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Q9BQB6

- VKOR1_HUMAN

UniProt

Q9BQB6 - VKOR1_HUMAN

Protein

Vitamin K epoxide reductase complex subunit 1

Gene

VKORC1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 1 (01 Jun 2001)
      Previous versions | rss
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    Functioni

    Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.6 Publications

    Catalytic activityi

    2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol = 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol.4 Publications

    Enzyme regulationi

    Inhibited by warfarin (coumadin).3 Publications

    GO - Molecular functioni

    1. quinone binding Source: UniProtKB-KW
    2. vitamin-K-epoxide reductase (warfarin-sensitive) activity Source: UniProtKB

    GO - Biological processi

    1. blood coagulation Source: UniProtKB
    2. bone development Source: UniProtKB
    3. cellular protein metabolic process Source: Reactome
    4. drug metabolic process Source: UniProtKB
    5. peptidyl-glutamic acid carboxylation Source: UniProtKB
    6. post-translational protein modification Source: Reactome
    7. vitamin K metabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Oxidoreductase

    Enzyme and pathway databases

    BRENDAi1.1.4.1. 2681.
    ReactomeiREACT_1132. Gamma-carboxylation, transport, and amino-terminal cleavage of proteins.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Vitamin K epoxide reductase complex subunit 1 (EC:1.1.4.1)
    Alternative name(s):
    Vitamin K1 2,3-epoxide reductase subunit 1
    Gene namesi
    Name:VKORC1
    Synonyms:VKOR
    ORF Names:MSTP134, MSTP576, UNQ308/PRO351
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:23663. VKORC1.

    Subcellular locationi

    Endoplasmic reticulum membrane 5 Publications; Multi-pass membrane protein 5 Publications

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: Reactome
    2. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Combined deficiency of vitamin K-dependent clotting factors 2 (VKCFD2) [MIM:607473]: VKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti98 – 981R → W in VKCFD2; strongly reduced enzyme activity. 1 Publication
    VAR_021824
    Coumarin resistance (CMRES) [MIM:122700]: A condition characterized by partial or complete resistance to warfarin or other 4-hydroxycoumarin derivatives. These drugs are used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti26 – 261A → T in CMRES. 1 Publication
    VAR_065785
    Natural varianti29 – 291V → L in CMRES. 2 Publications
    Corresponds to variant rs104894539 [ dbSNP | Ensembl ].
    VAR_021821
    Natural varianti36 – 361D → G in CMRES. 1 Publication
    VAR_065786
    Natural varianti36 – 361D → Y in CMRES. 1 Publication
    VAR_065787
    Natural varianti45 – 451V → A in CMRES. 1 Publication
    Corresponds to variant rs104894540 [ dbSNP | Ensembl ].
    VAR_021822
    Natural varianti52 – 521S → W in CMRES. 1 Publication
    VAR_065788
    Natural varianti56 – 561S → F in CMRES. 1 Publication
    VAR_065789
    Natural varianti58 – 581R → G in CMRES. 1 Publication
    Corresponds to variant rs104894541 [ dbSNP | Ensembl ].
    VAR_021823
    Natural varianti59 – 591W → C in CMRES. 1 Publication
    VAR_065790
    Natural varianti59 – 591W → L in CMRES. 1 Publication
    VAR_065791
    Natural varianti66 – 661V → G in CMRES. 1 Publication
    VAR_065792
    Natural varianti66 – 661V → M in CMRES. 1 Publication
    Corresponds to variant rs72547529 [ dbSNP | Ensembl ].
    VAR_065793
    Natural varianti71 – 711G → A in CMRES. 1 Publication
    VAR_065794
    Natural varianti77 – 771N → S in CMRES. 1 Publication
    VAR_065795
    Natural varianti77 – 771N → Y in CMRES. 1 Publication
    VAR_065796
    Natural varianti123 – 1231I → N in CMRES. 1 Publication
    VAR_065797
    Natural varianti128 – 1281L → R in CMRES. 1 Publication
    Corresponds to variant rs104894542 [ dbSNP | Ensembl ].
    VAR_021825
    Natural varianti139 – 1391Y → H in CMRES. 1 Publication
    VAR_065798

