Reviewed, UniProtKB/Swiss-Prot Q6TEK4 (VKOR1_RAT)

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

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	161 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.
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 By similarity.
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
Domain	Redox-active center Transmembrane
Molecular function	Oxidoreductase
PTM	Disulfide bond
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW regulation of blood coagulation Ref.1 Inferred from mutant phenotype. Source: RGD response to antibiotic Inferred from direct assay. Source: RGD response to organic cyclic substance Inferred from direct assay. Source: RGD response to organic nitrogen Inferred from direct assay. Source: RGD
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microsome Inferred from direct assay. Source: RGD
Molecular function	vitamin-K-epoxide reductase (warfarin-insensitive) activity Inferred from direct assay. Source: RGD vitamin-K-epoxide reductase (warfarin-sensitive) activity Ref.2 Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 161	161	Vitamin K epoxide reductase complex subunit 1		PRO_0000191670
Regions
	Topological domain	1 – 10	10	Lumenal Potential
	Transmembrane	11 – 31	21	Potential
	Topological domain	32 – 80	49	Cytoplasmic Potential
	Transmembrane	81 – 97	17	Potential
	Topological domain	98 – 100	3	Lumenal Potential
	Transmembrane	101 – 123	23	Potential
	Topological domain	124 – 126	3	Cytoplasmic Potential
	Transmembrane	127 – 149	23	Potential
	Topological domain	150 – 161	12	Lumenal Potential
Amino acid modifications
	Disulfide bond	132 ↔ 135		Redox-active Potential
Experimental info
	Mutagenesis	132	1	C → S: No increased VKOR activity when overexpressed together with GGCX. Ref.2
	Mutagenesis	135	1	C → S: No increased VKOR activity when overexpressed together with GGCX. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q6TEK4-1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: BBCE9897B00807DD	FASTA	161	17,783
	10 20 30 40 50 60 MGTTWRSPGR LRLALCLAGL ALSLYALHVK AARARNEDYR ALCDVGTAIS CSRVFSSRWG 70 80 90 100 110 120 RGFGLVEHVL GADSILNQSN SIFGCMFYTI QLLLGCLRGR WASILLILSS LVSVAGSLYL 130 140 150 160 AWILFFVLYD FCIVCITTYA INAGLMLLSF QKVPEHKVKK P

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]. Strain: Sprague-Dawley. Tissue: Liver.
[2]	"Engineering of a recombinant vitamin K-dependent (gamma)-carboxylation system with enhanced (gamma)-carboxyglutamic acid forming capacity: evidence for a functional CxxC redox center in the system." Wajih N., Sane D.C., Hutson S.M., Wallin R. J. Biol. Chem. 280:10540-10547(2005) [PubMed: 15640149] [Abstract] Cited for: MUTAGENESIS OF CYS-132 AND CYS-135.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY423047 mRNA. Translation: AAR82917.1.
IPI	IPI00359900.
RefSeq	NP_976080.1.
UniGene	Rn.97942
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	Q6TEK4.
Genome annotation databases
Ensembl	ENSRNOG00000019399. Rattus norvegicus. [Contig view]
GeneID	309004.
KEGG	rno:309004.
NMPDR	fig|10116.3.peg.3056.
Organism-specific databases
RGD	1303107. Vkorc1.
Phylogenomic databases
HOVERGEN	Q6TEK4.
OMA	Q6TEK4. QGKVKGH.
Enzyme and pathway databases
BRENDA	1.1.4.1. 248.
Gene expression databases
ArrayExpress	Q6TEK4.
GermOnline	ENSRNOG00000019399. Rattus norvegicus.
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
NextBio	659981.

Entry information

Entry name

VKOR1_RAT

Accession

Primary (citable) accession number: Q6TEK4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	July 5, 2004
Last modified:	June 16, 2009
This is version 36 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)