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P10635

- CP2D6_HUMAN

UniProt

P10635 - CP2D6_HUMAN

Protein

Cytochrome P450 2D6

Gene

CYP2D6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 163 (01 Oct 2014)
      Sequence version 2 (20 Dec 2005)
      Previous versions | rss
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    Functioni

    Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.1 Publication

    Catalytic activityi

    RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.

    Cofactori

    Heme group.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei301 – 3011SubstrateCurated
    Metal bindingi443 – 4431Iron (heme axial ligand)

    GO - Molecular functioni

    1. aromatase activity Source: UniProtKB-EC
    2. drug binding Source: BHF-UCL
    3. heme binding Source: UniProtKB
    4. iron ion binding Source: InterPro
    5. monooxygenase activity Source: BHF-UCL
    6. oxidoreductase activity Source: BHF-UCL

    GO - Biological processi

    1. alkaloid catabolic process Source: BHF-UCL
    2. alkaloid metabolic process Source: BHF-UCL
    3. coumarin metabolic process Source: BHF-UCL
    4. drug catabolic process Source: BHF-UCL
    5. drug metabolic process Source: BHF-UCL
    6. heterocycle metabolic process Source: BHF-UCL
    7. isoquinoline alkaloid metabolic process Source: BHF-UCL
    8. monoterpenoid metabolic process Source: BHF-UCL
    9. negative regulation of binding Source: BHF-UCL
    10. negative regulation of cellular organofluorine metabolic process Source: BHF-UCL
    11. oxidation-reduction process Source: BHF-UCL
    12. oxidative demethylation Source: BHF-UCL
    13. small molecule metabolic process Source: Reactome
    14. steroid metabolic process Source: BHF-UCL
    15. xenobiotic metabolic process Source: BHF-UCL

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_13425. Miscellaneous substrates.
    REACT_13543. Xenobiotics.
    REACT_13797. CYP2E1 reactions.
    REACT_13814. Fatty acids.
    SABIO-RKP10635.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 2D6 (EC:1.14.14.1)
    Alternative name(s):
    CYPIID6
    Cytochrome P450-DB1
    Debrisoquine 4-hydroxylase
    Gene namesi
    Name:CYP2D6
    Synonyms:CYP2DL1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 22

    Organism-specific databases

    HGNCiHGNC:2625. CYP2D6.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum Source: BHF-UCL
    2. endoplasmic reticulum membrane Source: Reactome
    3. mitochondrion Source: BHF-UCL

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    MIMi608902. phenotype.
    Orphaneti240847. Amitriptyline toxicity.
    240849. Antipsychotics toxicity.
    240865. Clomipramine toxicity.
    240867. Codeine toxicity.
    240883. Imipramine toxicity.
    240893. Nortriptyline toxicity.
    240931. Resistance to amitriptyline in the treatment of depression.
    240933. Resistance to clomipramine in the treatment of depression.
    240939. Resistance to imipramine in the treatment of depression.
    240941. Resistance to nortripilline in the treatment of depression.
    240947. Resistance to tamoxifene in breast cancer.
    240949. Resistance to trimipramine in the treatment of depression.
    240951. Resistance to venlafaxine in the treatment of depression.
    240957. Susceptibility to adverse reaction due to amitriptyline treatment.
    240959. Susceptibility to adverse reaction due to antipsychotics treatment.
    240965. Susceptibility to adverse reaction due to clomipramine treatment.
    240967. Susceptibility to adverse reaction due to codeine treatment.
    240971. Susceptibility to adverse reaction due to imipramine treatment.
    240979. Susceptibility to adverse reaction due to nortriptyline treatment.
    240987. Susceptibility to adverse reaction due to trimipramine treatment.
    240989. Susceptibility to adverse reaction due to venlafaxine treatment.
    240915. Trimipramine toxicity.
    240919. Venlafaxine toxicity.
    PharmGKBiPA128.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 497497Cytochrome P450 2D6PRO_0000051731Add
    BLAST

    Proteomic databases

    PaxDbiP10635.
    PRIDEiP10635.

    PTM databases

    PhosphoSiteiP10635.

    Expressioni

    Inductioni

    By pregnancy.

    Gene expression databases

    BgeeiP10635.
    CleanExiHS_CYP2D6.
    GenevestigatoriP10635.

    Organism-specific databases

    HPAiHPA045223.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000353820.