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi16 – 161C → A or S: Reduces enzyme activity by about 80%. 1 Publication
    Mutagenesisi35 – 351R → P: Nearly abolishes enzyme activity. 1 Publication
    Mutagenesisi43 – 431C → A or S: Reduces enzyme activity. 2 Publications
    Mutagenesisi51 – 511C → A or S: Reduces enzyme activity. 2 Publications
    Mutagenesisi56 – 561S → P: Nearly abolishes enzyme activity. 1 Publication
    Mutagenesisi57 – 571S → A: Nearly abolishes enzyme activity. 1 Publication
    Mutagenesisi85 – 851C → A: Reduces enzyme activity by about 25%. 1 Publication
    Mutagenesisi85 – 851C → S: Reduces enzyme activity by about 75%. 1 Publication
    Mutagenesisi96 – 961C → A or S: Reduces enzyme activity by about 70%. 1 Publication
    Mutagenesisi98 – 981R → D or E: Reduces enzyme activity by about 80%. Decreases inhibition by warfarin. 1 Publication
    Mutagenesisi98 – 981R → K: No effect on enzyme activity. Decreases inhibition by warfarin. 1 Publication
    Mutagenesisi120 – 1201L → Q: Decreases enzyme activity moderately. Decreases inhibition by warfarin. 1 Publication
    Mutagenesisi128 – 1281L → Q or S: Decreases enzyme activity by about 80%. Decreases inhibition by warfarin. 1 Publication
    Mutagenesisi132 – 1321C → S: Nearly abolishes enzyme activity. 1 Publication
    Mutagenesisi135 – 1351C → S: Nearly abolishes enzyme activity. 1 Publication
    Mutagenesisi139 – 1391Y → C, G or S: Decreases enzyme activity moderately. Strongly decreases inhibition by warfarin. 2 Publications
    Mutagenesisi139 – 1391Y → F: No effect on enzyme activity. Strongly decreases inhibition by warfarin. 2 Publications

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi122700. phenotype.
    607473. phenotype.
    Orphaneti240843. Acenocoumarol toxicity.
    240873. Fluindione toxicity.
    98434. Hereditary combined deficiency of vitamin K-dependent clotting factors.
    240897. Phenprocoumon toxicity.
    240929. Resistance to acenocoumarol in venous thrombosis and atrial fibrillation.
    240937. Resistance to fluindione in venous thrombosis and atrial fibrillation.
    240943. Resistance to phenprocoumon in venous thrombosis and atrial fibrillation.
    240953. Resistance to warfarine in venous thrombosis and atrial fibrillation.
    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.
    241045. Warfarine dose selection in the treatment of venous thrombosis and atrial fibrillation.
    240923. Warfarine toxicity.
    PharmGKBiPA133787052.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 163163Vitamin K epoxide reductase complex subunit 1PRO_0000191668Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi132 ↔ 135Redox-active

    Keywords - PTMi

    Disulfide bond, Quinone

    Proteomic databases

    MaxQBiQ9BQB6.
    PaxDbiQ9BQB6.
    PRIDEiQ9BQB6.

    PTM databases

    PhosphoSiteiQ9BQB6.

    Expressioni

    Tissue specificityi

    Expressed at highest levels in fetal and adult liver, followed by fetal heart, kidney, and lung, adult heart, and pancreas.1 Publication

    Gene expression databases

    ArrayExpressiQ9BQB6.
    BgeeiQ9BQB6.
    CleanExiHS_VKORC1.
    GenevestigatoriQ9BQB6.

    Organism-specific databases

    HPAiHPA042720.

