CP2A1_RAT
ID CP2A1_RAT Reviewed; 492 AA.
AC P11711; Q642C5;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Cytochrome P450 2A1;
DE EC=1.14.14.1;
DE AltName: Full=CYPIIA1;
DE AltName: Full=Cytochrome P450-UT-F;
DE AltName: Full=Steroid hormones 7-alpha-hydroxylase;
DE AltName: Full=Testosterone 7-alpha-hydroxylase;
GN Name=Cyp2a1; Synonyms=Cyp2a-1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=3818621; DOI=10.1016/s0021-9258(18)61575-3;
RA Nagata K., Matsunaga T., Gillette J., Gelboin H.V., Gonzalez F.J.;
RT "Rat testosterone 7 alpha-hydroxylase. Isolation, sequence, and expression
RT of cDNA and its developmental regulation and induction by 3-
RT methylcholanthrene.";
RL J. Biol. Chem. 262:2787-2793(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2322568; DOI=10.1021/bi00457a032;
RA Matsunaga T., Nomoto M., Kozak C.A., Gonzalez F.J.;
RT "Structure and in vitro transcription of the rat CYP2A1 and CYP2A2 genes
RT and regional localization of the CYP2A gene subfamily on mouse chromosome
RT 7.";
RL Biochemistry 29:1329-1341(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 PROTEIN SEQUENCE OF 1-20.
RC TISSUE=Liver;
RX PubMed=2650624; DOI=10.1016/0003-9861(89)90526-2;
RA Arlotto M.P., Greenway D.J., Parkinson A.;
RT "Purification of two isozymes of rat liver microsomal cytochrome P450 with
RT testosterone 7 alpha-hydroxylase activity.";
RL Arch. Biochem. Biophys. 270:441-457(1989).
RN [5]
RP PROTEIN SEQUENCE OF 1-12.
RC TISSUE=Liver;
RX PubMed=3436956; DOI=10.1093/oxfordjournals.jbchem.a122124;
RA Imaoka S., Kamataki T., Funae Y.;
RT "Purification and characterization of six cytochromes P-450 from hepatic
RT microsomes of immature female rats.";
RL J. Biochem. 102:843-851(1987).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Highly active in the 7-alpha-hydroxylation of testosterone,
CC progesterone and androstenedione.
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 and testis.
CC -!- INDUCTION: By 3-methylcholanthrene (3MC).
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; J02669; AAA41030.1; -; mRNA.
DR EMBL; M33312; AAA41020.1; -; Genomic_DNA.
DR EMBL; BC081848; AAH81848.1; -; mRNA.
DR PIR; A34272; A34272.
DR RefSeq; NP_036824.1; NM_012692.1.
DR RefSeq; XP_008757327.1; XM_008759105.1.
DR RefSeq; XP_008757328.1; XM_008759106.1.
DR AlphaFoldDB; P11711; -.
DR SMR; P11711; -.
DR IntAct; P11711; 1.
DR STRING; 10116.ENSRNOP00000028237; -.
DR ChEMBL; CHEMBL3509602; -.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB08834; Tauroursodeoxycholic acid.
DR iPTMnet; P11711; -.
DR PhosphoSitePlus; P11711; -.
DR PaxDb; P11711; -.
DR PRIDE; P11711; -.
DR Ensembl; ENSRNOT00000028237; ENSRNOP00000028237; ENSRNOG00000020817.
DR GeneID; 24894; -.
DR KEGG; rno:24894; -.
DR UCSC; RGD:2463; rat.
DR CTD; 24894; -.
DR RGD; 2463; Cyp2a1.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000154117; -.
DR InParanoid; P11711; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P11711; -.
DR TreeFam; TF352043; -.
DR Reactome; R-RNO-211935; Fatty acids.
DR Reactome; R-RNO-211981; Xenobiotics.
DR Reactome; R-RNO-211999; CYP2E1 reactions.
DR Reactome; R-RNO-5423646; Aflatoxin activation and detoxification.
DR PRO; PR:P11711; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020817; Expressed in liver and 15 other tissues.
DR ExpressionAtlas; P11711; baseline and differential.
DR Genevisible; P11711; RN.
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; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0009804; P:coumarin metabolic process; IDA:RGD.
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 Direct protein sequencing; Endoplasmic reticulum; Heme; Iron; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..492
FT /note="Cytochrome P450 2A1"
FT /id="PRO_0000051663"
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 MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 386
FT /note="G -> A (in Ref. 1; AAA41030)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 492 AA; 55995 MW; 58A187F9F10A1D85 CRC64;
MLDTGLLLVV ILASLSVMLL VSLWQQKIRG RLPPGPTPLP FIGNYLQLNT KDVYSSITQL
SERYGPVFTI HLGPRRVVVL YGYDAVKEAL VDQAEEFSGR GEQATYNTLF KGYGVAFSSG
ERAKQLRRLS IATLRDFGVG KRGVEERILE EAGYLIKMLQ GTCGAPIDPT IYLSKTVSNV
ISSIVFGERF DYEDTEFLSL LQMMGQMNRF AASPTGQLYD MFHSVMKYLP GPQQQIIKVT
QKLEDFMIEK VRQNHSTLDP NSPRNFIDSF LIRMQEEKNG NSEFHMKNLV MTTLSLFFAG
SETVSSTLRY GFLLLMKHPD VEAKVHEEIE QVIGRNRQPQ YEDHMKMPYT QAVINEIQRF
SNLAPLGIPR RIIKNTTFRG FFLPKGTDVF PILGSLMTDP KFFPSPKDFD PQNFLDDKGQ
LKKNAAFLPF STGKRFCLGD GLAKMELFLL LTTILQNFRF KFPMKLEDIN ESPKPLGFTR
IIPKYTMSFM PI
