CP2D7_HUMAN
ID CP2D7_HUMAN Reviewed; 515 AA.
AC A0A087X1C5; Q6XP50;
DT 01-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 29-OCT-2014, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Putative cytochrome P450 2D7 {ECO:0000305};
DE EC=1.14.14.1 {ECO:0000269|PubMed:15051713};
GN Name=CYP2D7 {ECO:0000312|HGNC:HGNC:2624};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ASN-70; LEU-311; SER-337 INS;
RP 369-ALA--CYS-373 DELINS VAL-HIS-MET-PRO-TYR; ARG-383 AND GLU-428, FUNCTION,
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain cortex;
RX PubMed=15051713; DOI=10.1074/jbc.m402337200;
RA Pai H.V., Kommaddi R.P., Chinta S.J., Mori T., Boyd M.R., Ravindranath V.;
RT "A frameshift mutation and alternate splicing in human brain generate a
RT functional form of the pseudogene cytochrome P4502D7 that demethylates
RT codeine to morphine.";
RL J. Biol. Chem. 279:27383-27389(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [3]
RP POLYMORPHISM, AND CAUTION.
RX PubMed=16169517; DOI=10.1016/j.bbrc.2005.08.255;
RA Gaedigk A., Gaedigk R., Leeder J.S.;
RT "CYP2D7 splice variants in human liver and brain: does CYP2D7 encode
RT functional protein?";
RL Biochem. Biophys. Res. Commun. 336:1241-1250(2005).
RN [4]
RP POLYMORPHISM, AND CAUTION.
RX PubMed=17494644; DOI=10.1124/dmd.107.014993;
RA Bhathena A., Mueller T., Grimm D.R., Idler K., Tsurutani A., Spear B.B.,
RA Katz D.A.;
RT "Frequency of the frame-shifting CYP2D7 138delT polymorphism in a large,
RT ethnically diverse sample population.";
RL Drug Metab. Dispos. 35:1251-1253(2007).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18838503; DOI=10.1124/dmd.108.023663;
RA Zhang W.Y., Tu Y.B., Haining R.L., Yu A.M.;
RT "Expression and functional analysis of CYP2D6.24, CYP2D6.26, CYP2D6.27, and
RT CYP2D7 isozymes.";
RL Drug Metab. Dispos. 37:1-4(2009).
CC -!- FUNCTION: May be responsible for the metabolism of many drugs and
CC environmental chemicals that it oxidizes. It may be involved in the
CC metabolism of codeine to morphine (PubMed:15051713). However, another
CC study could not confirm it (PubMed:18838503).
CC {ECO:0000269|PubMed:15051713, ECO:0000269|PubMed:18838503}.
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 Evidence={ECO:0000269|PubMed:15051713};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}. Cytoplasm {ECO:0000305|PubMed:15051713}.
CC Mitochondrion {ECO:0000269|PubMed:18838503}.
CC -!- TISSUE SPECIFICITY: Expressed in brain cortex (at protein level).
CC {ECO:0000269|PubMed:15051713}.
CC -!- POLYMORPHISM: A rare double polymorphism may allow the expression of a
CC functional protein (PubMed:15051713). However, following studies could
CC not confirm the combined existence of both polymorphisms and therefore
CC question the existence of that protein (PubMed:16169517,
CC PubMed:17494644). {ECO:0000269|PubMed:15051713,
CC ECO:0000269|PubMed:16169517, ECO:0000269|PubMed:17494644}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000255|RuleBase:RU000461}.
CC -!- CAUTION: Could be the product of a pseudogene.
CC {ECO:0000305|PubMed:15051713, ECO:0000305|PubMed:16169517,
CC ECO:0000305|PubMed:17494644, ECO:0000305|PubMed:18838503}.
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DR EMBL; AY220845; AAO49806.1; -; mRNA.
DR EMBL; AC254562; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001335315.1; NM_001348386.1.
DR AlphaFoldDB; A0A087X1C5; -.
DR SMR; A0A087X1C5; -.
DR ChEMBL; CHEMBL3542437; -.
DR GlyGen; A0A087X1C5; 1 site.
DR BioMuta; CYP2D7; -.
DR jPOST; A0A087X1C5; -.
DR MassIVE; A0A087X1C5; -.