    Structurei

    Secondary structure

    1
    497
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni41 – 433
    Helixi46 – 483
    Helixi54 – 6512
    Beta strandi67 – 737
    Beta strandi76 – 816
    Helixi83 – 919
    Turni92 – 943
    Helixi95 – 973
    Helixi105 – 1106
    Turni118 – 1214
    Helixi126 – 14116
    Turni143 – 1453
    Helixi148 – 16518
    Turni166 – 1694
    Helixi175 – 19117
    Helixi200 – 21415
    Helixi219 – 2268
    Helixi228 – 2325
    Helixi234 – 2407
    Helixi242 – 26120
    Helixi271 – 28111
    Turni282 – 2843
    Helixi292 – 32332
    Helixi325 – 33814
    Beta strandi341 – 3433
    Helixi347 – 3504
    Helixi354 – 36714
    Beta strandi370 – 3723
    Beta strandi382 – 3843
    Beta strandi387 – 3893
    Beta strandi394 – 3974
    Helixi399 – 4035
    Turni406 – 4083
    Beta strandi409 – 4113
    Helixi417 – 4204
    Helixi446 – 46318
    Beta strandi464 – 4674
    Beta strandi479 – 4879
    Beta strandi492 – 4965

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2F9QX-ray3.00A/B/C/D34-497[»]
    3QM4X-ray2.85A/B34-497[»]
    3TBGX-ray2.10A/B/C/D34-497[»]
    3TDAX-ray2.67A/B/C/D34-497[»]
    ProteinModelPortaliP10635.
    SMRiP10635. Positions 48-497.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP10635.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiCOG2124.
    HOVERGENiHBG015789.
    KOiK17712.
    PhylomeDBiP10635.
    TreeFamiTF352043.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    IPR008069. Cyt_P450_E_grp-I_CYP2D-like.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR01686. EP450ICYP2D.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P10635-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGLEALVPLA VIVAIFLLLV DLMHRRQRWA ARYPPGPLPL PGLGNLLHVD    50
    FQNTPYCFDQ LRRRFGDVFS LQLAWTPVVV LNGLAAVREA LVTHGEDTAD 100
    RPPVPITQIL GFGPRSQGVF LARYGPAWRE QRRFSVSTLR NLGLGKKSLE 150
    QWVTEEAACL CAAFANHSGR PFRPNGLLDK AVSNVIASLT CGRRFEYDDP 200
    RFLRLLDLAQ EGLKEESGFL REVLNAVPVL LHIPALAGKV LRFQKAFLTQ 250
    LDELLTEHRM TWDPAQPPRD LTEAFLAEME KAKGNPESSF NDENLRIVVA 300
    DLFSAGMVTT STTLAWGLLL MILHPDVQRR VQQEIDDVIG QVRRPEMGDQ 350
    AHMPYTTAVI HEVQRFGDIV PLGVTHMTSR DIEVQGFRIP KGTTLITNLS 400
    SVLKDEAVWE KPFRFHPEHF LDAQGHFVKP EAFLPFSAGR RACLGEPLAR 450
    MELFLFFTSL LQHFSFSVPT GQPRPSHHGV FAFLVSPSPY ELCAVPR 497
    Length:497
    Mass (Da):55,769
    Last modified:December 20, 2005 - v2
    Checksum:i542B1D505DF3CDAC
    GO
    Isoform 2 (identifier: P10635-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         118-168: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:446
    Mass (Da):50,061
    Checksum:iD1FB49C5A4B10965
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti374 – 3741V → M in AAA52153. (PubMed:3410476)Curated
    Sequence conflicti374 – 3741V → M in CAA30807. (PubMed:3123997)Curated

