChEBI:CHEBI:43474, ChEBI:CHEBI:58601; EC=2.4.1.1;
null
null
null
null
FUNCTION: Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
Escherichia coli (strain K12)
P00491
PNPH_HUMAN
MENGYTYEDYKNTAEWLLSHTKHRPQVAIICGSGLGGLTDKLTQAQIFDYGEIPNFPRSTVPGHAGRLVFGFLNGRACVMMQGRFHMYEGYPLWKVTFPVRVFHLLGVDTLVVTNAAGGLNPKFEVGDIMLIRDHINLPGFSGQNPLRGPNDERFGDRFPAMSDAYDRTMRQRALSTWKQMGEQRELQEGTYVMVAGPSFETVAECRVLQKLGADAVGMSTVPEVIVARHCGLRVFGFSLITNKVIMDYESLEKANHEEVLAAGKQAAQKLEQFVSILMASIPLPDKAS
2.4.2.1
null
allantoin metabolic process [GO:0000255]; dAMP catabolic process [GO:0046059]; deoxyadenosine catabolic process [GO:0006157]; deoxyinosine catabolic process [GO:0006149]; immune response [GO:0006955]; IMP catabolic process [GO:0006204]; inosine catabolic process [GO:0006148]; nicotinamide riboside catabolic process [GO:0006738]; nucleobase-containing compound metabolic process [GO:0006139]; nucleotide biosynthetic process [GO:0009165]; positive regulation of alpha-beta T cell differentiation [GO:0046638]; positive regulation of interleukin-2 production [GO:0032743]; positive regulation of T cell proliferation [GO:0042102]; purine ribonucleoside salvage [GO:0006166]; purine-containing compound salvage [GO:0043101]; response to xenobiotic stimulus [GO:0009410]; urate biosynthetic process [GO:0034418]
cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular exosome [GO:0070062]; extracellular region [GO:0005576]; ficolin-1-rich granule lumen [GO:1904813]; secretory granule lumen [GO:0034774]
guanosine phosphorylase activity [GO:0047975]; identical protein binding [GO:0042802]; nucleoside binding [GO:0001882]; phosphate ion binding [GO:0042301]; purine nucleobase binding [GO:0002060]; purine-nucleoside phosphorylase activity [GO:0004731]
PF01048;
3.40.50.1580;
PNP/MTAP phosphorylase family
null
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22509282}.
CATALYTIC ACTIVITY: Reaction=inosine + phosphate = alpha-D-ribose 1-phosphate + hypoxanthine; Xref=Rhea:RHEA:27646, ChEBI:CHEBI:17368, ChEBI:CHEBI:17596, ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1; Evidence={ECO:0000269|PubMed:23438750, ECO:0000269|PubMed:9305964}; CATALYTIC ACTIVITY: Reaction=guanosine + phosphate = alpha-D-ribose 1-phosphate + guanine; Xref=Rhea:RHEA:13233, ChEBI:CHEBI:16235, ChEBI:CHEBI:16750, ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1; Evidence={ECO:0000269|PubMed:9305964}; CATALYTIC ACTIVITY: Reaction=2'-deoxyguanosine + phosphate = 2-deoxy-alpha-D-ribose 1-phosphate + guanine; Xref=Rhea:RHEA:27738, ChEBI:CHEBI:16235, ChEBI:CHEBI:17172, ChEBI:CHEBI:43474, ChEBI:CHEBI:57259; EC=2.4.2.1; Evidence={ECO:0000250|UniProtKB:P23492}; CATALYTIC ACTIVITY: Reaction=2'-deoxyinosine + phosphate = 2-deoxy-alpha-D-ribose 1-phosphate + hypoxanthine; Xref=Rhea:RHEA:27750, ChEBI:CHEBI:17368, ChEBI:CHEBI:28997, ChEBI:CHEBI:43474, ChEBI:CHEBI:57259; EC=2.4.2.1; Evidence={ECO:0000250|UniProtKB:P23492};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=45 uM for inosine (at 30 degrees Celsius and pH 7) {ECO:0000269|PubMed:9305964}; KM=68 uM for inosine (at 25 degrees Celsius and pH 7.4) {ECO:0000269|PubMed:23438750}; KM=10 uM for hypoxanthine (at 30 degrees Celsius and pH 7) {ECO:0000269|PubMed:9305964}; KM=6 uM for guanosine (at 30 degrees Celsius and pH 7) {ECO:0000269|PubMed:9305964}; KM=12 uM for guanine (at 30 degrees Celsius and pH 