CP240_MOUSE
ID CP240_MOUSE Reviewed; 491 AA.
AC P56657; B2RTP3;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Cytochrome P450 2C40;
DE EC=1.14.14.- {ECO:0000269|PubMed:10908295};
DE AltName: Full=CYPIIC40;
DE Flags: Precursor;
GN Name=Cyp2c40 {ECO:0000303|PubMed:9721182, ECO:0000312|MGI:MGI:1306815};
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], TISSUE SPECIFICITY, AND FUNCTION.
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 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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND PATHWAY.
RX PubMed=10908295; DOI=10.1124/mol.58.2.279;
RA Tsao C.C., Foley J., Coulter S.J., Maronpot R., Zeldin D.C.,
RA Goldstein J.A.;
RT "CYP2C40, a unique arachidonic acid 16-hydroxylase, is the major CYP2C in
RT murine intestinal tract.";
RL Mol. Pharmacol. 58:279-287(2000).
RN [4]
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 may play a major role in
CC the metabolism of arachidonic acid in the intestinal tract
CC (PubMed:10908295, PubMed:9721182). Exhibits regioselective hydroxylase
CC and epoxidase activity toward arachidonic acid, producing 16(R)-
CC hydroxyeicosatetraenoic acid (HETE) and (14R,15S)-epoxyeicosatrienoic
CC acid (EpETrE) as major products (PubMed:10908295). Mechanistically,
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 (CPR; NADPH-ferrihemoprotein
CC reductase) (PubMed:10908295). {ECO:0000269|PubMed:10908295,
CC ECO:0000269|PubMed:9721182}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 16(R)-hydroxy-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:53308, 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:137166; Evidence={ECO:0000269|PubMed:10908295};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53309;
CC Evidence={ECO:0000305|PubMed:10908295};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 16(S)-hydroxy-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:53312, 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:137167; Evidence={ECO:0000269|PubMed:10908295};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53313;
CC Evidence={ECO:0000305|PubMed:10908295};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49860, 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:131965; Evidence={ECO:0000269|PubMed:10908295};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861;
CC Evidence={ECO:0000305|PubMed:10908295};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49856, 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:131964; Evidence={ECO:0000269|PubMed:10908295};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857;
CC Evidence={ECO:0000305|PubMed:10908295};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P08684};
CC -!- PATHWAY: Lipid metabolism; arachidonate metabolism.
CC {ECO:0000305|PubMed:10908295}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Liver, brain, kidney, and intestine, with trace
CC amounts in lung and heart (PubMed:9721182, PubMed:10908295). Expressed
CC throughout the intestinal tract, with higher expression levels in
CC jejunum, cecum and colon (PubMed:10908295).
CC {ECO:0000269|PubMed:10908295, ECO:0000269|PubMed:9721182}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF047727; AAD13722.1; -; mRNA.
DR EMBL; BC139471; AAI39472.1; -; mRNA.
DR EMBL; BC139472; AAI39473.1; -; mRNA.
DR CCDS; CCDS29798.3; -.
DR RefSeq; NP_034134.2; NM_010004.2.
DR AlphaFoldDB; P56657; -.
DR SMR; P56657; -.
DR BioGRID; 199019; 1.
DR STRING; 10090.ENSMUSP00000125217; -.
DR SwissLipids; SLP:000001672; -.
DR iPTMnet; P56657; -.
DR PhosphoSitePlus; P56657; -.
DR SwissPalm; P56657; -.
DR jPOST; P56657; -.
DR MaxQB; P56657; -.
DR PaxDb; P56657; -.
DR PRIDE; P56657; -.
DR ProteomicsDB; 284108; -.
DR Ensembl; ENSMUST00000160476; ENSMUSP00000125217; ENSMUSG00000025004.
DR GeneID; 13099; -.
DR KEGG; mmu:13099; -.
DR CTD; 13099; -.
DR MGI; MGI:1306815; Cyp2c40.
DR VEuPathDB; HostDB:ENSMUSG00000025004; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000155736; -.
DR InParanoid; P56657; -.
DR OMA; EMREEPF; -.
DR OrthoDB; 702827at2759; -.
DR UniPathway; UPA00383; -.
DR BioGRID-ORCS; 13099; 2 hits in 43 CRISPR screens.
DR PRO; PR:P56657; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; P56657; protein.
DR Bgee; ENSMUSG00000025004; Expressed in liver and 16 other tissues.
DR ExpressionAtlas; P56657; baseline and differential.
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:0008404; F:arachidonic acid 14,15-epoxygenase activity; IDA:UniProtKB.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; ISO:MGI.
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: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..491
FT /note="Cytochrome P450 2C40"
FT /evidence="ECO:0000255"
FT /id="PRO_0000051723"
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|UniProtKB:P08684"
FT CONFLICT 382
FT /note="P -> L (in Ref. 1; AAD13722)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 491 AA; 55763 MW; 2F4CCEC2F219EA4F CRC64;
MDPFVVLVLC LSFLLVLSLW RQRSARGNLP PGPTPLPIIG NYHLIDMKDI GQCLTNFSKT
YGPVFTLYFG SQPIVVLHGY EAIKEALIDH GEEFSGRGRI PVFDKVSTGK GIGFSHGNVW
KATRVFTVNT LRNLGMGKRT IENKVQEEAQ WLMKELKKTN GSPCDPQFII GCAPCNVICS
IVFQNRFDYK DKDFLSLIGK VNECTEILSS PGCQIFNAVP ILIDYCPGSH NKLFKNHTWI
KSYLLGKIKE HEESLDVTNP RDFIDYFLIQ RRQKNGIEHM DYTIEHLATL VTDLVFGGTE
TLSSTMRFAL LLLMKHTHIT AKVQEEIDNV IGRHRSPCMQ DRNHMPYTNA MVHEVQRYID
LGPNGVVHEV TCDTKFRNYF IPKGTQVMTS LTSVLHDSTE FPNPEVFDPG HFLDDNGNFK
KSDYFVPFSA GKRICVGESL ARMELFLFLT TILQNFKLKP LVDPKDIDMT PKHSGFSKIP
PNFQMCFIPV E