    Interactioni

    Protein-protein interaction databases

    BioGridi122472. 86 interactions.
    IntActiQ9BQB6. 2 interactions.
    STRINGi9606.ENSP00000378426.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9BQB6.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 88LumenalSequence Analysis
    Topological domaini30 – 7445CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini124 – 1263LumenalCurated
    Topological domaini150 – 16314CytoplasmicCuratedAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei9 – 2921HelicalCuratedAdd
    BLAST
    Transmembranei75 – 9521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei101 – 12323HelicalCuratedAdd
    BLAST
    Transmembranei127 – 14923HelicalCuratedAdd
    BLAST

    Family & Domainsi

    Domaini

    The number of transmembrane domains and the membrane topology are controversial; supporting evidence is available both for models with three transmembrane domains (PubMed:15716279 and PubMed:22923610) and four transmembrane domains (PubMed:20696932 and PubMed:20978134). According to PubMed:15716279 and PubMed:22923610 the N-terminus of the protein is in the endoplasmic reticulum lumen, while the C-terminus is in the cytosol, which is in favor of three transmembrane domains. According to PubMed:20696932, both N-terminus and C-terminus are in the cytosol, indicating the presence of four transmembrane domains. Besides, the 3D-structure of a bacterial ortholog shows four transmembrane domains. Moreover, proteins that reside in the endoplasmic reticulum lumen can catalyze the reduction of the active site cysteines, possibly via Cys-43 and Cys-51 (PubMed:20696932 and PubMed:20978134), but less efficiently than the synthetic compound dithiothreitol (in vitro). Location of Cys-43 and Cys-51 in the endoplasmic reticulum lumen would be in agreement with four transmembrane domains. Again, these data are controversial, and papers do not agree on the effects of mutating Cys-43 and Cys-51, probably because of differences in the assay systems.

    Sequence similaritiesi

    Belongs to the VKOR family.Curated

    Keywords - Domaini

    Redox-active center, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG46570.
    HOGENOMiHOG000230752.
    HOVERGENiHBG076672.
    InParanoidiQ9BQB6.
    KOiK05357.
    OMAiYSCNGSI.
    PhylomeDBiQ9BQB6.
    TreeFamiTF328467.

    Family and domain databases

    InterProiIPR012932. VKOR.
    [Graphical view]
    PfamiPF07884. VKOR. 1 hit.
    [Graphical view]
    SMARTiSM00756. VKc. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9BQB6-1) [UniParc]FASTAAdd to Basket

    Also known as: MST576

    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

    MGSTWGSPGW VRLALCLTGL VLSLYALHVK AARARDRDYR ALCDVGTAIS    50
    CSRVFSSRWG RGFGLVEHVL GQDSILNQSN SIFGCIFYTL QLLLGCLRTR 100
    WASVLMLLSS LVSLAGSVYL AWILFFVLYD FCIVCITTYA INVSLMWLSF 150
    RKVQEPQGKA KRH 163
    Length:163
    Mass (Da):18,235
    Last modified:June 1, 2001 - v1
    Checksum:i2F00526A6C561D5A
    GO
    Isoform 2 (identifier: Q9BQB6-2) [UniParc]FASTAAdd to Basket

    Also known as: MST134

    The sequence of this isoform differs from the canonical sequence as follows:
         95-163: GCLRTRWASV...QEPQGKAKRH → DGVSPCCPGW...PGLDPVLRAL

    Show »
    Length:156
    Mass (Da):16,701
    Checksum:iFBB87922208F471C
    GO
    Isoform 3 (identifier: Q9BQB6-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         59-163: WGRGFGLVEH...QEPQGKAKRH → LPADTLGLCPDAAELPGVSRWFCLPGLDPVLRAL

    Note: No experimental confirmation available.

