KEGG   ENZYME: 1.17.4.4
Entry
EC 1.17.4.4                 Enzyme                                 
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
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)
R03511;
(other) R03645 R09992
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
ec01100  Metabolic pathways
ec01110  Biosynthesis of secondary metabolites
Orthology
K05357  vitamin-K-epoxide reductase (warfarin-sensitive)
Genes
HSA154807(VKORC1L1) 79001(VKORC1)
PTR100610370(VKORC1) 472396(VKORC1L1)
PPS100979578(VKORC1L1) 103784246(VKORC1)
GGO101127117(VKORC1) 101145443(VKORC1L1)
PON100434981(VKORC1) 100458063(VKORC1L1) 112134373
NLE100591850(VKORC1) 100601157 100601262(VKORC1L1)
MCC114676888 697591(VKORC1L1) 714412(VKORC1)
MCF101926368(VKORC1) 102131386 102143754(VKORC1L1)
CSAB103231221(VKORC1) 103246568(VKORC1L1) 103246572 103246927
CATY105574592 105581545 105593305(VKORC1L1) 105599496(VKORC1)
PANU101007749(VKORC1L1) 101025627(VKORC1)
TGE112614204(VKORC1) 112620261 112620583
RRO104661567(VKORC1) 104678399 104678964(VKORC1L1)
RBB108529701(VKORC1)
TFN117072927(VKORC1L1) 117072933 117073356 117087689(VKORC1)
PTEH111525670(VKORC1) 111530454 111535958 113219667
CJC100386573(VKORC1) 100388998(VKORC1L1)
SBQ101041739(VKORC1) 101051522(VKORC1L1)
CSYR103264390(VKORC1)
MMUR105871014(VKORC1L1) 105871049(VKORC1)
OGA100947581(VKORC1) 100952951(VKORC1L1)
MMU27973(Vkorc1) 69568(Vkorc1l1)
MCAL110295344(Vkorc1l1) 110298355(Vkorc1)
MPAH110332422(Vkorc1)
RNO309004(Vkorc1) 399684(Vkorc1l1)
MCOC116068488(Vkorc1l1) 116100916(Vkorc1)
MUN110560966(Vkorc1l1) 110564537(Vkorc1)
CGE100755703(Vkorc1) 100757934(Vkorc1l1)
PLEU114693670(Vkorc1l1) 114704396(Vkorc1)
NGI103726327(Vkorc1) 103738949(Vkorc1l1)
HGL101708956(Vkorc1l1) 101712053 101712530(Vkorc1)
CPOC100717597(Vkorc1) 100720684(Vkorc1l1)
CCAN109682419(Vkorc1)
DORD105982096(Vkorc1)
DSP122096196(Vkorc1) 122114838(Vkorc1l1)
NCAR124969992 124970058
OCU100348035(VKORC1L1) 100352876(VKORC1)
OPI101519736(VKORC1L1) 101520237 101524326
TUP102473374(VKORC1L1) 102489609(VKORC1)
CFA479775(VKORC1) 606915(VKORC1L1)
VVP112929263(VKORC1) 112934105(VKORC1L1)
VLG121486425(VKORC1L1) 121487294(VKORC1)
AML100473818(VKORC1L1) 100476494(VKORC1)
UMR103657883(VKORC1) 103670242(VKORC1L1)
UAH113267716(VKORC1) 113267747(VKORC1L1)
UAR123784675(VKORC1) 123784703(VKORC1L1)
ELK111146341 111162267
LLV125090151 125090200
MPUF101677403(VKORC1) 101685820(VKORC1L1)
ORO101365518(VKORC1L1) 101379206(VKORC1)
EJU114214375(VKORC1L1) 114214419(VKORC1)
ZCA113932409(VKORC1) 113933167(VKORC1L1)
MLX117999538(VKORC1L1) 117999567(VKORC1)
FCA101085010(VKORC1L1) 101089669(VKORC1)
PYU121017459(VKORC1L1) 121022198(VKORC1)
PBG122471386(VKORC1L1) 122471420(VKORC1)
PTG102964464(VKORC1) 102969550(VKORC1L1)
PPAD109250658(VKORC1L1) 109259045(VKORC1) 109261808
AJU106972842(VKORC1L1) 106979129(VKORC1)
