Entry
Name
vitamin-K-epoxide reductase (warfarin-sensitive);
VKORC1 (gene name);
VKORC1L1 (gene name)
Class
Oxidoreductases;
Acting on CH or CH2 groups;
With a disulfide as acceptor
BRITE hierarchy
Sysname
phylloquinone:disulfide oxidoreductase
Reaction(IUBMB)
(1) phylloquinone + a protein with a disulfide bond + H2O = 2,3-epoxyphylloquinone + a protein with reduced L-cysteine residues [RN:
R03511 ];
(2) phylloquinol + a protein with a disulfide bond = phylloquinone + a protein with reduced L-cysteine residues
Reaction(KEGG)
Substrate
phylloquinone [CPD:
C02059 ];
protein with a disulfide bond;
H2O [CPD:
C00001 ];
phylloquinol [CPD:
C03313 ]
Product
2,3-epoxyphylloquinone [CPD:
C05849 ];
protein with reduced L-cysteine residues;
phylloquinone [CPD:
C02059 ]
Comment
The enzyme catalyses the reduction of vitamin K 2,3-epoxide, which is formed by the activity of EC
4.1.1.90 , peptidyl-glutamate 4-carboxylase, back to its phylloquinol active form. The enzyme forms a tight complex with EC
5.3.4.1 , protein disulfide-isomerase, which transfers the required electrons from newly-synthesized proteins by catalysing the formation of disulfide bridges. The enzyme acts on the epoxide forms of both phylloquinone (vitamin K1) and menaquinone (vitamin K2). Inhibited strongly by (S)-warfarin and ferulenol.
History
EC 1.17.4.4 created 1989 as EC 1.1.4.1, transferred 2014 to EC 1.17.4.4, modified 2018
Pathway
ec00130 Ubiquinone and other terpenoid-quinone biosynthesis
ec01110 Biosynthesis of secondary metabolites
Orthology
K05357 vitamin-K-epoxide reductase (warfarin-sensitive)
Genes
HSA : 154807(VKORC1L1) 79001(VKORC1)
PTR : 100610370(VKORC1) 472396(VKORC1L1)
PPS : 100979578(VKORC1L1) 103784246(VKORC1)
GGO : 101127117(VKORC1) 101145443(VKORC1L1)
PON : 100434981(VKORC1) 100458063(VKORC1L1) 112134373
NLE : 100591850(VKORC1) 100601157 100601262(VKORC1L1)
MCC : 114676888 697591(VKORC1L1) 714412(VKORC1)
MCF : 101926368(VKORC1) 102131386 102143754(VKORC1L1)
CSAB : 103231221(VKORC1) 103246568(VKORC1L1) 103246572 103246927
CATY : 105574592 105581545 105593305(VKORC1L1) 105599496(VKORC1)
PANU : 101007749(VKORC1L1) 101025627(VKORC1)
TGE : 112614204(VKORC1) 112620261 112620583
RRO : 104661567(VKORC1) 104678399 104678964(VKORC1L1)
TFN : 117072927(VKORC1L1) 117072933 117073356 117087689(VKORC1)
PTEH : 111525670(VKORC1) 111530454 111535958 113219667
CJC : 100386573(VKORC1) 100388998(VKORC1L1)
SBQ : 101041739(VKORC1) 101051522(VKORC1L1)
MMUR : 105871014(VKORC1L1) 105871049(VKORC1)
OGA : 100947581(VKORC1) 100952951(VKORC1L1)
MMU : 27973(Vkorc1) 69568(Vkorc1l1)
MCAL : 110295344(Vkorc1l1) 110298355(Vkorc1)
RNO : 309004(Vkorc1) 399684(Vkorc1l1)
MCOC : 116068488(Vkorc1l1) 116100916(Vkorc1)
MUN : 110560966(Vkorc1l1) 110564537(Vkorc1)
CGE : 100755703(Vkorc1) 100757934(Vkorc1l1)
PLEU : 114693670(Vkorc1l1) 114704396(Vkorc1)
NGI : 103726327(Vkorc1) 103738949(Vkorc1l1)
HGL : 101708956(Vkorc1l1) 101712053 101712530(Vkorc1)
CPOC : 100717597(Vkorc1) 100720684(Vkorc1l1)
DSP : 122096196(Vkorc1) 122114838(Vkorc1l1)
OCU : 100348035(VKORC1L1) 100352876(VKORC1)
OPI : 101519736(VKORC1L1) 101520237 101524326