    Polymorphismi

    Genetic variations in CYP2D6 are the cause of poor drug metabolism CYP2D6-related [MIMi:608902]. The CYP2D6 gene is highly polymorphic. CYP2D6 activity ranges widely within a population comprising ultrarapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizer phenotypes. UM and PM are those most at risk for treatment failure or dose-dependent drug toxicity, respectively. Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize the antihypersensitive drug debrisoquine and numerous other drugs.
    Allele CYP2D6*7 was also known as CYP2D6E, allele CYP2D6*9 as CYP2D6C, allele CYP2D6*10 as CYP2D6J, allele CYP2D6*17 as CYP2D6Z.
    Isozymes CYP2D6.45 (Lys-155, Cys-296 and Thr-486) and CYP2D6.46 (His-26, Lys-155, Cys-296 and Thr-486) are functional.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti11 – 111V → M in allele CYP2D6*35. 1 Publication
    Corresponds to variant rs769258 [ dbSNP | Ensembl ].
    VAR_008366
    Natural varianti26 – 261R → H in allele CYP2D6*21 and allele CYP2D6*46. 3 Publications
    Corresponds to variant rs28371696 [ dbSNP | Ensembl ].
    VAR_008367
    Natural varianti28 – 281R → C in allele CYP2D6*22.
    VAR_008368
    Natural varianti34 – 341P → S in allele CYP2D6*10 and allele CYP2D6*14; poor debrisquone metabolism. 2 Publications
    Corresponds to variant rs1065852 [ dbSNP | Ensembl ].
    VAR_008336
    Natural varianti42 – 421G → R in allele CYP2D6*12; impaired metabolism of sparteine. 1 Publication
    Corresponds to variant rs5030862 [ dbSNP | Ensembl ].
    VAR_001256
    Natural varianti85 – 851A → V in allele CYP2D6*23.
    VAR_008369
    Natural varianti91 – 911L → M.1 Publication
    Corresponds to variant rs28371703 [ dbSNP | Ensembl ].
    VAR_024720
    Natural varianti94 – 941H → R.1 Publication
    Corresponds to variant rs28371704 [ dbSNP | Ensembl ].
    VAR_024721
    Natural varianti107 – 1071T → I in allele CYP2D6*17; poor debrisquone metabolism. 2 Publications
    Corresponds to variant rs28371706 [ dbSNP | Ensembl ].
    VAR_008337
    Natural varianti120 – 1201F → I.1 Publication
    Corresponds to variant rs1135822 [ dbSNP | Ensembl ].
    VAR_024722
    Natural varianti155 – 1551E → K in allele CYP2D6*45A, allele CYP2D6*45B and allele CYP2D6*46. 2 Publications
    Corresponds to variant rs28371710 [ dbSNP | Ensembl ].
    VAR_024723
    Natural varianti169 – 1691G → R in allele CYP2D6*14; poor debrisquone metabolism. 1 Publication
    VAR_008338
    Natural varianti212 – 2121G → E in allele CYP2D6*6B and allele CYP2D6*6C. 1 Publication
    Corresponds to variant rs5030866 [ dbSNP | Ensembl ].
    VAR_008339
    Natural varianti231 – 2311L → P.
    Corresponds to variant rs17002853 [ dbSNP | Ensembl ].
    VAR_045679
    Natural varianti237 – 2371A → S in allele CYP2D6*33. 1 Publication
    Corresponds to variant rs28371717 [ dbSNP | Ensembl ].
    VAR_008370
    Natural varianti281 – 2811Missing in allele CYP2D6*9. 1 Publication
    VAR_008347
    Natural varianti296 – 2961R → C in allele CYP2D6*2, allele CYP2D6*12, allele CYP2D6*14, allele CYP2D6*17, allele CYP2D6*45A, allele CYP2D6*45B and allele CYP2D6*46. 4 Publications
    Corresponds to variant rs16947 [ dbSNP | Ensembl ].
    VAR_008340
    Natural varianti297 – 2971I → L in allele CYP2D6*24.
    VAR_008371
    Natural varianti300 – 3001A → G.
    Corresponds to variant rs1058170 [ dbSNP | Ensembl ].
    VAR_045680
    Natural varianti311 – 3111S → L.
    Corresponds to variant rs1800754 [ dbSNP | Ensembl ].
    VAR_014633
    Natural varianti324 – 3241H → P in allele CYP2D6*7; loss of activity. 1 Publication
    Corresponds to variant rs5030867 [ dbSNP | Ensembl ].
    VAR_008348
    Natural varianti329 – 3291R → L.
    Corresponds to variant rs3915951 [ dbSNP | Ensembl ].
    VAR_059150
    Natural varianti343 – 3431R → G in allele CYP2D6*25.
    VAR_008372
    Natural varianti365 – 3651R → H.
    Corresponds to variant rs1058172 [ dbSNP | Ensembl ].
    VAR_045681
    Natural varianti369 – 3691I → T in allele CYP2D6*26.
    VAR_008373
    Natural varianti373 – 3731G → S.
    Corresponds to variant rs2856959 [ dbSNP | Ensembl ].
    VAR_059151
    Natural varianti410 – 4101E → K in allele CYP2D6*27.
    VAR_008374
    Natural varianti418 – 4181E → K.1 Publication
    VAR_024724
    Natural varianti469 – 4691P → A.1 Publication
    Corresponds to variant rs1135833 [ dbSNP | Ensembl ].
    VAR_024725
    Natural varianti478 – 4781H → Y.1 Publication
    Corresponds to variant rs28371735 [ dbSNP | Ensembl ].
    VAR_024726
    Natural varianti486 – 4861S → T in allele CYP2D6*2, allele CYP2D6*10, allele CYP2D6*12, allele CYP2D6*14, allele CYP2D6*17, allele CYP2D6*45A, allele CYP2D6*45B and allele CYP2D6*46; impaired metabolism of sparteine. 5 Publications
    Corresponds to variant rs1135840 [ dbSNP | Ensembl ].
    VAR_008341

