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P10632

- CP2C8_HUMAN

UniProt

P10632 - CP2C8_HUMAN

Protein

Cytochrome P450 2C8

Gene

CYP2C8

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 2 (01 Nov 1990)
      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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).1 Publication

    Catalytic activityi

    RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.1 Publication

    Cofactori

    Heme group.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei100 – 1001Substrate
    Binding sitei204 – 2041Substrate
    Binding sitei241 – 2411Substrate
    Metal bindingi435 – 4351Iron (heme axial ligand)

    GO - Molecular functioni

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

    GO - Biological processi

    1. arachidonic acid metabolic process Source: Reactome
    2. drug metabolic process Source: BHF-UCL
    3. epoxygenase P450 pathway Source: Reactome
    4. exogenous drug catabolic process Source: BHF-UCL
    5. omega-hydroxylase P450 pathway Source: Reactome
    6. organic acid metabolic process Source: BHF-UCL
    7. oxidation-reduction process Source: BHF-UCL
    8. oxidative demethylation Source: BHF-UCL
    9. small molecule metabolic process Source: Reactome
    10. xenobiotic metabolic process Source: Reactome

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    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-RKP10632.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 2C8 (EC:1.14.14.1)
    Alternative name(s):
    CYPIIC8
    Cytochrome P450 IIC2
    Cytochrome P450 MP-12
    Cytochrome P450 MP-20
    Cytochrome P450 form 1
    S-mephenytoin 4-hydroxylase
    Gene namesi
    Name:CYP2C8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:2622. CYP2C8.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: Reactome

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    MIMi601129. gene+phenotype.
    PharmGKBiPA125.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 490490Cytochrome P450 2C8PRO_0000051699Add
    BLAST

    Proteomic databases

    PaxDbiP10632.
    PRIDEiP10632.

    PTM databases

    PhosphoSiteiP10632.

    Expressioni

    Inductioni

    By phenobarbital.

    Gene expression databases

    ArrayExpressiP10632.
    BgeeiP10632.
    CleanExiHS_CYP2C8.
    GenevestigatoriP10632.

    Organism-specific databases

    HPAiHPA013547.
    HPA013970.
    HPA015066.

    Interactioni

    Protein-protein interaction databases

    BioGridi107936. 12 interactions.
    IntActiP10632. 9 interactions.
    STRINGi9606.ENSP00000360317.

    Structurei

    Secondary structure

    1
    490
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni37 – 393
    Helixi42 – 443
    Beta strandi47 – 493
    Helixi50 – 6112
    Beta strandi63 – 697
    Beta strandi72 – 776
    Helixi80 – 878
    Turni88 – 947
    Helixi101 – 1077
    Turni111 – 1133
    Helixi117 – 13014
    Turni133 – 1364
    Beta strandi137 – 1393
    Helixi141 – 15717
    Turni158 – 1614
    Helixi167 – 18216
    Beta strandi183 – 1853
    Helixi192 – 20817
    Helixi212 – 2187
    Helixi220 – 2256
    Helixi227 – 25226
    Helixi263 – 27311
    Helixi284 – 29815
    Helixi300 – 31516
    Helixi317 – 33014
    Beta strandi333 – 3353
    Helixi339 – 3446
    Helixi346 – 35914
    Beta strandi374 – 3763
    Beta strandi379 – 3813
    Beta strandi386 – 3894
    Helixi391 – 3955
    Turni398 – 4003
    Beta strandi401 – 4033
    Helixi409 – 4124
    Helixi431 – 4333
    Helixi438 – 45518
    Beta strandi456 – 4594
    Helixi464 – 4663
    Beta strandi472 – 4798
    Beta strandi485 – 4895

