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P11712

- CP2C9_HUMAN

UniProt

P11712 - CP2C9_HUMAN

Protein

Cytochrome P450 2C9

Gene

CYP2C9

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 167 (01 Oct 2014)
      Sequence version 3 (30 May 2000)
      Previous versions | rss
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    Functioni

    Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.

    Catalytic activityi

    +-(R)-limonene + NADPH + O2 = (+)-trans-carveol + NADP+ + H2O.
    --(S)-limonene + NADPH + O2 = (-)-trans-carveol + NADP+ + H2O.
    --(S)-limonene + NADPH + O2 = (-)-perillyl alcohol + NADP+ + H2O.

    Cofactori

    Heme group.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi435 – 4351Iron (heme axial ligand)

    GO - Molecular functioni

    1. (R)-limonene 6-monooxygenase activity Source: UniProtKB-EC
    2. (S)-limonene 6-monooxygenase activity Source: UniProtKB-EC
    3. (S)-limonene 7-monooxygenase activity Source: UniProtKB-EC
    4. caffeine oxidase activity Source: BHF-UCL
    5. drug binding Source: BHF-UCL
    6. heme binding Source: InterPro
    7. iron ion binding Source: InterPro
    8. monooxygenase activity Source: UniProtKB
    9. oxidoreductase activity Source: BHF-UCL
    10. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen Source: InterPro
    11. steroid hydroxylase activity Source: BHF-UCL

    GO - Biological processi

    1. arachidonic acid metabolic process Source: Reactome
    2. cellular amide metabolic process Source: BHF-UCL
    3. drug catabolic process Source: BHF-UCL
    4. drug metabolic process Source: UniProtKB
    5. epoxygenase P450 pathway Source: Reactome
    6. exogenous drug catabolic process Source: BHF-UCL
    7. monocarboxylic acid metabolic process Source: BHF-UCL
    8. monoterpenoid metabolic process Source: BHF-UCL
    9. omega-hydroxylase P450 pathway Source: Reactome
    10. oxidation-reduction process Source: BHF-UCL
    11. oxidative demethylation Source: BHF-UCL
    12. small molecule metabolic process Source: Reactome
    13. steroid metabolic process Source: BHF-UCL
    14. urea metabolic process Source: BHF-UCL
    15. xenobiotic metabolic process Source: Reactome

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding, NADP

    Enzyme and pathway databases

    ReactomeiREACT_13543. Xenobiotics.
    REACT_13797. CYP2E1 reactions.
    REACT_150134. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
    REACT_150417. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
    SABIO-RKP11712.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 2C9 (EC:1.14.13.-)
    Alternative name(s):
    (R)-limonene 6-monooxygenase (EC:1.14.13.80)
    (S)-limonene 6-monooxygenase (EC:1.14.13.48)
    (S)-limonene 7-monooxygenase (EC:1.14.13.49)
    CYPIIC9
    Cytochrome P-450MP
    Cytochrome P450 MP-4
    Cytochrome P450 MP-8
    Cytochrome P450 PB-1
    S-mephenytoin 4-hydroxylase
    Gene namesi
    Name:CYP2C9
    Synonyms:CYP2C10
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:2623. CYP2C9.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: Reactome
    2. intracellular membrane-bounded organelle Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    Orphaneti240843. Acenocoumarol toxicity.
    240859. Carbutamide toxicity.
    240873. Fluindione toxicity.
    240875. Glibenclamide toxicity.
    240877. Gliclazide toxicity.
    240879. Glimepiride toxicity.
    240881. Glipizide toxicity.
    240897. Phenprocoumon toxicity.
    240991. Susceptibility to bleeding due to acenocoumarol treatment.
    240993. Susceptibility to bleeding due to fluindione treatment.
    240995. Susceptibility to bleeding due to phenprocoumon treatment.
    240997. Susceptibility to bleeding due to warfarine treatment.
    241007. Susceptibility to hypoglycemia due to carbutamide treatment.
    241009. Susceptibility to hypoglycemia due to glibenclamide treatment.
    241011. Susceptibility to hypoglycemia due to gliclazide treatment.
    241013. Susceptibility to hypoglycemia due to glimepiride treatment.
    241015. Susceptibility to hypoglycemia due to glipizide treatment.
    241045. Warfarine dose selection in the treatment of venous thrombosis and atrial fibrillation.
    240923. Warfarine toxicity.
    PharmGKBiPA126.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 490490Cytochrome P450 2C9PRO_0000051700Add
    BLAST

    Proteomic databases

    PaxDbiP11712.
    PRIDEiP11712.