    Show »
    Length:92
    Mass (Da):9,875
    Checksum:iCB4ADA0C5ED486BD
    GO

    Sequence cautioni

    The sequence AAQ88821.1 differs from that shown. Reason: Erroneous initiation.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti26 – 261A → T in CMRES. 1 Publication
    VAR_065785
    Natural varianti29 – 291V → L in CMRES. 2 Publications
    Corresponds to variant rs104894539 [ dbSNP | Ensembl ].
    VAR_021821
    Natural varianti36 – 361D → G in CMRES. 1 Publication
    VAR_065786
    Natural varianti36 – 361D → Y in CMRES. 1 Publication
    VAR_065787
    Natural varianti45 – 451V → A in CMRES. 1 Publication
    Corresponds to variant rs104894540 [ dbSNP | Ensembl ].
    VAR_021822
    Natural varianti52 – 521S → W in CMRES. 1 Publication
    VAR_065788
    Natural varianti56 – 561S → F in CMRES. 1 Publication
    VAR_065789
    Natural varianti58 – 581R → G in CMRES. 1 Publication
    Corresponds to variant rs104894541 [ dbSNP | Ensembl ].
    VAR_021823
    Natural varianti59 – 591W → C in CMRES. 1 Publication
    VAR_065790
    Natural varianti59 – 591W → L in CMRES. 1 Publication
    VAR_065791
    Natural varianti66 – 661V → G in CMRES. 1 Publication
    VAR_065792
    Natural varianti66 – 661V → M in CMRES. 1 Publication
    Corresponds to variant rs72547529 [ dbSNP | Ensembl ].
    VAR_065793
    Natural varianti71 – 711G → A in CMRES. 1 Publication
    VAR_065794
    Natural varianti77 – 771N → S in CMRES. 1 Publication
    VAR_065795
    Natural varianti77 – 771N → Y in CMRES. 1 Publication
    VAR_065796
    Natural varianti98 – 981R → W in VKCFD2; strongly reduced enzyme activity. 1 Publication
    VAR_021824
    Natural varianti123 – 1231I → N in CMRES. 1 Publication
    VAR_065797
    Natural varianti128 – 1281L → R in CMRES. 1 Publication
    Corresponds to variant rs104894542 [ dbSNP | Ensembl ].
    VAR_021825
    Natural varianti139 – 1391Y → H in CMRES. 1 Publication
    VAR_065798

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei59 – 163105WGRGF…KAKRH → LPADTLGLCPDAAELPGVSR WFCLPGLDPVLRAL in isoform 3. 1 PublicationVSP_043407Add
    BLAST
    Alternative sequencei95 – 16369GCLRT…KAKRH → DGVSPCCPGWSQAICLPQPP KVLGGLQALPADTLGLCPDA AELPGVSRWFCLPGLDPVLR AL in isoform 2. 1 PublicationVSP_013363Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY423044 mRNA. Translation: AAR82914.1.
    AY521634 mRNA. Translation: AAS01052.1.
    AF176924 mRNA. Translation: AAQ13668.1.
    AY466113 mRNA. Translation: AAR28759.1.
    AY587020 Genomic DNA. Translation: AAS83106.1.
    AK289790 mRNA. Translation: BAF82479.1.
    AK312005 mRNA. Translation: BAG34943.1.
    AC135050 Genomic DNA. No translation available.
    CH471192 Genomic DNA. Translation: EAW52167.1.
    CH471192 Genomic DNA. Translation: EAW52168.1.
    BC002911 mRNA. Translation: AAH02911.1.
    AY358456 mRNA. Translation: AAQ88821.1. Different initiation.
    CCDSiCCDS10703.1. [Q9BQB6-1]
    CCDS10704.1. [Q9BQB6-3]
    RefSeqiNP_076869.1. NM_024006.4. [Q9BQB6-1]
    NP_996560.1. NM_206824.1. [Q9BQB6-3]
    UniGeneiHs.324844.

    Genome annotation databases

    EnsembliENST00000319788; ENSP00000326135; ENSG00000167397. [Q9BQB6-2]
    ENST00000354895; ENSP00000346969; ENSG00000167397. [Q9BQB6-3]
    ENST00000394975; ENSP00000378426; ENSG00000167397. [Q9BQB6-1]
    GeneIDi79001.
    KEGGihsa:79001.
    UCSCiuc002eas.3. human. [Q9BQB6-1]
    uc002eat.3. human. [Q9BQB6-3]
    uc002eau.3. human. [Q9BQB6-2]

    Polymorphism databases

    DMDMi62511226.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY423044 mRNA. Translation: AAR82914.1 .
    AY521634 mRNA. Translation: AAS01052.1 .
    AF176924 mRNA. Translation: AAQ13668.1 .
    AY466113 mRNA. Translation: AAR28759.1 .
    AY587020 Genomic DNA. Translation: AAS83106.1 .
    AK289790 mRNA. Translation: BAF82479.1 .
    AK312005 mRNA. Translation: BAG34943.1 .
    AC135050 Genomic DNA. No translation available.
    CH471192 Genomic DNA. Translation: EAW52167.1 .
    CH471192 Genomic DNA. Translation: EAW52168.1 .
    BC002911 mRNA. Translation: AAH02911.1 .
    AY358456 mRNA. Translation: AAQ88821.1 . Different initiation.
    CCDSi CCDS10703.1. [Q9BQB6-1 ]
    CCDS10704.1. [Q9BQB6-3 ]
    RefSeqi NP_076869.1. NM_024006.4. [Q9BQB6-1 ]
    NP_996560.1. NM_206824.1. [Q9BQB6-3 ]
    UniGenei Hs.324844.

