VKORL_RAT
ID VKORL_RAT Reviewed; 176 AA.
AC Q6TEK3;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 96.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
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 TISSUE SPECIFICITY, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP SUBCELLULAR LOCATION.
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:0000305|PubMed:23928358}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:23928358}.
CC -!- TISSUE SPECIFICITY: Detected in lung, liver, testis, and at lower
CC levels in kidney and brain. {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 -!- SIMILARITY: Belongs to the VKOR family. {ECO:0000305}.
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DR EMBL; AY423048; AAR82918.1; -; mRNA.
DR RefSeq; NP_976083.1; NM_203338.1.
DR RefSeq; XP_008764222.1; XM_008766000.2.
DR AlphaFoldDB; Q6TEK3; -.
DR SMR; Q6TEK3; -.
DR STRING; 10116.ENSRNOP00000024691; -.
DR BindingDB; Q6TEK3; -.
DR jPOST; Q6TEK3; -.
DR PaxDb; Q6TEK3; -.
DR PRIDE; Q6TEK3; -.
DR GeneID; 399684; -.
DR KEGG; rno:399684; -.
DR CTD; 154807; -.
DR RGD; 1303249; Vkorc1l1.
DR VEuPathDB; HostDB:ENSRNOG00000000901; -.
DR eggNOG; ENOG502S4E7; Eukaryota.
DR HOGENOM; CLU_105471_0_0_1; -.
DR InParanoid; Q6TEK3; -.
DR OMA; CDISENI; -.
DR OrthoDB; 1611169at2759; -.
DR PhylomeDB; Q6TEK3; -.
DR Reactome; R-RNO-6806664; Metabolism of vitamin K.
DR PRO; PR:Q6TEK3; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000018291; Expressed in frontal cortex and 2 other tissues.
DR Genevisible; Q6TEK3; RN.
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_0000191673"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..91
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 92..112
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 113
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 135..155
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 156..176
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
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
