ID   CP3A2_RAT               Reviewed;         504 AA.
AC   P05183; Q5FVU5; Q64629; Q64672;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1999, sequence version 2.
DT   02-SEP-2026, entry version 176.
DE   RecName: Full=Cytochrome P450 3A2;
DE            EC=1.14.14.1;
DE   AltName: Full=CYPIIIA2;
DE   AltName: Full=Cytochrome P450-PCN2;
DE   AltName: Full=Cytochrome P450/6-beta-A;
DE   AltName: Full=Testosterone 6-beta-hydroxylase;
GN   Name=Cyp3a2; Synonyms=Cyp3a-2, Cyp3a11;
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].
RX   PubMed=3785219; DOI=10.1128/mcb.6.8.2969-2976.1986;
RA   Gonzalez F.J., Song B.-J., Hardwick J.P.;
RT   "Pregnenolone 16 alpha-carbonitrile-inducible P-450 gene family: gene
RT   conversion and differential regulation.";
RL   Mol. Cell. Biol. 6:2969-2976(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=2043144; DOI=10.1016/0006-291x(91)91949-d;
RA   Miyata M., Nagata K., Yamazoe Y., Kato R.;
RT   "A gene structure of testosterone 6 beta-hydroxylase (P450IIIA).";
RL   Biochem. Biophys. Res. Commun. 177:68-73(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=7979376; DOI=10.1006/abbi.1994.1453;
RA   Miyata M., Nagata K., Shimada M., Yamazoe Y., Kato R.;
RT   "Structure of a gene and cDNA of a major constitutive form of testosterone
RT   6 beta-hydroxylase (P450/6 beta A) encoding CYP3A2: comparison of the cDNA
RT   with P450PCN2.";
RL   Arch. Biochem. Biophys. 314:351-359(1994).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   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   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-36, AND INDUCTION.
RC   TISSUE=Liver;
RX   PubMed=1417000; DOI=10.1016/0003-9861(92)90471-8;
RA   Telhada M.B., Pereira T.M., Lechner M.C.;
RT   "Effect of dexamethasone and phenobarbital on run-on transcription rate and
RT   CYP3A mRNA concentration in rat liver: changes during development.";
RL   Arch. Biochem. Biophys. 298:715-725(1992).
RN   [6]
RP   PROTEIN SEQUENCE OF 1-33, TISSUE SPECIFICITY, AND INDUCTION.
RC   TISSUE=Liver;
RX   PubMed=2398038; DOI=10.1093/oxfordjournals.jbchem.a123115;
RA   Nagata K., Gonzalez F.J., Yamazoe Y., Kato R.;
RT   "Purification and characterization of four catalytically active
RT   testosterone 6 beta-hydroxylase P-450s from rat liver microsomes:
RT   comparison of a novel form with three structurally and functionally related
RT   forms.";
RL   J. Biochem. 107:718-725(1990).
RN   [7]
RP   PROTEIN SEQUENCE OF 1-25, TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=7681660; DOI=10.1006/abbi.1993.1154;
RA   Cooper K.O., Reik L.M., Jayyosi Z., Bandiera S., Kelley M., Ryan D.E.,
RA   Daniel R., McCluskey S.A., Levin W., Thomas P.E.;
RT   "Regulation of two members of the steroid-inducible cytochrome P450
RT   subfamily (3A) in rats.";
RL   Arch. Biochem. Biophys. 301:345-354(1993).
CC   -!- FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases.
CC       In liver microsomes, this enzyme is involved in an NADPH-dependent
CC       electron transport pathway. It oxidizes a variety of structurally
CC       unrelated compounds, including steroids, fatty acids, and xenobiotics.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an organic molecule + reduced [NADPH--hemoprotein reductase] +
CC         O2 = an alcohol + oxidized [NADPH--hemoprotein reductase] + H2O +
CC         H(+); 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: Expressed in liver. {ECO:0000269|PubMed:2398038,
CC       ECO:0000269|PubMed:7681660}.
CC   -!- INDUCTION: By pregnenolone 16-alpha-carbonitrile (PNCN) and
CC       dexamethasone. {ECO:0000269|PubMed:1417000, ECO:0000269|PubMed:2398038,
CC       ECO:0000269|PubMed:7681660}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; M13646; AAA41051.1; -; mRNA.
