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Conserved domains on  [gi|912758878|ref|NP_001298240|]
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vitamin K epoxide reductase complex subunit 1 isoform 3 [Homo sapiens]

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 ...
 10-177 1.97e-62

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: 189.74  E-value: 1.97e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  10 WVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRWGRGFGLVEHVLGQDSILNQSNSIFGCIFYT 89
Cdd:cd12917    1 LLRLALCLAGLLLSLYALYVELKKERDPDYRALCDISESISCSKVFSSRYGRGFGLLGLILGKDSILNQPNSVFGIIFYI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  90 LQLLLEMV-SRHVAQAGLKQSVCLSLPkcwgdyrrclrtrwasvlmllsslvslagSVYLAWILFFVLYDFCIVCITTYA 168
Cdd:cd12917   81 LQLLLGLTnSAVAALLLLTLSILSVVG-----------------------------SLYLAYILYFVLKDFCIVCVSTYV 131


                 ....*....
gi 912758878 169 INVSLMWLS 177
Cdd:cd12917  132 VNFLLLILN 140
 
Name Accession Description Interval E-value
VKOR_euk cd12917
Vitamin K epoxide reductase family in eukaryotes, excluding plants; This family includes ...
 10-177 1.97e-62

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: 189.74  E-value: 1.97e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  10 WVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRWGRGFGLVEHVLGQDSILNQSNSIFGCIFYT 89
Cdd:cd12917    1 LLRLALCLAGLLLSLYALYVELKKERDPDYRALCDISESISCSKVFSSRYGRGFGLLGLILGKDSILNQPNSVFGIIFYI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  90 LQLLLEMV-SRHVAQAGLKQSVCLSLPkcwgdyrrclrtrwasvlmllsslvslagSVYLAWILFFVLYDFCIVCITTYA 168
Cdd:cd12917   81 LQLLLGLTnSAVAALLLLTLSILSVVG-----------------------------SLYLAYILYFVLKDFCIVCVSTYV 131


                 ....*....
gi 912758878 169 INVSLMWLS 177
Cdd:cd12917  132 VNFLLLILN 140
VKc smart00756
Family of likely enzymes that includes the catalytic subunit of vitamin K epoxide reductase; ...
 5-181 9.04e-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: 112.04  E-value: 9.04e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878     5 WGSPGWVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRWGRGFGlvehvlgqdsilnQSNSIFG 84
Cdd:smart00756   1 PRWTRWILLILGLIGLLASLYLTYEKLTLLEDPDYVASCDINPVVSCGKVLSSPYASIFG-------------IPLSLLG 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878    85 CIFYTLQLLLemvsrhvaqaglkqSVCLSLPKCWgdyrrclrTRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCI 164
Cdd:smart00756  68 IAAYLVVLAL--------------AVLGLLGVTL--------PRWTWRLLFLGSLAGAVFSVYLIYLLVFVIKALCLYCI 125

                          170
                   ....*....|....*..
gi 912758878   165 TTYAINVSLMWLSFRKV 181
Cdd:smart00756 126 LSAVVSISLFILVTIGR 142
VKOR pfam07884
Vitamin K epoxide reductase family; Vitamin K epoxide reductase (VKOR) recycles reduced ...
 10-178 3.27e-19

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: 79.19  E-value: 3.27e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878   10 WVRLALCLTGLVLSLYALHVKaaRARDRDYRALCDVGTAISCSRVFSSRWGrgfglvehvlgqdSILNQSNSIFGCIFYT 89
Cdd:pfam07884   1 LLLLVLALIGLLASAYLTLEK--LGPDPGYAASCDINGVVSCGKVLTSPYA-------------SVFGIPNALLGLLAYA 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878   90 LQLLLemvsrhvaqaglkqSVCLSLPKCWgdyrrclrTRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAI 169
Cdd:pfam07884  66 VVAVL--------------ALAGLAGARL--------PRWPWLLLLLGSLAGVVFSLYLIYISLFVIGALCPYCLVSAVV 123