    PTM databases

    PhosphoSiteiP11712.

    Expressioni

    Inductioni

    By rifampicin.

    Gene expression databases

    ArrayExpressiP11712.
    BgeeiP11712.
    CleanExiHS_CYP2C9.
    GenevestigatoriP11712.

    Organism-specific databases

    HPAiCAB016123.
    HPA015066.

    Interactioni

    Protein-protein interaction databases

    BioGridi107937. 9 interactions.
    IntActiP11712. 6 interactions.
    STRINGi9606.ENSP00000260682.

    Structurei

    Secondary structure

    1
    490
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi33 – 353
    Turni37 – 393
    Helixi42 – 454
    Helixi47 – 6115
    Beta strandi63 – 719
    Beta strandi73 – 775
    Helixi80 – 878
    Turni88 – 947
    Turni105 – 1073
    Beta strandi111 – 1144
    Helixi117 – 13115
    Beta strandi134 – 1363
    Helixi141 – 15717
    Turni158 – 1614
    Helixi167 – 18317
    Helixi192 – 20817
    Helixi213 – 2186
    Helixi222 – 2254
    Helixi230 – 25324
    Helixi263 – 27412
    Beta strandi275 – 2773
    Helixi284 – 31532
    Helixi317 – 33014
    Beta strandi333 – 3353
    Helixi339 – 3446
    Helixi346 – 35914
    Beta strandi374 – 3763
    Beta strandi379 – 3813
    Beta strandi386 – 3894
    Helixi392 – 3954
    Turni398 – 4003
    Beta strandi401 – 4033
    Helixi409 – 4124
    Beta strandi415 – 4173
    Helixi431 – 4333
    Helixi438 – 45518
    Beta strandi456 – 4627
    Helixi464 – 4663
    Beta strandi475 – 4773
    Beta strandi485 – 4895

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1OG2X-ray2.60A/B30-490[»]
    1OG5X-ray2.55A/B30-490[»]
    1R9OX-ray2.00A18-490[»]
    ProteinModelPortaliP11712.
    SMRiP11712. Positions 44-490.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11712.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiCOG2124.
    HOGENOMiHOG000036992.
    HOVERGENiHBG015789.
    InParanoidiP11712.
    KOiK17719.
    OMAiNVAFMKS.
    OrthoDBiEOG7RBZ85.
    PhylomeDBiP11712.
    TreeFamiTF352043.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    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: P11712-1) [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