HHV120235669(VKORC1L1) 120242261(VKORC1)
BTA445422(VKORC1) 506318(VKORC1L1)
BOM102273264(VKORC1) 102276117(VKORC1L1)
BIU109578500(VKORC1)
BBUB102399074(VKORC1L1) 102404250(VKORC1)
CHX102171296(VKORC1) 102174084(VKORC1L1)
OAS101108541(VKORC1L1) 105604738(VKORC1)
ODA120860595 120860596 120877656(VKORC1) 120877982(VKORC1L1)
CCAD122432710(VKORC1) 122432970(VKORC1L1)
SSC100518062(VKORC1L1) 100522924(VKORC1)
CFR102506472(VKORC1L1) 102515335(VKORC1)
CBAI105082780(VKORC1) 105082868(VKORC1L1)
CDK105089738(VKORC1L1) 105102715(VKORC1)
VPC102530603(VKORC1) 102542192(VKORC1L1)
BACU103001696(VKORC1) 103011563(VKORC1L1)
LVE103077074(VKORC1) 103091469(VKORC1L1)
OOR101271099(VKORC1L1) 101284991(VKORC1)
DLE111182082(VKORC1L1) 111182114(VKORC1)
PCAD102979206(VKORC1L1) 102984282(VKORC1)
PSIU116739769(VKORC1L1) 116740166(VKORC1)
ECB100063360(VKORC1) 100629446(VKORC1L1)
EPZ103547239(VKORC1) 103558037(VKORC1L1)
EAI106831834(VKORC1L1) 106831891(VKORC1)
MYB102239240 102239782(VKORC1) 102255608(VKORC1L1) 102259131
MYD102764792(VKORC1L1) 102771765(VKORC1)
MMYO118656148(VKORC1) 118657014(VKORC1L1)
MLF102419906(VKORC1L1) 102435302(VKORC1)
MNA107524390(VKORC1L1) 107540826(VKORC1)
PKL118702921(VKORC1L1) 118704943(VKORC1)
HAI109374189(VKORC1) 109376915(VKORC1L1)
DRO112304769(VKORC1) 112314697(VKORC1L1)
SHON118976266(VKORC1L1)
AJM119041138(VKORC1) 119055020(VKORC1L1)
PDIC114496038(VKORC1L1) 114506193(VKORC1)
PHAS123806404(VKORC1L1) 123825695(VKORC1)
MMF118641647(VKORC1L1) 118641657(VKORC1)
RFQ117019671(VKORC1) 117025035(VKORC1L1)
PALE102880782(VKORC1L1) 102886750(VKORC1)
PGIG120591823(VKORC1L1) 120620061(VKORC1)
PVP105296731(VKORC1L1) 105304510(VKORC1)
RAY107503984(VKORC1) 107507444(VKORC1L1)
MJV108385526(VKORC1) 108408939(VKORC1L1)
TOD119241467 119241709(VKORC1) 119242320
SARA101549306(VKORC1) 101549307(VKORC1L1)
LAV100663455(VKORC1)
TMU101346924 101356156
DNM101442019(VKORC1L1) 101445935(VKORC1)
MDO100010095(VKORC1L1) 100019247(VKORC1)
GAS123231144(VKORC1) 123244517(VKORC1L1)
SHR100914533(VKORC1) 100916214(VKORC1L1)
PCW110222147(VKORC1L1) 110223223(VKORC1)
OAA100085063(VKORC1) 103166981(VKORC1L1)
GGA408253(VKORC1L1)
PCOC116228113(VKORC1L1) 116240258
MGP100550207(VKORC1L1) 104915861
CJO107322449(VKORC1L1)
NMEL110391899 110407843(VKORC1L1)
APLA101798787(VKORC1L1)
ACYG106041424(VKORC1L1)
AFUL116497308(VKORC1L1)
TGU100230928(VKORC1L1)
LSR110481996(VKORC1L1) 110483486
SCAN103820095(VKORC1L1) 103824717
PMOA120507865(VKORC1L1) 120508519
OTC121344773 121345750(VKORC1L1)
PRUF121352738 121361665(VKORC1L1)
GFR102033623(VKORC1L1)
FAB101810261(VKORC1L1)
PHI102104161(VKORC1L1)
PMAJ107212753(VKORC1L1)
CCAE111922267 111937938(VKORC1L1)
CCW104691083(VKORC1L1)
ETL114060508(VKORC1L1)
ZAB102075491(VKORC1L1)
FPG101920959(VKORC1L1)
CLV102085852(VKORC1L1)
EGZ104131820(VKORC1L1)
NNI104016793(VKORC1L1)
