ID CP2S1_MOUSE Reviewed; 501 AA. AC Q9DBX6; DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 27-MAR-2024, entry version 160. DE RecName: Full=Cytochrome P450 2S1; DE EC=1.14.14.- {ECO:0000250|UniProtKB:Q96SQ9}; DE AltName: Full=CYPIIS1; DE AltName: Full=Hydroperoxy icosatetraenoate dehydratase; DE EC=4.2.1.152 {ECO:0000250|UniProtKB:Q96SQ9}; DE AltName: Full=Thromboxane-A synthase; DE EC=5.3.99.5 {ECO:0000250|UniProtKB:Q96SQ9}; GN Name=Cyp2s1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Lung; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Embryonic germ cell; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Lung; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of CC retinoids and eicosanoids. In epidermis, may contribute to the CC oxidative metabolism of all-trans-retinoic acid. For this activity, CC uses molecular oxygen inserting one oxygen atom into a substrate, and CC reducing the second into a water molecule, with two electrons provided CC by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). CC Additionally, displays peroxidase and isomerase activities toward CC various oxygenated eicosanoids such as prostaglandin H2 (PGH2) and CC hydroperoxyeicosatetraenoates (HPETEs). Independently of cytochrome CC P450 reductase, NADPH, and O2, catalyzes the breakdown of PGH2 to CC hydroxyheptadecatrienoic acid (HHT) and malondialdehyde (MDA), which is CC known to act as a mediator of DNA damage. CC {ECO:0000250|UniProtKB:Q96SQ9}. CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein CC reductase] = all-trans-5,6-epoxyretinoate + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:55860, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:139183; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55861; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein CC reductase] = all-trans-4-hydroxyretinoate + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:51984, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:134178; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51985; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; 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:0000250|UniProtKB:Q96SQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48633; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; 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:0000250|UniProtKB:Q96SQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37948; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; 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:0000250|UniProtKB:Q96SQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin H2 = thromboxane A2; Xref=Rhea:RHEA:17137, CC ChEBI:CHEBI:57405, ChEBI:CHEBI:57445; EC=5.3.99.5; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17138; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin H2 = (12S)-hydroxy-(5Z,8E,10E)- CC heptadecatrienoate + malonaldehyde; Xref=Rhea:RHEA:48644, CC ChEBI:CHEBI:57405, ChEBI:CHEBI:90694, ChEBI:CHEBI:566274; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48645; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; 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:0000250|UniProtKB:Q96SQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48717; CC Evidence={ECO:0000250|UniProtKB:Q96SQ9}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250}; CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism. CC {ECO:0000250|UniProtKB:Q96SQ9}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q96SQ9}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q96SQ9}. Microsome membrane CC {ECO:0000250|UniProtKB:Q96SQ9}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q96SQ9}. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. 