    MDSLVVLVLC LSCLLLLSLW RQSSGRGKLP PGPTPLPVIG NILQIGIKDI    50
    SKSLTNLSKV YGPVFTLYFG LKPIVVLHGY EAVKEALIDL GEEFSGRGIF 100
    PLAERANRGF GIVFSNGKKW KEIRRFSLMT LRNFGMGKRS IEDRVQEEAR 150
    CLVEELRKTK ASPCDPTFIL GCAPCNVICS IIFHKRFDYK DQQFLNLMEK 200
    LNENIKILSS PWIQICNNFS PIIDYFPGTH NKLLKNVAFM KSYILEKVKE 250
    HQESMDMNNP QDFIDCFLMK MEKEKHNQPS EFTIESLENT AVDLFGAGTE 300
    TTSTTLRYAL LLLLKHPEVT AKVQEEIERV IGRNRSPCMQ DRSHMPYTDA 350
    VVHEVQRYID LLPTSLPHAV TCDIKFRNYL IPKGTTILIS LTSVLHDNKE 400
    FPNPEMFDPH HFLDEGGNFK KSKYFMPFSA GKRICVGEAL AGMELFLFLT 450
    SILQNFNLKS LVDPKNLDTT PVVNGFASVP PFYQLCFIPV 490
    Length:490
    Mass (Da):55,628
    Last modified:May 30, 2000 - v3
    Checksum:i4FDFC395303A4E3E
    GO
    Isoform 2 (identifier: P11712-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         161-162: AS → GG
         163-490: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:162
    Mass (Da):18,005
    Checksum:iB59C8888ED45AD09
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti4 – 41L → I no nucleotide entry (PubMed:3697070)Curated
    Sequence conflicti6 – 61V → S no nucleotide entry (PubMed:3697070)Curated
    Sequence conflicti14 – 141L → M in AAB23864. (PubMed:1445376)Curated
    Sequence conflicti175 – 1751C → Y no nucleotide entry (PubMed:2827463)Curated
    Sequence conflicti239 – 2391F → L no nucleotide entry (PubMed:2827463)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti19 – 191L → I in allele CYP2C9*7.
    VAR_018862
    Natural varianti144 – 1441R → C in allele CYP2C9*2. 7 Publications
    Corresponds to variant rs1799853 [ dbSNP | Ensembl ].
    VAR_008343
    Natural varianti150 – 1501R → H in allele CYP2C9*8. 2 Publications
    Corresponds to variant rs7900194 [ dbSNP | Ensembl ].
    VAR_018863
    Natural varianti251 – 2511H → R in allele CYP2C9*9. 2 Publications
    Corresponds to variant rs2256871 [ dbSNP | Ensembl ].
    VAR_018864
    Natural varianti272 – 2721E → G in allele CYP2C9*10. 1 Publication
    Corresponds to variant rs9332130 [ dbSNP | Ensembl ].
    VAR_018865
    Natural varianti335 – 3351R → W in allele CYP2C9*11. 2 Publications
    Corresponds to variant rs28371685 [ dbSNP | Ensembl ].
    VAR_018866
    Natural varianti358 – 3581Y → C.3 Publications
    Corresponds to variant rs1057909 [ dbSNP | Ensembl ].
    VAR_008344
    Natural varianti359 – 3591I → L in allele CYP2C9*3; responsible for the tolbutamide poor metabolizer phenotype. 4 Publications
    Corresponds to variant rs1057910 [ dbSNP | Ensembl ].
    VAR_008345
    Natural varianti359 – 3591I → T in allele CYP2C9*4. 1 Publication
    Corresponds to variant rs56165452 [ dbSNP | Ensembl ].
    VAR_013515
    Natural varianti360 – 3601D → E in allele CYP2C9*5; increases the K(m) value for substrates tested. 2 Publications
    Corresponds to variant rs28371686 [ dbSNP | Ensembl ].
    VAR_013516
    Natural varianti413 – 4131L → P.1 Publication
    Corresponds to variant rs28371687 [ dbSNP | Ensembl ].
    VAR_024717
    Natural varianti417 – 4171G → D.3 Publications
    VAR_008346
    Natural varianti489 – 4891P → S in allele CYP2C9*12. 1 Publication
    Corresponds to variant rs9332239 [ dbSNP | Ensembl ].
    VAR_018867

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei161 – 1622AS → GG in isoform 2. 1 PublicationVSP_055573
    Alternative sequencei163 – 490328Missing in isoform 2. 1 PublicationVSP_055574Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY341248 Genomic DNA. Translation: AAP88931.1.
    AY702706 Genomic DNA. Translation: AAT94065.1.
    AK289420 mRNA. Translation: BAF82109.1.
    AL359672 Genomic DNA. Translation: CAH71303.1.
    CH471066 Genomic DNA. Translation: EAW50019.1.
    CH471066 Genomic DNA. Translation: EAW50020.1.
    BC020754 mRNA. Translation: AAH20754.1.
    BC070317 mRNA. Translation: AAH70317.1.
    BC125054 mRNA. Translation: AAI25055.1.
    D00173 mRNA. Translation: BAA00123.1.
    M15331 mRNA. Translation: AAA52157.1.
    M21939 mRNA. Translation: AAA52158.1.
    M21940 mRNA. Translation: AAA52159.1.
    S46963 mRNA. Translation: AAB23864.2. Sequence problems.
    CCDSiCCDS7437.1.
    PIRiB38462.
    D28951.
    RefSeqiNP_000762.2. NM_000771.3.
    UniGeneiHs.282624.

    Genome annotation databases

    EnsembliENST00000260682; ENSP00000260682; ENSG00000138109. [P11712-1]
    GeneIDi1559.
    KEGGihsa:1559.
    UCSCiuc001kka.4. human.

