ID   CP238_MOUSE             Reviewed;         490 AA.
AC   P56655; B2RWV4; F8VPK7;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2012, sequence version 2.
DT   27-MAR-2024, entry version 163.
DE   RecName: Full=Cytochrome P450 2C38;
DE            EC=1.14.14.1 {ECO:0000269|PubMed:9721182};
DE   AltName: Full=CYPIIC38;
DE   Flags: Precursor;
GN   Name=Cyp2c38 {ECO:0000303|PubMed:9721182,
GN   ECO:0000312|MGI:MGI:1306819};
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 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).
CC   -!- FUNCTION: A cytochrome P450 monooxygenase that primarily catalyzes the
CC       epoxidation of 11,12 double bond of (5Z,8Z,11Z,14Z)-eicosatetraenoic
CC       acid (arachidonate) forming 11,12-epoxyeicosatrienoic acid (11,12-EET)
CC       regioisomer. Mechanistically, uses molecular oxygen inserting one
CC       oxygen atom into a substrate, and reducing the second into a water
CC       molecule, with two electrons provided by NADPH via cytochrome P450
CC       reductase (CPR; NADPH--hemoprotein reductase).
CC       {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
CC         [NADPH--hemoprotein reductase] = 11,12-epoxy-(5Z,8Z,14Z)-
CC         eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:51480, 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:76625; Evidence={ECO:0000269|PubMed:9721182};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51481;
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, brain, kidney, and intestine, with trace
CC       amounts in lung and heart. {ECO:0000269|PubMed:9721182}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; AF047725; AAD13720.1; -; mRNA.
DR   EMBL; AC139233; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC150721; AAI50722.1; -; mRNA.
DR   CCDS; CCDS29794.1; -.
DR   RefSeq; NP_034132.2; NM_010002.3.
DR   AlphaFoldDB; P56655; -.
DR   SMR; P56655; -.
DR   STRING; 10090.ENSMUSP00000044722; -.
DR   SwissLipids; SLP:000001669; -.
DR   iPTMnet; P56655; -.
DR   PhosphoSitePlus; P56655; -.
DR   jPOST; P56655; -.
DR   MaxQB; P56655; -.
DR   PaxDb; 10090-ENSMUSP00000044722; -.
DR   PeptideAtlas; P56655; -.
DR   ProteomicsDB; 283436; -.
DR   DNASU; 13097; -.
DR   Ensembl; ENSMUST00000035488.3; ENSMUSP00000044722.3; ENSMUSG00000032808.3.
DR   GeneID; 13097; -.
DR   KEGG; mmu:13097; -.
DR   UCSC; uc008hka.1; mouse.
DR   AGR; MGI:1306819; -.
DR   CTD; 13097; -.
DR   MGI; MGI:1306819; Cyp2c38.
DR   VEuPathDB; HostDB:ENSMUSG00000032808; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   GeneTree; ENSGT00940000155736; -.
DR   HOGENOM; CLU_001570_22_0_1; -.
DR   InParanoid; P56655; -.
DR   OMA; MQWRAMF; -.
DR   OrthoDB; 2900138at2759; -.
DR   PhylomeDB; P56655; -.
DR   TreeFam; TF352043; -.
DR   UniPathway; UPA00383; -.
DR   BioGRID-ORCS; 13097; 2 hits in 79 CRISPR screens.
DR   ChiTaRS; Cyp2c38; mouse.
DR   PRO; PR:P56655; -.
DR   Proteomes; UP000000589; Chromosome 19.
DR   RNAct; P56655; Protein.
DR   Bgee; ENSMUSG00000032808; Expressed in liver and 8 other cell types or tissues.
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; IDA:UniProtKB.
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:0101020; F:estrogen 16-alpha-hydroxylase activity; 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:0008401; F:retinoic acid 4-hydroxylase activity; ISO:MGI.
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: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:SF374; CYTOCHROME P450 2C18; 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.
DR   Genevisible; P56655; MM.
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..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..490
FT                   /note="Cytochrome P450 2C38"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000051721"
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        60
FT                   /note="T -> A (in Ref. 1; AAD13720 and 3; AAI50722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        98
FT                   /note="E -> G (in Ref. 1; AAD13720 and 3; AAI50722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        125
FT                   /note="R -> H (in Ref. 1; AAD13720 and 3; AAI50722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        188
FT                   /note="D -> H (in Ref. 1; AAD13720 and 3; AAI50722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        253
FT                   /note="E -> A (in Ref. 1; AAD13720 and 3; AAI50722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        257
FT                   /note="V -> F (in Ref. 1; AAD13720 and 3; AAI50722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        344
FT                   /note="R -> H (in Ref. 1; AAD13720 and 3; AAI50722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        470
FT                   /note="I -> M (in Ref. 1; AAD13720 and 3; AAI50722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        478
FT                   /note="T -> A (in Ref. 1; AAD13720 and 3; AAI50722)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   490 AA;  56229 MW;  876444B4A6C1343A CRC64;
     MDLVTFLVLT LSSLILLSLW RQRSRRGRLP PGPTPFPIIG NFLQIDVKNF NQSLTNFSKT
     YGPVFTLYLG SRPIVVLHGY EAVKEALIDH GEEFSGRENI PMSEKINNGL GITFSNGNSW
     KETRRFTLMT LRNLGMGKRN IEDRVREEAQ CLVEELRKTK GSPCDPTFIL SCAPCNVICS
     IIFQDRFDYK DKDFLMLMKK LNENVKILSS PWLQVCNNFP LLIDYCPGSH HKVLKNFKYI
     RSYLLEKVKE HQESLDVTNP RDFIDYFLIK QKQANHIEQA EYSLENLVCT INNLFAAGTE
     TTSTTLRYAL LLLMKYPDVT AKVQEEIDHV VGRHRSPCMQ DRSRMPYTDA MIHEVQRFIN
     LVPNNLPHAV TCDIKFRNYI IPKGTTVVTS LTSVLHDSKE FPNPEMFDPG HFLDANGNFK
     KSDYFMTFSA GKRVCAGEGL ARMELFLILT TILQNFKLKS LVHPKDIDMI PFVNGLITLP
     PHYQLCFIPL
//