CP2DQ_RAT
ID CP2DQ_RAT Reviewed; 500 AA.
AC P10634;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Cytochrome P450 2D26;
DE EC=1.14.14.1;
DE AltName: Full=CYPIID26;
DE AltName: Full=Cytochrome P450-CMF2;
DE AltName: Full=Cytochrome P450-DB2;
DE AltName: Full=Debrisoquine 4-hydroxylase;
GN Name=Cyp2d26; Synonyms=Cyp2d-26, Cyp2d2;
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=3582092; DOI=10.1089/dna.1987.6.149;
RA Gonzalez F.J., Matsunaga T., Nagata K., Meyer U.A., Nebert D.W.,
RA Pastewka J., Kozak C.A., Gillette J., Gelboin H.V., Hardwick J.P.;
RT "Debrisoquine 4-hydroxylase: characterization of a new P450 gene subfamily,
RT regulation, chromosomal mapping, and molecular analysis of the DA rat
RT polymorphism.";
RL DNA 6:149-161(1987).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
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).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, 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: 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; M16655; AAA41055.1; -; mRNA.
DR EMBL; M22330; AAA41049.1; -; mRNA.
DR EMBL; X52027; CAA36269.1; -; Genomic_DNA.
DR EMBL; AB008423; BAA23123.1; -; mRNA.
DR EMBL; BC078897; AAH78897.1; -; mRNA.
DR PIR; B26822; B26822.
DR RefSeq; NP_036862.1; NM_012730.1.
DR AlphaFoldDB; P10634; -.
DR SMR; P10634; -.
DR IntAct; P10634; 8.
DR STRING; 10116.ENSRNOP00000012413; -.
DR BindingDB; P10634; -.
DR ChEMBL; CHEMBL2483; -.
DR iPTMnet; P10634; -.
DR PhosphoSitePlus; P10634; -.
DR PaxDb; P10634; -.
DR PRIDE; P10634; -.
DR Ensembl; ENSRNOT00000012413; ENSRNOP00000012413; ENSRNOG00000008988.
DR GeneID; 25053; -.
DR KEGG; rno:25053; -.
DR UCSC; RGD:2471; rat.
DR CTD; 25053; -.
DR RGD; 2471; Cyp2d2.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000153331; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; P10634; -.
DR OMA; VKCLVYE; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P10634; -.
DR TreeFam; TF352043; -.
DR SABIO-RK; P10634; -.
DR PRO; PR:P10634; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000008988; Expressed in liver and 15 other tissues.
DR Genevisible; P10634; 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: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:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IBA:GO_Central.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
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; 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 1: Evidence at protein level;
KW Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome;
KW Monooxygenase; Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..500
FT /note="Cytochrome P450 2D26"
FT /id="PRO_0000051747"
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 MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 117
FT /note="N -> D (in Ref. 3; AAA41049)"
FT /evidence="ECO:0000305"
FT CONFLICT 346
FT /note="R -> L (in Ref. 1; AAA41055 and 2; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="F -> L (in Ref. 1; AAA41055 and 2; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="K -> E (in Ref. 1; AAA41055 and 2; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 56684 MW; 23E99250734C2215 CRC64;
MGLLIGDDLW AVVIFTAIFL LLVDLVHRHK FWTAHYPPGP VPLPGLGNLL QVDFENMPYS
LYKLRSRYGD VFSLQIAWKP VVVINGLKAV RELLVTYGED TADRPLLPIY NHLGYGNKSK
GVVLAPYGPE WREQRRFSVS TLRDFGVGKK SLEQWVTEEA GHLCDTFAKE AEHPFNPSIL
LSKAVSNVIA SLVYARRFEY EDPFFNRMLK TLKESFGEDT GFMAEVLNAI PILLQIPGLP
GKVFPKLNSF IALVDKMLIE HKKSWDPAQP PRDMTDAFLA EMQKAKGNPE SSFNDENLRL
VVIDLFMAGM VTTSTTLSWA LLLMILHPDV QRRVHEEIDE VIGQVRRPEM ADQARMPFTN
AVIHEVQRFA DIVPTNIPHM TSRDIKFQGF LIPKGTTLIP NLSSVLKDET VWEKPLRFHP
EHFLDAQGNF VKHEAFMPFS AGRRACLGEP LARMELFLFF TCLLQRFSFS VLAGRPRPST
HGVYALPVTP QPYQLCAVAR
