EC                 Enzyme                                 

vitamin-K-epoxide reductase (warfarin-sensitive);
VKORC1 (gene name);
VKORC1L1 (gene name)
Acting on CH or CH2 groups;
With a disulfide as acceptor
phylloquinone:disulfide oxidoreductase
(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
(other) R03645 R09992
phylloquinone [CPD:C02059];
protein with a disulfide bond;
H2O [CPD:C00001];
phylloquinol [CPD:C03313]
2,3-epoxyphylloquinone [CPD:C05849];
protein with reduced L-cysteine residues;
phylloquinone [CPD:C02059]
The enzyme catalyses the reduction of vitamin K 2,3-epoxide, which is formed by the activity of EC, peptidyl-glutamate 4-carboxylase, back to its phylloquinol active form. The enzyme forms a tight complex with EC, 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.
EC created 1989 as EC, transferred 2014 to EC, modified 2018
ec00130  Ubiquinone and other terpenoid-quinone biosynthesis
ec01100  Metabolic pathways
ec01110  Biosynthesis of secondary metabolites
K05357  vitamin-K-epoxide reductase (warfarin-sensitive)
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 102142587 102143754
CSAB: 103231221(VKORC1) 103246568(VKORC1L1) 103246572 103246927
RRO: 104661567(VKORC1) 104678399 104678964(VKORC1L1)
RBB: 108529701(VKORC1)
CJC: 100386573(VKORC1) 100388998(VKORC1L1)
SBQ: 101041739(VKORC1) 101051522(VKORC1L1)
MMU: 27973(Vkorc1) 69568(Vkorc1l1)
MCAL: 110295344(Vkorc1l1) 110298355(Vkorc1)
MPAH: 110332422(Vkorc1)
RNO: 309004(Vkorc1) 399684(Vkorc1l1)
MUN: 110560966(Vkorc1l1) 110564537(Vkorc1)
CGE: 100755703(Vkorc1) 100757934(Vkorc1l1)
NGI: 103726327(Vkorc1) 103738949(Vkorc1l1)
HGL: 101708956(Vkorc1l1) 101712053 101712530(Vkorc1)
CCAN: 109682419(Vkorc1)
OCU: 100348035(VKORC1L1) 100352876(VKORC1)
TUP: 102473374(VKORC1L1) 102489609(VKORC1)
CFA: 479775(VKORC1) 606915(VKORC1L1)
VVP: 112929263(VKORC1) 112934105(VKORC1L1)
AML: 100473818(VKORC1L1) 100476494(VKORC1)
UMR: 103657883(VKORC1) 103670242(VKORC1L1)
UAH: 113267716(VKORC1) 113267747(VKORC1L1)
ORO: 101365518(VKORC1L1) 101379206(VKORC1)
FCA: 101085010(VKORC1L1) 101089669(VKORC1)
PTG: 102964464(VKORC1) 102969550(VKORC1L1)
PPAD: 109250658(VKORC1L1) 109259045(VKORC1) 109261808
AJU: 106972842(VKORC1L1) 106979129(VKORC1)
BTA: 445422(VKORC1) 506318(VKORC1L1)
BOM: 102273264(VKORC1) 102276117(VKORC1L1)
BIU: 109578500(VKORC1)
BBUB: 102399074(VKORC1L1) 102404250(VKORC1)
CHX: 102171296(VKORC1) 102174084(VKORC1L1)
OAS: 101108541(VKORC1L1) 105604738(VKORC1)
SSC: 100518062(VKORC1L1) 100522924(VKORC1)
CFR: 102506472(VKORC1L1) 102515335(VKORC1)
CDK: 105089738(VKORC1L1) 105102715(VKORC1)
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)
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)
MNA: 107524390(VKORC1L1) 107540826(VKORC1)
HAI: 109374189(VKORC1) 109376915(VKORC1L1)
DRO: 112304769(VKORC1) 112314697(VKORC1L1)
MMF: 118641647(VKORC1L1) 118641657(VKORC1)
PALE: 102880782(VKORC1L1) 102886750(VKORC1)
RAY: 107503984(VKORC1) 107507444(VKORC1L1)
MJV: 108385526(VKORC1) 108408939(VKORC1L1)
LAV: 100663455(VKORC1)
MDO: 100010095(VKORC1L1) 100019247(VKORC1)
SHR: 100914533(VKORC1) 100916214(VKORC1L1)
PCW: 110222147(VKORC1L1) 110223223(VKORC1)
OAA: 100085063(VKORC1) 103166981(VKORC1L1)
GGA: 408253(VKORC1L1)
MGP: 100550207(VKORC1L1) 104915861
CJO: 107322449(VKORC1L1)
NMEL: 110391899 110407843(VKORC1L1)
APLA: 101798787(VKORC1L1)
ACYG: 106041424(VKORC1L1)
TGU: 100230928(VKORC1L1)
LSR: 110481996(VKORC1L1) 110483486
SCAN: 103820095(VKORC1L1) 103824717
GFR: 102033623(VKORC1L1)
FAB: 101810261(VKORC1L1)
PHI: 102104161(VKORC1L1)
PMAJ: 107212753(VKORC1L1)
CCAE: 111922267 111937938(VKORC1L1)
CCW: 104691083(VKORC1L1)
ETL: 114060508(VKORC1L1)
FPG: 101920959(VKORC1L1)
CLV: 102085852(VKORC1L1)
EGZ: 104131820(VKORC1L1)
NNI: 104016793(VKORC1L1)
ACUN: 113487087(VKORC1L1)
PADL: 103925608(VKORC1L1)
AAM: 106495348(VKORC1L1)
ASN: 102373007(VKORC1L1) 112548693(VKORC1)
AMJ: 102575124(VKORC1L1) 102577367
PSS: 102455189(VKORC1L1) 102455458
CMY: 102931890(VKORC1L1) 102937112
CPIC: 101932287(VKORC1L1) 101952869(VKORC1)
