CP2W1_MOUSE
ID CP2W1_MOUSE Reviewed; 493 AA.
AC E9Q816;
DT 04-FEB-2015, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Cytochrome P450 2W1;
DE EC=1.14.14.- {ECO:0000250|UniProtKB:Q8TAV3};
DE Flags: Precursor;
GN Name=Cyp2w1;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=21920951; DOI=10.1093/toxsci/kfr240;
RA Renaud H.J., Cui J.Y., Khan M., Klaassen C.D.;
RT "Tissue distribution and gender-divergent expression of 78 cytochrome P450
RT mRNAs in mice.";
RL Toxicol. Sci. 124:261-277(2011).
CC -!- FUNCTION: A cytochrome P450 monooxygenase that may play a role in
CC retinoid and phospholipid metabolism. Catalyzes the hydroxylation of
CC saturated carbon hydrogen bonds. Hydroxylates all trans-retinoic acid
CC (atRA) to 4-hydroxyretinoate and may regulate atRA clearance. Other
CC retinoids such as all-trans retinol and all-trans retinal are potential
CC endogenous substrates. Catalyzes both epoxidation of double bonds and
CC hydroxylation of carbon hydrogen bonds of the fatty acyl chain of 1-
CC acylphospholipids/2-lysophospholipids. Can metabolize various
CC lysophospholipids classes including lysophosphatidylcholines (LPCs),
CC lysophosphatidylinositols (LPIs), lysophosphatidylserines (LPSs),
CC lysophosphatidylglycerols (LPGs), lysophosphatidylethanolamines (LPEs)
CC and lysophosphatidic acids (LPAs). Has low or no activity toward 2-
CC acylphospholipids/1-lysophospholipids, diacylphospholipids and free
CC fatty acids. May play a role in tumorigenesis by activating
CC procarcinogens such as aflatoxin B1, polycyclic aromatic hydrocarbon
CC dihydrodiols and aromatic amines. Mechanistically, uses molecular
CC oxygen inserting one oxygen atom into a substrate, and reducing the
CC second into a water molecule, with two electrons provided by NADPH via
CC cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).
CC {ECO:0000250|UniProtKB:Q8TAV3}.
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:Q8TAV3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51985;
CC Evidence={ECO:0000250|UniProtKB:Q8TAV3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + O2 + reduced
CC [NADPH--hemoprotein reductase] = 1-[8-hydroxy-(9Z)-octadecenoyl]-sn-
CC glycero-3-phosphocholine + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:50328, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28610, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:132285; Evidence={ECO:0000250|UniProtKB:Q8TAV3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50329;
CC Evidence={ECO:0000250|UniProtKB:Q8TAV3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + O2 + reduced
CC [NADPH--hemoprotein reductase] = 1-[11-hydroxy-(9Z)-octadecenoyl]-sn-
CC glycero-3-phosphocholine + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:50332, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28610, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:132286; Evidence={ECO:0000250|UniProtKB:Q8TAV3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50333;
CC Evidence={ECO:0000250|UniProtKB:Q8TAV3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + O2 + reduced
CC [NADPH--hemoprotein reductase] = 1-[(9S,10R)-epoxy-octadecanoyl]-sn-
CC glycero-3-phosphocholine + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:50324, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28610, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:132278; Evidence={ECO:0000250|UniProtKB:Q8TAV3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50325;
CC Evidence={ECO:0000250|UniProtKB:Q8TAV3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + O2 + reduced
CC [NADPH--hemoprotein reductase] = 1-[(9R,10S)-epoxy-octadecanoyl]-sn-
CC glycero-3-phosphocholine + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:50320, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28610, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:132280; Evidence={ECO:0000250|UniProtKB:Q8TAV3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50321;
CC Evidence={ECO:0000250|UniProtKB:Q8TAV3};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q6VVX0};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:Q8TAV3}. Cell membrane
CC {ECO:0000250|UniProtKB:Q8TAV3}. Microsome membrane
CC {ECO:0000250|UniProtKB:Q8TAV3}.
