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Conserved domains on  [gi|62471731|ref|NP_001014533|]
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Vitamin-K epoxide reductase [Drosophila melanogaster]

Protein Classification

vitamin K epoxide reductase family protein( domain architecture ID 10191574)

vitamin K epoxide reductase (VKOR) family protein similar to human VKOR complex subunit 1 (VKORC1), an integral membrane protein and the catalytic subunit of the VKOR complex that reduces inactive vitamin K 2,3-epoxide to active vitamin K

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
VKOR_euk cd12917
Vitamin K epoxide reductase family in eukaryotes, excluding plants; This family includes ...
 9-135 2.58e-45

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.


:

Pssm-ID: 240600 [Multi-domain]  Cd Length: 140  Bit Score: 144.67  E-value: 2.58e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731   9 SRLRGICVCGLAISVYSLYVKMKLKEDENYRPMCDVNDNISCSLVFKSGYGDGFGL-----GNITQVNAPNGAIGCAFYI 83
Cdd:cd12917   1 LLRLALCLAGLLLSLYALYVELKKERDPDYRALCDISESISCSKVFSSRYGRGFGLlglilGKDSILNQPNSVFGIIFYI 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 62471731  84 LYFLSSFFNHRWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIYFI 135
Cdd:cd12917  81 LQLLLGLTNSAVAALLLLTLSILSVVGSLYLAYILYFVLKDFCIVCVSTYVV 132
 
Name Accession Description Interval E-value
VKOR_euk cd12917
Vitamin K epoxide reductase family in eukaryotes, excluding plants; This family includes ...
 9-135 2.58e-45

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.


Pssm-ID: 240600 [Multi-domain]  Cd Length: 140  Bit Score: 144.67  E-value: 2.58e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731   9 SRLRGICVCGLAISVYSLYVKMKLKEDENYRPMCDVNDNISCSLVFKSGYGDGFGL-----GNITQVNAPNGAIGCAFYI 83
Cdd:cd12917   1 LLRLALCLAGLLLSLYALYVELKKERDPDYRALCDISESISCSKVFSSRYGRGFGLlglilGKDSILNQPNSVFGIIFYI 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 62471731  84 LYFLSSFFNHRWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIYFI 135
Cdd:cd12917  81 LQLLLGLTNSAVAALLLLTLSILSVVGSLYLAYILYFVLKDFCIVCVSTYVV 132
VKc smart00756
Family of likely enzymes that includes the catalytic subunit of vitamin K epoxide reductase; ...
 4-146 2.97e-32

Family of likely enzymes that includes the catalytic subunit of vitamin K epoxide reductase; Bacterial homologues are fused to members of the thioredoxin family of oxidoreductases.


Pssm-ID: 214805  Cd Length: 142  Bit Score: 111.66  E-value: 2.97e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731      4 AYSTASRLRGICVCGLAISVYSLYVKMKLKEDENYRPMCDVNDNISCSLVFKSGYGDGFGLgnitqvnaPNGAIGCAFYI 83
Cdd:smart00756   1 PRWTRWILLILGLIGLLASLYLTYEKLTLLEDPDYVASCDINPVVSCGKVLSSPYASIFGI--------PLSLLGIAAYL 72

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62471731     84 LYFLSSFFNH------RWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIYFIHTWLFQEVLRR 146
Cdd:smart00756  73 VVLALAVLGLlgvtlpRWTWRLLFLGSLAGAVFSVYLIYLLVFVIKALCLYCILSAVVSISLFILVTIG 141
VKOR pfam07884
Vitamin K epoxide reductase family; Vitamin K epoxide reductase (VKOR) recycles reduced ...
 13-140 1.74e-17

Vitamin K epoxide reductase family; Vitamin K epoxide reductase (VKOR) recycles reduced vitamin K, which is used subsequently as a co-factor in the gamma-carboxylation of glutamic acid residues in blood coagulation enzymes. VKORC1 is a member of a large family of predicted enzymes that are present in vertebrates, Drosophila, plants, bacteria and archaea. Four cysteine residues and one residue, which is either serine or threonine, are identified as likely active-site residues. In some plant and bacterial homologs the VKORC1 homologous domain is fused with domains of the thioredoxin family of oxidoreductases.