                  ....*....
gi 912758878  170 NVSLMWLSF 178
Cdd:pfam07884 124 SLLLFVLTL 132
COG4243 COG4243
Vitamin K epoxide reductase (VKOR) family protein, predicted involvement in disulfide bond ...
 1-178 1.76e-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: 56.93  E-value: 1.76e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878   1 MGSTWGSPGWVR---LALCLTGLVLSLYaLHVKAARARDRDYRALCDVGTAISCSRVFSSRWGRGFGLvehvlgqdsiln 77
Cdd:COG4243    1 MTSTRRRSRWLAwllLVLALIGLLASFY-LTLEKLTLLAPGGVLSCDINPVVSCGSVLNSPQASVFGF------------ 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  78 qSNSIFGCIFYTLQLLLEMVSrhvaqaglkqsvclslpkcwgdYRRCLRTRWASVLMLLSSLVSLAGSVYLAWILFFVLY 157
Cdd:COG4243   68 -PNALLGLAAFAVVITLAVAL----------------------LAGARLPRWLWLALLAGALAGVVFSVWLIYQSLFVIG 124

                        170       180
                 ....*....|....*....|.
gi 912758878 158 DFCIVCITTYAINVSLMWLSF 178
Cdd:COG4243  125 ALCPYCLVVWAVTIPLFVLTT 145
 
Name Accession Description Interval E-value
VKOR_euk cd12917
Vitamin K epoxide reductase family in eukaryotes, excluding plants; This family includes ...
 10-177 1.97e-62

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: 189.74  E-value: 1.97e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  10 WVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRWGRGFGLVEHVLGQDSILNQSNSIFGCIFYT 89
Cdd:cd12917    1 LLRLALCLAGLLLSLYALYVELKKERDPDYRALCDISESISCSKVFSSRYGRGFGLLGLILGKDSILNQPNSVFGIIFYI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  90 LQLLLEMV-SRHVAQAGLKQSVCLSLPkcwgdyrrclrtrwasvlmllsslvslagSVYLAWILFFVLYDFCIVCITTYA 168
Cdd:cd12917   81 LQLLLGLTnSAVAALLLLTLSILSVVG-----------------------------SLYLAYILYFVLKDFCIVCVSTYV 131


                 ....*....
gi 912758878 169 INVSLMWLS 177
Cdd:cd12917  132 VNFLLLILN 140
VKc smart00756
Family of likely enzymes that includes the catalytic subunit of vitamin K epoxide reductase; ...
 5-181 9.04e-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: 112.04  E-value: 9.04e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878     5 WGSPGWVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRWGRGFGlvehvlgqdsilnQSNSIFG 84
Cdd:smart00756   1 PRWTRWILLILGLIGLLASLYLTYEKLTLLEDPDYVASCDINPVVSCGKVLSSPYASIFG-------------IPLSLLG 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878    85 CIFYTLQLLLemvsrhvaqaglkqSVCLSLPKCWgdyrrclrTRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCI 164
Cdd:smart00756  68 IAAYLVVLAL--------------AVLGLLGVTL--------PRWTWRLLFLGSLAGAVFSVYLIYLLVFVIKALCLYCI 125

                          170
                   ....*....|....*..
gi 912758878   165 TTYAINVSLMWLSFRKV 181
Cdd:smart00756 126 LSAVVSISLFILVTIGR 142
VKOR pfam07884
Vitamin K epoxide reductase family; Vitamin K epoxide reductase (VKOR) recycles reduced ...
 10-178 3.27e-19

