| IED ID | IndEnz0018000529 |
| Enzyme Type ID | peroxidase000529 |
| Protein Name |
Cytochrome P450 2S1 EC 1.14.14.- CYPIIS1 Hydroperoxy icosatetraenoate dehydratase EC 4.2.1.152 Thromboxane-A synthase EC 5.3.99.5 |
| Gene Name | CYP2S1 UNQ891/PRO1906 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MEATGTWALLLALALLLLLTLALSGTRARGHLPPGPTPLPLLGNLLQLRPGALYSGLMRLSKKYGPVFTIYLGPWRPVVVLVGQEAVREALGGQAEEFSGRGTVAMLEGTFDGHGVFFSNGERWRQLRKFTMLALRDLGMGKREGEELIQAEARCLVETFQGTEGRPFDPSLLLAQATSNVVCSLLFGLRFSYEDKEFQAVVRAAGGTLLGVSSQGGQTYEMFSWFLRPLPGPHKQLLHHVSTLAAFTVRQVQQHQGNLDASGPARDLVDAFLLKMAQEEQNPGTEFTNKNMLMTVIYLLFAGTMTVSTTVGYTLLLLMKYPHVQKWVREELNRELGAGQAPSLGDRTRLPYTDAVLHEAQRLLALVPMGIPRTLMRTTRFRGYTLPQGTEVFPLLGSILHDPNIFKHPEEFNPDRFLDADGRFRKHEAFLPFSLGKRVCLGEGLAKAELFLFFTTILQAFSLESPCPPDTLSLKPTVSGLFNIPPAFQLQVRPTDLHSTTQTR |
| Enzyme Length | 504 |
| Uniprot Accession Number | Q96SQ9 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-5,6-epoxyretinoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:55860, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:139183; Evidence={ECO:0000269|PubMed:12711469};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55861; Evidence={ECO:0000305|PubMed:12711469}; CATALYTIC ACTIVITY: Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-4-hydroxyretinoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:51984, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:134178; Evidence={ECO:0000269|PubMed:12711469};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51985; Evidence={ECO:0000305|PubMed:12711469}; CATALYTIC ACTIVITY: Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = 5-oxo-(6E,8Z,11Z,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48632, ChEBI:CHEBI:15377, ChEBI:CHEBI:57450, ChEBI:CHEBI:65342; Evidence={ECO:0000269|PubMed:21068195};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48633; Evidence={ECO:0000305|PubMed:21068195}; CATALYTIC ACTIVITY: Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = 12-oxo-(5Z,8Z,10E,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:37947, ChEBI:CHEBI:15377, ChEBI:CHEBI:57444, ChEBI:CHEBI:75231; EC=4.2.1.152; Evidence={ECO:0000269|PubMed:21068195};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37948; Evidence={ECO:0000305|PubMed:21068195}; CATALYTIC ACTIVITY: Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48636, ChEBI:CHEBI:15377, ChEBI:CHEBI:57410, ChEBI:CHEBI:57446; Evidence={ECO:0000269|PubMed:21068195};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637; Evidence={ECO:0000305|PubMed:21068195}; CATALYTIC ACTIVITY: Reaction=prostaglandin H2 = thromboxane A2; Xref=Rhea:RHEA:17137, ChEBI:CHEBI:57405, ChEBI:CHEBI:57445; EC=5.3.99.5; Evidence={ECO:0000269|PubMed:21068195};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17138; Evidence={ECO:0000305|PubMed:21068195}; CATALYTIC ACTIVITY: Reaction=prostaglandin H2 = (12S)-hydroxy-(5Z,8E,10E)-heptadecatrienoate + malonaldehyde; Xref=Rhea:RHEA:48644, ChEBI:CHEBI:57405, ChEBI:CHEBI:90694, ChEBI:CHEBI:566274; Evidence={ECO:0000269|PubMed:21068195};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48645; Evidence={ECO:0000305|PubMed:21068195}; CATALYTIC ACTIVITY: Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 13-oxo-(9Z,11E)-octadecadienoate + H2O; Xref=Rhea:RHEA:48716, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466, ChEBI:CHEBI:90781; Evidence={ECO:0000269|PubMed:21068195};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48717; Evidence={ECO:0000305|PubMed:21068195}; |
| DNA Binding | |
| EC Number | 1.14.14.-; 4.2.1.152; 5.3.99.5 |
| Enzyme Function | FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of retinoids and eicosanoids (PubMed:12711469, PubMed:21068195). In epidermis, may contribute to the oxidative metabolism of all-trans-retinoic acid. For this activity, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12711469). Additionally, displays peroxidase and isomerase activities toward various oxygenated eicosanoids such as prostaglandin H2 (PGH2) and hydroperoxyeicosatetraenoates (HPETEs) (PubMed:21068195). Independently of cytochrome P450 reductase, NADPH, and O2, catalyzes the breakdown of PGH2 to hydroxyheptadecatrienoic acid (HHT) and malondialdehyde (MDA), which is known to act as a mediator of DNA damage (PubMed:21068195). {ECO:0000269|PubMed:12711469, ECO:0000269|PubMed:21068195}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000269|PubMed:21068195}. |
| nucleotide Binding | |
| Features | Alternative sequence (1); Chain (1); Metal binding (1); Natural variant (1) |
| Keywords | Alternative splicing;Endoplasmic reticulum;Fatty acid metabolism;Heme;Iron;Isomerase;Lipid metabolism;Lyase;Membrane;Metal-binding;Microsome;Monooxygenase;Oxidoreductase;Reference proteome |
| Interact With | Q6UY14-3; P60410 |
| Induction | INDUCTION: Up-regulated in skin upon exposure to ultraviolet radiation or treatment with all-trans retinoic acid (substrate-inducible). {ECO:0000269|PubMed:12711469}. |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:11181079}; Peripheral membrane protein {ECO:0000269|PubMed:11181079}. Microsome membrane {ECO:0000269|PubMed:11181079}; Peripheral membrane protein {ECO:0000269|PubMed:11181079}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10383923; 10731522; 10741631; 11701230; 12629583; 15450424; 16359177; 1664256; 17277313; 17280660; 17495422; 17529885; 19343046; 19368491; 19713358; 2025243; 21430234; 21516116; 22039172; 22232929; 22863683; 23224081; 23648403; 23682735; 25416956; 25557876; 27609465; 30019995; 32385743; 32913191; 32924783; 33377261; 34275895; 497175; 8627510; 8637342; 8647857; 9028626; 9103523; 9842986; 9884161; |
| Motif | |
| Gene Encoded By | |
| Mass | 55,817 |
| Kinetics | |
| Metal Binding | METAL 440; /note=Iron (heme axial ligand); /evidence=ECO:0000250 |
| Rhea ID | RHEA:55860; RHEA:55861; RHEA:51984; RHEA:51985; RHEA:48632; RHEA:48633; RHEA:37947; RHEA:37948; RHEA:48636; RHEA:48637; RHEA:17137; RHEA:17138; RHEA:48644; RHEA:48645; RHEA:48716; RHEA:48717 |
| Cross Reference Brenda |