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1PQ2X-ray2.70A/B19-490[»]
    2NNHX-ray2.60A/B28-490[»]
    2NNIX-ray2.80A28-490[»]
    2NNJX-ray2.28A28-490[»]
    2VN0X-ray2.70A28-490[»]
    ProteinModelPortaliP10632.
    SMRiP10632. Positions 28-490.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP10632.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiCOG2124.
    HOGENOMiHOG000036992.
    HOVERGENiHBG015789.
    InParanoidiP10632.
    KOiK17718.
    OMAiMLQIDIK.
    PhylomeDBiP10632.
    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: P10632-1) [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

    MEPFVVLVLC LSFMLLFSLW RQSCRRRKLP PGPTPLPIIG NMLQIDVKDI    50
    CKSFTNFSKV YGPVFTVYFG MNPIVVFHGY EAVKEALIDN GEEFSGRGNS 100
    PISQRITKGL GIISSNGKRW KEIRRFSLTT LRNFGMGKRS IEDRVQEEAH 150
    CLVEELRKTK ASPCDPTFIL GCAPCNVICS VVFQKRFDYK DQNFLTLMKR 200
    FNENFRILNS PWIQVCNNFP LLIDCFPGTH NKVLKNVALT RSYIREKVKE 250
    HQASLDVNNP RDFIDCFLIK MEQEKDNQKS EFNIENLVGT VADLFVAGTE 300
    TTSTTLRYGL LLLLKHPEVT AKVQEEIDHV IGRHRSPCMQ DRSHMPYTDA 350
    VVHEIQRYSD LVPTGVPHAV TTDTKFRNYL IPKGTTIMAL LTSVLHDDKE 400
    FPNPNIFDPG HFLDKNGNFK KSDYFMPFSA GKRICAGEGL ARMELFLFLT 450
    TILQNFNLKS VDDLKNLNTT AVTKGIVSLP PSYQICFIPV 490
    Length:490
    Mass (Da):55,825
    Last modified:November 1, 1990 - v2
    Checksum:iE920EB2084F477E1
    GO
    Isoform 2 (identifier: P10632-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-8: MEPFVVLV → MFLQPIAK
         9-110: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:388
    Mass (Da):44,358
    Checksum:i0A9312FD6D4B9634
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti54 – 541F → L no nucleotide entry (PubMed:2729895)Curated
    Sequence conflicti67 – 671V → L no nucleotide entry (PubMed:2729895)Curated
    Sequence conflicti76 – 761V → C no nucleotide entry (PubMed:2729895)Curated
    Sequence conflicti82 – 821A → S in AAH20596. (PubMed:15489334)Curated
    Sequence conflicti130 – 1301T → N in AAA35739. (PubMed:3500169)Curated
    Sequence conflicti130 – 1301T → N in AAA35740. (PubMed:3500169)Curated
    Sequence conflicti130 – 1301T → N no nucleotide entry (PubMed:2009263)Curated
    Sequence conflicti209 – 2091N → S no nucleotide entry (PubMed:2729895)Curated
    Sequence conflicti384 – 39310GTTIMALLTS → SFDNKIMLAA in AAA35740. (PubMed:3500169)Curated
    Sequence conflicti386 – 3861T → A in BAF85442. (PubMed:14702039)Curated

    Polymorphismi

    CYP2C8 genetic variations may be associated with adverse effects of cerivastatin including acute rhabdomyolysis [MIMi:601129].

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti139 – 1391R → K in allele CYP2C8*3. 6 Publications
    Corresponds to variant rs11572080 [ dbSNP | Ensembl ].
    VAR_012238
    Natural varianti154 – 1541E → D in clone MP-12. 1 Publication
    VAR_001250
    Natural varianti193 – 1931N → K in MP-20. 1 Publication
    VAR_001251
    Natural varianti244 – 2441I → V.1 Publication
    Corresponds to variant rs11572102 [ dbSNP | Ensembl ].
    VAR_018958
    Natural varianti249 – 2491K → R in clone MP-12. 1 Publication
    VAR_001252
    Natural varianti264 – 2641I → M in allele CYP2C8*4. 5 Publications
    Corresponds to variant rs1058930 [ dbSNP | Ensembl ].
    VAR_011754
    Natural varianti269 – 2691I → F in allele CYP2C8*2; only found in African-Americans. 4 Publications
    Corresponds to variant rs11572103 [ dbSNP | Ensembl ].
    VAR_012239
    Natural varianti390 – 3901L → S.1 Publication
    VAR_016947
    Natural varianti399 – 3991K → R in allele CYP2C8*3. 6 Publications
    Corresponds to variant rs10509681 [ dbSNP | Ensembl ].
    VAR_012240
    Natural varianti411 – 4111H → L in clone MP-20. 2 Publications
    VAR_001253

