CP2S1_MOUSE
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 03-AUG-2022, entry version 151.
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}.
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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; Q9DBX6; -.
DR PeptideAtlas; Q9DBX6; -.
DR PRIDE; Q9DBX6; -.
DR ProteomicsDB; 278007; -.
DR Antibodypedia; 45241; 218 antibodies from 29 providers.
DR DNASU; 74134; -.
DR Ensembl; ENSMUST00000043314; ENSMUSP00000041175; ENSMUSG00000040703.
DR GeneID; 74134; -.
DR KEGG; mmu:74134; -.
DR UCSC; uc009fub.1; mouse.
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; YEMFSRL; -.
DR OrthoDB; 702827at2759; -.
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 74 CRISPR screens.
DR PRO; PR:Q9DBX6; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9DBX6; protein.
DR Bgee; ENSMUSG00000040703; Expressed in epithelium of stomach and 149 other tissues.
DR ExpressionAtlas; Q9DBX6; baseline and differential.
DR Genevisible; Q9DBX6; MM.
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; ISO:MGI.
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:0008395; F:steroid hydroxylase activity; 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:0006082; P:organic acid metabolic process; IBA:GO_Central.
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 Gene3D; 1.10.630.10; -; 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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01684; EP450ICYP2A.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
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
