GEPHE SUMMARY
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Gephebase Gene
Entry Status
Published
GepheID
GP00001182
Main curator
Martin
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Rattus norvegicus
Trait State in Taxon B
Rattus norvegicus - Japan
Ancestral State
Data not curated
Taxonomic Status
Taxon A
Latin Name
Common Name
Norway rat
Synonyms
rat; rats; Norway rat; brown rat; Rattus norvegicus8; Rattus norwegicus
Rank
species
Lineage
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omi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Parent
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Latin Name
Common Name
Norway rat
Synonyms
rat; rats; Norway rat; brown rat; Rattus norvegicus8; Rattus norwegicus
Rank
species
Lineage
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omi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Parent
NCBI Taxonomy ID
is Taxon B an Infraspecies?
Yes
Taxon B Description
Rattus norvegicus - Japan
GENOTYPIC CHANGE
Generic Gene Name
VKORC1
Synonyms
VKOR; MST134; MST576; VKCFD2; EDTP308; MSTP134; MSTP576; UNQ308/PRO351
String
Sequence Similarities
Belongs to the VKOR family.
GO - Molecular Function
GO:0048038 : quinone binding
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GO - Biological Process
GO:0014070 : response to organic cyclic compound
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GO - Cellular Component
GO:0016021 : integral component of membrane
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Presumptive Null
Molecular Type
Aberration Type
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
R33P
Experimental Evidence
Taxon A | Taxon B | Position | |
---|---|---|---|
Codon | - | - | - |
Amino-acid | - | - | - |
Main Reference
Authors
Tanaka KD; Kawai YK; Ikenaka Y; Harunari T; Tanikawa T; Fujita S; Ishizuka M
Abstract
Warfarin is a rodenticide commonly used worldwide. It inhibits coagulation of blood by inhibiting vitamin K 2,3-epoxide reductase (VKOR) activity. An inadequate supply of vitamin K blocks the production of prothrombin and causes hemorrhage. Recently, warfarin-resistant brown rats (Rattus norvegicus) were found around the Aomori area of Japan. There is no significant difference in the metabolic activity of warfarin in sensitive and resistant brown rats. To clarify the mechanism underlying warfarin resistance, we cloned the VKORC1 gene from rats and identified a novel substitution of arginine to proline at position 33 of the VKORC1 amino acid sequence. Then, we determined the differences in kinetics of VKOR activity between warfarin-resistant and sensitive rats. Hepatic microsomal VKOR-dependent activity was measured over a range of vitamin K epoxide concentrations from 6.25 to 150 µM. The Vmax values of resistant rats (0.0029 ± 0.020 nmol/min/mg) were about one tenth of those of sensitive rats (0.29 ± 0.12 nmol/min/mg). The Km values of resistant rats (47 ± 32 µM) were similar to those of sensitive rats (59 ± 18 µM). Warfarin-sensitive rats exhibited enzyme efficiencies (Vmax/Km) which were ten-fold greater than those observed in resistant rats. It may mean that VKOR activity of warfarin-resistant Aomori rats is almost lost, because their enzymatic efficiencies are very low even without warfarin. Further studies are needed to clarify how these rats can survive with a markedly reduced VKOR activity and how they simultaneously exhibit warfarin resistance.
Additional References
RELATED GEPHE
Related Genes
Related Haplotypes
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