ACUN113487087(VKORC1L1)
TALA104366804(VKORC1L1)
PADL103925608(VKORC1L1)
ACHC115338558 115347142(VKORC1L1)
AAM106495348(VKORC1L1)
AROW112961823 112978587(VKORC1L1)
NPD112945368(VKORC1L1)
DNE112987420
ASN102373007(VKORC1L1) 112548693(VKORC1)
AMJ102575124(VKORC1L1) 102577367
CPOO109316933(VKORC1L1)
GGN109293442(VKORC1L1)
PSS102455189(VKORC1L1) 102455458
CMY102931890(VKORC1L1) 102937112
CPIC101932287(VKORC1L1) 101952869
TST117867437(VKORC1L1) 117888239
CABI116815531(VKORC1) 116821334(VKORC1L1)
MRV120387374(VKORC1L1) 120403351 120403473
ACS100555617(vkorc1)
PVT110084532(VKORC1L1) 110086404 110086406
SUND121916934(VKORC1L1) 121933336(VKORC1)
PBI103052312 103064445(VKORC1L1)
PMUR107287076(VKORC1L1) 107294319 107299076
TSR106543821(VKORC1L1) 106545499(VKORC1)
PGUT117666827(VKORC1) 117667535(VKORC1L1)
VKO123019596(VKORC1) 123036705(VKORC1L1)
PMUA114582862 114582863 114585928(VKORC1L1)
ZVI118094680(VKORC1) 118096703(VKORC1L1)
GJA107106645(VKORC1) 107112507(VKORC1L1)
STOW125444557(VKORC1) 125445465(VKORC1L1)
XLA108709644(vkorc1l1.S) 398467(vkorc1.S) 733276(vkorc1l1.L)
XTR448775(vkorc1) 549523(vkorc1l1)
NPR108799191(VKORC1L1) 108800672
RTEM120926639(VKORC1L1) 120942978
BBUF120995518(VKORC1L1) 121007962
BGAR122931659(VKORC1L1) 122945556
DRE100000559(vkorc1) 553717(vkorc1l1)
SRX107719344 107719575 107734370
SANH107654009 107654281(vkorc1l1) 107701846
SGH107563435 107598672
CCAR109051702 109058151 109081541
CAUA113068058 113070150 113070234 113070775 113112000
PPRM120468976(vkorc1) 120471681(vkorc1l1)
MAMB125255907(vkorc1) 125266285(vkorc1l1)
IPU100528488(vkorc1) 108259877(vkorc1l1)
PHYP113527539 113531399(vkorc1l1)
SMEO124378900(vkorc1l1) 124389036(vkorc1)
TFD113637233(vkorc1l1) 113653535(vkorc1)
AMEX103029702 103037761
EEE113577552(vkorc1l1) 113591952
TRU115248692 446034(vkorc1) 446035(vkorc1l1)
TNGGSTEN00016275G001 GSTEN00028302G001
LCO104928769(vkorc1l1) 104935549
NCC104956341(vkorc1l1) 104967444
CGOB115018980(vkorc1l1) 115025109
ELY117246706(vkorc1) 117267407(vkorc1l1)
PLEP121952702(vkorc1l1) 121958389(vkorc1)
SLUC116058102(vkorc1l1) 116061570(vkorc1)
ECRA117937341(vkorc1) 117956082(vkorc1l1)
PFLV114548348 114566835(vkorc1l1)
GAT120819142(vkorc1) 120821346(vkorc1l1)
PPUG119212699(vkorc1) 119215732(vkorc1l1)
MSAM119894921(vkorc1l1) 119915941(vkorc1)
CUD121518681(vkorc1l1) 121527885(vkorc1)
MZE101466626 101476827(vkorc1l1)
ONL100705457(vkorc1l1) 100706346
OAU116321898(vkorc1) 116324375(vkorc1l1)
OLA101166326(vkorc1l1) 101175272(vkorc1)
OML112142385(vkorc1l1) 112154204(vkorc1)
XMA102224968 102236035(vkorc1l1)
XCO114150296 114152577(vkorc1l1)
XHE116727136 116728597(vkorc1l1)
PRET103476055(vkorc1l1) 103481412
PFOR103133842(vkorc1l1) 103156839
PLAI106939030 106956650(vkorc1l1)
PMEI106908662 106934299(vkorc1l1)
GAF122823577(vkorc1) 122845224(vkorc1l1)
CVG107090350(vkorc1l1) 107097194