Pssm-ID: 429714  Cd Length: 132  Bit Score: 73.41  E-value: 1.74e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731    13 GICVCGLAISVYSLYVKmkLKEDENYRPMCDVNDNISCSLVFKSGYGDGFGLgnitqvnaPNGAIGCAFYILYFLSSFFN 92
Cdd:pfam07884   5 VLALIGLLASAYLTLEK--LGPDPGYAASCDINGVVSCGKVLTSPYASVFGI--------PNALLGLLAYAVVAVLALAG 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 62471731    93 ------HRWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIYFIHTWLF 140
Cdd:pfam07884  75 lagarlPRWPWLLLLLGSLAGVVFSLYLIYISLFVIGALCPYCLVSAVVSLLLF 128
COG4243 COG4243
Vitamin K epoxide reductase (VKOR) family protein, predicted involvement in disulfide bond ...
 13-140 2.94e-10

Vitamin K epoxide reductase (VKOR) family protein, predicted involvement in disulfide bond formation [General function prediction only];


Pssm-ID: 443385  Cd Length: 161  Bit Score: 55.39  E-value: 2.94e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731  13 GICVCGLAISVYSLYVKMKLKEdENYRPMCDVNDNISCSLVFKSGYGDGFGLgnitqvnaPNGAIGCAFYI------LYF 86
Cdd:COG4243  17 VLALIGLLASFYLTLEKLTLLA-PGGVLSCDINPVVSCGSVLNSPQASVFGF--------PNALLGLAAFAvvitlaVAL 87

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 62471731  87 LSSFFNHRWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIYFIHTWLF 140
Cdd:COG4243  88 LAGARLPRWLWLALLAGALAGVVFSVWLIYQSLFVIGALCPYCLVVWAVTIPLF 141
 
Name Accession Description Interval E-value
VKOR_euk cd12917
Vitamin K epoxide reductase family in eukaryotes, excluding plants; This family includes ...
 9-135 2.58e-45

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.


Pssm-ID: 240600 [Multi-domain]  Cd Length: 140  Bit Score: 144.67  E-value: 2.58e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731   9 SRLRGICVCGLAISVYSLYVKMKLKEDENYRPMCDVNDNISCSLVFKSGYGDGFGL-----GNITQVNAPNGAIGCAFYI 83
Cdd:cd12917   1 LLRLALCLAGLLLSLYALYVELKKERDPDYRALCDISESISCSKVFSSRYGRGFGLlglilGKDSILNQPNSVFGIIFYI 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 62471731  84 LYFLSSFFNHRWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIYFI 135
Cdd:cd12917  81 LQLLLGLTNSAVAALLLLTLSILSVVGSLYLAYILYFVLKDFCIVCVSTYVV 132
VKc smart00756
Family of likely enzymes that includes the catalytic subunit of vitamin K epoxide reductase; ...
 4-146 2.97e-32

Family of likely enzymes that includes the catalytic subunit of vitamin K epoxide reductase; Bacterial homologues are fused to members of the thioredoxin family of oxidoreductases.


Pssm-ID: 214805  Cd Length: 142  Bit Score: 111.66  E-value: 2.97e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731      4 AYSTASRLRGICVCGLAISVYSLYVKMKLKEDENYRPMCDVNDNISCSLVFKSGYGDGFGLgnitqvnaPNGAIGCAFYI 83
Cdd:smart00756   1 PRWTRWILLILGLIGLLASLYLTYEKLTLLEDPDYVASCDINPVVSCGKVLSSPYASIFGI--------PLSLLGIAAYL 72

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62471731     84 LYFLSSFFNH------RWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIYFIHTWLFQEVLRR 146
Cdd:smart00756  73 VVLALAVLGLlgvtlpRWTWRLLFLGSLAGAVFSVYLIYLLVFVIKALCLYCILSAVVSISLFILVTIG 141
VKOR pfam07884
Vitamin K epoxide reductase family; Vitamin K epoxide reductase (VKOR) recycles reduced ...
 13-140 1.74e-17

Vitamin K epoxide reductase family; Vitamin K epoxide reductase (VKOR) recycles reduced vitamin K, which is used subsequently as a co-factor in the gamma-carboxylation of glutamic acid residues in blood coagulation enzymes. VKORC1 is a member of a large family of predicted enzymes that are present in vertebrates, Drosophila, plants, bacteria and archaea. Four cysteine residues and one residue, which is either serine or threonine, are identified as likely active-site residues. In some plant and bacterial homologs the VKORC1 homologous domain is fused with domains of the thioredoxin family of oxidoreductases.