7) {ECO:0000269|PubMed:9305964}; KM=650 uM for adenosine (at 30 degrees Celsius and pH 7) {ECO:0000269|PubMed:9305964}; KM=440 uM for adenine (at 30 degrees Celsius and pH 7) {ECO:0000269|PubMed:9305964}; Note=kcat is 57 sec(-1) with inosine as substrate (PubMed:9305964). kcat is 47 sec(-1) with inosine as substrate (PubMed:23438750). kcat is 70 sec(-1) with hypoxanthine as substrate (PubMed:9305964). kcat is 28 sec(-1) with guanosine as substrate (PubMed:9305964). kcat is 48 sec(-1) with guanine as substrate (PubMed:9305964). kcat is 0.0024 sec(-1) with adenosine as substrate (PubMed:9305964). kcat is 0.31 sec(-1) with adenine as substrate (PubMed:9305964). {ECO:0000269|PubMed:23438750, ECO:0000269|PubMed:9305964};
PATHWAY: Purine metabolism; purine nucleoside salvage. {ECO:0000269|PubMed:9305964}.
null
null
FUNCTION: Catalyzes the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate (PubMed:23438750, PubMed:9305964). Preferentially acts on 6-oxopurine nucleosides including inosine and guanosine (PubMed:9305964). {ECO:0000269|PubMed:23438750, ECO:0000269|PubMed:9305964}.
Homo sapiens (Human)
P00492
HPRT_HUMAN
MATRSPGVVISDDEPGYDLDLFCIPNHYAEDLERVFIPHGLIMDRTERLARDVMKEMGGHHIVALCVLKGGYKFFADLLDYIKALNRNSDRSIPMTVDFIRLKSYCNDQSTGDIKVIGGDDLSTLTGKNVLIVEDIIDTGKTMQTLLSLVRQYNPKMVKVASLLVKRTPRSVGYKPDFVGFEIPDKFVVGYALDYNEYFRDLNHVCVISETGKAKYKA
2.4.2.8
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=Binds 2 magnesium ions per subunit. The magnesium ions are essentially bound to the substrate and have few direct interactions with the protein.;
adenine metabolic process [GO:0046083]; AMP salvage [GO:0044209]; central nervous system neuron development [GO:0021954]; cerebral cortex neuron differentiation [GO:0021895]; dendrite morphogenesis [GO:0048813]; dopamine metabolic process [GO:0042417]; dopaminergic neuron differentiation [GO:0071542]; GMP catabolic process [GO:0046038]; GMP salvage [GO:0032263]; grooming behavior [GO:0007625]; guanine salvage [GO:0006178]; hypoxanthine metabolic process [GO:0046100]; hypoxanthine salvage [GO:0043103]; IMP metabolic process [GO:0046040]; IMP salvage [GO:0032264]; locomotory behavior [GO:0007626]; lymphocyte proliferation [GO:0046651]; positive regulation of dopamine metabolic process [GO:0045964]; protein homotetramerization [GO:0051289]; purine nucleotide biosynthetic process [GO:0006164]; purine ribonucleoside salvage [GO:0006166]; response to amphetamine [GO:0001975]; striatum development [GO:0021756]; T cell mediated cytotoxicity [GO:0001913]
cytoplasm [GO:0005737]; cytosol [GO:0005829]; extracellular exosome [GO:0070062]
guanine phosphoribosyltransferase activity [GO:0052657]; hypoxanthine phosphoribosyltransferase activity [GO:0004422]; identical protein binding [GO:0042802]; magnesium ion binding [GO:0000287]; nucleotide binding [GO:0000166]
PF00156;
3.40.50.2020;
Purine/pyrimidine phosphoribosyltransferase family
null
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=diphosphate + IMP = 5-phospho-alpha-D-ribose 1-diphosphate + hypoxanthine; Xref=Rhea:RHEA:17973, ChEBI:CHEBI:17368, ChEBI:CHEBI:33019, ChEBI:CHEBI:58017, ChEBI:CHEBI:58053; EC=2.4.2.8; Evidence={ECO:0000269|PubMed:10338013, ECO:0000269|PubMed:19527031}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17975; Evidence={ECO:0000269|PubMed:10338013, ECO:0000269|PubMed:19527031}; CATALYTIC ACTIVITY: Reaction=diphosphate + GMP = 5-phospho-alpha-D-ribose 1-diphosphate + guanine; Xref=Rhea:RHEA:25424, ChEBI:CHEBI:16235, ChEBI:CHEBI:33019, ChEBI:CHEBI:58017, ChEBI:CHEBI:58115; EC=2.4.2.8; Evidence={ECO:0000269|PubMed:10338013, ECO:0000269|PubMed:19527031}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25426; Evidence={ECO:0000269|PubMed:10338013, ECO:0000269|PubMed:19527031};
