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Protein

Vitamin K epoxide reductase complex subunit 1-like protein 1

Gene

VKORC1L1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in vitamin K metabolism. Can reduce inactive vitamin K 2,3-epoxide to active vitamin K (in vitro), and may contribute to vitamin K-mediated protection against oxidative stress. Plays a role in vitamin K-dependent gamma-carboxylation of Glu residues in target proteins.3 Publications

Catalytic activityi

Phylloquinone + oxidized dithiothreitol + H2O = 2,3-epoxy-2-methyl-3-phytyl-2,3-dihydro-1,4-naphthoquinone + 1,4-dithiothreitol.3 Publications

Enzyme regulationi

Inhibited by warfarin (coumadin).3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei50 – 501Important for the reduction of the redox-active cysteinesCurated
Sitei58 – 581Important for the reduction of the redox-active cysteinesCurated

GO - Molecular functioni

  • quinone binding Source: UniProtKB-KW
  • vitamin-K-epoxide reductase (warfarin-sensitive) activity Source: UniProtKB

GO - Biological processi

  • cellular response to oxidative stress Source: UniProtKB
  • fat-soluble vitamin metabolic process Source: Reactome
  • peptidyl-glutamic acid carboxylation Source: UniProtKB
  • small molecule metabolic process Source: Reactome
  • vitamin K metabolic process Source: UniProtKB
  • vitamin metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Enzyme and pathway databases

BRENDAi1.1.4.2. 2681.
ReactomeiR-HSA-6806664. Metabolism of vitamin K.

Names & Taxonomyi

Protein namesi
Recommended name:
Vitamin K epoxide reductase complex subunit 1-like protein 1 (EC:1.17.4.43 Publications)
Short name:
VKORC1-like protein 1
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:21492. VKORC1L1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1616Cytoplasmic1 PublicationAdd
BLAST
Transmembranei17 – 3721HelicalSequence analysisAdd
BLAST
Topological domaini38 – 9154LumenalSequence analysisAdd
BLAST
Transmembranei92 – 11221HelicalSequence analysisAdd
BLAST
Topological domaini113 – 1131CytoplasmicSequence analysis
Transmembranei114 – 13421HelicalSequence analysisAdd
BLAST
Transmembranei135 – 15521HelicalSequence analysisAdd
BLAST
Topological domaini156 – 17621Cytoplasmic1 PublicationAdd
BLAST

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi50 – 501C → S: Abolishes enzyme activity in cell-based assays. Reduces enzyme activity moderately in assays that regenerate the redox-active cysteines with dithiothreitol (in vitro). 1 Publication
Mutagenesisi58 – 581C → S: Abolishes enzyme activity in cell-based assays. Reduces enzyme activity moderately in assays that regenerate the redox-active cysteines with dithiothreitol (in vitro). 1 Publication

Organism-specific databases

PharmGKBiPA134931578.

Chemistry

DrugBankiDB00170. Menadione.

Polymorphism and mutation databases

DMDMi62511214.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 176176Vitamin K epoxide reductase complex subunit 1-like protein 1PRO_0000191671Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi139 ↔ 142Redox-activeBy similarity

Keywords - PTMi

Disulfide bond, Quinone

Proteomic databases

EPDiQ8N0U8.
MaxQBiQ8N0U8.
PaxDbiQ8N0U8.
PRIDEiQ8N0U8.

PTM databases

iPTMnetiQ8N0U8.
PhosphoSiteiQ8N0U8.
SwissPalmiQ8N0U8.

Expressioni

Inductioni

Up-regulated in response to oxidative stress induced by hydrogen peroxide treatment.1 Publication

Gene expression databases

BgeeiQ8N0U8.
CleanExiHS_VKORC1L1.
GenevisibleiQ8N0U8. HS.

Organism-specific databases

HPAiHPA053954.

Interactioni

Protein-protein interaction databases

BioGridi127558. 17 interactions.
IntActiQ8N0U8. 4 interactions.
STRINGi9606.ENSP00000353998.

