ID   CP2AC_MOUSE             Reviewed;         492 AA.
AC   P56593; Q8VCW9;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   27-MAR-2024, entry version 171.
DE   RecName: Full=Cytochrome P450 2A12;
DE            EC=1.14.14.1;
DE   AltName: Full=CYPIIA12;
DE   AltName: Full=Steroid hormones 7-alpha-hydroxylase;
DE   AltName: Full=Testosterone 7-alpha-hydroxylase;
GN   Name=Cyp2a12;
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], AND MUTAGENESIS.
RC   STRAIN=AKR/J; TISSUE=Liver;
RX   PubMed=8484736; DOI=10.1042/bj2910569;
RA   Iwasaki M., Lindberg R.L.P., Juvonen R.O., Negishi M.;
RT   "Site-directed mutagenesis of mouse steroid 7 alpha-hydroxylase (cytochrome
RT   P-450(7) alpha): role of residue-209 in determining steroid-cytochrome P-
RT   450 interaction.";
RL   Biochem. J. 291:569-573(1993).
RN   [2]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Liver;
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   [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: Highly active in the 7-alpha-hydroxylation of testosterone.
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   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC       membrane protein. Microsome membrane; Peripheral membrane protein.
CC   -!- TISSUE SPECIFICITY: Liver.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; L06463; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; CH466593; EDL24208.1; -; Genomic_DNA.
DR   EMBL; BC018356; AAH18356.1; -; mRNA.
DR   EMBL; BC094017; AAH94017.1; -; mRNA.
DR   CCDS; CCDS21009.1; -.
DR   PIR; S32491; S32491.
DR   RefSeq; NP_598418.1; NM_133657.1.
DR   AlphaFoldDB; P56593; -.
DR   SMR; P56593; -.
DR   BioGRID; 199008; 26.
DR   STRING; 10090.ENSMUSP00000074990; -.
DR   iPTMnet; P56593; -.
DR   PhosphoSitePlus; P56593; -.
DR   SwissPalm; P56593; -.
DR   jPOST; P56593; -.
DR   MaxQB; P56593; -.
DR   PaxDb; 10090-ENSMUSP00000074990; -.
DR   PeptideAtlas; P56593; -.
DR   ProteomicsDB; 278004; -.
DR   DNASU; 13085; -.
DR   Ensembl; ENSMUST00000075552.7; ENSMUSP00000074990.6; ENSMUSG00000060407.7.
DR   GeneID; 13085; -.
DR   KEGG; mmu:13085; -.
DR   UCSC; uc009fux.1; mouse.
DR   AGR; MGI:105055; -.
DR   CTD; 13085; -.
DR   MGI; MGI:105055; Cyp2a12.
DR   VEuPathDB; HostDB:ENSMUSG00000060407; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   GeneTree; ENSGT00940000154117; -.
DR   HOGENOM; CLU_001570_22_3_1; -.
DR   InParanoid; P56593; -.
DR   OMA; QLYEIFY; -.
DR   OrthoDB; 2900138at2759; -.
DR   PhylomeDB; P56593; -.
DR   TreeFam; TF352043; -.
DR   Reactome; R-MMU-211935; Fatty acids.
DR   Reactome; R-MMU-211981; Xenobiotics.
DR   Reactome; R-MMU-211999; CYP2E1 reactions.
DR   Reactome; R-MMU-5423646; Aflatoxin activation and detoxification.
DR   BioGRID-ORCS; 13085; 1 hit in 77 CRISPR screens.
DR   PRO; PR:P56593; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; P56593; Protein.
DR   Bgee; ENSMUSG00000060407; Expressed in liver and 22 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; IBA:GO_Central.
DR   GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central.
DR   GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
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:0009804; P:coumarin metabolic process; 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; cd20668; CYP2A; 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; IPR008067; Cyt_P450_E_grp-I_CYP2A-like.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1.
DR   PANTHER; PTHR24300:SF103; CYTOCHROME P450-RELATED; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR01684; EP450ICYP2A.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
DR   Genevisible; P56593; MM.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome;
KW   Monooxygenase; Oxidoreductase; Reference proteome.
FT   CHAIN           1..492
FT                   /note="Cytochrome P450 2A12"
FT                   /id="PRO_0000051675"
FT   BINDING         437
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   MUTAGEN         206
FT                   /note="Q->G: Same as wild-type."
FT                   /evidence="ECO:0000269|PubMed:8484736"
FT   MUTAGEN         208
FT                   /note="N->L: Stabilizes the protein, 17-fold lower Vmax."
FT                   /evidence="ECO:0000269|PubMed:8484736"
FT   MUTAGEN         209
FT                   /note="K->Q: Same as wild-type."
FT                   /evidence="ECO:0000269|PubMed:8484736"
FT   CONFLICT        147
FT                   /note="R -> H (in Ref. 1; L06463)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        375
FT                   /note="D -> N (in Ref. 1; L06463)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        386
FT                   /note="G -> A (in Ref. 1; L06463)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        449..450
FT                   /note="LF -> FL (in Ref. 1; L06463)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   492 AA;  56179 MW;  38FD449996825F44 CRC64;
     MLGSGLLLLA ILAFLSVMVL VSVWQQKIRG KLPPGPIPLP FIGNYLQLNR KDVYSSITQL
     QEHYGPVFTI HLGPRRVVVL YGYDAVKEAL VDHAEEFSGR GEQATFNTLF KGYGVAFSNG
     ERAKQLRRFS IATLRDFGMG KRGVEERIQE EAGCLIKMLQ GTCGAPIDPT IYLSKTASNV
     ISSIVFGDRF NYEDKEFLSL LQMMGQVNKF AASPTGQLYD MFHSVMKYLP GPQQQIIKDS
     HKLEDFMIQK VKQNQSTLDP NSPRDFIDSF LIHMQKEKYV NSEFHMKNLV MTSLNLFFAG
     SETVSSTLRY GFLLLMKHPD VEAKVHEEID RVIGRNRQPQ YEDHMKMPYT QAVINEIQRF
     SNFAPLGIPR RITKDTSFRG FFLPKGTEVF PILGSLMTDP KFFSSPKDFN PQHFLDDKGQ
     LKKIPAFLPF STGKRFCLGD SLAKMELFLF FTTILQNFRF KFPRKLEDIN ESPTPEGFTR
     IIPKYTMSFV PI
//