    3D structure databases

    ProteinModelPortali Q9BQB6.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 122472. 86 interactions.
    IntActi Q9BQB6. 2 interactions.
    STRINGi 9606.ENSP00000378426.

    Chemistry

    ChEMBLi CHEMBL1930.
    DrugBanki DB01418. Acenocoumarol.
    DB00266. Dicumarol.
    DB00170. Menadione.
    DB00498. Phenindione.
    DB00946. Phenprocoumon.
    DB00682. Warfarin.
    GuidetoPHARMACOLOGYi 2645.

    PTM databases

    PhosphoSitei Q9BQB6.

    Polymorphism databases

    DMDMi 62511226.

    Proteomic databases

    MaxQBi Q9BQB6.
    PaxDbi Q9BQB6.
    PRIDEi Q9BQB6.

    Protocols and materials databases

    DNASUi 79001.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000319788 ; ENSP00000326135 ; ENSG00000167397 . [Q9BQB6-2 ]
    ENST00000354895 ; ENSP00000346969 ; ENSG00000167397 . [Q9BQB6-3 ]
    ENST00000394975 ; ENSP00000378426 ; ENSG00000167397 . [Q9BQB6-1 ]
    GeneIDi 79001.
    KEGGi hsa:79001.
    UCSCi uc002eas.3. human. [Q9BQB6-1 ]
    uc002eat.3. human. [Q9BQB6-3 ]
    uc002eau.3. human. [Q9BQB6-2 ]

    Organism-specific databases

    CTDi 79001.
    GeneCardsi GC16M031105.
    H-InvDB HIX0079837.
    HGNCi HGNC:23663. VKORC1.
    HPAi HPA042720.
    MIMi 122700. phenotype.
    607473. phenotype.
    608547. gene.
    neXtProti NX_Q9BQB6.
    Orphaneti 240843. Acenocoumarol toxicity.
    240873. Fluindione toxicity.
    98434. Hereditary combined deficiency of vitamin K-dependent clotting factors.
    240897. Phenprocoumon toxicity.
    240929. Resistance to acenocoumarol in venous thrombosis and atrial fibrillation.
    240937. Resistance to fluindione in venous thrombosis and atrial fibrillation.
    240943. Resistance to phenprocoumon in venous thrombosis and atrial fibrillation.
    240953. Resistance to warfarine in venous thrombosis and atrial fibrillation.
    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.
    241045. Warfarine dose selection in the treatment of venous thrombosis and atrial fibrillation.
    240923. Warfarine toxicity.
    PharmGKBi PA133787052.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG46570.
    HOGENOMi HOG000230752.
    HOVERGENi HBG076672.
    InParanoidi Q9BQB6.
    KOi K05357.
    OMAi YSCNGSI.
    PhylomeDBi Q9BQB6.
    TreeFami TF328467.

    Enzyme and pathway databases

    BRENDAi 1.1.4.1. 2681.
    Reactomei REACT_1132. Gamma-carboxylation, transport, and amino-terminal cleavage of proteins.

    Miscellaneous databases

    GeneWikii VKORC1.
    GenomeRNAii 79001.
    NextBioi 67615.
    PROi Q9BQB6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9BQB6.
    Bgeei Q9BQB6.
    CleanExi HS_VKORC1.
    Genevestigatori Q9BQB6.