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei118 – 16851Missing in isoform 2. 1 PublicationVSP_044486Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M20403 mRNA. Translation: AAA52153.1.
    X08006 mRNA. Translation: CAA30807.1.
    M33388 Genomic DNA. Translation: AAA53500.1.
    AY545216 Genomic DNA. Translation: AAS55001.1.
    DQ282144 Genomic DNA. Translation: ABB77895.1.
    DQ282145 Genomic DNA. Translation: ABB77896.1.
    DQ282146 Genomic DNA. Translation: ABB77897.1.
    DQ282151 Genomic DNA. Translation: ABB77899.1.
    DQ282154 Genomic DNA. Translation: ABB77902.1.
    DQ282155 Genomic DNA. Translation: ABB77903.1.
    BX247885 Genomic DNA. Translation: CAP58857.1.
    BC066877 mRNA. Translation: AAH66877.1.
    BC075023 mRNA. Translation: AAH75023.1.
    BC075024 mRNA. Translation: AAH75024.1.
    CCDSiCCDS33657.1. [P10635-2]
    CCDS46721.1. [P10635-1]
    PIRiS01199. O4HUD1.
    RefSeqiNP_000097.3. NM_000106.5. [P10635-1]
    NP_001020332.2. NM_001025161.2. [P10635-2]
    UniGeneiHs.333497.
    Hs.648256.

    Genome annotation databases

    EnsembliENST00000359033; ENSP00000351927; ENSG00000100197.
    GeneIDi1565.
    KEGGihsa:1565.
    UCSCiuc003bce.3. human. [P10635-1]
    uc003bcf.3. human. [P10635-2]

    Polymorphism databases

    DMDMi84028191.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Cytochrome P450 Allele Nomenclature Committee

    CYP2D6 alleles

    Wikipedia

    CYP2D6 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M20403 mRNA. Translation: AAA52153.1 .
    X08006 mRNA. Translation: CAA30807.1 .
    M33388 Genomic DNA. Translation: AAA53500.1 .
    AY545216 Genomic DNA. Translation: AAS55001.1 .
    DQ282144 Genomic DNA. Translation: ABB77895.1 .
    DQ282145 Genomic DNA. Translation: ABB77896.1 .
    DQ282146 Genomic DNA. Translation: ABB77897.1 .
    DQ282151 Genomic DNA. Translation: ABB77899.1 .
    DQ282154 Genomic DNA. Translation: ABB77902.1 .
    DQ282155 Genomic DNA. Translation: ABB77903.1 .
    BX247885 Genomic DNA. Translation: CAP58857.1 .
    BC066877 mRNA. Translation: AAH66877.1 .
    BC075023 mRNA. Translation: AAH75023.1 .
    BC075024 mRNA. Translation: AAH75024.1 .
    CCDSi CCDS33657.1. [P10635-2 ]
    CCDS46721.1. [P10635-1 ]
    PIRi S01199. O4HUD1.
    RefSeqi NP_000097.3. NM_000106.5. [P10635-1 ]
    NP_001020332.2. NM_001025161.2. [P10635-2 ]
    UniGenei Hs.333497.
    Hs.648256.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2F9Q X-ray 3.00 A/B/C/D 34-497 [» ]
    3QM4 X-ray 2.85 A/B 34-497 [» ]
    3TBG X-ray 2.10 A/B/C/D 34-497 [» ]
    3TDA X-ray 2.67 A/B/C/D 34-497 [» ]
    ProteinModelPortali P10635.
    SMRi P10635. Positions 48-497.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000353820.