TUP : 102473374(VKORC1L1) 102489609(VKORC1)
CFA : 479775(VKORC1) 606915(VKORC1L1)
VVP : 112929263(VKORC1) 112934105(VKORC1L1)
VLG : 121486425(VKORC1L1) 121487294(VKORC1)
AML : 100473818(VKORC1L1) 100476494(VKORC1)
UMR : 103657883(VKORC1) 103670242(VKORC1L1)
UAH : 113267716(VKORC1) 113267747(VKORC1L1)
UAR : 123784675(VKORC1) 123784703(VKORC1L1)
MPUF : 101677403(VKORC1) 101685820(VKORC1L1)
ORO : 101365518(VKORC1L1) 101379206(VKORC1)
EJU : 114214375(VKORC1L1) 114214419(VKORC1)
ZCA : 113932409(VKORC1) 113933167(VKORC1L1)
MLX : 117999538(VKORC1L1) 117999567(VKORC1)
FCA : 101085010(VKORC1L1) 101089669(VKORC1)
PYU : 121017459(VKORC1L1) 121022198(VKORC1)
PBG : 122471386(VKORC1L1) 122471420(VKORC1)
PTG : 102964464(VKORC1) 102969550(VKORC1L1)
PPAD : 109250658(VKORC1L1) 109259045(VKORC1) 109261808
AJU : 106972842(VKORC1L1) 106979129(VKORC1)
HHV : 120235669(VKORC1L1) 120242261(VKORC1)
BTA : 445422(VKORC1) 506318(VKORC1L1)
BOM : 102273264(VKORC1) 102276117(VKORC1L1)
BBUB : 102399074(VKORC1L1) 102404250(VKORC1)
CHX : 102171296(VKORC1) 102174084(VKORC1L1)
OAS : 101108541(VKORC1L1) 105604738(VKORC1)
ODA : 120860595 120860596 120877656(VKORC1) 120877982(VKORC1L1)
CCAD : 122432710(VKORC1) 122432970(VKORC1L1)
SSC : 100518062(VKORC1L1) 100522924(VKORC1)
CFR : 102506472(VKORC1L1) 102515335(VKORC1)
CBAI : 105082780(VKORC1) 105082868(VKORC1L1)
CDK : 105089738(VKORC1L1) 105102715(VKORC1)
VPC : 102530603(VKORC1) 102542192(VKORC1L1)
BACU : 103001696(VKORC1) 103011563(VKORC1L1)
LVE : 103077074(VKORC1) 103091469(VKORC1L1)
OOR : 101271099(VKORC1L1) 101284991(VKORC1)
DLE : 111182082(VKORC1L1) 111182114(VKORC1)
PCAD : 102979206(VKORC1L1) 102984282(VKORC1)
PSIU : 116739769(VKORC1L1) 116740166(VKORC1)
ECB : 100063360(VKORC1) 100629446(VKORC1L1)
EPZ : 103547239(VKORC1) 103558037(VKORC1L1)
EAI : 106831834(VKORC1L1) 106831891(VKORC1)
MYB : 102239240 102239782(VKORC1) 102255608(VKORC1L1) 102259131
MYD : 102764792(VKORC1L1) 102771765(VKORC1)
MMYO : 118656148(VKORC1) 118657014(VKORC1L1)
MLF : 102419906(VKORC1L1) 102435302(VKORC1)
MNA : 107524390(VKORC1L1) 107540826(VKORC1)
PKL : 118702921(VKORC1L1) 118704943(VKORC1)
HAI : 109374189(VKORC1) 109376915(VKORC1L1)
DRO : 112304769(VKORC1) 112314697(VKORC1L1)
SHON : 118976266(VKORC1L1)
AJM : 119041138(VKORC1) 119055020(VKORC1L1)
PDIC : 114496038(VKORC1L1) 114506193(VKORC1)
PHAS : 123806404(VKORC1L1) 123825695(VKORC1)
MMF : 118641647(VKORC1L1) 118641657(VKORC1)
RFQ : 117019671(VKORC1) 117025035(VKORC1L1)
PALE : 102880782(VKORC1L1) 102886750(VKORC1)
PGIG : 120591823(VKORC1L1) 120620061(VKORC1)
PVP : 105296731(VKORC1L1) 105304510(VKORC1)
RAY : 107503984(VKORC1) 107507444(VKORC1L1)
MJV : 108385526(VKORC1) 108408939(VKORC1L1)
TOD : 119241467 119241709(VKORC1) 119242320
SARA : 101549306(VKORC1) 101549307(VKORC1L1)
DNM : 101442019(VKORC1L1) 101445935(VKORC1)
MDO : 100010095(VKORC1L1) 100019247(VKORC1)
GAS : 123231144(VKORC1) 123244517(VKORC1L1)
SHR : 100914533(VKORC1) 100916214(VKORC1L1)
PCW : 110222147(VKORC1L1) 110223223(VKORC1)
OAA : 100085063(VKORC1) 103166981(VKORC1L1)
PCOC : 116228113(VKORC1L1) 116240258
MGP : 100550207(VKORC1L1) 104915861
