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Q9BQB6

- VKOR1_HUMAN

UniProt

Q9BQB6 - VKOR1_HUMAN

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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

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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiQ9BQB6.
CleanExiHS_VKORC1.
ExpressionAtlasiQ9BQB6. baseline.
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.
GeneTreeiENSGT00390000002103.
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) [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

        10         20         30         40         50
MGSTWGSPGW VRLALCLTGL VLSLYALHVK AARARDRDYR ALCDVGTAIS
60 70 80 90 100
CSRVFSSRWG RGFGLVEHVL GQDSILNQSN SIFGCIFYTL QLLLGCLRTR
110 120 130 140 150
WASVLMLLSS LVSLAGSVYL AWILFFVLYD FCIVCITTYA INVSLMWLSF
160
RKVQEPQGKA KRH
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. Dicoumarol.
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.
GeneTreei ENSGT00390000002103.
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

Bgeei Q9BQB6.
CleanExi HS_VKORC1.
ExpressionAtlasi Q9BQB6. baseline.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 112 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