Structurei

3D structure databases

ProteinModelPortaliQ8N0U8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the VKOR family.Curated

Keywords - Domaini

Redox-active center, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J0HT. Eukaryota.
ENOG4111UX7. LUCA.
GeneTreeiENSGT00700000105491.
HOGENOMiHOG000230752.
HOVERGENiHBG076672.
InParanoidiQ8N0U8.
KOiK05357.
OMAiVICITTY.
OrthoDBiEOG7TQV2D.
PhylomeDBiQ8N0U8.
TreeFamiTF328467.

Family and domain databases

InterProiIPR012932. VKOR.
[Graphical view]
PfamiPF07884. VKOR. 1 hit.
[Graphical view]
SMARTiSM00756. VKc. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N0U8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAPVLLRVS VPRWERVARY AVCAAGILLS IYAYHVEREK ERDPEHRALC
60 70 80 90 100
DLGPWVKCSA ALASRWGRGF GLLGSIFGKD GVLNQPNSVF GLIFYILQLL
110 120 130 140 150
LGMTASAVAA LILMTSSIMS VVGSLYLAYI LYFVLKEFCI ICIVTYVLNF
160 170
LLLIINYKRL VYLNEAWKRQ LQPKQD
Length:176
Mass (Da):19,836
Last modified:August 16, 2004 - v2
Checksum:i1AB0FCDCC2B00E00
GO
Isoform 2 (identifier: Q8N0U8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     66-176: WGRGFGLLGS...WKRQLQPKQD → HDSKRCGGFD...IIIIHNRHFP

Show »
Length:177
Mass (Da):19,753
Checksum:i0B2CCE4956AF46A0
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Isoform 2 (identifier: Q8N0U8-2)
Sequence conflicti163 – 1631F → FI in BAG64984 (PubMed:14702039).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei66 – 176111WGRGF…QPKQD → HDSKRCGGFDPHDVLHHVGR GVPVPGLHSVLCAEGVLHHL HRHVRAELPSSHYQLQTTSL LERGLEAAAATQAGLTPDRL HPNSLKPLSIQFILQQVFII IIIIIIHNRHFP in isoform 2. 1 PublicationVSP_055709Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY423045 mRNA. Translation: AAR82915.1.
AK304077 mRNA. Translation: BAG64984.1.
AC073261 Genomic DNA. No translation available.
AC093485 Genomic DNA. No translation available.
AC093582 Genomic DNA. No translation available.
BC027734 mRNA. Translation: AAH27734.2.
CR627471 mRNA. Translation: CAH10673.1.
CCDSiCCDS5529.1. [Q8N0U8-1]
CCDS64663.1. [Q8N0U8-2]
RefSeqiNP_001271271.1. NM_001284342.1. [Q8N0U8-2]
NP_775788.2. NM_173517.4. [Q8N0U8-1]
UniGeneiHs.427232.

Genome annotation databases

EnsembliENST00000360768; ENSP00000353998; ENSG00000196715. [Q8N0U8-1]
ENST00000434382; ENSP00000403077; ENSG00000196715. [Q8N0U8-2]
GeneIDi154807.
KEGGihsa:154807.
UCSCiuc003tum.3. human. [Q8N0U8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY423045 mRNA. Translation: AAR82915.1.
AK304077 mRNA. Translation: BAG64984.1.
AC073261 Genomic DNA. No translation available.
AC093485 Genomic DNA. No translation available.
AC093582 Genomic DNA. No translation available.
BC027734 mRNA. Translation: AAH27734.2.
CR627471 mRNA. Translation: CAH10673.1.
CCDSiCCDS5529.1. [Q8N0U8-1]
CCDS64663.1. [Q8N0U8-2]
RefSeqiNP_001271271.1. NM_001284342.1. [Q8N0U8-2]
NP_775788.2. NM_173517.4. [Q8N0U8-1]
UniGeneiHs.427232.

