VKOR1_MOUSE
ID VKOR1_MOUSE Reviewed; 161 AA.
AC Q9CRC0;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Vitamin K epoxide reductase complex subunit 1;
DE EC=1.17.4.4 {ECO:0000269|PubMed:15879509};
DE AltName: Full=Vitamin K1 2,3-epoxide reductase subunit 1;
GN Name=Vkorc1;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, Kidney, and Small intestine;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary gland;
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 DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19492146; DOI=10.1160/th09-03-0204;
RA Spohn G., Kleinridders A., Wunderlich F.T., Watzka M., Zaucke F.,
RA Blumbach K., Geisen C., Seifried E., Muller C., Paulsson M., Bruning J.C.,
RA Oldenburg J.;
RT "VKORC1 deficiency in mice causes early postnatal lethality due to severe
RT bleeding.";
RL Thromb. Haemost. 101:1044-1050(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, Lung, Pancreas, 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 [5]
RP VARIANTS SER-128 AND CYS-139, ACTIVITY REGULATION, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=15879509; DOI=10.1534/genetics.104.040360;
RA Pelz H.J., Rost S., Hunerberg M., Fregin A., Heiberg A.C., Baert K.,
RA MacNicoll A.D., Prescott C.V., Walker A.S., Oldenburg J., Muller C.R.;
RT "The genetic basis of resistance to anticoagulants in rodents.";
RL Genetics 170:1839-1847(2005).
CC -!- FUNCTION: Involved in vitamin K metabolism. Catalytic subunit of the
CC vitamin K epoxide reductase (VKOR) complex which reduces inactive
CC vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for
CC the gamma-carboxylation of various proteins, including clotting
CC factors, and is required for normal blood coagulation, but also for
CC normal bone development. {ECO:0000269|PubMed:15879509,
CC ECO:0000269|PubMed:19492146}.
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:15879509};
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:15879509};
CC -!- ACTIVITY REGULATION: Inhibited by warfarin (coumadin).
CC {ECO:0000269|PubMed:15879509}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in liver. {ECO:0000269|PubMed:19492146}.
CC -!- DOMAIN: The number of transmembrane domains and the membrane topology
CC are controversial; supporting evidence is available both for models
CC with three transmembrane domains and four transmembrane domains.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate and
CC appear normal, but die between one and twenty days after birth, due to
CC severe bleeding. In about 75% of the cases, subdural bleeding is
CC observed, in addition to intracerebral and intramuscular bleeding.
CC Daily oral administration of vitamin K to the mutant mice leads to
CC normal survival, but the mice die within seven days after the cessation
CC of vitamin K administration. Besides, both homozygous and heterozygous
CC mutant mice display defects in bone development with reduced length of
CC the calcified part of the long bones in front and hind limbs.
CC {ECO:0000269|PubMed:19492146}.
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; AK013996; BAB29106.1; -; mRNA.
DR EMBL; AK002742; BAB22320.1; -; mRNA.
DR EMBL; AK003237; BAB22661.1; -; mRNA.
DR EMBL; AK008509; BAB25708.1; -; mRNA.
DR EMBL; AK008578; BAB25757.1; -; mRNA.
DR EMBL; BC031732; AAH31732.1; -; mRNA.
DR CCDS; CCDS21883.1; -.
DR RefSeq; NP_848715.1; NM_178600.2.
DR AlphaFoldDB; Q9CRC0; -.
DR SMR; Q9CRC0; -.
DR BioGRID; 205697; 4.
DR STRING; 10090.ENSMUSP00000033074; -.
DR PhosphoSitePlus; Q9CRC0; -.
DR SwissPalm; Q9CRC0; -.
DR EPD; Q9CRC0; -.
DR jPOST; Q9CRC0; -.
DR MaxQB; Q9CRC0; -.
DR PaxDb; Q9CRC0; -.
DR PeptideAtlas; Q9CRC0; -.
DR PRIDE; Q9CRC0; -.
DR ProteomicsDB; 297605; -.
DR DNASU; 27973; -.
DR Ensembl; ENSMUST00000033074; ENSMUSP00000033074; ENSMUSG00000096145.
DR GeneID; 27973; -.
DR KEGG; mmu:27973; -.
DR UCSC; uc009jxe.1; mouse.
DR CTD; 79001; -.
DR MGI; MGI:106442; Vkorc1.
DR VEuPathDB; HostDB:ENSMUSG00000096145; -.
DR eggNOG; ENOG502S4E7; Eukaryota.
DR GeneTree; ENSGT00940000157421; -.
DR HOGENOM; CLU_105471_0_0_1; -.
DR InParanoid; Q9CRC0; -.
DR OMA; PWTRWAF; -.
DR OrthoDB; 1611169at2759; -.
DR PhylomeDB; Q9CRC0; -.
DR TreeFam; TF328467; -.
DR BRENDA; 1.17.4.4; 3474.
DR Reactome; R-MMU-6806664; Metabolism of vitamin K.
DR BioGRID-ORCS; 27973; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Vkorc1; mouse.
DR PRO; PR:Q9CRC0; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9CRC0; protein.
DR Bgee; ENSMUSG00000096145; Expressed in primary oocyte and 67 other tissues.
DR ExpressionAtlas; Q9CRC0; baseline and differential.
DR Genevisible; Q9CRC0; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0048038; F:quinone binding; IEA:UniProtKB-KW.
DR GO; GO:0047058; F:vitamin-K-epoxide reductase (warfarin-insensitive) activity; ISO:MGI.
DR GO; GO:0047057; F:vitamin-K-epoxide reductase (warfarin-sensitive) activity; IDA:MGI.
DR GO; GO:0007596; P:blood coagulation; IMP:UniProtKB.
DR GO; GO:0060348; P:bone development; IMP:UniProtKB.
DR GO; GO:0017187; P:peptidyl-glutamic acid carboxylation; ISS:UniProtKB.
DR GO; GO:0050820; P:positive regulation of coagulation; IMP:MGI.
DR GO; GO:0030193; P:regulation of blood coagulation; ISO:MGI.
DR GO; GO:0046677; P:response to antibiotic; ISO:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR GO; GO:0010243; P:response to organonitrogen compound; ISO:MGI.
DR GO; GO:0042371; P:vitamin K biosynthetic process; ISO:MGI.
DR GO; GO:0042373; P:vitamin K metabolic process; IDA:MGI.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISO:MGI.
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..161
FT /note="Vitamin K epoxide reductase complex subunit 1"
FT /id="PRO_0000191669"
FT TOPO_DOM 1..8
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 101..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..126
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..149
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 150..161
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DISULFID 132..135
FT /note="Redox-active"
FT /evidence="ECO:0000250"
FT VARIANT 128
FT /note="L -> S (identified in warfarin-resistant animals)"
FT /evidence="ECO:0000269|PubMed:15879509"
FT VARIANT 139
FT /note="Y -> C (identified in warfarin-resistant animals)"
FT /evidence="ECO:0000269|PubMed:15879509"
SQ SEQUENCE 161 AA; 17768 MW; 044BEED047A57FD9 CRC64;
MGTTWRSPGL VRLALCLAGL ALSLYALHVK AARARDENYR ALCDVGTAIS CSRVFSSRWG
RGFGLVEHML GADSVLNQSN SIFGCLFYTL QLLLGCLRGR WASILLVLSS LVSVAGSVYL
AWILFFVLYD FCIVCITTYA INVGLMLLSF QKVPEHKTKK H