    Polymorphism databases

    DMDMi6686268.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Cytochrome P450 Allele Nomenclature Committee

    CYP2C9 alleles

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY341248 Genomic DNA. Translation: AAP88931.1 .
    AY702706 Genomic DNA. Translation: AAT94065.1 .
    AK289420 mRNA. Translation: BAF82109.1 .
    AL359672 Genomic DNA. Translation: CAH71303.1 .
    CH471066 Genomic DNA. Translation: EAW50019.1 .
    CH471066 Genomic DNA. Translation: EAW50020.1 .
    BC020754 mRNA. Translation: AAH20754.1 .
    BC070317 mRNA. Translation: AAH70317.1 .
    BC125054 mRNA. Translation: AAI25055.1 .
    D00173 mRNA. Translation: BAA00123.1 .
    M15331 mRNA. Translation: AAA52157.1 .
    M21939 mRNA. Translation: AAA52158.1 .
    M21940 mRNA. Translation: AAA52159.1 .
    S46963 mRNA. Translation: AAB23864.2 . Sequence problems.
    CCDSi CCDS7437.1.
    PIRi B38462.
    D28951.
    RefSeqi NP_000762.2. NM_000771.3.
    UniGenei Hs.282624.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1OG2 X-ray 2.60 A/B 30-490 [» ]
    1OG5 X-ray 2.55 A/B 30-490 [» ]
    1R9O X-ray 2.00 A 18-490 [» ]
    ProteinModelPortali P11712.
    SMRi P11712. Positions 44-490.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107937. 9 interactions.
    IntActi P11712. 6 interactions.
    STRINGi 9606.ENSP00000260682.

    Chemistry

    BindingDBi P11712.
    ChEMBLi CHEMBL3397.
    DrugBanki DB01418. Acenocoumarol.
    DB00969. Alosetron.
    DB01118. Amiodarone.
    DB00025. Antihemophilic Factor.
    DB00673. Aprepitant.
    DB00559. Bosentan.
    DB00821. Carprofen.
    DB01136. Carvedilol.
    DB00482. Celecoxib.
    DB01242. Clomipramine.
    DB00250. Dapsone.
    DB00705. Delavirdine.
    DB00967. Desloratadine.
    DB00304. Desogestrel.
    DB00586. Diclofenac.
    DB00736. Esomeprazole.
    DB00749. Etodolac.
    DB00196. Fluconazole.
    DB00472. Fluoxetine.
    DB00712. Flurbiprofen.
    DB01095. Fluvastatin.
    DB00176. Fluvoxamine.
    DB00983. Formoterol.
    DB01241. Gemfibrozil.
    DB01381. Ginkgo biloba.
    DB01016. Glibenclamide.
    DB00222. Glimepiride.
    DB01067. Glipizide.
    DB01018. Guanfacine.
    DB00327. Hydromorphone.
    DB01050. Ibuprofen.
    DB00458. Imipramine.
    DB01029. Irbesartan.
    DB01026. Ketoconazole.
    DB00448. Lansoprazole.
    DB00678. Losartan.
    DB01283. Lumiracoxib.
    DB00470. Marinol.
    DB00784. Mefenamic acid.
    DB00814. Meloxicam.
    DB00532. Mephenytoin.
    DB00916. Metronidazole.
    DB01110. Miconazole.
    DB00683. Midazolam.
    DB00471. Montelukast.
    DB00731. Nateglinide.
    DB00220. Nelfinavir.
    DB00622. Nicardipine.
    DB01192. Oxymorphone.
    DB00213. Pantoprazole.
    DB00617. Paramethadione.
    DB00946. Phenprocoumon.
    DB00252. Phenytoin.
    DB00175. Pravastatin.
    DB00908. Quinidine.
    DB00503. Ritonavir.
    DB00412. Rosiglitazone.
    DB01104. Sertraline.
    DB00203. Sildenafil.
    DB01015. Sulfamethoxazole.
    DB00870. Suprofen.
    DB00675. Tamoxifen.
    DB00469. Tenoxicam.
    DB00342. Terfenadine.
    DB01124. Tolbutamide.
    DB00214. Torasemide.
    DB01361. Troleandomycin.
    DB00580. Valdecoxib.
    DB00177. Valsartan.
    DB00582. Voriconazole.
    DB00682. Warfarin.
    DB00549. Zafirlukast.
    DB00744. Zileuton.

    PTM databases

    PhosphoSitei P11712.

    Polymorphism databases

    DMDMi 6686268.

    Proteomic databases

    PaxDbi P11712.
    PRIDEi P11712.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000260682 ; ENSP00000260682 ; ENSG00000138109 . [P11712-1 ]
    GeneIDi 1559.
    KEGGi hsa:1559.
    UCSCi uc001kka.4. human.