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 88MEPFVVLV → MFLQPIAK in isoform 2. 1 PublicationVSP_043306
    Alternative sequencei9 – 110102Missing in isoform 2. 1 PublicationVSP_043307Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M17397 mRNA. Translation: AAA35739.1.
    M17398 mRNA. Translation: AAA35740.1.
    Y00498 mRNA. Translation: CAA68550.1.
    AK292753 mRNA. Translation: BAF85442.1.
    AK293328 mRNA. Translation: BAH11492.1.
    AK315823 mRNA. Translation: BAF98714.1.
    AY514490 Genomic DNA. Translation: AAR89907.1.
    AL359672 Genomic DNA. Translation: CAH71307.1.
    CH471066 Genomic DNA. Translation: EAW50018.1.
    BC020596 mRNA. Translation: AAH20596.1.
    X54807 Genomic DNA. Translation: CAA38578.1.
    M21941 mRNA. Translation: AAA52160.1.
    M21942 mRNA. Translation: AAA52161.1.
    X51535 mRNA. Translation: CAA35915.1.
    CCDSiCCDS55721.1. [P10632-2]
    CCDS7438.1. [P10632-1]
    PIRiA29782.
    RefSeqiNP_000761.3. NM_000770.3. [P10632-1]
    NP_001185782.1. NM_001198853.1.
    NP_001185783.1. NM_001198854.1. [P10632-2]
    NP_001185784.1. NM_001198855.1.
    UniGeneiHs.709188.

    Genome annotation databases

    EnsembliENST00000371270; ENSP00000360317; ENSG00000138115. [P10632-1]
    ENST00000535898; ENSP00000445062; ENSG00000138115. [P10632-2]
    GeneIDi1558.
    KEGGihsa:1558.
    UCSCiuc001kkb.3. human. [P10632-1]
    uc010qoc.2. human. [P10632-2]

    Polymorphism databases

    DMDMi117225.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Cytochrome P450 Allele Nomenclature Committee

    CYP2C8 alleles

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M17397 mRNA. Translation: AAA35739.1 .
    M17398 mRNA. Translation: AAA35740.1 .
    Y00498 mRNA. Translation: CAA68550.1 .
    AK292753 mRNA. Translation: BAF85442.1 .
    AK293328 mRNA. Translation: BAH11492.1 .
    AK315823 mRNA. Translation: BAF98714.1 .
    AY514490 Genomic DNA. Translation: AAR89907.1 .
    AL359672 Genomic DNA. Translation: CAH71307.1 .
    CH471066 Genomic DNA. Translation: EAW50018.1 .
    BC020596 mRNA. Translation: AAH20596.1 .
    X54807 Genomic DNA. Translation: CAA38578.1 .
    M21941 mRNA. Translation: AAA52160.1 .
    M21942 mRNA. Translation: AAA52161.1 .
    X51535 mRNA. Translation: CAA35915.1 .
    CCDSi CCDS55721.1. [P10632-2 ]
    CCDS7438.1. [P10632-1 ]
    PIRi A29782.
    RefSeqi NP_000761.3. NM_000770.3. [P10632-1 ]
    NP_001185782.1. NM_001198853.1.
    NP_001185783.1. NM_001198854.1. [P10632-2 ]
    NP_001185784.1. NM_001198855.1.
    UniGenei Hs.709188.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1PQ2 X-ray 2.70 A/B 19-490 [» ]
    2NNH X-ray 2.60 A/B 28-490 [» ]
    2NNI X-ray 2.80 A 28-490 [» ]
    2NNJ X-ray 2.28 A 28-490 [» ]
    2VN0 X-ray 2.70 A 28-490 [» ]
    ProteinModelPortali P10632.
    SMRi P10632. Positions 28-490.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107936. 12 interactions.
    IntActi P10632. 9 interactions.
    STRINGi 9606.ENSP00000360317.