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: 79.19  E-value: 3.27e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878   10 WVRLALCLTGLVLSLYALHVKaaRARDRDYRALCDVGTAISCSRVFSSRWGrgfglvehvlgqdSILNQSNSIFGCIFYT 89
Cdd:pfam07884   1 LLLLVLALIGLLASAYLTLEK--LGPDPGYAASCDINGVVSCGKVLTSPYA-------------SVFGIPNALLGLLAYA 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878   90 LQLLLemvsrhvaqaglkqSVCLSLPKCWgdyrrclrTRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAI 169
Cdd:pfam07884  66 VVAVL--------------ALAGLAGARL--------PRWPWLLLLLGSLAGVVFSLYLIYISLFVIGALCPYCLVSAVV 123


                  ....*....
gi 912758878  170 NVSLMWLSF 178
Cdd:pfam07884 124 SLLLFVLTL 132
COG4243 COG4243
Vitamin K epoxide reductase (VKOR) family protein, predicted involvement in disulfide bond ...
 1-178 1.76e-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: 56.93  E-value: 1.76e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878   1 MGSTWGSPGWVR---LALCLTGLVLSLYaLHVKAARARDRDYRALCDVGTAISCSRVFSSRWGRGFGLvehvlgqdsiln 77
Cdd:COG4243    1 MTSTRRRSRWLAwllLVLALIGLLASFY-LTLEKLTLLAPGGVLSCDINPVVSCGSVLNSPQASVFGF------------ 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  78 qSNSIFGCIFYTLQLLLEMVSrhvaqaglkqsvclslpkcwgdYRRCLRTRWASVLMLLSSLVSLAGSVYLAWILFFVLY 157
Cdd:COG4243   68 -PNALLGLAAFAVVITLAVAL----------------------LAGARLPRWLWLALLAGALAGVVFSVWLIYQSLFVIG 124

                        170       180
                 ....*....|....*....|.
gi 912758878 158 DFCIVCITTYAINVSLMWLSF 178
Cdd:COG4243  125 ALCPYCLVVWAVTIPLFVLTT 145
VKOR cd10546
Vitamin K epoxide reductase (VKOR) family; VKOR (also named VKORC1) is an integral membrane ...
 10-177 8.85e-08

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: 48.95  E-value: 8.85e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  10 WVRLALCLTGLVLSLYALHVKAARARDrdyrALCDVGTAISCSRVFSSRWGRGFGLvehvlgqdsilnqSNSIFGCIFYT 89
Cdd:cd10546    1 LILLLLAAIGLLVSLYLTYYELTEGAV----AGCDAGPSSSCDLVLTSRWSRIFGV-------------PLSLLGALYYL 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  90 LQLLLEMVSRHVAqaglkqsvclslpkcwgdyrrclrtRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAI 169
Cdd:cd10546   64 VVLGLLLSPPAGA-------------------------RLRWTALAAATFAGLGAAAWLIYLQLFVLGAFCPYCLVAHAA 118


                 ....*...
gi 912758878 170 NVSLMWLS 177
Cdd:cd10546  119 GLALLALT 126
VKOR_1 cd12916
Vitamin K epoxide reductase family in bacteria and plants; This family includes vitamin K ...
 10-179 9.31e-03

Vitamin K epoxide reductase family in bacteria and 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. 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.


Pssm-ID: 240599  Cd Length: 133  Bit Score: 34.92  E-value: 9.31e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  10 WVRLALCLTGLVLSLYALHVKAarardRDYRALCdvGTAISCSRVFSSRWGRgfglvehvlgqdsILNQSNSIFGCIFYT 89
Cdd:cd12916    3 RLIAGLALIGLLETAYLTYVKL-----TGSSAVC--PGGGGCDTVLNSPYAT-------------LLGIPLSLFGFLAYL 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 912758878  90 LQLLLEMVSRHVAQAGLKqsvclslpkcwgdyrrclrtRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAI 169
Cdd:cd12916   63 AILVLAVLPLLLKSEKLE--------------------RWTWLLLFGLATAGVVFSAYLTYLLAFVIGAFCPYCLTSAVL 122

                        170
                 ....*....|
gi 912758878 170 NVSLMWLSFR 179
Cdd:cd12916  123 STLLFLLTIL 132
 
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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