    Family and domain databases

    InterProi IPR012932. VKOR.
    [Graphical view ]
    Pfami PF07884. VKOR. 1 hit.
    [Graphical view ]
    SMARTi SM00756. VKc. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS CMRES LEU-29; ALA-45; GLY-58 AND ARG-128, VARIANT VKCFD2 TRP-98.
      Tissue: Kidney.
    2. "Identification of the gene for vitamin K epoxide reductase."
      Li T., Chang C.-Y., Jin D.-Y., Lin P.-J., Khvorova A., Stafford D.W.
      Nature 427:541-544(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Tissue: Aorta.
    4. SeattleSNPs variation discovery resource
      Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. "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 3).
      Tissue: Brain.
    6. "The sequence and analysis of duplication-rich human chromosome 16."
      Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
      , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
      Nature 432:988-994(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: Lung.
    9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 44-163 (ISOFORM 1).
    10. "Vitamin K epoxide reductase: homology, active site and catalytic mechanism."
      Goodstadt L., Ponting C.P.
      Trends Biochem. Sci. 29:289-292(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: POTENTIAL REDOX-ACTIVE SITE.
    11. Cited for: MUTAGENESIS OF ARG-35; SER-56; LEU-120; LEU-128 AND TYR-139, CATALYTIC ACTIVITY, ENZYME REGULATION, FUNCTION.
    12. "Membrane topology mapping of vitamin K epoxide reductase by in vitro translation/cotranslocation."
      Tie J.-K., Nicchitta C., von Heijne G., Stafford D.W.
      J. Biol. Chem. 280:16410-16416(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY, SUBCELLULAR LOCATION.
    13. "Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin."
      Rost S., Fregin A., Hunerberg M., Bevans C.G., Muller C.R., Oldenburg J.
      Thromb. Haemost. 94:780-786(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, POTENTIAL REDOX-ACTIVE SITE, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-16; CYS-43; CYS-51; SER-57; CYS-85; CYS-96; ARG-98; CYS-132; CYS-135 AND TYR-139, CHARACTERIZATION OF VARIANT VKCFD2 TRP-98.
    14. "Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners."
      Schulman S., Wang B., Li W., Rapoport T.A.
      Proc. Natl. Acad. Sci. U.S.A. 107:15027-15032(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY.
    15. "Novel insight into the mechanism of the vitamin K oxidoreductase (VKOR): electron relay through Cys43 and Cys51 reduces VKOR to allow vitamin K reduction and facilitation of vitamin K-dependent protein carboxylation."
      Rishavy M.A., Usubalieva A., Hallgren K.W., Berkner K.L.
      J. Biol. Chem. 286:7267-7278(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF CYS-43 AND CYS-51.
    16. "Human vitamin K epoxide reductase and its bacterial homologue have different membrane topologies and reaction mechanisms."
      Tie J.K., Jin D.Y., Stafford D.W.
      J. Biol. Chem. 287:33945-33955(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TOPOLOGY, CATALYTIC ACTIVITY, ENZYME REGULATION, FUNCTION.
    17. "Membrane topology for human vitamin K epoxide reductase."
      Wu S., Tie J.K., Stafford D.W., Pedersen L.G.
      J. Thromb. Haemost. 12:112-114(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: 3D-STRUCTURE MODELING.
    18. "Thirteen novel VKORC1 mutations associated with oral anticoagulant resistance: insights into improved patient diagnosis and treatment."
      Watzka M., Geisen C., Bevans C.G., Sittinger K., Spohn G., Rost S., Seifried E., Muller C.R., Oldenburg J.
      J. Thromb. Haemost. 9:109-118(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CMRES THR-26; LEU-29; GLY-36; TYR-36; TRP-52; PHE-56; LEU-59; CYS-59; GLY-66; MET-66; ALA-71; SER-77; TYR-77; ASN-123 AND HIS-139.

    Entry informationi

    Entry nameiVKOR1_HUMAN
    AccessioniPrimary (citable) accession number: Q9BQB6
    Secondary accession number(s): A6NIQ6
    , B2R4Z6, Q6UX90, Q7Z2R4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 12, 2005
    Last sequence update: June 1, 2001
    Last modified: October 1, 2014
    This is version 111 of the entry and version 1 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

    Miscellaneous

    The location of two cysteine active-site residues within a proposed transmembrane is consistent both with the known hydrophobic environment of the thiol redox site of the enzyme and with the lipophilicity of vitamin K and warfarin (coumadin).

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3