ID A0A8I6AD25_RAT Unreviewed; 533 AA. AC A0A8I6AD25; DT 25-MAY-2022, integrated into UniProtKB/TrEMBL. DT 25-MAY-2022, sequence version 1. DT 28-JUN-2023, entry version 7. DE RecName: Full=Cytochrome P450 1A {ECO:0000256|RuleBase:RU368045}; DE EC=1.14.14.1 {ECO:0000256|RuleBase:RU368045}; GN Name=Cyp1a2 {ECO:0000313|Ensembl:ENSRNOP00000090173.1, GN ECO:0000313|RGD:2459}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116 {ECO:0000313|Ensembl:ENSRNOP00000090173.1, ECO:0000313|Proteomes:UP000002494}; RN [1] {ECO:0000313|Ensembl:ENSRNOP00000090173.1, ECO:0000313|Proteomes:UP000002494} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000090173.1, RC ECO:0000313|Proteomes:UP000002494}; RX PubMed=15057822; DOI=10.1038/nature02426; RG Rat Genome Sequencing Project Consortium; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] {ECO:0000313|Ensembl:ENSRNOP00000090173.1} RP IDENTIFICATION. RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000090173.1}; RG Ensembl; RL Submitted (MAR-2023) to UniProtKB. CC -!- FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. CC They oxidize a variety of structurally unrelated compounds, including CC steroids, fatty acids, and xenobiotics. CC {ECO:0000256|RuleBase:RU368045}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = 12-oxo- CC (5Z,8Z,10E,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:37947, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57444, ChEBI:CHEBI:75231; CC EC=4.2.1.152; Evidence={ECO:0000256|ARBA:ARBA00001395}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37948; CC Evidence={ECO:0000256|ARBA:ARBA00001395}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 13-oxo-(9Z,11E)- CC octadecadienoate + H2O; Xref=Rhea:RHEA:48716, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57466, ChEBI:CHEBI:90781; CC Evidence={ECO:0000256|ARBA:ARBA00000408}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48717; CC Evidence={ECO:0000256|ARBA:ARBA00000408}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo- CC (5Z,8Z,11Z,13E)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48636, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57410, ChEBI:CHEBI:57446; CC Evidence={ECO:0000256|ARBA:ARBA00001143}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637; CC Evidence={ECO:0000256|ARBA:ARBA00001143}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)- CC docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52120, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:136410; Evidence={ECO:0000256|ARBA:ARBA00001204}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121; CC Evidence={ECO:0000256|ARBA:ARBA00001204}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = 5-oxo- CC (6E,8Z,11Z,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48632, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57450, ChEBI:CHEBI:65342; CC Evidence={ECO:0000256|ARBA:ARBA00001867}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48633; CC Evidence={ECO:0000256|ARBA:ARBA00001867}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, CC ChEBI:CHEBI:131965; Evidence={ECO:0000256|ARBA:ARBA00001225}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861; CC Evidence={ECO:0000256|ARBA:ARBA00001225}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:39759, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, CC ChEBI:CHEBI:76627; Evidence={ECO:0000256|ARBA:ARBA00000525}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39760; CC Evidence={ECO:0000256|ARBA:ARBA00000525}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:39779, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, CC ChEBI:CHEBI:76634; Evidence={ECO:0000256|ARBA:ARBA00000543}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780; CC Evidence={ECO:0000256|ARBA:ARBA00000543}; CC -!- CATALYTIC ACTIVITY: CC Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] CC = 2-hydroxy-17beta-estradiol + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, CC ChEBI:CHEBI:28744, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; CC Evidence={ECO:0000256|ARBA:ARBA00000499}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213; CC Evidence={ECO:0000256|ARBA:ARBA00000499}; CC -!- CATALYTIC ACTIVITY: CC Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] CC = 4-hydroxy-17beta-estradiol + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47280, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:62845; CC Evidence={ECO:0000256|ARBA:ARBA00001681}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47281; CC Evidence={ECO:0000256|ARBA:ARBA00001681}; CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-retinal + O2 + reduced [NADPH--hemoprotein CC reductase] = all-trans-retinoate + 2 H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42088, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17898, CC ChEBI:CHEBI:35291, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; CC Evidence={ECO:0000256|ARBA:ARBA00000119}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42089; CC Evidence={ECO:0000256|ARBA:ARBA00000119}; CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-retinol + O2 + reduced [NADPH--hemoprotein CC reductase] = all-trans-retinal + H(+) + 2 H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42092, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17336, CC ChEBI:CHEBI:17898, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; CC Evidence={ECO:0000256|ARBA:ARBA00000340}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093; CC Evidence={ECO:0000256|ARBA:ARBA00000340}; CC -!