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=5.4 uM for IMP {ECO:0000269|PubMed:10338013}; KM=0.45 uM for hypoxanthine {ECO:0000269|PubMed:10338013}; KM=25 uM for pyrophosphate {ECO:0000269|PubMed:10338013}; KM=31 uM for phosphoribosylpyrophosphate {ECO:0000269|PubMed:10338013};
PATHWAY: Purine metabolism; IMP biosynthesis via salvage pathway; IMP from hypoxanthine: step 1/1.
null
null
FUNCTION: Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
Homo sapiens (Human)
P00493
HPRT_MOUSE
MPTRSPSVVISDDEPGYDLDLFCIPNHYAEDLEKVFIPHGLIMDRTERLARDVMKEMGGHHIVALCVLKGGYKFFADLLDYIKALNRNSDRSIPMTVDFIRLKSYCNDQSTGDIKVIGGDDLSTLTGKNVLIVEDIIDTGKTMQTLLSLVKQYSPKMVKVASLLVKRTSRSVGYRPDFVGFEIPDKFVVGYALDYNEYFRDLNHVCVISETGKAKYKA
2.4.2.8
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions per subunit. The magnesium ions are essentially bound to the substrate and have few direct interactions with the protein. {ECO:0000250};
adenine metabolic process [GO:0046083]; AMP salvage [GO:0044209]; central nervous system neuron development [GO:0021954]; cerebral cortex neuron differentiation [GO:0021895]; dendrite morphogenesis [GO:0048813]; dopamine metabolic process [GO:0042417]; dopaminergic neuron differentiation [GO:0071542]; GMP catabolic process [GO:0046038]; GMP salvage [GO:0032263]; grooming behavior [GO:0007625]; guanine salvage [GO:0006178]; hypoxanthine metabolic process [GO:0046100]; hypoxanthine salvage [GO:0043103]; IMP metabolic process [GO:0046040]; IMP salvage [GO:0032264]; locomotory behavior [GO:0007626]; lymphocyte proliferation [GO:0046651]; positive regulation of dopamine metabolic process [GO:0045964]; protein homotetramerization [GO:0051289]; purine ribonucleoside salvage [GO:0006166]; response to amphetamine [GO:0001975]; striatum development [GO:0021756]; T cell mediated cytotoxicity [GO:0001913]
cytoplasm [GO:0005737]; cytosol [GO:0005829]
guanine phosphoribosyltransferase activity [GO:0052657]; hypoxanthine phosphoribosyltransferase activity [GO:0004422]; identical protein binding [GO:0042802]; magnesium ion binding [GO:0000287]; nucleotide binding [GO:0000166]
PF00156;
3.40.50.2020;
Purine/pyrimidine phosphoribosyltransferase family
null
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=diphosphate + IMP = 5-phospho-alpha-D-ribose 1-diphosphate + hypoxanthine; Xref=Rhea:RHEA:17973, ChEBI:CHEBI:17368, ChEBI:CHEBI:33019, ChEBI:CHEBI:58017, ChEBI:CHEBI:58053; EC=2.4.2.8; Evidence={ECO:0000250|UniProtKB:P00492}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17975; Evidence={ECO:0000250|UniProtKB:P00492}; CATALYTIC ACTIVITY: Reaction=diphosphate + GMP = 5-phospho-alpha-D-ribose 1-diphosphate + guanine; Xref=Rhea:RHEA:25424, ChEBI:CHEBI:16235, ChEBI:CHEBI:33019, ChEBI:CHEBI:58017, ChEBI:CHEBI:58115; EC=2.4.2.8; Evidence={ECO:0000250|UniProtKB:P00492}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25426; Evidence={ECO:0000250|UniProtKB:P00492};
null
PATHWAY: Purine metabolism; IMP biosynthesis via salvage pathway; IMP from hypoxanthine: step 1/1.