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 EMBL; AK004699; BAB23484.1; -; mRNA. DR EMBL; AK087069; BAC39794.1; -; mRNA. DR EMBL; BC064733; AAH64733.1; -; mRNA. DR CCDS; CCDS20997.1; -. DR RefSeq; NP_083051.1; NM_028775.3. DR AlphaFoldDB; Q9DBX6; -. DR SMR; Q9DBX6; -. DR STRING; 10090.ENSMUSP00000041175; -. DR iPTMnet; Q9DBX6; -. DR PhosphoSitePlus; Q9DBX6; -. DR EPD; Q9DBX6; -. DR jPOST; Q9DBX6; -. DR MaxQB; Q9DBX6; -. DR PaxDb; 10090-ENSMUSP00000041175; -. DR PeptideAtlas; Q9DBX6; -. DR ProteomicsDB; 278007; -. DR Antibodypedia; 45241; 251 antibodies from 29 providers. DR DNASU; 74134; -. DR Ensembl; ENSMUST00000043314.10; ENSMUSP00000041175.4; ENSMUSG00000040703.12. DR GeneID; 74134; -. DR KEGG; mmu:74134; -. DR UCSC; uc009fub.1; mouse. DR AGR; MGI:1921384; -. DR CTD; 29785; -. DR MGI; MGI:1921384; Cyp2s1. DR VEuPathDB; HostDB:ENSMUSG00000040703; -. DR eggNOG; KOG0156; Eukaryota. DR GeneTree; ENSGT00940000162131; -. DR HOGENOM; CLU_001570_22_3_1; -. DR InParanoid; Q9DBX6; -. DR OMA; MFSWFLR; -. DR OrthoDB; 2900138at2759; -. DR PhylomeDB; Q9DBX6; -. DR TreeFam; TF352043; -. DR Reactome; R-MMU-211958; Miscellaneous substrates. DR Reactome; R-MMU-211981; Xenobiotics. DR Reactome; R-MMU-211999; CYP2E1 reactions. DR UniPathway; UPA00199; -. DR BioGRID-ORCS; 74134; 3 hits in 79 CRISPR screens. DR PRO; PR:Q9DBX6; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; Q9DBX6; Protein. DR Bgee; ENSMUSG00000040703; Expressed in epithelium of stomach and 152 other cell types or tissues. DR ExpressionAtlas; Q9DBX6; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central. DR GO; GO:0036134; F:12-hydroxyheptadecatrienoic acid synthase activity; IEA:RHEA. DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central. DR GO; GO:0020037; F:heme binding; IBA:GO_Central. DR GO; GO:0016836; F:hydro-lyase activity; ISO:MGI. DR GO; GO:0106256; F:hydroperoxy icosatetraenoate dehydratase activity; IEA:UniProtKB-EC. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0004497; F:monooxygenase activity; ISO:MGI. DR GO; GO:0016712; F: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; IBA:GO_Central. DR GO; GO:0004796; F:thromboxane-A synthase activity; ISO:MGI. DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central. DR GO; GO:0006690; P:icosanoid metabolic process; ISO:MGI. DR GO; GO:0006693; P:prostaglandin metabolic process; ISO:MGI. DR GO; GO:0042573; P:retinoic acid metabolic process; ISO:MGI. DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central. DR CDD; cd11026; CYP2; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 1. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR002401; Cyt_P450_E_grp-I. DR InterPro; IPR008067; Cyt_P450_E_grp-I_CYP2A-like. DR InterPro; IPR036396; Cyt_P450_sf. DR PANTHER; PTHR24300:SF23; CYTOCHROME P450 2S1; 1. DR PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR01684; EP450ICYP2A. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR Genevisible; Q9DBX6; MM. PE 1: Evidence at protein level; KW Endoplasmic reticulum; Fatty acid metabolism; Heme; Iron; Isomerase; KW Lipid metabolism; Lyase; Membrane; Metal-binding; Microsome; Monooxygenase; KW Oxidoreductase; Reference proteome. FT CHAIN 1..501 FT /note="Cytochrome P450 2S1" FT /id="PRO_0000051781" FT BINDING 441 FT /ligand="heme" FT /ligand_id="ChEBI:CHEBI:30413" FT /ligand_part="Fe" FT /ligand_part_id="ChEBI:CHEBI:18248" FT /note="axial binding residue" FT /evidence="ECO:0000250" SQ SEQUENCE 501 AA; 55632 MW; D12575F3F8D7B019 CRC64; MEAASTWALL LALLLLLLLL SLTLFRTPAR GYLPPGPTPL PLLGNLLQLR PGALYSGLLR LSKKYGPVFT VYLGPWRRVV VLVGHDAVRE ALGGQAEEFS GRGTLATLDK TFDGHGVFFA NGERWKQLRK FTLLALRDLG MGKREGEELI QAEVQSLVEA FQKTEGRPFN PSMLLAQATS NVVCSLVFGI RLPYDDKEFQ AVIQAASGTL LGISSPWGQA YEMFSWLLQP LPGPHTQLQH HLGTLAAFTI QQVQKHQGRF QTSGPARDVV DAFLLKMAQE KQDPGTEFTE KNLLMTVTYL LFAGTMTIGA TIRYALLLLL RYPQVQQRVR EELIQELGPG RAPSLSDRVR LPYTDAVLHE AQRLLALVPM GMPHTITRTT CFRGYTLPKG TEVFPLIGSI LHDPAVFQNP GEFHPGRFLD EDGRLRKHEA FLPYSLGKRV CLGEGLARAE LWLFFTSILQ AFSLETPCPP GDLSLKPAIS GLFNIPPDFQ LRVWPTGDQS R //