DR   EMBL; X79319; CAA55887.1; -; Genomic_DNA.
DR   EMBL; X79320; CAA55888.1; -; mRNA.
DR   EMBL; U09742; AAA82168.1; -; mRNA.
DR   EMBL; U09734; AAB60492.1; -; Genomic_DNA.
DR   EMBL; U09725; AAB60492.1; JOINED; Genomic_DNA.
DR   EMBL; U09726; AAB60492.1; JOINED; Genomic_DNA.
DR   EMBL; U09727; AAB60492.1; JOINED; Genomic_DNA.
DR   EMBL; U09728; AAB60492.1; JOINED; Genomic_DNA.
DR   EMBL; U09729; AAB60492.1; JOINED; Genomic_DNA.
DR   EMBL; U09730; AAB60492.1; JOINED; Genomic_DNA.
DR   EMBL; U09731; AAB60492.1; JOINED; Genomic_DNA.
DR   EMBL; U09732; AAB60492.1; JOINED; Genomic_DNA.
DR   EMBL; U09733; AAB60492.1; JOINED; Genomic_DNA.
DR   EMBL; BC089765; AAH89765.1; -; mRNA.
DR   PIR; A25222; A25222.
DR   RefSeq; NP_695224.3; NM_153312.3.
DR   AlphaFoldDB; P05183; -.
DR   SMR; P05183; -.
DR   FunCoup; P05183; 41.
DR   BindingDB; P05183; -.
DR   ChEMBL; CHEMBL3324; -.
DR   DrugBank; DB13746; Bioallethrin.
DR   DrugBank; DB13975; Black cohosh.
DR   DrugBank; DB00869; Dorzolamide.
DR   DrugBank; DB01645; Genistein.
DR   DrugBank; DB08834; Tauroursodeoxycholic acid.
DR   iPTMnet; P05183; -.
DR   PhosphoSitePlus; P05183; -.
DR   Ensembl; ENSRNOT00000120620.2; ENSRNOP00000098255.2; ENSRNOG00000032560.5.
DR   GeneID; 266682; -.
DR   KEGG; rno:266682; -.
DR   AGR; RGD:708379; -.
DR   CTD; 266682; -.
DR   RGD; 708379; Cyp3a2.
DR   GeneTree; ENSGT00950000182958; -.
DR   InParanoid; P05183; -.
DR   PhylomeDB; P05183; -.
DR   Reactome; R-RNO-211945; Phase I - Functionalization of compounds.
DR   Reactome; R-RNO-211958; Miscellaneous substrates.
DR   Reactome; R-RNO-211981; Xenobiotics.
DR   Reactome; R-RNO-5423646; Aflatoxin activation and detoxification.
DR   Reactome; R-RNO-9027307; Biosynthesis of maresin-like SPMs.
DR   Reactome; R-RNO-9749641; Aspirin ADME.
DR   Reactome; R-RNO-9754706; Atorvastatin ADME.
DR   Reactome; R-RNO-9757110; Prednisone ADME.
DR   SABIO-RK; P05183; -.
DR   PRO; PR:P05183; -.
DR   Proteomes; UP000002494; Chromosome 12.
DR   ExpressionAtlas; P05183; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0102320; F:1,8-cineole 2-exo-monooxygenase activity; ISO:RGD.
DR   GO; GO:0062181; F:1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity; ISO:RGD.
DR   GO; GO:0062188; F:anandamide 11,12 epoxidase activity; ISO:RGD.
DR   GO; GO:0062189; F:anandamide 14,15 epoxidase activity; ISO:RGD.
DR   GO; GO:0062187; F:anandamide 8,9 epoxidase activity; ISO:RGD.
DR   GO; GO:0034875; F:caffeine oxidase activity; ISO:RGD.
DR   GO; GO:0032451; F:demethylase activity; IDA:RGD.
DR   GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR   GO; GO:0101020; F:estrogen 16-alpha-hydroxylase activity; ISO:RGD.
DR   GO; GO:0101021; F:estrogen 2-hydroxylase activity; ISO:RGD.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; ISO:RGD.
DR   GO; GO:0004497; F:monooxygenase activity; IDA:RGD.
DR   GO; GO:0016491; F:oxidoreductase activity; ISO: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; ISO:RGD.
DR   GO; GO:0050591; F:quinine 3-monooxygenase activity; ISO:RGD.