CC -!- TISSUE SPECIFICITY: Detected in colon, ileum, and testes.
CC {ECO:0000269|PubMed:21920951}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000255|RuleBase:RU000461}.
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DR EMBL; AC161058; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS51683.1; -.
DR RefSeq; NP_001153737.1; NM_001160265.1.
DR AlphaFoldDB; E9Q816; -.
DR SMR; E9Q816; -.
DR STRING; 10090.ENSMUSP00000031521; -.
DR GlyGen; E9Q816; 1 site.
DR PhosphoSitePlus; E9Q816; -.
DR jPOST; E9Q816; -.
DR MaxQB; E9Q816; -.
DR PaxDb; E9Q816; -.
DR PRIDE; E9Q816; -.
DR ProteomicsDB; 278011; -.
DR Antibodypedia; 1974; 222 antibodies from 29 providers.
DR Ensembl; ENSMUST00000031521; ENSMUSP00000031521; ENSMUSG00000029541.
DR GeneID; 545817; -.
DR KEGG; mmu:545817; -.
DR UCSC; uc012efv.1; mouse.
DR CTD; 54905; -.
DR MGI; MGI:3616076; Cyp2w1.
DR VEuPathDB; HostDB:ENSMUSG00000029541; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000161956; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; E9Q816; -.
DR OMA; VPRCTAV; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; E9Q816; -.
DR TreeFam; TF352043; -.
DR Reactome; R-MMU-211958; Miscellaneous substrates.
DR Reactome; R-MMU-211981; Xenobiotics.
DR BioGRID-ORCS; 545817; 0 hits in 74 CRISPR screens.
DR PRO; PR:E9Q816; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; E9Q816; protein.
DR Bgee; ENSMUSG00000029541; Expressed in lip and 13 other tissues.
DR ExpressionAtlas; E9Q816; baseline and differential.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005503; F:all-trans retinal binding; ISS:UniProtKB.
DR GO; GO:1904768; F:all-trans-retinol binding; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
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:0008401; F:retinoic acid 4-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0001972; F:retinoic acid binding; ISS:UniProtKB.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0046222; P:aflatoxin metabolic process; ISS:UniProtKB.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0006644; P:phospholipid metabolic process; ISS:UniProtKB.
DR GO; GO:0034653; P:retinoic acid catabolic process; ISS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISS:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Endoplasmic reticulum; Glycoprotein; Heme; Iron;
KW Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase;
KW Oxidoreductase; Reference proteome; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..493
FT /note="Cytochrome P450 2W1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000431705"
FT BINDING 436
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|UniProtKB:Q6VVX0"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 493 AA; 54438 MW; BFD0F2958C443F62 CRC64;
MALLLLGVWG ILLLLGLWGL LQGCTRSPSL APRWPPGPRP LPFLGNLHLL GVTQQDRALM
ELSERYGPMF TIHLGSQKTV VLSGYEVVRE ALVGTGHELA DRPPIPIFQH IQRGGGIFFS
SGARWRAGRQ FTVRTLQSLG VQQPSMVGKV LQELACLKGQ LDSYGGQPLP LALLGWAPCN
ITFTLLFGQR FDYQDPVFVS LLSLIDQVMV LLGSPGIQLF NTFPRLGAFL RLHRPVLSKI
EEVRTILRTL LETRRPPLPT GGPAQSYVEA LLQQGQEDDP EDMFGEANVL ACTLDMVMAG
TETTAATLQW AVFLMVKHPH VQGRVQEELD RVLGPGQLPQ PEHQRALPYT SAVLHEVQRY
ITLLPHVPRC TAADIQLGGY LLPKGTPVIP LLTSVLLDKT QWETPSQFNP NHFLDAKGRF
MKRGAFLPFS AGRRVCVGKS LARTELFLLF AGLLQRYRLL PPPGLSPADL DLRPAPAFTM
RPPAQTLCVV PRS