CTUL119775639(vkorc1l1) 119796754(vkorc1)
GMU124874787(vkorc1) 124876281(vkorc1l1)
NFU107387049(vkorc1l1) 107387978
KMR108233845(vkorc1l1) 108237265(vkorc1)
ALIM106521363 106525412(vkorc1)
NWH119420067(vkorc1l1) 119423595(vkorc1)
AOCE111572720(vkorc1l1) 111581582
CSEM103382040 103394913(vkorc1l1)
POV109628628(vkorc1l1) 109646209
SSEN122762756(vkorc1) 122780047(vkorc1l1)
HHIP117752784(vkorc1) 117774060(vkorc1l1)
LCF108884459 108893410(vkorc1l1)
SDU111220323 111222156(vkorc1l1)
SLAL111658706 111663852(vkorc1l1)
XGL120794874(vkorc1) 120802311(vkorc1l1)
HCQ109508799(vkorc1l1) 109524007
BPEC110159643 110165064(vkorc1l1)
MALB109960444(vkorc1l1) 109963618
SASA106567394(vkorc1l1) 106577046
OTW112253079(vkorc1) 112258348 121841387
OMY110529490(vkorc1) 110537845 118966696
OGO123999324 124014982 124040746(vkorc1)
ONE115105380 115136237 115136328
SALP111951604 111963498 111980926
SNH120017939(vkorc1) 120032726 120056816
ELS105007720 105008282(vkorc1l1)
SFM108921596(vkorc1l1) 108938295 108941679
PKI111836830 111854712(vkorc1l1) 111859697
AANG118209798 118220282(vkorc1) 118235633(vkorc1l1)
LOC102693652(vkorc1l1) 102696686
PSPA121305140 121308568(vkorc1l1)
ARUT117398336 117429891 117430605
LCM102345266(VKORC1L1) 102357927
CMK103180624(vkorc1l1)
RTP109925205 109928519(vkorc1l1)
BFO118425571 118426307
BBEL109463634 109466245
CIN100178185 780870(vkor)
SPU763699
APLC110988312
SKO100376428 102805472
DMEDmel_CG33544(Vkor)
DER6548496
DSE6609493
DSIDsimw501_GD11216(Dsim_GD11216)
DYADyak_GE11817
DSR110180445
DPODpse_GA24080
DPE6601584
DMN108158370 117192983
DWI6640946
DGR6571186
DMODmoj_GI21152
DNV108653874
DHE111594945
CCAT101455423
BOD106617881
MDE101888998
SCAC106088686
LCQ111682432
AGAAgaP_AGAP000543
ACOZ120956807
AARA120906674
AAG5574649
AALB109415799 109431186
CQUCpipJ_CPIJ003816
CPII120430280 120431217
CNS116344816
AME724791
ACER107995061
ALAB122718185
BIM100746180
BBIF117207068
BVK117237317
BVAN117160893
BTER100647907
BPYO122572804
CCAL108622863
OBB114878863
MGEN117229918
NMEA116428177
CGIG122404484
SOC105199915
MPHA105838573
AEC105148077
ACEP105624125
PBAR105423896
VEM105565949
HST105189853
DQU106741085
CFO105256425
FEX115240480
LHU105671028
PGC109856097
OBO105284994
PCF106790230
PFUC122513406
VPS122637170
NVI100121150
CSOL105364056
TPRE106654656
MDL103578951
CGLO123271579
FAS105264909
DAM107043343
AGIF122851518
CCIN107272607
TCA103315249
DPA109544649
SOY115879210
ATD109609280
CSET123317026
AGB108912240
NVL108562475
APLN112906499
PPYR116177948
OTU111426474
BMOR101746818
BMAN114252611
MSEX115456116
DPLKGM_206433
BANY112044458
PMAC106717878
PPOT106108589
PXU106115825
PRAP111003414
ZCE119830629
HAW110374796
TNL113498914
SLIU111347859
OFU114360700
PXY105381639
API100573656 103309105
DNX107161956
AGS114121307
RMD113554155
BTAB109041108
DCI103511493 103511494
CLEC106663678