NMEL : 110391899 110407843(VKORC1L1)
APLA : 101798787(VKORC1L1)
ACYG : 106041424(VKORC1L1)
AFUL : 116497308(VKORC1L1)
LSR : 110481996(VKORC1L1) 110483486
SCAN : 103820095(VKORC1L1) 103824717
PMOA : 120507865(VKORC1L1) 120508519
OTC : 121344773 121345750(VKORC1L1)
PRUF : 121352738 121361665(VKORC1L1)
PMAJ : 107212753(VKORC1L1)
CCAE : 111922267 111937938(VKORC1L1)
ACUN : 113487087(VKORC1L1)
TALA : 104366804(VKORC1L1)
PADL : 103925608(VKORC1L1)
ACHC : 115338558 115347142(VKORC1L1)
AROW : 112961823 112978587(VKORC1L1)
ASN : 102373007(VKORC1L1) 112548693(VKORC1)
AMJ : 102575124(VKORC1L1) 102577367
CPOO : 109316933(VKORC1L1)
PSS : 102455189(VKORC1L1) 102455458
CMY : 102931890(VKORC1L1) 102937112
CPIC : 101932287(VKORC1L1) 101952869
TST : 117867437(VKORC1L1) 117888239
CABI : 116815531(VKORC1) 116821334(VKORC1L1)
MRV : 120387374(VKORC1L1) 120403351 120403473
PVT : 110084532(VKORC1L1) 110086404 110086406
SUND : 121916934(VKORC1L1) 121933336(VKORC1)
PBI : 103052312 103064445(VKORC1L1)
PMUR : 107287076(VKORC1L1) 107294319 107299076
TSR : 106543821(VKORC1L1) 106545499(VKORC1)
PGUT : 117666827(VKORC1) 117667535(VKORC1L1)
VKO : 123019596(VKORC1) 123036705(VKORC1L1)
PMUA : 114582862 114582863 114585928(VKORC1L1)
ZVI : 118094680(VKORC1) 118096703(VKORC1L1)
GJA : 107106645(VKORC1) 107112507(VKORC1L1)
XLA : 108709644(vkorc1l1.S) 398467(vkorc1.S) 733276(vkorc1l1.L)
XTR : 448775(vkorc1) 549523(vkorc1l1)
NPR : 108799191(VKORC1L1) 108800672
RTEM : 120926639(VKORC1L1) 120942978
BBUF : 120995518(VKORC1L1) 121007962
BGAR : 122931659(VKORC1L1) 122945556
DRE : 100000559(vkorc1) 553717(vkorc1l1)
SRX : 107719344 107719575 107734370
SANH : 107654009 107654281(vkorc1l1) 107701846
CCAR : 109051702 109058151 109081541
CAUA : 113068058 113070150 113070234 113070775 113112000
IPU : 100528488(vkorc1) 108259877(vkorc1l1)
PHYP : 113527539 113531399(vkorc1l1)
SMEO : 124378900(vkorc1l1) 124389036(vkorc1)
AMEX : 103029702 103037761
EEE : 113577552(vkorc1l1) 113591952
TRU : 115248692 446034(vkorc1) 446035(vkorc1l1)
TNG : GSTEN00016275G001 GSTEN00028302G001
LCO : 104928769(vkorc1l1) 104935549
NCC : 104956341(vkorc1l1) 104967444
CGOB : 115018980(vkorc1l1) 115025109
ELY : 117246706(vkorc1) 117267407(vkorc1l1)
PLEP : 121952702(vkorc1l1) 121958389(vkorc1)
SLUC : 116058102(vkorc1l1) 116061570(vkorc1)
ECRA : 117937341(vkorc1) 117956082(vkorc1l1)
PFLV : 114548348 114566835(vkorc1l1)
GAT : 120819142(vkorc1) 120821346(vkorc1l1)
PPUG : 119212699(vkorc1) 119215732(vkorc1l1)
MSAM : 119894921(vkorc1l1) 119915941(vkorc1)
CUD : 121518681(vkorc1l1) 121527885(vkorc1)
MZE : 101466626 101476827(vkorc1l1)
ONL : 100705457(vkorc1l1) 100706346
OAU : 116321898(vkorc1) 116324375(vkorc1l1)
OLA : 101166326(vkorc1l1) 101175272(vkorc1)
OML : 112142385(vkorc1l1) 112154204(vkorc1)
XMA : 102224968 102236035(vkorc1l1)
XCO : 114150296 114152577(vkorc1l1)
XHE : 116727136 116728597(vkorc1l1)
PRET : 103476055(vkorc1l1) 103481412
PFOR : 103133842(vkorc1l1) 103156839
PLAI : 106939030 106956650(vkorc1l1)
PMEI : 106908662 106934299(vkorc1l1)
GAF : 122823577(vkorc1) 122845224(vkorc1l1)
CVG : 107090350(vkorc1l1) 107097194
