LIPID MAPS

LMPD ID

LMP003452

Gene ID

79001

Species

Homo sapiens (Human)

Gene Name

vitamin K epoxide reductase complex, subunit 1

Gene Symbol

VKORC1

Synonyms

EDTP308; IMAGE3455200; MST134; MST576; VKCFD2; VKOR

Alternate Names

vitamin K epoxide reductase complex subunit 1; phylloquinone epoxide reductase; vitamin K1 2,3-epoxide reductase subunit 1; vitamin K dependent clotting factors deficiency 2; vitamin K1 epoxide reductase (warfarin-sensitive)

Chromosome

16

Map Location

16p11.2

EC Number

1.1.4.1

Summary

Vitamin K is essential for blood clotting but must be enzymatically activated. This enzymatically activated form of vitamin K is a reduced form required for the carboxylation of glutamic acid residues in some blood-clotting proteins. The product of this gene encodes the enzyme that is responsible for reducing vitamin K 2,3-epoxide to the enzymatically activated form. Fatal bleeding can be caused by vitamin K deficiency and by the vitamin K antagonist warfarin, and it is the product of this gene that is sensitive to warfarin. In humans, mutations in this gene can be associated with deficiencies in vitamin-K-dependent clotting factors and, in humans and rats, with warfarin resistance. Two pseudogenes have been identified on chromosome 1 and the X chromosome. Two alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Orthologs

View orthologs and multiple alignments for VKORC1

vitamin K epoxide reductase complex subunit 1 isoform 1 precursor
Refseq ID	NP_076869
Protein GI	13124770
UniProt ID	Q9BQB6
mRNA ID	NM_024006
Length	163
RefSeq Status	REVIEWED
MGSTWGSPGWVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRWGRGFGLVEHVLGQDSILNQSNSIFGCIFYTLQLLLGCLRTRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAINVSLMWLSFRKVQEPQGKAKRH

vitamin K epoxide reductase complex subunit 1 isoform 2 precursor
Refseq ID	NP_996560
Protein GI	45827739
UniProt ID	Q9BQB6
mRNA ID	NM_206824
Length	92
RefSeq Status	REVIEWED
MGSTWGSPGWVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRLPADTLGLCPDAAELPGVSRWFCLPGLDPVLRAL
sig_peptide: 1..31 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 3301 peptide sequence: MGSTWGSPGWVRLALCLTGLVLSLYALHVKA sig_peptide: 1..31 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 3301 peptide sequence: MGSTWGSPGWVRLALCLTGLVLSLYALHVKA

Entrez Gene ID

79001

Gene Name

vitamin K epoxide reductase complex, subunit 1

Gene Symbol

VKORC1

Species

Homo sapiens

Gene Ontology (GO Annotations)

GO ID	Source	Type	Description
GO:0005789	TAS:Reactome	C	endoplasmic reticulum membrane
GO:0016021	IEA:UniProtKB-KW	C	integral component of membrane
GO:0048038	IEA:UniProtKB-KW	F	quinone binding
GO:0047057	IDA:UniProtKB	F	vitamin-K-epoxide reductase (warfarin-sensitive) activity
GO:0007596	IMP:UniProtKB	P	blood coagulation
GO:0060348	ISS:UniProtKB	P	bone development
GO:0044267	TAS:Reactome	P	cellular protein metabolic process
GO:0017144	IMP:UniProtKB	P	drug metabolic process
GO:0017187	IMP:UniProtKB	P	peptidyl-glutamic acid carboxylation
GO:0043687	TAS:Reactome	P	post-translational protein modification
GO:0042373	IDA:UniProtKB	P	vitamin K metabolic process

KEGG Pathway Links

KEGG Pathway ID	Description
hsa00130	Ubiquinone and other terpenoid-quinone biosynthesis
ko00130	Ubiquinone and other terpenoid-quinone biosynthesis

REACTOME Pathway Links

REACTOME Pathway ID	Description
REACT_1132	Gamma-carboxylation, transport, and amino-terminal cleavage of proteins
REACT_1069	PTM: gamma carboxylation, hypusine formation and arylsulfatase activation