HHAL106689846
NLU111046624 120355860
PHUPhum_PHUM098450
FOC113207895
ZNE110831183
CSEC111873453
FCD110856806
DPXDAPPUDRAFT_304442
DMK123471513
PVM113823507
PJA122260330
PCHN125025702
HAME121875687
PCLA123764994
PTRU123518769
HAZT108676735
EAF111699917
LSM121122276
ISCIscW_ISCW024282
DSV119446301
RSAN119389877
RMP119175932
VDE111251999
VJA111260006
TUT107362817
DPTE113792512
DFR124497101
CSCU111629235
PTEP107451341
SDM118196454
BMYBM_BM605(Bm605)
LOALOAG_06369
HROHELRODRAFT_88258
LGILOTGIDRAFT_114833 LOTGIDRAFT_115113
PCAN112561177 112562931
BGT106056179 106056190
GAE121369461 121390761
HRF124147730 124147731
HRJ124286966 124286967
CRG105338127
MYI110460140
PMAX117333684
MMER123535186
OBI106870276 106877249
OSN115222593 115224536
LAK106150415 106150416
NVE5506957 5515586
EPA110250868
ATEN116292045 116293954
ADF107340505
AMIL114960653
PDAM113676685
SPIS111331307
DGT114520441
XEN124433813
HMG101235337
TADTRIADDRAFT_6927
AQU100633778
MBRMONBRDRAFT_29821
SREPTSG_04186
TGOTGME49_203720 TGME49_249760
FCYFRACYDRAFT_267199
PSOJPHYSODRAFT_472863
EHXEMIHUDRAFT_361809 EMIHUDRAFT_440728
GTTGUITHDRAFT_106868
TBRTb927.2.4840
TBGTbgDal_II2880
TCR504741.190
LMALMJF_27_2190
LIFLINJ_27_2110
LDOLDBPK_272110
LMILMXM_27_2190
LBZLBRM_27_2370
LPANLPMP_272190
ACAACP_3002
ACMAciX9_0903
GRWFTO74_03180
TRSTerro_1053
ABASACPOL_1085
 » show all
Reference
1  [PMID:646989]
  Authors
Whitlon DS, Sadowski JA, Suttie JW.
  Title
Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition.
  Journal
Biochemistry 17:1371-7 (1978)
DOI:10.1021/bi00601a003
Reference
2  [PMID:6733086]
  Authors
Lee JJ, Fasco MJ.
  Title
Metabolism of vitamin K and vitamin K 2,3-epoxide via interaction with a common disulfide.
  Journal
Biochemistry 23:2246-52 (1984)
DOI:10.1021/bi00305a024
Reference
3  [PMID:3857611]
  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
Proc Natl Acad Sci U S A 82:2713-7 (1985)
DOI:10.1073/pnas.82.9.2713
Reference
4  [PMID:14765195]
  Authors
Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW
  Title
Identification of the gene for vitamin K epoxide reductase.
  Journal
Nature 427:541-4 (2004)
DOI:10.1038/nature02254
Reference
5  [PMID:17124179]
  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
J Biol Chem 282:2626-35 (2007)
DOI:10.1074/jbc.M608954200
Reference
6  [PMID:19492146]
  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
7  [PMID:20696932]
  Authors
Schulman S, Wang B, Li W, Rapoport TA
  Title
Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners.
  Journal
Proc Natl Acad Sci U S A 107:15027-32 (2010)
DOI:10.1073/pnas.1009972107
Other DBs
ExplorEnz - The Enzyme Database: 1.17.4.4
IUBMB Enzyme Nomenclature: 1.17.4.4
ExPASy - ENZYME nomenclature database: 1.17.4.4
BRENDA, the Enzyme Database: 1.17.4.4
CAS: 55963-40-1

DBGET integrated database retrieval system