CP239_MOUSE
ID CP239_MOUSE Reviewed; 490 AA.
AC P56656; B9EIA6; G5E854;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Cytochrome P450 2C39;
DE EC=1.14.14.1 {ECO:0000269|PubMed:9721182};
DE AltName: Full=CYPIIC39;
DE Flags: Precursor;
GN Name=Cyp2c39 {ECO:0000303|PubMed:9721182, ECO:0000312|MGI:MGI:1306818};
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 [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND PATHWAY.
RC STRAIN=CD-1;
RX PubMed=9721182; DOI=10.1006/abbi.1998.0806;
RA Luo G., Zeldin D.C., Blaisdell J.A., Hodgson E., Goldstein J.A.;
RT "Cloning and expression of murine CYP2Cs and their ability to metabolize
RT arachidonic acid.";
RL Arch. Biochem. Biophys. 357:45-57(1998).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
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 that primarily catalyzes the
CC epoxidation of 11,12 and 14,15 double bonds of (5Z,8Z,11Z,14Z)-
CC eicosatetraenoic acid (arachidonate) forming 11,12- and 14,15-
CC epoxyeicosatrienoic acids (11,12- and 14,15-EET) regioisomers.
CC Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC substrate, and reducing the second into a water molecule, with two
CC electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH--
CC hemoprotein reductase). {ECO:0000269|PubMed:9721182}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC Evidence={ECO:0000269|PubMed:9721182};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000305|PubMed:9721182};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:51480, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76625; Evidence={ECO:0000269|PubMed:9721182};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51481;
CC Evidence={ECO:0000305|PubMed:9721182};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:51472, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:84024; Evidence={ECO:0000269|PubMed:9721182};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51473;
CC Evidence={ECO:0000305|PubMed:9721182};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; arachidonate metabolism.
CC {ECO:0000305|PubMed:9721182}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Liver. {ECO:0000269|PubMed:9721182}.
CC -!- INDUCTION: P450 can be induced to high levels in liver and other
CC tissues by various foreign compounds, including drugs, pesticides, and
CC carcinogens.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF047726; AAD13721.1; -; mRNA.
DR EMBL; AC117790; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC139233; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466534; EDL41819.1; -; Genomic_DNA.
DR EMBL; BC139290; AAI39291.1; -; mRNA.
DR EMBL; BC139291; AAI39292.1; -; mRNA.
DR CCDS; CCDS29795.1; -.
DR RefSeq; NP_034133.2; NM_010003.2.
DR AlphaFoldDB; P56656; -.
DR SMR; P56656; -.
DR STRING; 10090.ENSMUSP00000025968; -.
DR SwissLipids; SLP:000001670; -.
DR iPTMnet; P56656; -.
DR PhosphoSitePlus; P56656; -.
DR SwissPalm; P56656; -.
DR jPOST; P56656; -.
DR MaxQB; P56656; -.
DR PaxDb; P56656; -.
DR PeptideAtlas; P56656; -.
DR PRIDE; P56656; -.
DR ProteomicsDB; 283809; -.
DR DNASU; 13098; -.
DR Ensembl; ENSMUST00000025968; ENSMUSP00000025968; ENSMUSG00000025003.
DR GeneID; 13098; -.
DR KEGG; mmu:13098; -.
DR UCSC; uc008hkb.2; mouse.
DR CTD; 13098; -.
DR MGI; MGI:1306818; Cyp2c39.
DR VEuPathDB; HostDB:ENSMUSG00000025003; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000155736; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; P56656; -.
DR OMA; IIDMFVA; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P56656; -.
DR TreeFam; TF352043; -.
DR SABIO-RK; P56656; -.
DR UniPathway; UPA00383; -.
DR BioGRID-ORCS; 13098; 1 hit in 71 CRISPR screens.
DR PRO; PR:P56656; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; P56656; protein.
DR Bgee; ENSMUSG00000025003; Expressed in liver and 1 other tissue.
DR Genevisible; P56656; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0008405; F:arachidonic acid 11,12-epoxygenase activity; IDA:UniProtKB.
DR GO; GO:0008404; F:arachidonic acid 14,15-epoxygenase activity; IEA:RHEA.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; ISO:MGI.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0034875; F:caffeine oxidase activity; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0020037; F:heme binding; ISO:MGI.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0120319; F:long-chain fatty acid omega-1 hydroxylase activity; ISO:MGI.
DR GO; GO:0004497; F:monooxygenase activity; ISO:MGI.
DR GO; GO:0016491; F:oxidoreductase 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; ISO:MGI.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
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; 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 1: Evidence at protein level;
KW Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..490
FT /note="Cytochrome P450 2C39"
FT /evidence="ECO:0000255"
FT /id="PRO_0000051722"
FT BINDING 435
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"
FT CONFLICT 47
FT /note="I -> M (in Ref. 1; AAD13721 and 4; AAI39291/
FT AAI39292)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="V -> F (in Ref. 1; AAD13721 and 4; AAI39291/
FT AAI39292)"
FT /evidence="ECO:0000305"
FT CONFLICT 460
FT /note="S -> P (in Ref. 1; AAD13721 and 4; AAI39291/
FT AAI39292)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 490 AA; 55827 MW; EE583A2B53CFC410 CRC64;
MDLVTFLVLT LSSLILLSLW RQSCGRGSLP PGPTPFPIIG NFLQIDIKNV SQSLTNFSKA
YGPVFTLYLG SRPTVVLHGY EAVKEALIDH GEEFSDRGSI PMVEKINNGL GIVFSNGNRW
KEIRRFTLTT LRNLGMGKRN IEDRVQEEAQ CLVEELRKTK GSPCDPTFIL SCAPCNVICS
IIFQDRFDYK DKDFLMLMEK LNENVKILSS PWLQVCNNFP LLIDYCPGSH HKVLKNVKYI
RSYLLEKIKE HQESLDVTNP RDFIDYYLIK QKQANHIQQA EFSLENLACT INNLFAAGTE
TTSTTLRYAL LLLMKYPDVT AKVQEEIDHV IGRHRSPCMQ DRNHMPYTDA MIHEVQRFIN
LVPNNIPRAV TCDIKFRNYL IPKGTTVVTS LTSVLHDSKE FPNPELFDPG HFLDANGNFK
KSDHFMPFSA GKRVCAGEGL ARMELFLFLT TILQNFKLKS LVHPKDIDMI PFVNGLIALP
PHYQVCIIPR
