Reviewed, UniProtKB/Swiss-Prot Q9BQB6 (VKOR1_HUMAN)

Names and origin

Protein names

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 names

Name:	VKORC1
Synonyms:	VKOR
ORF Names:	MSTP134, MSTP576, UNQ308/PRO351

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	163 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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. Ref.1 Ref.2
Catalytic activity	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.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Ref.1
Tissue specificity	Expressed at highest levels in fetal and adult liver, followed by fetal heart, kidney, and lung, adult heart, and pancreas. Ref.1
Involvement in disease	Defects in VKORC1 are a cause of combined eficiency of all vitamin K-dependent clotting factors type 2 (VKCFD2) [MIM:607473]. VKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. Ref.1 Defects in VKORC1 are a cause of coumarin resistance [MIM:122700]; also known as warfarin resistance. Warfarin and other coumarin-type anticoagulants are used to reduce blood viscosity in the treatment of thromboembolic disorders. Ref.1
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.
Sequence similarities	Belongs to the VKOR family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Redox-active center Transmembrane
Molecular function	Oxidoreductase
PTM	Disulfide bond
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	vitamin-K-epoxide reductase (warfarin-sensitive) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BQB6-1)

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.

Isoform 2 (identifier: Q9BQB6-2)

Also known as: MST134;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 163	163	Vitamin K epoxide reductase complex subunit 1		PRO_0000191668
Regions
	Topological domain	1 – 8	8	Lumenal Potential
	Transmembrane	9 – 29	21	Potential
	Topological domain	30 – 100	71	Cytoplasmic Potential
	Transmembrane	101 – 123	23	Potential
	Topological domain	124 – 126	3	Lumenal Potential
	Transmembrane	127 – 149	23	Potential
	Topological domain	150 – 163	14	Cytoplasmic Potential
Amino acid modifications
	Disulfide bond	132 ↔ 135		Redox-active Potential
Natural variations
	Alternative sequence	95 – 163	69	GCLRT…KAKRH → DGVSPCCPGWSQAICLPQPP KVLGGLQALPADTLGLCPDA AELPGVSRWFCLPGLDPVLR AL in isoform 2.		VSP_013363
	Natural variant	29	1	V → L in coumarin resistance. Ref.1		VAR_021821
	Natural variant	45	1	V → A in coumarin resistance. Ref.1		VAR_021822
	Natural variant	58	1	R → G in coumarin resistance. Ref.1		VAR_021823
	Natural variant	98	1	R → W in VKCFD2. Ref.1		VAR_021824
	Natural variant	128	1	L → R in coumarin resistance. Ref.1		VAR_021825

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MST576) [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 2F00526A6C561D5A	FASTA	163	18,235
	10 20 30 40 50 60 MGSTWGSPGW VRLALCLTGL VLSLYALHVK AARARDRDYR ALCDVGTAIS CSRVFSSRWG 70 80 90 100 110 120 RGFGLVEHVL GQDSILNQSN SIFGCIFYTL QLLLGCLRTR WASVLMLLSS LVSLAGSVYL 130 140 150 160 AWILFFVLYD FCIVCITTYA INVSLMWLSF RKVQEPQGKA KRH
	Isoform 2 (MST134). Checksum: FBB87922208F471C	FASTA	156	16,701
	10 20 30 40 50 60 MGSTWGSPGW VRLALCLTGL VLSLYALHVK AARARDRDYR ALCDVGTAIS CSRVFSSRWG 70 80 90 100 110 120 RGFGLVEHVL GQDSILNQSN SIFGCIFYTL QLLLDGVSPC CPGWSQAICL PQPPKVLGGL 130 140 150 QALPADTLGL CPDAAELPGV SRWFCLPGLD PVLRAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2." Rost S., Fregin A., Ivaskevicius V., Conzelmann E., Hoertnagel K., Pelz H.-J., Lappegard K., Seifried E., Scharrer I., Tuddenham E.G.D., Mueller C.R., Strom T.M., Oldenburg J. Nature 427:537-541(2004) [PubMed: 14765194] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS COUMARIN RESISTANCE 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: 14765195] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[3]	Liu B., Qin B.M., Sheng H., Zhao B., Liu Y.Q., Wang X.Y., Zhang Q., Song L., Lu H., Xu H.S., Zheng W.Y., Gong J., Wang Y.B., Liu Y.Q., Zhang C.N., Shi Y., Wang W., Zhang Z. , Yang X., Han Y., Chen J.Z., Liu B.H., Hui R.T. Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases 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]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[6]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 44-163 (ISOFORM 1).
[7]	"Vitamin K epoxide reductase: homology, active site and catalytic mechanism." Goodstadt L., Ponting C.P. Trends Biochem. Sci. 29:289-292(2004) [PubMed: 15276181] [Abstract] Cited for: POTENTIAL REDOX ACTIVE SITE.
[8]	"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: 15716279] [Abstract] Cited for: TOPOLOGY.
[9]	"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: 16270630] [Abstract] Cited for: MUTAGENESIS, POTENTIAL REDOX ACTIVE SITE.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	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. BC002911 mRNA. Translation: AAH02911.1. AY358456 mRNA. Translation: AAQ88821.1. Different initiation.
IPI	IPI00031000. IPI00384902.
RefSeq	NP_076869.1.
UniGene	Hs.324844
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	Q9BQB6.
Genome annotation databases
Ensembl	ENSG00000167397. Homo sapiens. [Contig view]
GeneID	79001.
KEGG	hsa:79001.
UCSC	uc002eas.1. human. uc002eau.1. human.
Organism-specific databases
GeneCards	GC16M031009.
H-InvDB	HIX0012979. HIX0079837.
HGNC	HGNC:23663. VKORC1.
MIM	122700. phenotype. 607473. phenotype. 608547. gene.
Orphanet	98434. Vitamin K-dependent clotting factors, combined deficiency of.
PharmGKB	PA133787052.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9BQB6.
HOVERGEN	Q9BQB6.
OMA	Q9BQB6. QGKVKGH.
Enzyme and pathway databases
BRENDA	1.1.4.1. 247.
Gene expression databases
ArrayExpress	Q9BQB6.
Bgee	Q9BQB6.
CleanEx	HS_VKORC1.
GermOnline	ENSG00000167397. Homo sapiens.
Family and domain databases
InterPro	IPR012932. VKOR. [Graphical view]
Pfam	PF07884. VKOR. 1 hit. [Graphical view]
SMART	SM00756. VKc. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB01418. Acenocoumarol. DB00266. Dicumarol. DB00170. Menadione. DB00498. Phenindione. DB00946. Phenprocoumon. DB00682. Warfarin.
NextBio	67615.
SOURCE	Search...

Entry information

Entry name

VKOR1_HUMAN

Accession

Primary (citable) accession number: Q9BQB6
Secondary accession number(s): Q6UX90, Q7Z2R4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	June 1, 2001
Last modified:	July 7, 2009
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)