DR   GO; GO:0008401; F:retinoic acid 4-hydroxylase activity; ISO:RGD.
DR   GO; GO:0005496; F:steroid binding; ISO:RGD.
DR   GO; GO:0008395; F:steroid hydroxylase activity; ISO:RGD.
DR   GO; GO:0050649; F:testosterone 6-beta-hydroxylase activity; IMP:RGD.
DR   GO; GO:0070576; F:vitamin D 24-hydroxylase activity; ISO:RGD.
DR   GO; GO:0030343; F:vitamin D 25-hydroxylase activity; ISO:RGD.
DR   GO; GO:0009822; P:alkaloid catabolic process; ISO:RGD.
DR   GO; GO:0008210; P:estrogen metabolic process; ISO:RGD.
DR   GO; GO:0006751; P:glutathione catabolic process; IDA:RGD.
DR   GO; GO:0002933; P:lipid hydroxylation; ISO:RGD.
DR   GO; GO:0016098; P:monoterpenoid metabolic process; ISO:RGD.
DR   GO; GO:0070989; P:oxidative demethylation; IDA:RGD.
DR   GO; GO:0042573; P:retinoic acid metabolic process; ISO:RGD.
DR   GO; GO:0042572; P:retinol metabolic process; ISO:RGD.
DR   GO; GO:0006706; P:steroid catabolic process; ISO:RGD.
DR   GO; GO:0008202; P:steroid metabolic process; ISO:RGD.
DR   GO; GO:0019417; P:sulfur oxidation; IDA:RGD.
DR   GO; GO:0042369; P:vitamin D catabolic process; ISO:RGD.
DR   GO; GO:0042359; P:vitamin D metabolic process; ISO:RGD.
DR   GO; GO:0042178; P:xenobiotic catabolic process; ISO:RGD.
DR   GO; GO:0006805; P:xenobiotic metabolic process; IDA:RGD.
DR   CDD; cd20650; CYP3A; 1.
DR   FunFam; 1.10.630.10:FF:000096; Cytochrome P450 3A4; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR008072; Cyt_P450_E_CYP3A.
DR   InterPro; IPR002402; Cyt_P450_E_grp-II.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   InterPro; IPR050705; Cytochrome_P450_3A.
DR   PANTHER; PTHR24302:SF49; CYTOCHROME P450 3A-RELATED; 1.
DR   PANTHER; PTHR24302; CYTOCHROME P450 FAMILY 3; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00464; EP450II.
DR   PRINTS; PR01689; EP450IICYP3A.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 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;
KW   Reference proteome.
FT   CHAIN           1..504
FT                   /note="Cytochrome P450 3A2"
FT                   /id="PRO_0000051784"
FT   BINDING         443
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   CONFLICT        56..57
FT                   /note="GL -> AV (in Ref. 2; CAA55887)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        429
FT                   /note="D -> H (in Ref. 1; AAA41051)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        445
FT                   /note="G -> D (in Ref. 1; AAA41051)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   504 AA;  57732 MW;  C2C84AF736035AB2 CRC64;
     MDLLSALTLE TWVLLAVILV LLYRLGTHRH GIFKKQGIPG PKPLPFLGTV LNYYKGLGRF
     DMECYKKYGK IWGLFDGQTP VFAIMDTEMI KNVLVKECFS VFTNRRDFGP VGIMGKAVSV
     AKDEEWKRYR ALLSPTFTSG RLKEMFPIIE QYGDILVKYL KQEAETGKPV TMKKVFGAYS
     MDVITSTSFG VNVDSLNNPK DPFVEKTKKL LRFDFFDPLF LSVVLFPFLT PIYEMLNICM
     FPKDSIAFFQ KFVHRIKETR LDSKHKHRVD FLQLMLNAHN NSKDEVSHKA LSDVEIIAQS
     VIFIFAGYET TSSTLSFVLY FLATHPDIQK KLQEEIDGAL PSKAPPTYDI VMEMEYLDMV
     LNETLRLYPI GNRLERVCKK DIELDGLFIP KGSVVTIPTY ALHHDPQHWP KPEEFHPERF
     SKENKGSIDP YVYLPFGNGP RNCIGMRFAL MNMKLALTKV LQNFSFQPCK ETQIPLKLSR
     QAILEPEKPI VLKVLPRDAV INGA
//