3D structure databases

ProteinModelPortaliQ8N0U8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127558. 17 interactions.
IntActiQ8N0U8. 4 interactions.
STRINGi9606.ENSP00000353998.

Chemistry

DrugBankiDB00170. Menadione.

PTM databases

iPTMnetiQ8N0U8.
PhosphoSiteiQ8N0U8.
SwissPalmiQ8N0U8.

Polymorphism and mutation databases

DMDMi62511214.

Proteomic databases

EPDiQ8N0U8.
MaxQBiQ8N0U8.
PaxDbiQ8N0U8.
PRIDEiQ8N0U8.

Protocols and materials databases

DNASUi154807.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360768; ENSP00000353998; ENSG00000196715. [Q8N0U8-1]
ENST00000434382; ENSP00000403077; ENSG00000196715. [Q8N0U8-2]
GeneIDi154807.
KEGGihsa:154807.
UCSCiuc003tum.3. human. [Q8N0U8-1]

Organism-specific databases

CTDi154807.
GeneCardsiVKORC1L1.
H-InvDBHIX0006716.
HGNCiHGNC:21492. VKORC1L1.
HPAiHPA053954.
MIMi608838. gene.
neXtProtiNX_Q8N0U8.
PharmGKBiPA134931578.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0HT. Eukaryota.
ENOG4111UX7. LUCA.
GeneTreeiENSGT00700000105491.
HOGENOMiHOG000230752.
HOVERGENiHBG076672.
InParanoidiQ8N0U8.
KOiK05357.
OMAiVICITTY.
OrthoDBiEOG7TQV2D.
PhylomeDBiQ8N0U8.
TreeFamiTF328467.

Enzyme and pathway databases

BRENDAi1.1.4.2. 2681.
ReactomeiR-HSA-6806664. Metabolism of vitamin K.

Miscellaneous databases

ChiTaRSiVKORC1L1. human.
GenomeRNAii154807.
NextBioi35477180.
PROiQ8N0U8.
SOURCEiSearch...

Gene expression databases

BgeeiQ8N0U8.
CleanExiHS_VKORC1L1.
GenevisibleiQ8N0U8. HS.

Family and domain databases

InterProiIPR012932. VKOR.
[Graphical view]
PfamiPF07884. VKOR. 1 hit.
[Graphical view]
SMARTiSM00756. VKc. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Kidney.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Trachea.
  3. "The DNA sequence of human chromosome 7."
    Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
    , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
    Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Lymph.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 71-176 (ISOFORM 1).
    Tissue: Melanoma.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "Human vitamin K 2,3-epoxide reductase complex subunit 1-like 1 (VKORC1L1) mediates vitamin K-dependent intracellular antioxidant function."
    Westhofen P., Watzka M., Marinova M., Hass M., Kirfel G., Muller J., Bevans C.G., Muller C.R., Oldenburg J.
    J. Biol. Chem. 286:15085-15094(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, INDUCTION BY OXIDATIVE STRESS.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "VKORC1L1, an enzyme rescuing the vitamin K 2,3-epoxide reductase activity in some extrahepatic tissues during anticoagulation therapy."
    Hammed A., Matagrin B., Spohn G., Prouillac C., Benoit E., Lattard V.
    J. Biol. Chem. 288:28733-28742(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION.
  10. "Conserved loop cysteines of vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) are involved in its active site regeneration."
    Tie J.K., Jin D.Y., Stafford D.W.
    J. Biol. Chem. 289:9396-9407(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY, SUBCELLULAR LOCATION, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, MUTAGENESIS OF CYS-50 AND CYS-58.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiVKORL_HUMAN
AccessioniPrimary (citable) accession number: Q8N0U8
Secondary accession number(s): B4E222
, E7ETM5, Q6AHW9, Q6TEK6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: August 16, 2004
Last modified: March 16, 2016
This is version 99 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

The location of two cysteine active-site residues within a proposed transmembrane is consistent both with the known hydrophobic environment of the thiol redox site of the enzyme and with the lipophilicity of vitamin K and warfarin (coumadin).

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.