    Organism-specific databases

    CTDi 1559.
    GeneCardsi GC10P096688.
    HGNCi HGNC:2623. CYP2C9.
    HPAi CAB016123.
    HPA015066.
    MIMi 601130. gene.
    neXtProti NX_P11712.
    Orphaneti 240843. Acenocoumarol toxicity.
    240859. Carbutamide toxicity.
    240873. Fluindione toxicity.
    240875. Glibenclamide toxicity.
    240877. Gliclazide toxicity.
    240879. Glimepiride toxicity.
    240881. Glipizide toxicity.
    240897. Phenprocoumon toxicity.
    240991. Susceptibility to bleeding due to acenocoumarol treatment.
    240993. Susceptibility to bleeding due to fluindione treatment.
    240995. Susceptibility to bleeding due to phenprocoumon treatment.
    240997. Susceptibility to bleeding due to warfarine treatment.
    241007. Susceptibility to hypoglycemia due to carbutamide treatment.
    241009. Susceptibility to hypoglycemia due to glibenclamide treatment.
    241011. Susceptibility to hypoglycemia due to gliclazide treatment.
    241013. Susceptibility to hypoglycemia due to glimepiride treatment.
    241015. Susceptibility to hypoglycemia due to glipizide treatment.
    241045. Warfarine dose selection in the treatment of venous thrombosis and atrial fibrillation.
    240923. Warfarine toxicity.
    PharmGKBi PA126.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2124.
    HOGENOMi HOG000036992.
    HOVERGENi HBG015789.
    InParanoidi P11712.
    KOi K17719.
    OMAi NVAFMKS.
    OrthoDBi EOG7RBZ85.
    PhylomeDBi P11712.
    TreeFami TF352043.

    Enzyme and pathway databases

    Reactomei REACT_13543. Xenobiotics.
    REACT_13797. CYP2E1 reactions.
    REACT_150134. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
    REACT_150417. Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
    SABIO-RK P11712.

    Miscellaneous databases

    ChiTaRSi CYP2C9. human.
    EvolutionaryTracei P11712.
    GeneWikii CYP2C9.
    GenomeRNAii 1559.
    NextBioi 6438.
    PROi P11712.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P11712.
    Bgeei P11712.
    CleanExi HS_CYP2C9.
    Genevestigatori P11712.