CTUL : 119775639(vkorc1l1) 119796754(vkorc1)
GMU : 124874787(vkorc1) 124876281(vkorc1l1)
NFU : 107387049(vkorc1l1) 107387978
KMR : 108233845(vkorc1l1) 108237265(vkorc1)
ALIM : 106521363 106525412(vkorc1)
NWH : 119420067(vkorc1l1) 119423595(vkorc1)
AOCE : 111572720(vkorc1l1) 111581582
CSEM : 103382040 103394913(vkorc1l1)
POV : 109628628(vkorc1l1) 109646209
SSEN : 122762756(vkorc1) 122780047(vkorc1l1)
HHIP : 117752784(vkorc1) 117774060(vkorc1l1)
LCF : 108884459 108893410(vkorc1l1)
SDU : 111220323 111222156(vkorc1l1)
SLAL : 111658706 111663852(vkorc1l1)
XGL : 120794874(vkorc1) 120802311(vkorc1l1)
HCQ : 109508799(vkorc1l1) 109524007
BPEC : 110159643 110165064(vkorc1l1)
MALB : 109960444(vkorc1l1) 109963618
SASA : 106567394(vkorc1l1) 106577046
OTW : 112253079(vkorc1) 112258348 121841387
OMY : 110529490(vkorc1) 110537845 118966696
OGO : 123999324 124014982 124040746(vkorc1)
ONE : 115105380 115136237 115136328
SALP : 111951604 111963498 111980926
SNH : 120017939(vkorc1) 120032726 120056816
ELS : 105007720 105008282(vkorc1l1)
SFM : 108921596(vkorc1l1) 108938295 108941679
PKI : 111836830 111854712(vkorc1l1) 111859697
AANG : 118209798 118220282(vkorc1) 118235633(vkorc1l1)
LOC : 102693652(vkorc1l1) 102696686
PSPA : 121305140 121308568(vkorc1l1)
ARUT : 117398336 117429891 117430605
LCM : 102345266(VKORC1L1) 102357927
RTP : 109925205 109928519(vkorc1l1)
BBEL : 109463634 109466245
CIN : 100178185 780870(vkor)
DSI : Dsimw501_GD11216(Dsim_GD11216)
AALB : 109415799 109431186
CPII : 120430280 120431217
LGI : LOTGIDRAFT_114833 LOTGIDRAFT_115113
PCAN : 112561177 112562931
ATEN : 116292045 116293954
TGO : TGME49_203720 TGME49_249760
EHX : EMIHUDRAFT_361809 EMIHUDRAFT_440728
» show all
Taxonomy
Reference
Authors
Whitlon DS, Sadowski JA, Suttie JW.
Title
Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition.
Journal
Reference
Authors
Lee JJ, Fasco MJ.
Title
Metabolism of vitamin K and vitamin K 2,3-epoxide via interaction with a common disulfide.
Journal
Reference
Authors
Mukharji I, Silverman RB.
Title
Purification of a vitamin K epoxide reductase that catalyzes conversion of vitamin K 2,3-epoxide to 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone.
Journal
Reference
Authors
Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW
Title
Identification of the gene for vitamin K epoxide reductase.
Journal
Reference
Authors
Wajih N, Hutson SM, Wallin R
Title
Disulfide-dependent protein folding is linked to operation of the vitamin K cycle in the endoplasmic reticulum. A protein disulfide isomerase-VKORC1 redox enzyme complex appears to be responsible for vitamin K1 2,3-epoxide reduction.
Journal
Reference
Authors
Spohn G, Kleinridders A, Wunderlich FT, Watzka M, Zaucke F, Blumbach K, Geisen C, Seifried E, Muller C, Paulsson M, Bruning JC, Oldenburg J
Title
VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding.
Journal
Thromb Haemost 101:1044-50 (2009)
Reference
Authors
Schulman S, Wang B, Li W, Rapoport TA
Title
Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners.
Journal
Other DBs
ExplorEnz - The Enzyme Database: 1.17.4.4
ExPASy - ENZYME nomenclature database: 1.17.4.4