InterPro Annotations

Accession	Description
IPR012932	Vitamin K epoxide reductase

Entry Information

Gene Name

vitamin K epoxide reductase complex, subunit 1

Protein Entry

VKOR1_HUMAN

UniProt ID

Q9BQB6

Species

Human

Comments

Comment Type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=1; Synonyms=MST576; IsoId=Q9BQB6-1; Sequence=Displayed; Name=2; Synonyms=MST134; IsoId=Q9BQB6-2; Sequence=VSP_013363; Name=3; IsoId=Q9BQB6-3; Sequence=VSP_043407; Note=No experimental confirmation available.;
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. {ECO
Disease	Combined deficiency of vitamin K-dependent clotting factors 2 (VKCFD2) [MIM
Disease	Coumarin resistance (CMRES) [MIM
Domain	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.
Enzyme Regulation	Inhibited by warfarin (coumadin). {ECO
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. 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. {ECO
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).
Sequence Caution	Sequence=AAQ88821.1; Type=Erroneous initiation; Evidence= ;
Similarity	Belongs to the VKOR family.
Subcellular Location	Endoplasmic reticulum membrane {ECO
Tissue Specificity	Expressed at highest levels in fetal and adult liver, followed by fetal heart, kidney, and lung, adult heart, and pancreas.
Web Resource	Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/vkorc1/";

Unique RefSeq proteins for LMP003452 (as displayed in Record Overview)

Protein GI	Database	Accession	Length	Protein Name
13124770	RefSeq	NP_076869	163	vitamin K epoxide reductase complex subunit 1 isoform 1 precursor
45827739	RefSeq	NP_996560	92	vitamin K epoxide reductase complex subunit 1 isoform 2 precursor

Identical Sequences to LMP003452 proteins

Reference	Database	Accession	Length	Protein Name
GI:45827739	GenBank	ADT50060.1	92	Sequence 2077 from patent US 7842467
GI:45827739	GenBank	AFL26369.1	92	Sequence 718 from patent US 8168586
GI:13124770	GenBank	JAA14858.1	163	vitamin K epoxide reductase complex, subunit 1 [Pan troglodytes]
GI:13124770	GenBank	JAA33850.1	163	vitamin K epoxide reductase complex, subunit 1 [Pan troglodytes]
GI:13124770	GenBank	AGM77014.1	163	Sequence 10 from patent US 8426128
GI:45827739	GenBank	AGV82396.1	92	Sequence 718 from patent US 8524238
GI:13124770	GenBank	AGV82397.1	163	Sequence 719 from patent US 8524238
GI:13124770	GenBank	AIC52205.1	163	VKORC1, partial [synthetic construct]
GI:13124770	RefSeq	XP_003807542.1	163	PREDICTED: vitamin K epoxide reductase complex subunit 1 isoform X1 [Pan paniscus]
GI:45827739	RefSeq	XP_008957878.1	92	PREDICTED: vitamin K epoxide reductase complex subunit 1 isoform X2 [Pan paniscus]
GI:45827739	RefSeq	XP_009248946.1	92	PREDICTED: vitamin K epoxide reductase complex subunit 1 isoform X2 [Pongo abelii]
GI:45827739	RefSeq	XP_009428908.1	92	PREDICTED: vitamin K epoxide reductase complex subunit 1 isoform X1 [Pan troglodytes]

Related Sequences to LMP003452 proteins

Reference	Database	Accession	Length	Protein Name
GI:45827739	GenBank	ACE24036.1	92	Sequence 9271 from patent US 7368531
GI:45827739	GenBank	ACE24079.1	92	Sequence 9314 from patent US 7368531
GI:45827739	GenBank	ACH34787.1	92	Sequence 9271 from patent US 7411051
GI:45827739	GenBank	ACH34830.1	92	Sequence 9314 from patent US 7411051
GI:45827739	GenBank	AEJ71818.1	92	Sequence 1605 from patent US 7968689
GI:13124770	GenBank	EHH31612.1	163	Vitamin K epoxide reductase complex subunit 1 [Macaca mulatta]
GI:13124770	GenBank	JAA05868.1	163	vitamin K epoxide reductase complex, subunit 1 [Pan troglodytes]
GI:13124770	GenBank	JAA26992.1	163	vitamin K epoxide reductase complex, subunit 1 [Pan troglodytes]
GI:13124770	RefSeq	XP_003280502.1	163	PREDICTED: vitamin K epoxide reductase complex subunit 1 isoform 1 [Nomascus leucogenys]
GI:45827739	RefSeq	XP_003280503.1	92	PREDICTED: vitamin K epoxide reductase complex subunit 1 isoform 2 [Nomascus leucogenys]
GI:13124770	RefSeq	XP_003916841.1	163	PREDICTED: vitamin K epoxide reductase complex subunit 1 isoform X1 [Papio anubis]
GI:13124770	RefSeq	XP_003930102.1	163	PREDICTED: vitamin K epoxide reductase complex subunit 1 isoform X1 [Saimiri boliviensis boliviensis]