Homo sapiens complex locus VKORC1andPRSS53, encoding vitamin K epoxide reductase complex, subunit 1 and protease, serine, 53.
SUMMARY back to top
RefSeq summary
[VKORC1] 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].

RefSeq annotates 3 representative transcripts from 2 genes that we see as a complex (NM included in AceView variants .a, .i and .o), but Homo sapiens cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 18 spliced variants.

AceView synopsis, each blue text links to tables and details
Note that this locus is complex: it appears to produce several proteins with no sequence overlap, and it merges 2 different NCBI genes.
Expression: According to AceView, this gene is expressed at very high level, 4.6 times the average gene in this release. The sequence of this gene is defined by 548 GenBank accessions from 464 cDNA clones, some from brain (seen 43 times), lung (32), pancreas (32), purified pancreatic islet (23), kidney (21), prostate (20), eye (19) and 158 other tissues. We annotate structural defects or features in 107 cDNA clones.
Alternative mRNA variants and regulation: The gene contains 24 distinct introns (23 gt-ag, 1 gc-ag). Transcription produces 19 different mRNAs, 18 alternatively spliced variants and 1 unspliced form. There are 6 probable alternative promotors, 2 non overlapping alternative last exons and 10 validated alternative polyadenylation sites (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 8 cassette exons, overlapping exons with different boundaries, splicing versus retention of 10 introns. 495 bp of this gene are antisense to spliced gene ZNF646, raising the possibility of regulated alternate expression.
Note that mRNA .cAug10 was found in vivo, although it is a predicted target of nonsense mediated mRNA decay (NMD).
Function: There are 173 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (Cerebrovascular Disorders; Coagulation Protein Disorders; Coronary Disease; Coumarin resistance; Hemorrhage; Hemorrhagic Disorders; Lung Diseases; Thrombosis; Vitamin K-dependent clotting factors, combined deficiency of, 2; Warfarin resistance) and proposed to participate in processes (oxidation reduction, positive regulation of coagulation, proteolysis, regulation of blood coagulation, response to antibiotic, response to organic cyclic substance, response to organic nitrogen, vitamin K metabolic process). Proteins are expected to have molecular functions (oxidoreductase activity, peptidase activity, serine-type endopeptidase activity, vitamin-K-epoxide reductase (warfarin-insensitive) activity, vitamin-K-epoxide reductase (warfarin-sensitive) activity) and to localize in various compartments (extracellular space, membrane, endoplasmic reticulum, endoplasmic reticulum membrane and 4 others).
Protein coding potential: 15 spliced and the unspliced mRNAs putatively encode good proteins, altogether 16 different isoforms (9 complete, 4 COOH complete, 3 partial), some containing domains Trypsin, Vitamin K epoxide reductase family [Pfam]; 1 of the 9 complete proteins appears to be secreted. The remaining 3 mRNA variants (3 spliced) appear not to encode good proteins.
2 isoforms are annotated using as Met a Kozak-compatible non-AUG start, thereby gaining a minimum of 154 amino acids N-terminal to the first AUG.

Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12.
Map on chromosome 16, links to other databases and other names
Map: This gene VKORC1andPRSS53 maps on chromosome 16, at 16p11.2 according to Entrez Gene. In AceView, it covers 12.93 kb, from 31107264 to 31094335 (NCBI 37, August 2010), on the reverse strand.
Links to: manual annotations from OMIM_122700, OMIM_607473, GAD, the SNP view, SNP view, gene overviews from Entrez Gene 339105, 79001, GeneCards, expression data from ECgene, UniGene Hs.324844, Hs.569575, molecular and other annotations from UCSC, or our GOLD analysis.
The previous AceView annotation is here.
Other names: The gene is also known as VKORC1andPRSS53, MSTP134, VKOR, MST134, MST576, VKCFD2, EDTP308, MGC2694, FLJ00289, IMAGE3455200, POL3S, UNQ308, VKORC1, PRSS53 or LOC339105, LOC79001. It has been described as 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), serine protease 53, EDTP308, polyserase 3, polyserase-3, polyserine protease 3.
EC number: This gene encodes proteins number:, 3.4.21.-.
Closest AceView homologs in other species ?
The closest mouse gene, according to BlastP, is the AceView gene BC039632 (e=3 10^-40).
The closest C.elegans gene, according to BlastP, is the AceView/WormGene try-1 (e=6 10^-21), which may contain interesting functional annotation.
The closest A.thaliana gene, according to BlastP, is the AceView gene AT4G21650andAT4G21630 (e=0.52), which may contain interesting functional annotation
          Complete gene on genome diagram: back to top
Please choose between the zoomable GIF version., and the Flash version.
This diagram shows in true scale the gene on the genome, the mRNAs and the cDNA clones.
Compact gene diagram back to top
Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron. Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript.
Sequences: click on the numbers to get the DNA back to top
mRNA variant mRNA matching the genome Best predicted protein 5' UTR 3' UTR uORF Upstream sequence Transcription
Downstream sequence
aAug10 2028 bp 553 aa 366 bp 2kb 5386 bp 1kb
bAug10 2783 bp 500 aa 508 bp 772 bp 2kb possibly including promoter 11585 bp 1kb
cAug10 5913 bp 244 aa 2969 bp 2209 bp 30 bp 2kb including Promoter 6616 bp 1kb
dAug10 737 bp 235 aa 27 bp 2kb 1120 bp 1kb
eAug10 991 bp 232 aa 290 bp 2kb probably including promoter 4011 bp 1kb
fAug10 1103 bp 224 aa 430 bp 2kb possibly including promoter 2035 bp 1kb
gAug10 827 bp 194 aa 243 bp 2kb including Promoter 8191 bp 1kb
hAug10-unspliced 2217 bp 190 aa 1214 bp 430 bp 42 bp 2kb including Promoter 2217 bp 1kb
iAug10 1013 bp 163 aa 231 bp 290 bp 2kb including Promoter 4117 bp 1kb
jAug10 1064 bp 156 aa 211 bp 382 bp 2kb possibly including promoter 4086 bp 1kb
kAug10 793 bp 159 aa 31 bp 312 bp 2kb probably including promoter 3836 bp 1kb
lAug10 643 bp 131 aa 247 bp 2kb possibly including promoter 1154 bp 1kb
mAug10 788 bp 130 aa 13 bp 382 bp 2kb possibly including promoter 2757 bp 1kb
nAug10 498 bp 104 aa 186 bp 2kb including Promoter 8156 bp 1kb
oAug10 998 bp 92 aa 249 bp 470 bp 96 bp 2kb possibly including promoter 4212 bp 1kb
pAug10 672 bp 91 aa 394 bp 2kb 4718 bp 1kb
qAug10 3089 bp 169 aa 1243 bp 1666 bp 2kb including Promoter 4430 bp 1kb
rAug10 940 bp 60 aa 269 bp 488 bp 2kb including Promoter 4144 bp 1kb
sAug10 584 bp 58 aa 192 bp 215 bp 2kb 3361 bp 1kb

Gene neighbors on chromosome 16p11.2 back to top
ZOOM IN                D:disease,C:conserved,I:interactions,R:regulation,P:publications        
Annotated mRNA diagrams back to top
Bibliography:               173 articles in PubMed back to top
? Gene Summary Gene on genome mRNA:.a, .b, .c, .d, .e, .f, .g, .h-u, .i, .j, .k, .l, .m, .n, .o, .p, .q, .r, .s Alternative mRNAs features, proteins, introns, exons, sequences Expression Tissue Function, regulation, related genes DC

To mine knowledge about the gene, please click the 'Gene Summary' or the 'Function, regulation, related genes ' tab at the top of the page. The 'Gene Summary' page includes all we learnt about the gene, functional annotations of neighboring genes, maps, links to other sites and the bibliography. The 'Function, regulation, related genes ' page includes Diseases (D), Pathways, GO annotations, conserved domains (C), interactions (I) reference into function, and pointers to all genes with the same functional annotation.
To compare alternative variants, their summarized annotations, predicted proteins, introns and exons, or to access any sequence, click the 'Alternative mRNAs features' tab. To see a specific mRNA variant diagram, sequence and annotation, click the variant name in the 'mRNA' tab. To examine expression data from all cDNAs clustered in this gene by AceView, click the 'Expression tissue'.

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