null
null
FUNCTION: Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway (By similarity). {ECO:0000250}.
Mus musculus (Mouse)
P00494
HPRT_CRIGR
MATRSPSVVISDDEPGYDLDLFCIPNHYVEDLEKVFIPHGVIMDRTERLARDVMKEMGGHHIVALCVLKGGYKFFADLLDYIKALNRNSDRSIPMTVDFIRLKSYCNDQSTGDIKVIGGDDLSTLTGKNVLIVEDIIDTGKTMQTLLSLVKRYNLKMVKVASLLVKRTSRSVGYRPDFVGFEIPDKFVVGYALDYNEYFRDLNHICVISETGKAKYKA
2.4.2.8
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Note=Binds 2 magnesium ions per subunit. The magnesium ions are essentially bound to the substrate and have few direct interactions with the protein. {ECO:0000250};
GMP catabolic process [GO:0046038]; GMP salvage [GO:0032263]; guanine salvage [GO:0006178]; hypoxanthine metabolic process [GO:0046100]; hypoxanthine salvage [GO:0043103]; IMP metabolic process [GO:0046040]; IMP salvage [GO:0032264]; positive regulation of dopamine metabolic process [GO:0045964]; purine nucleotide biosynthetic process [GO:0006164]; purine ribonucleoside salvage [GO:0006166]
cytoplasm [GO:0005737]; cytosol [GO:0005829]
guanine phosphoribosyltransferase activity [GO:0052657]; hypoxanthine phosphoribosyltransferase activity [GO:0004422]; identical protein binding [GO:0042802]; magnesium ion binding [GO:0000287]; nucleotide binding [GO:0000166]
PF00156;
3.40.50.2020;
Purine/pyrimidine phosphoribosyltransferase family
null
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=diphosphate + IMP = 5-phospho-alpha-D-ribose 1-diphosphate + hypoxanthine; Xref=Rhea:RHEA:17973, ChEBI:CHEBI:17368, ChEBI:CHEBI:33019, ChEBI:CHEBI:58017, ChEBI:CHEBI:58053; EC=2.4.2.8; Evidence={ECO:0000250|UniProtKB:P00492}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17975; Evidence={ECO:0000250|UniProtKB:P00492}; CATALYTIC ACTIVITY: Reaction=diphosphate + GMP = 5-phospho-alpha-D-ribose 1-diphosphate + guanine; Xref=Rhea:RHEA:25424, ChEBI:CHEBI:16235, ChEBI:CHEBI:33019, ChEBI:CHEBI:58017, ChEBI:CHEBI:58115; EC=2.4.2.8; Evidence={ECO:0000250|UniProtKB:P00492}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25426; Evidence={ECO:0000250|UniProtKB:P00492};
null
PATHWAY: Purine metabolism; IMP biosynthesis via salvage pathway; IMP from hypoxanthine: step 1/1.
null
null
FUNCTION: Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway (By similarity). {ECO:0000250}.
