VKORL_MOUSE
ID VKORL_MOUSE Reviewed; 176 AA.
AC Q6TEK5; Q05AD4;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Vitamin K epoxide reductase complex subunit 1-like protein 1;
DE Short=VKORC1-like protein 1;
DE EC=1.17.4.4 {ECO:0000269|PubMed:23928358};
GN Name=Vkorc1l1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Kidney;
RX PubMed=14765194; DOI=10.1038/nature02214;
RA Rost S., Fregin A., Ivaskevicius V., Conzelmann E., Hoertnagel K.,
RA Pelz H.-J., Lappegard K., Seifried E., Scharrer I., Tuddenham E.G.D.,
RA Mueller C.R., Strom T.M., Oldenburg J.;
RT "Mutations in VKORC1 cause warfarin resistance and multiple coagulation
RT factor deficiency type 2.";
RL Nature 427:537-541(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION, CATALYTIC ACTIVITY, AND
RP ACTIVITY REGULATION.
RX PubMed=23928358; DOI=10.1074/jbc.m113.457119;
RA Hammed A., Matagrin B., Spohn G., Prouillac C., Benoit E., Lattard V.;
RT "VKORC1L1, an enzyme rescuing the vitamin K 2,3-epoxide reductase activity
RT in some extrahepatic tissues during anticoagulation therapy.";
RL J. Biol. Chem. 288:28733-28742(2013).
CC -!- FUNCTION: Involved in vitamin K metabolism. Can reduce inactive vitamin
CC K 2,3-epoxide to active vitamin K (in vitro), and may contribute to
CC vitamin K-mediated protection against oxidative stress. Plays a role in
CC vitamin K-dependent gamma-carboxylation of Glu residues in target
CC proteins. {ECO:0000269|PubMed:23928358}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-disulfide + H2O + phylloquinone = 2,3-
CC epoxyphylloquinone + [protein]-dithiol; Xref=Rhea:RHEA:13817,
CC Rhea:RHEA-COMP:10593, Rhea:RHEA-COMP:10594, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15759, ChEBI:CHEBI:18067, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:50058; EC=1.17.4.4;
CC Evidence={ECO:0000269|PubMed:23928358};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-disulfide + phylloquinol = [protein]-dithiol +
CC phylloquinone; Xref=Rhea:RHEA:57744, Rhea:RHEA-COMP:10593, Rhea:RHEA-
CC COMP:10594, ChEBI:CHEBI:18067, ChEBI:CHEBI:28433, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:50058; EC=1.17.4.4;
CC Evidence={ECO:0000269|PubMed:23928358};
CC -!- ACTIVITY REGULATION: Inhibited by warfarin (coumadin).
CC {ECO:0000269|PubMed:23928358}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23928358}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:23928358}.
CC -!- TISSUE SPECIFICITY: Detected in testis and lung.
CC {ECO:0000269|PubMed:23928358}.
CC -!- MISCELLANEOUS: The location of two cysteine active-site residues within
CC a proposed transmembrane is consistent both with the known hydrophobic
CC environment of the thiol redox site of the enzyme and with the
CC lipophilicity of vitamin K and warfarin (coumadin).
CC -!- MISCELLANEOUS: Vkorc1l1 overexpression cannot rescue the lethal
CC phenotype of Vkorc1-deficient mice, suggesting that the protein does
CC not play a major role in vitamin K-dependent blood coagulation.
CC -!- SIMILARITY: Belongs to the VKOR family. {ECO:0000305}.
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DR EMBL; AY423046; AAR82916.1; -; mRNA.
DR EMBL; BC125315; AAI25316.1; -; mRNA.
DR EMBL; BC138132; AAI38133.1; -; mRNA.
DR CCDS; CCDS19703.1; -.
DR RefSeq; NP_081397.1; NM_027121.4.
DR AlphaFoldDB; Q6TEK5; -.
DR SMR; Q6TEK5; -.
