CP2AC_MOUSE
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 03-AUG-2022, entry version 162.
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}.
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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; P56593; -.
DR PeptideAtlas; P56593; -.
DR PRIDE; P56593; -.
DR ProteomicsDB; 278004; -.
DR DNASU; 13085; -.
DR Ensembl; ENSMUST00000075552; ENSMUSP00000074990; ENSMUSG00000060407.
DR GeneID; 13085; -.
DR KEGG; mmu:13085; -.
DR UCSC; uc009fux.1; mouse.
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; NRQPQFE; -.
DR OrthoDB; 702827at2759; -.
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; 0 hits in 72 CRISPR screens.
DR PRO; PR:P56593; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P56593; protein.
DR Bgee; ENSMUSG00000060407; Expressed in liver and 22 other tissues.
DR Genevisible; P56593; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005881; C:cytoplasmic microtubule; ISO:MGI.
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:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0008389; F:coumarin 7-hydroxylase 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: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: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; IPR008067; Cyt_P450_E_grp-I_CYP2A-like.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01684; EP450ICYP2A.
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; 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