ACS: 100555617(vkorc1)
PVT: 110084532(VKORC1L1) 110086404 110086406
PBI: 103052312 103064445(VKORC1L1)
PMUR: 107287076(VKORC1L1) 107294319 107299076
TSR: 106543821(VKORC1L1) 106545499(VKORC1)
PMUA: 114582862 114582863 114585928(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
DRE: 100000559(vkorc1) 553717(vkorc1l1)
SANH: 107654009 107654281(vkorc1l1) 107701846
IPU: 100528488(vkorl) 108259877(vkorc1l1)
PHYP: 113527539 113531399(vkorc1l1)
EEE: 113577552(vkorc1l1) 113591952
TRU: 115248692 446034(vkorc1) 446035(vkorc1l1)
LCO: 104928769(vkorc1l1) 104935549
NCC: 104956341(vkorc1l1) 104967444
MZE: 101466626 101476827(vkorc1l1)
ONL: 100705457(vkorc1l1) 100706346
OLA: 101166326(vkorc1l1) 101175272(vkorc1)
XMA: 102224968 102236035(vkorc1l1)
XCO: 114150296 114152577(vkorc1l1)
PRET: 103476055(vkorc1l1) 103481412
CVG: 107090350(vkorc1l1) 107097194
NFU: 107387049(vkorc1l1) 107387978
KMR: 108233845(vkorc1l1) 108237265(vkorc1)
ALIM: 106521363 106525412(vkorc1)
AOCE: 111572720(vkorc1l1) 111581582
CSEM: 103382040 103394913(vkorc1l1)
POV: 109628628(vkorc1l1) 109646209
LCF: 108884459 108893410(vkorc1l1)
SDU: 111220323 111222156(vkorc1l1)
SLAL: 111658706 111663852(vkorc1l1)
HCQ: 109508799(vkorc1l1) 109524007
BPEC: 110159643 110165064(vkorc1l1)
MALB: 109960444(vkorc1l1) 109963618
SASA: 106567394(vkorc1l1) 106577046
OTW: 112253079 112258348(vkorc1l1)
ELS: 105007720 105008282(vkorc1l1)
SFM: 108921596(vkorc1l1) 108938295 108941679
PKI: 111836830 111854712(vkorc1l1) 111859697
LCM: 102345266(VKORC1L1) 102357927
CMK: 103180624(vkorc1l1)
RTP: 109925205 109928519(vkorc1l1)
CIN: 100178185 780870(vkor)
SPU: 763699
APLC: 110988312
DME: Dmel_CG33544(Vkor)
DER: 6548496
DSE: 6609493
DSI: Dsimw501_GD11216(Dsim_GD11216)
DSR: 110180445
DPE: 6601584
DWI: 6640946
DNV: 108653874
DHE: 111594945
MDE: 101888998
LCQ: 111682432
AAG: 5574649
AME: 724791
BIM: 100746180
BTER: 100647907
CCAL: 108622863
OBB: 114878863
SOC: 105199915
MPHA: 105838573
AEC: 105148077
ACEP: 105624125
PBAR: 105423896
VEM: 105565949
HST: 105189853
DQU: 106741085
CFO: 105256425
LHU: 105671028
PGC: 109856097
OBO: 105284994
PCF: 106790230
NVI: 100121150
CSOL: 105364056
MDL: 103578951
TCA: 103315249
DPA: 109544649
ATD: 109609280
NVL: 108562475
BMOR: 101746818
BMAN: 114252611
PMAC: 106717878
PRAP: 111003414
HAW: 110374796
TNL: 113498914
PXY: 105381639
DNX: 107161956
AGS: 114121307
RMD: 113554155
BTAB: 109041108
CLEC: 106663678
ZNE: 110831183
FCD: 110856806
PVM: 113823507
TUT: 107362817
DPTE: 113792512
CSCU: 111629235
PTEP: 107451341
BMY: Bm1_44490
CRG: 105338127
MYI: 110460140
EPA: 110250868
ADF: 107340505
AMIL: 114960653
PDAM: 113676685
SPIS: 111331307
DGT: 114520441
HMG: 101235337
AQU: 100633778
ACA: ACP_3002
 » show all
1  [PMID:646989]
Whitlon DS, Sadowski JA, Suttie JW.
Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition.
Biochemistry 17:1371-7 (1978)
2  [PMID:6733086]
Lee JJ, Fasco MJ.
Metabolism of vitamin K and vitamin K 2,3-epoxide via interaction with a common disulfide.
Biochemistry 23:2246-52 (1984)
3  [PMID:3857611]
Mukharji I, Silverman RB.
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.
Proc Natl Acad Sci U S A 82:2713-7 (1985)
4  [PMID:14765195]
Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW
Identification of the gene for vitamin K epoxide reductase.
Nature 427:541-4 (2004)
5  [PMID:17124179]
Wajih N, Hutson SM, Wallin R
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.
J Biol Chem 282:2626-35 (2007)
6  [PMID:19492146]
Spohn G, Kleinridders A, Wunderlich FT, Watzka M, Zaucke F, Blumbach K, Geisen C, Seifried E, Muller C, Paulsson M, Bruning JC, Oldenburg J
VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding.
Thromb Haemost 101:1044-50 (2009)
7  [PMID:20696932]
Schulman S, Wang B, Li W, Rapoport TA
Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners.
Proc Natl Acad Sci U S A 107:15027-32 (2010)
Other DBs
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CAS: 55963-40-1

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