Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
5  structures 2464  species 0  interactions 3206  sequences 31  architectures

Family: VKOR (PF07884)

Summary: Vitamin K epoxide reductase family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Vitamin K epoxide reductase". More...

Vitamin K epoxide reductase Edit Wikipedia article

Vitamin K epoxide reductase (warfarin-sensitive)
Vitamin K epoxide reductase.svg
Reaction
Identifiers
EC number1.17.4.4
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Vitamin K epoxide reductase
EBI PDB 3kp9 transmembrane.png
Structure of a bacterial VKOR, membrane denoted as lines (PDB: 3KP9​).
Identifiers
SymbolVKOR
PfamPF07884
InterProIPR012932
CATH3kp9
TCDB9.B.265
OPM superfamily18
OPM protein3kp9

Vitamin K epoxide reductase (VKOR) is an enzyme (EC 1.17.4.4) that reduces vitamin K after it has been oxidised in the carboxylation of glutamic acid residues in blood coagulation enzymes. VKOR is a member of a large family of predicted enzymes that are present in vertebrates, Drosophila, plants, bacteria and archaea.[1] In some plant and bacterial homologues, the VKOR domain is fused with domains of the thioredoxin family of oxidoreductases.[1]

Four cysteine residues and one residue, which is either serine or threonine, are identified as likely active-site residues.[1] Solved bacterial VKOR structures has enabled more insights into the catalytic mechanism. All VKORs are transmembrane proteins with at least three TM helices at the catalytic core. The quinone to be reduced is bound by a redox-active CXXC motif in the C-terminal helices, similar to the DsbB active site. Two other cysteines to the N-terminal are located in a loop outside of the transmembrane region; they relay electrons with a redox protein (or in the case of the bacterial homolog, its own fused domain).[2][3]

The human gene for VKOR is called VKORC1 (VKOR complex subunit 1). It is the target of anticoagulant warfarin. Its partner is a redox protein with an unknown identity.[4][5] There is also a similar gene called VKORC1L1.

References

  1. ^ a b c Goodstadt L, Ponting CP (June 2004). "Vitamin K epoxide reductase: homology, active site and catalytic mechanism". Trends in Biochemical Sciences. 29 (6): 289–92. doi:10.1016/j.tibs.2004.04.004. PMID 15276181.
  2. ^ Li W, Schulman S, Dutton RJ, Boyd D, Beckwith J, Rapoport TA (January 2010). "Structure of a bacterial homologue of vitamin K epoxide reductase". Nature. 463 (7280): 507–12. Bibcode:2010Natur.463..507L. doi:10.1038/nature08720. PMC 2919313. PMID 20110994.
  3. ^ Rishavy MA, Usubalieva A, Hallgren KW, Berkner KL (March 2011). "Novel insight into the mechanism of the vitamin K oxidoreductase (VKOR): electron relay through Cys43 and Cys51 reduces VKOR to allow vitamin K reduction and facilitation of vitamin K-dependent protein carboxylation". The Journal of Biological Chemistry. 286 (9): 7267–78. doi:10.1074/jbc.M110.172213. PMC 3044983. PMID 20978134.
  4. ^ Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW (February 2004). "Identification of the gene for vitamin K epoxide reductase". Nature. 427 (6974): 541–4. Bibcode:2004Natur.427..541L. doi:10.1038/nature02254. PMID 14765195.
  5. ^ Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hörtnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Müller CR, Strom TM, Oldenburg J (February 2004). "Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2". Nature. 427 (6974): 537–41. Bibcode:2004Natur.427..537R. doi:10.1038/nature02214. PMID 14765194.
This article incorporates text from the public domain Pfam and InterPro: IPR012932

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Vitamin K epoxide reductase family Provide feedback

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 [1]. Four cysteine residues and one residue, which is either serine or threonine, are identified as likely active-site residues [1]. In some plant and bacterial homologues the VKORC1 homologous domain is fused with domains of the thioredoxin family of oxidoreductases [1].

Literature references

  1. Goodstadt L, Ponting CP; , Trends Biochem Sci 2004;29:289-292.: Vitamin K epoxide reductase: homology, active site and catalytic mechanism. PUBMED:15276181 EPMC:15276181


This tab holds annotation information from the InterPro database.

InterPro entry IPR012932

Vitamin K epoxide reductase (VKOR) recycles vitamin K 2,3-epoxide to vitamin K hydroquinone, a co-factor that is essential for the posttranslational gamma-carboxylation of several blood coagulation factors [PUBMED:14765194]. VKORC1, the catalytic subunit of the VKOR complex, is a member of a large family of predicted enzymes that are present in vertebrates, Drosophila, plants, bacteria and archaea [PUBMED:15276181]. Bacterial VKOR homologues catalyse disulphide bridge formation in secreted proteins by cooperating with a periplasmic, Trx-like redox partner [PUBMED:18413314, PUBMED:18695247]. In fact, in some plant and bacterial homologues the VKORC1 homologous domain is fused with domains of the thioredoxin family of oxidoreductases [PUBMED:15276181]. VKOR is part of a disulphide bond formation pathway that uses electrons from cysteines of newly synthesized proteins to reduce a quinone [PUBMED:20110994].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(286)
Full
(3206)
Representative proteomes UniProt
(7153)
NCBI
(8989)
Meta
(299)
RP15
(912)
RP35
(2200)
RP55
(3276)
RP75
(4295)
Jalview View  View  View  View  View  View  View  View  View 
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(286)
Full
(3206)
Representative proteomes UniProt
(7153)
NCBI
(8989)
Meta
(299)
RP15
(912)
RP35
(2200)
RP55
(3276)
RP75
(4295)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(286)
Full
(3206)
Representative proteomes UniProt
(7153)
NCBI
(8989)
Meta
(299)
RP15
(912)
RP35
(2200)
RP55
(3276)
RP75
(4295)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: [1]
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 286
Number in full: 3206
Average length of the domain: 130.00 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 46.97 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.5 27.5
Trusted cut-off 27.6 27.6
Noise cut-off 27.3 27.4
Model length: 124
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the VKOR domain has been found. There are 5 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

Loading structure mapping...