ID   CP2D3_RAT               Reviewed;         500 AA.
AC   P12938; O35106; Q5FVU3;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-1998, sequence version 2.
DT   24-JAN-2024, entry version 170.
DE   RecName: Full=Cytochrome P450 2D3;
DE            EC=1.14.14.1;
DE   AltName: Full=CYPIID3;
DE   AltName: Full=Cytochrome P450-DB3;
DE   AltName: Full=Debrisoquine 4-hydroxylase;
GN   Name=Cyp2d3; Synonyms=Cyp2d-3;
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=2819073; DOI=10.1021/bi00444a030;
RA   Matsunaga E., Zanger U.M., Hardwick J.P., Gelboin H.V., Meyer U.A.,
RA   Gonzalez F.J.;
RT   "The CYP2D gene subfamily: analysis of the molecular basis of the
RT   debrisoquine 4-hydroxylase deficiency in DA rats.";
RL   Biochemistry 28:7349-7355(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=2107330; DOI=10.1007/bf02099942;
RA   Matsunaga E., Umeno M., Gonzalez F.J.;
RT   "The rat P450 IID subfamily: complete sequences of four closely linked
RT   genes and evidence that gene conversions maintained sequence homogeneity at
RT   the heme-binding region of the cytochrome P450 active site.";
RL   J. Mol. Evol. 30:155-169(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=9434752; DOI=10.1006/abbi.1997.0402;
RA   Wan J., Imaoka S., Chow T., Hiroi T., Yabusaki Y., Funae Y.;
RT   "Expression of four rat CYP2D isoforms in Saccharomyces cerevisiae and
RT   their catalytic specificity.";
RL   Arch. Biochem. Biophys. 348:383-390(1997).
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).
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 + 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   -!- INDUCTION: P450 can be induced to high levels in liver and other
CC       tissues by various foreign compounds, including drugs, pesticides, and
CC       carcinogens.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; J02868; AAA41002.1; -; mRNA.
DR   EMBL; X52028; CAA36270.1; -; Genomic_DNA.
DR   EMBL; AB008424; BAA23124.1; -; mRNA.
DR   EMBL; BC089769; AAH89769.1; -; mRNA.
DR   PIR; S16872; S16872.
DR   RefSeq; NP_775116.1; NM_173093.1.
DR   AlphaFoldDB; P12938; -.
DR   SMR; P12938; -.
DR   STRING; 10116.ENSRNOP00000070699; -.
DR   BindingDB; P12938; -.
DR   ChEMBL; CHEMBL3057; -.
DR   iPTMnet; P12938; -.
DR   PhosphoSitePlus; P12938; -.
DR   PaxDb; 10116-ENSRNOP00000048711; -.
DR   Ensembl; ENSRNOT00055051616; ENSRNOP00055042558; ENSRNOG00055029785.
DR   GeneID; 24303; -.
DR   KEGG; rno:24303; -.
DR   UCSC; RGD:2472; rat.
DR   AGR; RGD:2472; -.
DR   CTD; 24303; -.
DR   RGD; 2472; Cyp2d3.
DR   VEuPathDB; HostDB:ENSRNOG00000029179; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   HOGENOM; CLU_001570_22_0_1; -.
DR   InParanoid; P12938; -.
DR   OrthoDB; 2900138at2759; -.
DR   PhylomeDB; P12938; -.
DR   SABIO-RK; P12938; -.
DR   PRO; PR:P12938; -.
DR   Proteomes; UP000002494; Chromosome 7.
DR   Bgee; ENSRNOG00000029179; Expressed in liver and 17 other cell types or tissues.
DR   ExpressionAtlas; P12938; baseline and differential.
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: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:0004497; F:monooxygenase 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:0019369; P:arachidonic acid metabolic process; IBA:GO_Central.
DR   GO; GO:0001889; P:liver development; IEP:RGD.
DR   GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
DR   CDD; cd20663; CYP2D; 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; IPR008069; Cyt_P450_E_grp-I_CYP2D-like.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   PANTHER; PTHR24300:SF109; CYTOCHROME P450 2D26; 1.
DR   PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR01686; EP450ICYP2D.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
DR   Genevisible; P12938; RN.
PE   2: Evidence at transcript level;
KW   Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome;
KW   Monooxygenase; Oxidoreductase; Reference proteome.
FT   CHAIN           1..500
FT                   /note="Cytochrome P450 2D3"
FT                   /id="PRO_0000051729"
FT   BINDING         446
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        125..126
FT                   /note="AP -> CT (in Ref. 1; AAA41002 and 2; CAA36270)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   500 AA;  56642 MW;  C54727C2C00F73F6 CRC64;
     MELLAGTGLW PMAIFTVIFI LLVDLMHRRQ RWTSRYPPGP VPWPVLGNLL QVDLCNMPYS
     MYKLQNRYGD VFSLQMGWKP VVVINGLKAV QELLVTCGED TADRPEMPIF QHIGYGHKAK
     GVVLAPYGPE WREQRRFSVS TLRNFGVGKK SLEQWVTDEA SHLCDALTAE AGRPLDPYTL
     LNKAVCNVIA SLIYARRFDY GDPDFIKVLK ILKESMGEQT GLFPEVLNMF PVLLRIPGLA
     DKVFPGQKTF LTMVDNLVTE HKKTWDPDQP PRDLTDAFLA EIEKAKGNPE SSFNDANLRL
     VVNDLFGAGM VTTSITLTWA LLLMILHPDV QCRVQQEIDE VIGQVRHPEM ADQAHMPFTN
     AVIHEVQRFA DIVPMNLPHK TSRDIEVQGF LIPKGTTLIP NLSSVLKDET VWEKPLRFHP
     EHFLDAQGNF VKHEAFMPFS AGRRACLGEP LARMELFLFF TCLLQRFSFS VPTGQPRPSD
     YGVFAFLLSP SPYQLCAFKR
//