DR PeptideAtlas; A0A087X1C5; -.
DR DNASU; 1564; -.
DR GeneID; 1564; -.
DR KEGG; hsa:1564; -.
DR UCSC; uc062eux.1; human.
DR CTD; 1564; -.
DR DisGeNET; 1564; -.
DR GeneCards; CYP2D7; -.
DR HGNC; HGNC:2624; CYP2D7.
DR neXtProt; NX_A0A087X1C5; -.
DR VEuPathDB; HostDB:ENSG00000205702; -.
DR HOGENOM; CLU_001570_22_0_1; -.
DR OMA; NIRPRNE; -.
DR OrthoDB; 702827at2759; -.
DR PathwayCommons; A0A087X1C5; -.
DR BioGRID-ORCS; 1564; 0 hits in 38 CRISPR screens.
DR GenomeRNAi; 1564; -.
DR Pharos; A0A087X1C5; Tbio.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; A0A087X1C5; protein.
DR Bgee; ENSG00000205702; Expressed in right lobe of liver and 91 other tissues.
DR ExpressionAtlas; A0A087X1C5; baseline and differential.
DR Genevisible; A0A087X1C5; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0070330; F:aromatase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
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:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0042178; P:xenobiotic catabolic process; IDA:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB.
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; 2.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01686; EP450ICYP2D.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 5: Uncertain;
KW Cytoplasm; Glycoprotein; Heme; Iron; Membrane; Metal-binding;
KW Mitochondrion; Monooxygenase; Oxidoreductase; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..515
FT /note="Putative cytochrome P450 2D7"
FT /id="PRO_0000432413"
FT TOPO_DOM 1..2
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 3..23
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 24..301
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 302..322
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 323..515
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT BINDING 461
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|UniProtKB:P10635"
FT CARBOHYD 416
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 70
FT /note="S -> N (in dbSNP:rs11090077)"
FT /evidence="ECO:0000269|PubMed:15051713"
FT /id="VAR_072632"
FT VARIANT 311
FT /note="S -> L (in dbSNP:rs1800754)"
FT /evidence="ECO:0000269|PubMed:15051713"
FT /id="VAR_072633"
FT VARIANT 337
FT /note="C -> CS"
FT /evidence="ECO:0000269|PubMed:15051713"
FT /id="VAR_072634"
FT VARIANT 369..373
FT /note="AHMPC -> VHMPY"
FT /evidence="ECO:0000269|PubMed:15051713"
FT /id="VAR_072635"
FT VARIANT 383
FT /note="H -> R (in dbSNP:rs56127449)"
FT /evidence="ECO:0000269|PubMed:15051713"
FT /id="VAR_072636"
FT VARIANT 428
FT /note="K -> E (in dbSNP:rs2070907)"
FT /evidence="ECO:0000269|PubMed:15051713"
FT /id="VAR_072637"
SQ SEQUENCE 515 AA; 57489 MW; E9331B1589161E03 CRC64;
MGLEALVPLA MIVAIFLLLV DLMHRHQRWA ARYPPGPLPL PGLGNLLHVD FQNTPYCFDQ
LRRRFGDVFS LQLAWTPVVV LNGLAAVREA MVTRGEDTAD RPPAPIYQVL GFGPRSQGVI
LSRYGPAWRE QRRFSVSTLR NLGLGKKSLE QWVTEEAACL CAAFADQAGR PFRPNGLLDK
AVSNVIASLT CGRRFEYDDP RFLRLLDLAQ EGLKEESGFL REVLNAVPVL PHIPALAGKV
LRFQKAFLTQ LDELLTEHRM TWDPAQPPRD LTEAFLAKKE KAKGSPESSF NDENLRIVVG
NLFLAGMVTT STTLAWGLLL MILHLDVQRG RRVSPGCPIV GTHVCPVRVQ QEIDDVIGQV
RRPEMGDQAH MPCTTAVIHE VQHFGDIVPL GVTHMTSRDI EVQGFRIPKG TTLITNLSSV
LKDEAVWKKP FRFHPEHFLD AQGHFVKPEA FLPFSAGRRA CLGEPLARME LFLFFTSLLQ
HFSFSVAAGQ PRPSHSRVVS FLVTPSPYEL CAVPR
