Vitamin K epoxide reductase (VKOR) family; VKOR (also named VKORC1) is an integral membrane protein that catalyzes the reduction of vitamin K 2,3-epoxide and vitamin K to vitamin K hydroquinone, an essential co-factor subsequently used in the gamma-carboxylation of glutamic acid residues in blood coagulation enzymes. This family includes enzymes that are present in vertebrates, Drosophila, plants, bacteria, and archaea. All homologs of VKOR contain an active site CXXC motif, which is switched between reduced and disulfide-bonded states during the reaction cycle. In some plant and bacterial homologs, the VKOR domain is fused with domains of the thioredoxin family of oxidoreductases which may function as redox partners in initiating the reduction cascade. Warfarin, a widely used oral anticoagulant used in medicine as well as rodenticides, inhibits the activity of VKOR, resulting in decreased levels of reduced vitamin K, which is required for the function of several clotting factors. However, anticoagulation effect of warfarin is significantly associated with polymorphism of certain genes, including VKORC1. Interestingly, in rodents, an adaptive trait appears to have evolved convergently by selection on new or standing genetic polymorphisms in VKORC1 as well as by adaptive introgressive hybridization between species, likely brought about by human-mediated dispersal.

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gi 2515601708   2 GRGFGLVEHVLGADSILNQSNSIFGCMFYTIQLLL 36
Cdd:cd12917    51 GRGFGLLGLILGKDSILNQPNSVFGIIFYILQLLL 85

Vitamin K epoxide reductase family in eukaryotes, excluding plants; This family includes vitamin K epoxide reductase (VKOR) present in bacteria and plant. VKOR (also named VKORC1) is an integral membrane protein that catalyzes the reduction of vitamin K 2,3-epoxide and vitamin K to vitamin K hydroquinone, an essential co-factor subsequently used in the gamma-carboxylation of glutamic acid residues in blood coagulation enzymes. All homologs of VKOR contain an active site CXXC motif, which is switched between reduced and disulfide-bonded states during the reaction cycle. Warfarin, a widely used oral anticoagulant used in medicine as well as rodenticides, inhibits the activity of VKOR, resulting in decreased levels of reduced vitamin K, which is required for the function of several clotting factors. However, anticoagulation effect of warfarin is significantly associated with polymorphism of certain genes, including VKORC1. Interestingly, in rodents, an adaptive trait appears to have evolved convergently by selection on new or standing genetic polymorphisms in VKORC1 as well as by adaptive introgressive hybridization between species, likely brought about by human-mediated dispersal.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2515601708   2 GRGFGLVEHVLGADSILNQSNSIFGCMFYTIQLLL 36
Cdd:cd12917    51 GRGFGLLGLILGKDSILNQPNSVFGIIFYILQLLL 85

Vitamin K epoxide reductase family in eukaryotes, excluding plants; This family includes vitamin K epoxide reductase (VKOR) present in bacteria and plant. VKOR (also named VKORC1) is an integral membrane protein that catalyzes the reduction of vitamin K 2,3-epoxide and vitamin K to vitamin K hydroquinone, an essential co-factor subsequently used in the gamma-carboxylation of glutamic acid residues in blood coagulation enzymes. All homologs of VKOR contain an active site CXXC motif, which is switched between reduced and disulfide-bonded states during the reaction cycle. Warfarin, a widely used oral anticoagulant used in medicine as well as rodenticides, inhibits the activity of VKOR, resulting in decreased levels of reduced vitamin K, which is required for the function of several clotting factors. However, anticoagulation effect of warfarin is significantly associated with polymorphism of certain genes, including VKORC1. Interestingly, in rodents, an adaptive trait appears to have evolved convergently by selection on new or standing genetic polymorphisms in VKORC1 as well as by adaptive introgressive hybridization between species, likely brought about by human-mediated dispersal.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2515601708   2 GRGFGLVEHVLGADSILNQSNSIFGCMFYTIQLLL 36
Cdd:cd12917    51 GRGFGLLGLILGKDSILNQPNSVFGIIFYILQLLL 85