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   27-MAR-2024, entry version 157.
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,
GN   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
CC         [NADPH--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
CC         [NADPH--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
CC         [NADPH--hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-
CC         eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:49860, 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: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
CC         [NADPH--hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-
CC         eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:49856, 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: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.ENSMUSP00000158887; -.
DR   SwissLipids; SLP:000001672; -.
DR   iPTMnet; P56657; -.
DR   PhosphoSitePlus; P56657; -.
DR   SwissPalm; P56657; -.
DR   jPOST; P56657; -.
DR   MaxQB; P56657; -.
DR   PaxDb; 10090-ENSMUSP00000125217; -.
DR   ProteomicsDB; 284108; -.
DR   Ensembl; ENSMUST00000160476.9; ENSMUSP00000125217.3; ENSMUSG00000025004.17.
DR   GeneID; 13099; -.
DR   KEGG; mmu:13099; -.
DR   AGR; MGI:1306815; -.
DR   CTD; 13099; -.
DR   MGI; MGI:1306815; Cyp2c40.
DR   VEuPathDB; HostDB:ENSMUSG00000025004; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   GeneTree; ENSGT00940000155736; -.
DR   InParanoid; P56657; -.
DR   OMA; VRSINHH; -.
DR   OrthoDB; 2900138at2759; -.
DR   UniPathway; UPA00383; -.
DR   BioGRID-ORCS; 13099; 2 hits in 48 CRISPR screens.
DR   PRO; PR:P56657; -.
DR   Proteomes; UP000000589; Chromosome 19.
DR   RNAct; P56657; Protein.
DR   Bgee; ENSMUSG00000025004; Expressed in liver and 16 other cell types or 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; IBA:GO_Central.
DR   GO; GO:0008404; F:arachidonic acid 14,15-epoxygenase activity; IDA:UniProtKB.
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: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:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR   GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
DR   CDD; cd20665; CYP2C-like; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 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   PANTHER; PTHR24300:SF140; CYTOCHROME P450 2C40-RELATED; 1.
DR   PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 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
//