    Chemistry

    BindingDBi P10635.
    ChEMBLi CHEMBL289.
    DrugBanki DB01193. Acebutolol.
    DB00918. Almotriptan.
    DB00866. Alprenolol.
    DB01118. Amiodarone.
    DB00321. Amitriptyline.
    DB00613. Amodiaquine.
    DB00182. Amphetamine.
    DB01274. Arformoterol.
    DB01238. Aripiprazole.
    DB00335. Atenolol.
    DB00289. Atomoxetine.
    DB00972. Azelastine.
    DB00612. Bisoprolol.
    DB00921. Buprenorphine.
    DB01156. Bupropion.
    DB01197. Captopril.
    DB00521. Carteolol.
    DB01136. Carvedilol.
    DB00482. Celecoxib.
    DB00185. Cevimeline.
    DB01114. Chlorpheniramine.
    DB00477. Chlorpromazine.
    DB00672. Chlorpropamide.
    DB00356. Chlorzoxazone.
    DB01410. Ciclesonide.
    DB00501. Cimetidine.
    DB01012. Cinacalcet.
    DB00215. Citalopram.
    DB01242. Clomipramine.
    DB00575. Clonidine.
    DB00257. Clotrimazole.
    DB00363. Clozapine.
    DB00318. Codeine.
    DB00496. Darifenacin.
    DB04840. Debrisoquin.
    DB00705. Delavirdine.
    DB01151. Desipramine.
    DB00967. Desloratadine.
    DB01191. Dexfenfluramine.
    DB01576. Dextroamphetamine.
    DB00514. Dextromethorphan.
    DB00527. Dibucaine.
    DB00586. Diclofenac.
    DB00343. Diltiazem.
    DB01075. Diphenhydramine.
    DB00757. Dolasetron.
    DB00843. Donepezil.
    DB01142. Doxepin.
    DB00476. Duloxetine.
    DB01228. Encainide.
    DB01175. Escitalopram.
    DB00736. Esomeprazole.
    DB00574. Fenfluramine.
    DB01195. Flecainide.
    DB00623. Fluphenazine.
    DB00176. Fluvoxamine.
    DB00983. Formoterol.
    DB00674. Galantamine.
    DB00317. Gefitinib.
    DB01218. Halofantrine.
    DB00502. Haloperidol.
    DB00956. Hydrocodone.
    DB00327. Hydromorphone.
    DB00557. Hydroxyzine.
    DB00458. Imipramine.
    DB00332. Ipratropium.
    DB01167. Itraconazole.
    DB01026. Ketoconazole.
    DB01210. Levobunolol.
    DB00281. Lidocaine.
    DB00455. Loratadine.
    DB00934. Maprotiline.
    DB00454. Meperidine.
    DB00532. Mephenytoin.
    DB01071. Mequitazine.
    DB00933. Mesoridazine.
    DB01403. Methotrimeprazine.
    DB01233. Metoclopramide.
    DB00264. Metoprolol.
    DB00379. Mexiletine.
    DB06148. Mianserin.
    DB01110. Miconazole.
    DB00683. Midazolam.
    DB00805. Minaprine.
    DB00370. Mirtazapine.
    DB01171. Moclobemide.
    DB00295. Morphine.
    DB01149. Nefazodone.
    DB00622. Nicardipine.
    DB00699. Nicergoline.
    DB01115. Nifedipine.
    DB00540. Nortriptyline.
    DB00904. Ondansetron.
    DB00497. Oxycodone.
    DB01192. Oxymorphone.
    DB01267. Paliperidone.
    DB00377. Palonosetron.
    DB00715. Paroxetine.
    DB01074. Perhexiline.
    DB00850. Perphenazine.
    DB00914. Phenformin.
    DB00830. Phenmetrazine.
    DB00960. Pindolol.
    DB01035. Procainamide.
    DB00433. Prochlorperazine.
    DB01131. Proguanil.
    DB01069. Promethazine.
    DB01182. Propafenone.
    DB00647. Propoxyphene.
    DB00571. Propranolol.
    DB01224. Quetiapine.
    DB00908. Quinidine.
    DB00468. Quinine.
    DB00863. Ranitidine.
    DB00243. Ranolazine.
    DB00234. Reboxetine.
    DB00734. Risperidone.
    DB00503. Ritonavir.
    DB01037. Selegiline.
    DB06144. Sertindole.
    DB01104. Sertraline.
    DB00675. Tamoxifen.
    DB00857. Terbinafine.
    DB00342. Terfenadine.
    DB00679. Thioridazine.
    DB00373. Timolol.
    DB01409. Tiotropium.
    DB01124. Tolbutamide.
    DB01036. Tolterodine.
    DB00193. Tramadol.
    DB00752. Tranylcypromine.
    DB00656. Trazodone.
    DB00726. Trimipramine.
    DB00285. Venlafaxine.
    DB01624. Zuclopenthixol.