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
P00497
PUR1_BACSU
MLAEIKGLNEECGVFGIWGHEEAPQITYYGLHSLQHRGQEGAGIVATDGEKLTAHKGQGLITEVFQNGELSKVKGKGAIGHVRYATAGGGGYENVQPLLFRSQNNGSLALAHNGNLVNATQLKQQLENQGSIFQTSSDTEVLAHLIKRSGHFTLKDQIKNSLSMLKGAYAFLIMTETEMIVALDPNGLRPLSIGMMGDAYVVASETCAFDVVGATYLREVEPGEMLIINDEGMKSERFSMNINRSICSMEYIYFSRPDSNIDGINVHSARKNLGKMLAQESAVEADVVTGVPDSSISAAIGYAEATGIPYELGLIKNRYVGRTFIQPSQALREQGVRMKLSAVRGVVEGKRVVMVDDSIVRGTTSRRIVTMLREAGATEVHVKISSPPIAHPCFYGIDTSTHEELIASSHSVEEIRQEIGADTLSFLSVEGLLKGIGRKYDDSNCGQCLACFTGKYPTEIYQDTVLPHVKEAVLTK
2.4.2.14
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-Rule:MF_01931, ECO:0000269|PubMed:9271502}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01931, ECO:0000269|PubMed:9271502}; COFACTOR: Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000269|PubMed:8197456}; Note=Binds 1 [4Fe-4S] cluster per subunit. The [4Fe-4S] cluster requires a potential lower than -600 mV for reduction. {ECO:0000269|PubMed:8197456};
'de novo' IMP biosynthetic process [GO:0006189]; glutamine metabolic process [GO:0006541]; purine nucleobase biosynthetic process [GO:0009113]; purine nucleotide biosynthetic process [GO:0006164]
cytoplasm [GO:0005737]
4 iron, 4 sulfur cluster binding [GO:0051539]; amidophosphoribosyltransferase activity [GO:0004044]; magnesium ion binding [GO:0000287]
PF13522;
3.40.50.2020;3.60.20.10;
Purine/pyrimidine phosphoribosyltransferase family
null
null
CATALYTIC ACTIVITY: Reaction=5-phospho-beta-D-ribosylamine + diphosphate + L-glutamate = 5-phospho-alpha-D-ribose 1-diphosphate + H2O + L-glutamine; Xref=Rhea:RHEA:14905, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:33019, ChEBI:CHEBI:58017, ChEBI:CHEBI:58359, ChEBI:CHEBI:58681; EC=2.4.2.14; Evidence={ECO:0000255|HAMAP-Rule:MF_01931, ECO:0000269|PubMed:6794613};
null
PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; N(1)-(5-phospho-D-ribosyl)glycinamide from 5-phospho-alpha-D-ribose 1-diphosphate: step 1/2. {ECO:0000255|HAMAP-Rule:MF_01931}.
null
null
FUNCTION: Catalyzes the formation of phosphoribosylamine from phosphoribosylpyrophosphate (PRPP) and glutamine. {ECO:0000255|HAMAP-Rule:MF_01931, ECO:0000269|PubMed:6794613}.
Bacillus subtilis (strain 168)
P00502
GSTA1_RAT
MSGKPVLHYFNARGRMECIRWLLAAAGVEFDEKFIQSPEDLEKLKKDGNLMFDQVPMVEIDGMKLAQTRAILNYIATKYDLYGKDMKERALIDMYTEGILDLTEMIMQLVICPPDQKEAKTALAKDRTKNRYLPAFEKVLKSHGQDYLVGNRLTRVDIHLLELLLYVEEFDASLLTSFPLLKAFKSRISSLPNVKKFLQPGSQRKLPVDAKQIEEARKIFKF
1.11.1.-; 2.5.1.18; 5.3.3.-
null
epithelial cell differentiation [GO:0030855]; glutathione derivative biosynthetic process [GO:1901687]; glutathione metabolic process [GO:0006749]; linoleic acid metabolic process [GO:0043651]; prostaglandin metabolic process [GO:0006693]; response to nutrient levels [GO:0031667]; response to xenobiotic stimulus [GO:0009410]; xenobiotic catabolic process [GO:0042178]; xenobiotic metabolic process [GO:0006805]
cytosol [GO:0005829]; extracellular exosome [GO:0070062]
dinitrosyl-iron complex binding [GO:0035731]; fatty acid binding [GO:0005504]; glutathione binding [GO:0043295]; glutathione peroxidase activity [GO:0004602]; glutathione transferase activity [GO:0004364]; protein homodimerization activity [GO:0042803]; steroid delta-isomerase activity [GO:0004769]
PF00043;PF02798;
1.20.1050.10;3.40.30.10;
GST superfamily, Alpha family
null
SUBCELLULAR LOCATION: Cytoplasm.