    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.
    [Graphical view ]
    Pfami PF00067. p450. 1 hit.
    [Graphical view ]
    PRINTSi PR00463. EP450I.
    PR00385. P450.
    SUPFAMi SSF48264. SSF48264. 1 hit.
    PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Human cytochrome P-450 PB-1: a multigene family involved in mephenytoin and steroid oxidations that maps to chromosome 10."
      Meehan R.R., Gosden J.R., Rout D., Hastie N.D., Friedberg T., Adesnik M., Buckland R., van Heyningen V., Fletcher J.M., Spurr N.K., Sweeney J., Wolf C.R.
      Am. J. Hum. Genet. 42:26-37(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT CYS-144.
    2. "cDNA and amino acid sequences of two members of the human P450IIC gene subfamily."
      Kimura S., Pastewka J., Gelboin H.V., Gonzalez F.J.
      Nucleic Acids Res. 15:10053-10054(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT CYS-144.
    3. NIEHS SNPs program
      Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-144; HIS-150; ARG-251; GLY-272; LEU-359 AND SER-489.
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Mammary gland.
    5. "The DNA sequence and comparative analysis of human chromosome 10."
      Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
      , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
      Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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), VARIANT CYS-144.
      Tissue: Liver.
    8. "Nucleotide sequence of a human liver cytochrome P-450 related to the rat male specific form."
      Yasumori T., Kawano S., Nagata K., Shimada M., Yamazoe Y., Kato R.
      J. Biochem. 102:1075-1082(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-490 (ISOFORM 1).
      Tissue: Liver.
    9. "Cloning and sequence determination of a complementary DNA related to human liver microsomal cytochrome P-450 S-mephenytoin 4-hydroxylase."
      Umbenhauer D.R., Martin M.V., Lloyd R.S., Guengerich F.P.
      Biochemistry 26:1094-1099(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-490 (ISOFORM 1), VARIANTS CYS-358 AND ASP-417.
      Tissue: Liver.
    10. "Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxylase."
      Ged C., Umbenhauer D.R., Bellew T.M., Bork R.W., Srivastava P.K., Shinriki N., Lloyd R.S., Guengerich F.P.
      Biochemistry 27:6929-6940(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-490 (ISOFORM 1), VARIANTS CYS-358 AND ASP-417.
    11. "Six-base deletion occurring in messages of human cytochrome P-450 in the CYP2C subfamily results in reduction of tolbutamide hydroxylase activity."
      Ohgiya S., Komori M., Ohi H., Shiramatsu K., Shinriki N., Kamataki T.
      Biochem. Int. 27:1073-1081(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-490 (ISOFORM 1).
    12. "Human liver microsomal cytochrome P-450 mephenytoin 4-hydroxylase, a prototype of genetic polymorphism in oxidative drug metabolism. Purification and characterization of two similar forms involved in the reaction."
      Shimada T., Misono K.S., Guengerich F.P.
      J. Biol. Chem. 261:909-921(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-29, CHARACTERIZATION.
    13. "Cytochrome P-450 in human liver microsomes: high-performance liquid chromatographic isolation of three forms and their characterization."
      Komori M., Hashizume T., Ohi H., Miura T., Kitada M., Nagashima K., Kamataki T.
      J. Biochem. 104:912-916(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-25.
    14. "Separation of human liver microsomal tolbutamide hydroxylase and (S)-mephenytoin 4'-hydroxylase cytochrome P-450 enzymes."
      Srivastava P.K., Yun C.H., Beaune P.H., Ged C., Guengerich F.P.
      Mol. Pharmacol. 40:69-79(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL PROTEIN SEQUENCE.
    15. "Allelic variants of human cytochrome P450 2C9: baculovirus-mediated expression, purification, structural characterization, substrate stereoselectivity, and prochiral selectivity of the wild-type and I359L mutant forms."
      Haining R.L., Hunter A.P., Veronese M.E., Trager W.F., Rettie A.E.
      Arch. Biochem. Biophys. 333:447-458(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-9; 21-157; 169-249; 264-424; 426-476 AND 484-487.
    16. "Expression of modified cytochrome P450 2C10 (2C9) in Escherichia coli, purification, and reconstitution of catalytic activity."
      Sandhu P., Baba T., Guengerich F.P.
      Arch. Biochem. Biophys. 306:443-450(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-20.
    17. "Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes."
      Miyazawa M., Shindo M., Shimada T.
      Drug Metab. Dispos. 30:602-607(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION.
    18. "Crystal structure of human cytochrome P450 2C9 with bound warfarin."
      Williams P.A., Cosme J., Ward A., Angove H.C., Matak-Vinkovic D., Jhoti H.
      Nature 424:464-468(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 30-490.
    19. "Genetic analysis of the human cytochrome P450 CYP2C9 locus."
      Stubbins M.J., Harries L.W., Smith G., Tarbit M.H., Wolf C.R.
      Pharmacogenetics 6:429-439(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CYP2C9*2 CYS-144 AND CYP2C9*3 LEU-359.
    20. "Allelic and functional variability of cytochrome P4502C9."
      Bhasker C.R., Miners J.O., Coulter S., Birkett D.J.
      Pharmacogenetics 7:51-58(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CYP2C9*2 CYS-144; CYS-358; CYP2C9*3 LEU-359 AND ASP-417.
    21. "Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients: genetic analysis of the CYP2C9 locus."
      Imai J., Ieiri I., Mamiya K., Miyahara S., Furuumi H., Nanba E., Yamane M., Fukumaki Y., Ninomiya H., Tashiro N., Otsubo K., Higuchi S.
      Pharmacogenetics 10:85-89(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CYP2C9*4 THR-359.
    22. "Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African Americans."
      Dickmann L.J., Rettie A.E., Kneller M.B., Kim R.B., Wood A.J., Stein C.M., Wilkinson G.R., Schwarz U.I.
      Mol. Pharmacol. 60:382-387(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CYP2C9*5 GLU-360.
    23. "Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy."
      Higashi M.K., Veenstra D.L., Kondo L.M., Wittkowsky A.K., Srinouanprachanh S.L., Farin F.M., Rettie A.E.
      JAMA 287:1690-1698(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CYP2C9*11 TRP-335.
    24. "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 CYS-144; HIS-150; ARG-251; TRP-335; LEU-359; GLU-360 AND PRO-413.

    Entry informationi

    Entry nameiCP2C9_HUMAN
    AccessioniPrimary (citable) accession number: P11712
    Secondary accession number(s): P11713
    , Q16756, Q16872, Q5VX92, Q6IRV8, Q8WW80
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: May 30, 2000
    Last modified: October 1, 2014
    This is version 167 of the entry and version 3 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, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: 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