- CATALYTIC ACTIVITY: CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 2- CC hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:47208, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:1156, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; Evidence={ECO:0000256|ARBA:ARBA00000504}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209; CC Evidence={ECO:0000256|ARBA:ARBA00000504}; CC -!- CATALYTIC ACTIVITY: CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 4- CC hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:47292, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, CC ChEBI:CHEBI:87602; Evidence={ECO:0000256|ARBA:ARBA00001752}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47293; CC Evidence={ECO:0000256|ARBA:ARBA00001752}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC Evidence={ECO:0000256|ARBA:ARBA00001971, CC ECO:0000256|PIRSR:PIRSR602401-1, ECO:0000256|RuleBase:RU368045}; CC -!- PATHWAY: Cofactor metabolism; retinol metabolism. CC {ECO:0000256|ARBA:ARBA00004891}. CC -!- PATHWAY: Lipid metabolism. {ECO:0000256|ARBA:ARBA00005189}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000256|RuleBase:RU368045}; Peripheral membrane protein CC {ECO:0000256|RuleBase:RU368045}. Microsome membrane CC {ECO:0000256|RuleBase:RU368045}; Peripheral membrane protein CC {ECO:0000256|RuleBase:RU368045}. Membrane CC {ECO:0000256|ARBA:ARBA00004170}; Peripheral membrane protein CC {ECO:0000256|ARBA:ARBA00004170}. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. CC {ECO:0000256|ARBA:ARBA00010617, ECO:0000256|RuleBase:RU000461}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR Ensembl; ENSRNOT00000104692.1; ENSRNOP00000090173.1; ENSRNOG00000016173.9. DR RGD; 2459; Cyp1a2. DR GeneTree; ENSGT00950000183037; -. DR OMA; AKWEIFL; -. DR UniPathway; UPA00912; -. DR Proteomes; UP000002494; Chromosome 8. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-UniRule. DR GO; GO:0020037; F:heme binding; IEA:UniProtKB-UniRule. DR GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW. DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway. DR CDD; cd20676; CYP1A; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 1. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR017972; Cyt_P450_CS. DR InterPro; IPR002401; Cyt_P450_E_grp-I. DR InterPro; IPR008066; Cyt_P450_E_grp-I_CYP1. DR InterPro; IPR036396; Cyt_P450_sf. DR PANTHER; PTHR24289; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; 1. DR PANTHER; PTHR24289:SF13; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR01683; EP450ICYP1A. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. PE 1: Evidence at protein level; KW Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824, KW ECO:0000256|RuleBase:RU368045}; KW Heme {ECO:0000256|ARBA:ARBA00022617, ECO:0000256|PIRSR:PIRSR602401-1}; KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|PIRSR:PIRSR602401-1}; KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023098}; KW Lyase {ECO:0000256|ARBA:ARBA00023239}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, KW ECO:0000256|PIRSR:PIRSR602401-1}; KW Microsome {ECO:0000256|ARBA:ARBA00022848, ECO:0000256|RuleBase:RU368045}; KW Monooxygenase {ECO:0000256|ARBA:ARBA00023033, KW ECO:0000256|RuleBase:RU000461}; KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002, KW ECO:0000256|RuleBase:RU000461}; KW Proteomics identification {ECO:0007829|PeptideAtlas:A0A8I6AD25}; KW Reference proteome {ECO:0000313|Proteomes:UP000002494}. FT BINDING 476 FT /ligand="heme" FT /ligand_id="ChEBI:CHEBI:30413" FT /evidence="ECO:0000256|PIRSR:PIRSR602401-1" SQ SEQUENCE 533 AA; 60365 MW; BCB8C52BDE4E63B5 CRC64; MEGSESIFNQ SISISPAVVQ MAFSQYISLA PELLLATAIF CLVFWVLRGT RTQVPKGLKS PPGPWGLPFI GHMLTLGKNP HLSLTKLSQQ YGDVLQIRIG STPVVVLSGL NTIKQALVKQ GDDFKGRPDL YSFTLITNGK SMTFNPDSGP VWAARRRLAQ DALKSFSIAS DPTSVSSCYL EEHVSKEANH LISKFQKLMA EVGHFEPVNQ VVESVANVIG AMCFGKNFPR KSEEMLNLVK SSKDFVENVT SGNAVDFFPV LRYLPNPALK RFKNFNDNFV LFLQKTVQEH YQDFNKNSIQ DITGALFKHS ENYKDNGGLI PQEKIVNIVN DIFGAGFETV TTAIFWSILL LVTEPKVQRK IHEELDTVIG RDRQPRLSDR PQLPYLEAFI LEIYRYTSFV PFTIPHSTTR DTSLNGFHIP KECCIFINQW QVNHDEKQWK DPFVFRPERF LTNDNTAIDK TLSEKVMLFG LGKRRCIGEI PAKWEVFLFL AILLHQLEFT VPPGVKVDLT PSYGLTMKPR TCEHVQAWPR FSK //