CATALYTIC ACTIVITY: Reaction=glutathione + RX = a halide anion + an S-substituted glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378, ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925, ChEBI:CHEBI:90779; EC=2.5.1.18; Evidence={ECO:0000269|PubMed:11119643}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16438; Evidence={ECO:0000305|PubMed:11119643}; CATALYTIC ACTIVITY: Reaction=glutathione + prostaglandin A2 = prostaglandin A2-S-(R)-glutathione; Xref=Rhea:RHEA:50796, ChEBI:CHEBI:57925, ChEBI:CHEBI:133370, ChEBI:CHEBI:133768; Evidence={ECO:0000250|UniProtKB:P08263}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50797; Evidence={ECO:0000250|UniProtKB:P08263}; CATALYTIC ACTIVITY: Reaction=glutathione + prostaglandin J2 = prostaglandin J2-S-(R)-glutathione; Xref=Rhea:RHEA:50804, ChEBI:CHEBI:57925, ChEBI:CHEBI:133396, ChEBI:CHEBI:133771; Evidence={ECO:0000250|UniProtKB:P08263}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50805; Evidence={ECO:0000250|UniProtKB:P08263}; CATALYTIC ACTIVITY: Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione = (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:48888, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90850; Evidence={ECO:0000250|UniProtKB:P08263}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48889; Evidence={ECO:0000250|UniProtKB:P08263}; CATALYTIC ACTIVITY: Reaction=androst-5-ene-3,17-dione = androst-4-ene-3,17-dione; Xref=Rhea:RHEA:43936, ChEBI:CHEBI:16422, ChEBI:CHEBI:83865; Evidence={ECO:0000250|UniProtKB:P08263}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937; Evidence={ECO:0000250|UniProtKB:P08263};
null
null
null
null
FUNCTION: Glutathione S-transferase that catalyzes the nucleophilic attack of the sulfur atom of glutathione on the electrophilic groups of a wide range of exogenous and endogenous compounds (Probable). Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). It also catalyzes the isomerization of D5-androstene-3,17-dione (AD) into D4-androstene-3,17-dione and may therefore play an important role in hormone biosynthesis. Through its glutathione-dependent peroxidase activity toward the fatty acid hydroperoxide (13S)-hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it is also involved in the metabolism of oxidized linoleic acid (By similarity). {ECO:0000250|UniProtKB:P08263, ECO:0000305|PubMed:11119643}.
Rattus norvegicus (Rat)
P00503
AATC_PIG
MAPPSVFAEVPQAQPVLVFKLIADFREDPDPRKVNLGVGAYRTDDCQPWVLPVVRKVEQRIANDSSLNHEYLPILGLAEFRTCASRLALGDDSPALQEKRVGGVQSLGGTGALRIGAEFLARWYNGTNNKDTPVYVSSPTWENHNGVFTTAGFKDIRSYRYWDTEKRGLDLQGFLSDLENAPEFSIFVLHACAHNPTGTDPTPEQWKQIASVMKRRFLFPFFDSAYQGFASGNLEKDAWAIRYFVSEGFELFCAQSFSKNFGLYNERVGNLTVVAKEPDSILRVLSQMEKIVRVTWSNPPAQGARIVARTLSDPELFHEWTGNVKTMADRILSMRSELRARLEALKTPGTWNHITDQIGMFSFTGLNPKQVEYLINEKHIYLLPSGRINMCGLTTKNLDYVATSIHEAVTKIQ
2.6.1.1; 2.6.1.3
COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000269|PubMed:5809231, ECO:0000269|PubMed:9211866};
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]; 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]; Notch signaling pathway [GO:0007219]; oxaloacetate metabolic process [GO:0006107]; response to glucocorticoid [GO:0051384]
cytosol [GO:0005829]
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:0000269|PubMed:4634443}; 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:0000269|PubMed:4634443}; 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 (PubMed:4634443). 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 (By similarity). {ECO:0000250|UniProtKB:P13221, ECO:0000269|PubMed:4634443}.
Sus scrofa (Pig)