    PTM databases

    PhosphoSitei P10635.

    Polymorphism databases

    DMDMi 84028191.

    Proteomic databases

    PaxDbi P10635.
    PRIDEi P10635.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000359033 ; ENSP00000351927 ; ENSG00000100197 .
    GeneIDi 1565.
    KEGGi hsa:1565.
    UCSCi uc003bce.3. human. [P10635-1 ]
    uc003bcf.3. human. [P10635-2 ]

    Organism-specific databases

    CTDi 1565.
    GeneCardsi GC22M042522.
    HGNCi HGNC:2625. CYP2D6.
    HPAi HPA045223.
    MIMi 124030. gene.
    608902. phenotype.
    neXtProti NX_P10635.
    Orphaneti 240847. Amitriptyline toxicity.
    240849. Antipsychotics toxicity.
    240865. Clomipramine toxicity.
    240867. Codeine toxicity.
    240883. Imipramine toxicity.
    240893. Nortriptyline toxicity.
    240931. Resistance to amitriptyline in the treatment of depression.
    240933. Resistance to clomipramine in the treatment of depression.
    240939. Resistance to imipramine in the treatment of depression.
    240941. Resistance to nortripilline in the treatment of depression.
    240947. Resistance to tamoxifene in breast cancer.
    240949. Resistance to trimipramine in the treatment of depression.
    240951. Resistance to venlafaxine in the treatment of depression.
    240957. Susceptibility to adverse reaction due to amitriptyline treatment.
    240959. Susceptibility to adverse reaction due to antipsychotics treatment.
    240965. Susceptibility to adverse reaction due to clomipramine treatment.
    240967. Susceptibility to adverse reaction due to codeine treatment.
    240971. Susceptibility to adverse reaction due to imipramine treatment.
    240979. Susceptibility to adverse reaction due to nortriptyline treatment.
    240987. Susceptibility to adverse reaction due to trimipramine treatment.
    240989. Susceptibility to adverse reaction due to venlafaxine treatment.
    240915. Trimipramine toxicity.
    240919. Venlafaxine toxicity.
    PharmGKBi PA128.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2124.
    HOVERGENi HBG015789.
    KOi K17712.
    PhylomeDBi P10635.
    TreeFami TF352043.

    Enzyme and pathway databases

    Reactomei REACT_13425. Miscellaneous substrates.
    REACT_13543. Xenobiotics.
    REACT_13797. CYP2E1 reactions.
    REACT_13814. Fatty acids.
    SABIO-RK P10635.

    Miscellaneous databases

    EvolutionaryTracei P10635.
    GeneWikii CYP2D6.
    GenomeRNAii 1565.
    NextBioi 6449.
    PROi P10635.
    SOURCEi Search...

    Gene expression databases

    Bgeei P10635.
    CleanExi HS_CYP2D6.
    Genevestigatori P10635.