    Chemistry

    BindingDBi P10632.
    ChEMBLi CHEMBL3721.
    DrugBanki DB01424. Aminophenazone.
    DB01118. Amiodarone.
    DB00613. Amodiaquine.
    DB00865. Benzphetamine.
    DB00564. Carbamazepine.
    DB00439. Cerivastatin.
    DB00586. Diclofenac.
    DB01095. Fluvastatin.
    DB01320. Fosphenytoin.
    DB01241. Gemfibrozil.
    DB01026. Ketoconazole.
    DB01259. Lapatinib.
    DB00227. Lovastatin.
    DB00683. Midazolam.
    DB00471. Montelukast.
    DB00622. Nicardipine.
    DB01229. Paclitaxel.
    DB00252. Phenytoin.
    DB01132. Pioglitazone.
    DB00912. Repaglinide.
    DB01045. Rifampin.
    DB00412. Rosiglitazone.
    DB00641. Simvastatin.
    DB01261. Sitagliptin.
    DB01124. Tolbutamide.
    DB00214. Torasemide.
    DB00755. Tretinoin.
    DB00440. Trimethoprim.
    DB00682. Warfarin.
    DB00549. Zafirlukast.
    DB01198. Zopiclone.

    PTM databases

    PhosphoSitei P10632.

    Polymorphism databases

    DMDMi 117225.

    Proteomic databases

    PaxDbi P10632.
    PRIDEi P10632.

    Protocols and materials databases

    DNASUi 1558.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000371270 ; ENSP00000360317 ; ENSG00000138115 . [P10632-1 ]
    ENST00000535898 ; ENSP00000445062 ; ENSG00000138115 . [P10632-2 ]
    GeneIDi 1558.
    KEGGi hsa:1558.
    UCSCi uc001kkb.3. human. [P10632-1 ]
    uc010qoc.2. human. [P10632-2 ]

    Organism-specific databases

    CTDi 1558.
    GeneCardsi GC10M096786.
    HGNCi HGNC:2622. CYP2C8.
    HPAi HPA013547.
    HPA013970.
    HPA015066.
    MIMi 601129. gene+phenotype.
    neXtProti NX_P10632.
    PharmGKBi PA125.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2124.
    HOGENOMi HOG000036992.
    HOVERGENi HBG015789.
    InParanoidi P10632.
    KOi K17718.
    OMAi MLQIDIK.
    PhylomeDBi P10632.
    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 P10632.

    Miscellaneous databases

    ChiTaRSi CYP2C8. human.
    EvolutionaryTracei P10632.
    GeneWikii CYP2C8.
    GenomeRNAii 1558.
    NextBioi 6434.
    PROi P10632.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P10632.
    Bgeei P10632.
    CleanExi HS_CYP2C8.
    Genevestigatori P10632.