Pssm-ID: 429714  Cd Length: 132  Bit Score: 73.41  E-value: 1.74e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731    13 GICVCGLAISVYSLYVKmkLKEDENYRPMCDVNDNISCSLVFKSGYGDGFGLgnitqvnaPNGAIGCAFYILYFLSSFFN 92
Cdd:pfam07884   5 VLALIGLLASAYLTLEK--LGPDPGYAASCDINGVVSCGKVLTSPYASVFGI--------PNALLGLLAYAVVAVLALAG 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 62471731    93 ------HRWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIYFIHTWLF 140
Cdd:pfam07884  75 lagarlPRWPWLLLLLGSLAGVVFSLYLIYISLFVIGALCPYCLVSAVVSLLLF 128
COG4243 COG4243
Vitamin K epoxide reductase (VKOR) family protein, predicted involvement in disulfide bond ...
 13-140 2.94e-10

Vitamin K epoxide reductase (VKOR) family protein, predicted involvement in disulfide bond formation [General function prediction only];


Pssm-ID: 443385  Cd Length: 161  Bit Score: 55.39  E-value: 2.94e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731  13 GICVCGLAISVYSLYVKMKLKEdENYRPMCDVNDNISCSLVFKSGYGDGFGLgnitqvnaPNGAIGCAFYI------LYF 86
Cdd:COG4243  17 VLALIGLLASFYLTLEKLTLLA-PGGVLSCDINPVVSCGSVLNSPQASVFGF--------PNALLGLAAFAvvitlaVAL 87

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 62471731  87 LSSFFNHRWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIYFIHTWLF 140
Cdd:COG4243  88 LAGARLPRWLWLALLAGALAGVVFSVWLIYQSLFVIGALCPYCLVVWAVTIPLF 141
VKOR_5 cd12922
Vitamin K epoxide reductase family in bacteria; This family includes vitamin K epoxide ...
 18-140 4.31e-05

Vitamin K epoxide reductase family in bacteria; This family includes vitamin K epoxide reductase (VKOR) mostly present in actinobacteria. 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. In some 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.


Pssm-ID: 240605  Cd Length: 133  Bit Score: 40.64  E-value: 4.31e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731  18 GLAISVYSLYVKMKLKEDENYRPMCDVNDNISCSLVFKSGYGDGFGLgnitqvnaPNGAIGCAFYI------LYFLSSFF 91
Cdd:cd12922  10 GLVASFVLTVEKIQLLEDPDYVLSCDINPVVSCGSVMQSWQASLFGF--------PNPLIGLAAFAvvitvgVALLAGAR 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 62471731  92 NHRWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIYFIHTWLF 140
Cdd:cd12922  82 LPRWFWVGLQAGLAAGLVFVHWLIYQSLFVIGALCPYCMVVWAVTIPLF 130
VKOR cd10546
Vitamin K epoxide reductase (VKOR) family; VKOR (also named VKORC1) is an integral membrane ...
 14-133 2.19e-03

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.


Pssm-ID: 240598  Cd Length: 126  Bit Score: 35.86  E-value: 2.19e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62471731  14 ICVCGLAISVYSLYVKMklkeDENYRPMCDVNDNISCSLVFKSGYGDGFGLgnitqvnaPNGAIGCAFYILYFLSSFF-- 91
Cdd:cd10546   6 LAAIGLLVSLYLTYYEL----TEGAVAGCDAGPSSSCDLVLTSRWSRIFGV--------PLSLLGALYYLVVLGLLLSpp 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 62471731  92 -NHRWLCLVQLIVCTLTLLLCVYLGFLLILVFYDFCLVCVTIY 133
Cdd:cd10546  74 aGARLRWTALAAATFAGLGAAAWLIYLQLFVLGAFCPYCLVAH 116
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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