DR BioGRID; 213537; 2.
DR STRING; 10090.ENSMUSP00000073601; -.
DR PhosphoSitePlus; Q6TEK5; -.
DR SwissPalm; Q6TEK5; -.
DR EPD; Q6TEK5; -.
DR MaxQB; Q6TEK5; -.
DR PaxDb; Q6TEK5; -.
DR PeptideAtlas; Q6TEK5; -.
DR PRIDE; Q6TEK5; -.
DR ProteomicsDB; 300170; -.
DR Antibodypedia; 57350; 98 antibodies from 17 providers.
DR DNASU; 69568; -.
DR Ensembl; ENSMUST00000051758; ENSMUSP00000059139; ENSMUSG00000066735.
DR GeneID; 69568; -.
DR KEGG; mmu:69568; -.
DR UCSC; uc008ztr.2; mouse.
DR CTD; 154807; -.
DR MGI; MGI:1916818; Vkorc1l1.
DR VEuPathDB; HostDB:ENSMUSG00000066735; -.
DR eggNOG; ENOG502S4E7; Eukaryota.
DR GeneTree; ENSGT00940000157044; -.
DR HOGENOM; CLU_105471_2_0_1; -.
DR InParanoid; Q6TEK5; -.
DR OMA; CDISENI; -.
DR OrthoDB; 1611169at2759; -.
DR PhylomeDB; Q6TEK5; -.
DR TreeFam; TF328467; -.
DR BRENDA; 1.17.4.4; 3474.
DR Reactome; R-MMU-6806664; Metabolism of vitamin K.
DR BioGRID-ORCS; 69568; 11 hits in 70 CRISPR screens.
DR ChiTaRS; Vkorc1l1; mouse.
DR PRO; PR:Q6TEK5; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q6TEK5; protein.
DR Bgee; ENSMUSG00000066735; Expressed in embryonic post-anal tail and 216 other tissues.
DR ExpressionAtlas; Q6TEK5; baseline and differential.
DR Genevisible; Q6TEK5; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048038; F:quinone binding; IEA:UniProtKB-KW.
DR GO; GO:0047057; F:vitamin-K-epoxide reductase (warfarin-sensitive) activity; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0017187; P:peptidyl-glutamic acid carboxylation; ISS:UniProtKB.
DR GO; GO:0042373; P:vitamin K metabolic process; IDA:UniProtKB.
DR CDD; cd12917; VKOR_euk; 1.
DR Gene3D; 1.20.1440.130; -; 1.
DR InterPro; IPR012932; VKOR.
DR InterPro; IPR038354; VKOR_sf.
DR InterPro; IPR042406; VKORC1/VKORC1L1.
DR PANTHER; PTHR14519; PTHR14519; 1.
DR Pfam; PF07884; VKOR; 1.
DR SMART; SM00756; VKc; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Endoplasmic reticulum; Membrane; Oxidoreductase; Quinone;
KW Redox-active center; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..176
FT /note="Vitamin K epoxide reductase complex subunit 1-like
FT protein 1"
FT /id="PRO_0000191672"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..88
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 89..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..117
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..135
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 136..139
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..176
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT SITE 50
FT /note="Important for the reduction of the redox-active
FT cysteines"
FT /evidence="ECO:0000250"
FT SITE 58
FT /note="Important for the reduction of the redox-active
FT cysteines"
FT /evidence="ECO:0000250"
FT DISULFID 139..142
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 176 AA; 19779 MW; 0B713A95CB3B0E00 CRC64;
MAAPVLLRVS VPRWERVARY AVCAAGILLS IYAYHVEREK ERDPEHRALC DLGPWVKCSA
ALASRWGRGF GLLGSIFGKD GVLNQPNSVF GLIFYILQLL LGMTASAVAA LVLMTSSIVS
VVGSLYLAYI LYFVLKEFCI ICVTTYVLNF LLLIINYKRL VYLNEAWKRQ LQPKED