    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. "Characterization of multiple human cytochrome P-450 1 cDNAs. The chromosomal localization of the gene and evidence for alternate RNA splicing."
      Okino S.T., Quattrochi L.C., Pendurthi U.R., McBride O.W., Tukey R.H.
      J. Biol. Chem. 262:16072-16079(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-264.
      Tissue: Liver.
    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).
      Tissue: Liver.
    3. "Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily."
      Romkes M., Faletto M.B., Blaisdell J.A., Raucy J.L., Goldstein J.A.
      Biochemistry 30:3247-3255(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-264.
    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] (ISOFORMS 1 AND 2), VARIANTS LYS-139 AND ARG-399.
      Tissue: Liver and Mammary gland.
    5. NIEHS SNPs program
      Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-139; VAL-244; MET-264; PHE-269 AND ARG-399.
    6. "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].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "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] (ISOFORM 1).
      Tissue: Liver.
    9. "Isolation of the human cytochrome P-450 IIC8 gene: multiple glucocorticoid responsive elements in the 5' region."
      Ged C., Beaune P.
      Biochim. Biophys. Acta 1088:433-435(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-56.
      Tissue: Blood.
    10. "Molecular cloning, expression and characterization of an endogenous human cytochrome P450 arachidonic acid epoxygenase isoform."
      Zeldin D.C., DuBois R.N., Falck J.R., Capdevila J.H.
      Arch. Biochem. Biophys. 322:76-86(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-15, NUCLEOTIDE SEQUENCE [MRNA] OF 6-490, FUNCTION, CATALYTIC ACTIVITY, VARIANT LEU-411.
      Tissue: Kidney.
    11. "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 11-490 (ISOFORM 1), VARIANTS ASP-154; LYS-193; ARG-249 AND LEU-411.
      Tissue: Liver.
    12. "Cloning, expression and chromosomal localization of a member of the human cytochrome P450IIC gene sub-family."
      Shephard E.A., Phillips I.R., Santisteban I., Palmer C.N., Povey S.
      Ann. Hum. Genet. 53:23-31(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 34-382 (ISOFORM 1), VARIANT LYS-139.
    13. "Sequence of a human liver cytochrome P-450 cDNA clone."
      Kolyada A.Y.
      Nucleic Acids Res. 18:5550-5550(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 281-490 (ISOFORM 1), VARIANT ARG-399.
    14. "A frameshift variant of CYP2C8 was identified in a patient who suffered from rhabdomyolysis after administration of cerivastatin."
      Ishikawa C., Ozaki H., Nakajima T., Ishii T., Kanai S., Anjo S., Shirai K., Inoue I.
      J. Hum. Genet. 49:582-585(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: POLYMORPHISM.
    15. "Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site."
      Schoch G.A., Yano J.K., Wester M.R., Griffin K.J., Stout C.D., Johnson E.F.
      J. Biol. Chem. 279:9497-9503(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 28-490.
    16. "Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid."
      Schoch G.A., Yano J.K., Sansen S., Dansette P.M., Stout C.D., Johnson E.F.
      J. Biol. Chem. 283:17227-17237(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 28-490 IN COMPLEX WITH INHIBITORS, SUBSTRATE-BINDING SITES.
    17. "Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid."
      Dai D., Zeldin D.C., Blaisdell J.A., Chanas B., Coulter S.J., Ghanayem B.I., Goldstein J.A.
      Pharmacogenetics 11:597-607(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LYS-139; PHE-269 AND ARG-399.
    18. "CYP2C8 polymorphisms in Caucasians and their relationship with paclitaxel 6alpha-hydroxylase activity in human liver microsomes."
      Bahadur N., Leathart J.B., Mutch E., Steimel-Crespi D., Dunn S.A., Gilissen R., Houdt J.V., Hendrickx J., Mannens G., Bohets H., Williams F.M., Armstrong M., Crespi C.L., Daly A.K.
      Biochem. Pharmacol. 64:1579-1589(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LYS-139; MET-264; PHE-269; SER-390 AND ARG-399.
    19. "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 LYS-139; MET-264; PHE-269 AND ARG-399.

    Entry informationi

    Entry nameiCP2C8_HUMAN
    AccessioniPrimary (citable) accession number: P10632
    Secondary accession number(s): A8K9N8
    , B0AZN2, B7Z1F6, Q5VX93, Q8WWB1, Q9UCZ9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: November 1, 1990
    Last modified: October 1, 2014
    This is version 167 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, 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