    Family and domain databases

    Gene3Di 1.10.630.10. 1 hit.
    InterProi IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    IPR008069. Cyt_P450_E_grp-I_CYP2D-like.
    [Graphical view ]
    Pfami PF00067. p450. 1 hit.
    [Graphical view ]
    PRINTSi PR00463. EP450I.
    PR01686. EP450ICYP2D.
    PR00385. P450.
    SUPFAMi SSF48264. SSF48264. 1 hit.
    PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Human debrisoquine 4-hydroxylase (P450IID1): cDNA and deduced amino acid sequence and assignment of the CYP2D locus to chromosome 22."
      Gonzalez F.J., Vilbois F., Hardwick J.P., McBride O.W., Nebert D.W., Gelboin H.V., Meyer U.A.
      Genomics 2:174-179(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Characterization of the common genetic defect in humans deficient in debrisoquine metabolism."
      Gonzalez F.J., Skoda R.C., Kimura S., Umeno M., Zanger U.M., Nebert D.W., Gelboin H.V., Hardwick J.P., Meyer U.A.
      Nature 331:442-446(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Liver.
    3. "The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene."
      Kimura S., Umeno M., Skoda R.C., Meyer U.A., Gonzalez F.J.
      Am. J. Hum. Genet. 45:889-904(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Identification and characterization of novel sequence variations in the cytochrome P4502D6 (CYP2D6) gene in African Americans."
      Gaedigk A., Bhathena A., Ndjountche L., Pearce R.E., Abdel-Rahman S.M., Alander S.W., Bradford L.D., Rogan P.K., Leeder J.S.
      Pharmacogenomics J. 5:173-182(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE CYP2D6*1), IDENTIFICATION OF ALLELES CYP2D6*41B; CYP2D6*45A; CYP2D6*45B AND CYP2D6*46, VARIANTS HIS-26; LYS-155; CYS-296 AND THR-486, CHARACTERIZATION OF ISOZYMES CYP2D6.45 AND CYP2D6.46.
    5. "CYP2D6 evolution and allele diversity among human races."
      Koch W.H., Nikoloff D.M., Lu W., Pan R.M., deLeon J., Wedlund P.J.
      Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-26.
    6. "The DNA sequence of human chromosome 22."
      Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M.
      , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
      Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS CYS-296 AND THR-486.
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS CYS-296 AND THR-486.
    8. Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-497 IN COMPLEX WITH HEME, FUNCTION.
    9. "Identification of a new variant CYP2D6 allele lacking the codon encoding Lys-281: possible association with the poor metabolizer phenotype."
      Tyndale R., Aoyama T., Broly F., Matsunaga T., Inaba T., Kalow W., Gelboin H.V., Meyer U.A., Gonzalez F.J.
      Pharmacogenetics 1:26-32(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CYP2D6*9 LYS-281 DEL.
    10. "Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese population associated with lower in vivo rates of sparteine metabolism."
      Yokota H., Tamura S., Furuya H., Kimura S., Watanabe M., Kanazawa I., Kondo I., Gonzalez F.J.
      Pharmacogenetics 3:256-263(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CYP2D6*10 SER-34 AND THR-486.
    11. "A missense mutation in exon 6 of the CYP2D6 gene leading to a histidine 324 to proline exchange is associated with the poor metabolizer phenotype of sparteine."
      Evert B., Griese E.U., Eichelbaum M.
      Naunyn Schmiedebergs Arch. Pharmacol. 350:434-439(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CYP2D6*7 PRO-324.
    12. "An inactive cytochrome P450 CYP2D6 allele containing a deletion and a base substitution."
      Daly A.K., Leathart J.B., London S.J., Idle J.R.
      Hum. Genet. 95:337-341(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CYP2D6*6B/6C GLU-212.
    13. "A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity."
      Masimirembwa C., Persson I., Bertilsson L., Hasler J., Ingelman-Sundberg M.
      Br. J. Clin. Pharmacol. 42:713-719(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CYP2D6*17 ILE-107.
    14. "An additional allelic variant of the CYP2D6 gene causing impaired metabolism of sparteine."
      Marez D., Legrand M., Sabbagh N., Lo-Guidice J.-M., Boone P., Broly F.
      Hum. Genet. 97:668-670(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CYP2D6*12 ARG-42.
    15. "Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution."
      Marez D., Legrand M., Sabbagh N., Guidice J.M., Spire C., Lafitte J.J., Meyer U.A., Broly F.
      Pharmacogenetics 7:193-202(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS.
    16. "G169R mutation diminishes the metabolic activity of CYP2D6 in Chinese."
      Wang S.L., Lai M.D., Huang J.D.
      Drug Metab. Dispos. 27:385-388(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CYP2D6*14 ARG-169.
    17. "Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population."
      Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q., McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.
      Pharmacogenomics 5:895-931(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MET-11; HIS-26; SER-34; MET-91; ARG-94; ILE-107; ILE-120; LYS-155; SER-237; CYS-296; LYS-418; ALA-469; TYR-478 AND THR-486.

    Entry informationi

    Entry nameiCP2D6_HUMAN
    AccessioniPrimary (citable) accession number: P10635
    Secondary accession number(s): Q16752
    , Q2XND6, Q2XND7, Q2XNE0, Q6B012, Q6NXU8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: December 20, 2005
    Last modified: October 1, 2014
    This is version 163 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 22
      Human chromosome 22: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3