CP2D4_RAT
ID CP2D4_RAT Reviewed; 500 AA.
AC Q64680; O35107; P13108; Q566D3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Cytochrome P450 2D4;
DE EC=1.14.14.1;
DE AltName: Full=CYPIID18;
DE AltName: Full=CYPIID4;
DE AltName: Full=Cytochrome P450 2D-29;
DE AltName: Full=Cytochrome P450 2D-35;
DE AltName: Full=Cytochrome P450 2D18;
DE AltName: Full=Cytochrome P450-CMF3;
DE AltName: Full=Cytochrome P450-DB4;
DE AltName: Full=Debrisoquine 4-hydroxylase;
GN Name=Cyp2d4; Synonyms=Cyp2d-18, Cyp2d-4, Cyp2d18;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=7733922; DOI=10.1006/bbrc.1995.1534;
RA Kawashima H., Strobel H.W.;
RT "cDNA cloning of a novel rat brain cytochrome P450 belonging to the CYP2D
RT subfamily.";
RL Biochem. Biophys. Res. Commun. 209:535-540(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
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=Brain;
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 177-500.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=3190674; DOI=10.1016/s0006-291x(88)80896-9;
RA Ishida N., Tawaragi Y., Inuzuka C., Sugita O., Kubota I., Nakazato H.,
RA Noguchi T., Sassa S.;
RT "Four species of cDNAs for cytochrome P450 isozymes immunorelated to P450C-
RT M/F encode for members of P450IID subfamily, increasing the number of
RT members within the subfamily.";
RL Biochem. Biophys. Res. Commun. 156:681-688(1988).
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 -!- TISSUE SPECIFICITY: Brain.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; X52029; CAA36271.1; -; Genomic_DNA.
DR EMBL; U48220; AAC52883.1; -; mRNA.
DR EMBL; U48219; AAC52882.1; -; mRNA.
DR EMBL; AB008425; BAA23125.1; -; mRNA.
DR EMBL; BC093609; AAH93609.1; -; mRNA.
DR EMBL; M22331; AAA41052.1; -; mRNA.
DR RefSeq; NP_612524.1; NM_138515.2.
DR AlphaFoldDB; Q64680; -.
DR SMR; Q64680; -.
DR STRING; 10116.ENSRNOP00000011880; -.
DR ChEMBL; CHEMBL4982; -.
DR PaxDb; Q64680; -.
DR PRIDE; Q64680; -.
DR Ensembl; ENSRNOT00000011880; ENSRNOP00000011880; ENSRNOG00000032261.
DR GeneID; 171522; -.
DR KEGG; rno:171522; -.
DR UCSC; RGD:620640; rat.
DR CTD; 171522; -.
DR RGD; 620640; Cyp2d4.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000153331; -.
DR HOGENOM; CLU_001570_22_0_1; -.
DR InParanoid; Q64680; -.
DR OMA; GIHTTKM; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; Q64680; -.
DR TreeFam; TF352043; -.
DR Reactome; R-RNO-211935; Fatty acids.
DR Reactome; R-RNO-211958; Miscellaneous substrates.
DR Reactome; R-RNO-211981; Xenobiotics.
DR Reactome; R-RNO-211999; CYP2E1 reactions.
DR Reactome; R-RNO-9027307; Biosynthesis of maresin-like SPMs.
DR Reactome; R-RNO-9749641; Aspirin ADME.
DR PRO; PR:Q64680; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000032261; Expressed in jejunum and 18 other tissues.
DR Genevisible; Q64680; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
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:0005739; C:mitochondrion; 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:0008391; F:arachidonic acid monooxygenase activity; IDA:RGD.
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: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; IBA:GO_Central.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0009822; P:alkaloid catabolic process; ISO:RGD.
DR GO; GO:0009820; P:alkaloid metabolic process; ISO:RGD.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:RGD.
DR GO; GO:0008207; P:C21-steroid hormone metabolic process; IMP:RGD.
DR GO; GO:0009804; P:coumarin metabolic process; ISO:RGD.
DR GO; GO:0042416; P:dopamine biosynthetic process; IDA:RGD.
DR GO; GO:0042417; P:dopamine metabolic process; IDA:RGD.
DR GO; GO:0008210; P:estrogen metabolic process; ISO:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0046483; P:heterocycle metabolic process; ISO:RGD.
DR GO; GO:0033076; P:isoquinoline alkaloid metabolic process; ISO:RGD.
DR GO; GO:0016098; P:monoterpenoid metabolic process; ISO:RGD.
DR GO; GO:0051100; P:negative regulation of binding; ISO:RGD.
DR GO; GO:0090350; P:negative regulation of cellular organofluorine metabolic process; ISO:RGD.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0070989; P:oxidative demethylation; ISO:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0042572; P:retinol metabolic process; ISO:RGD.
DR GO; GO:0006587; P:serotonin biosynthetic process from tryptophan; IDA:RGD.
DR GO; GO:0008202; P:steroid 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 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; IPR008069; Cyt_P450_E_grp-I_CYP2D-like.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01686; EP450ICYP2D.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
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 2D4"
FT /id="PRO_0000051742"
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 /evidence="ECO:0000250"
FT CONFLICT 327
FT /note="R -> H (in Ref. 1; CAA36271, 3; BAA23125 and 5;
FT AAA41052)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="I -> T (in Ref. 1; CAA36271, 3; BAA23125 and 5;
FT AAA41052)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="A -> T (in Ref. 1; CAA36271 and 5; AAA41052)"
FT /evidence="ECO:0000305"
FT CONFLICT 480
FT /note="N -> D (in Ref. 1; CAA36271 and 5; AAA41052)"
FT /evidence="ECO:0000305"
FT CONFLICT 483
FT /note="V -> I (in Ref. 1; CAA36271 and 5; AAA41052)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 56684 MW; 9848A8BE5ABA09C5 CRC64;
MRMPTGSELW PIAIFTIIFL LLVDLMHRRQ RWTSRYPPGP VPWPVLGNLL QIDFQNMPAG
FQKLRCRFGD LFSLQLAFES VVVLNGLPAL REALVKYSED TADRPPLHFN DQSGFGPRSQ
GVVLARYGPA WRQQRRFSVS TFRHFGLGKK SLEQWVTEEA RCLCAAFADH SGFPFSPNTL
LDKAVCNVIA SLLFACRFEY NDPRFIRLLD LLKDTLEEES GFLPMLLNVF PMLLHIPGLL
GKVFSGKKAF VAMLDELLTE HKVTWDPAQP PRDLTDAFLA EVEKAKGNPE SSFNDENLRV
VVADLFMAGM VTTSTTLTWA LLFMILRPDV QCRVQQEIDE VIGQVRRPEM ADQARMPFTN
AVIHEVQRFA DILPLGVPHK TSRDIEVQGF LIPKGTTLII NLSSVLKDET VWEKPLRFHP
EHFLDAQGNF VKHEAFMPFS AGRRACLGEP LARMELFLFF TCLLQRFSFS VPAGQPRPSN
YGVFGALTTP RPYQLCASPR
