KEGG   ORTHOLOGY: K10106Help
Entry
K10106                      KO                                     

Name
GGCX
Definition
vitamin K-dependent gamma-carboxylase [EC:4.1.1.90]
Pathway
Ubiquinone and other terpenoid-quinone biosynthesis
Disease
H00560  
Pseudoxanthoma elasticum
H00995  
Combined deficiency of vitamin K-dependent clotting factors (VKCFD)
H01205  
Coumarin resistance
Brite
KEGG Orthology (KO) [BR:ko00001]
 Metabolism
  Metabolism of cofactors and vitamins
   00130 Ubiquinone and other terpenoid-quinone biosynthesis
    K10106  GGCX; vitamin K-dependent gamma-carboxylase
Enzymes [BR:ko01000]
 4. Lyases
  4.1  Carbon-carbon lyases
   4.1.1  Carboxy-lyases
    4.1.1.90  peptidyl-glutamate 4-carboxylase
     K10106  GGCX; vitamin K-dependent gamma-carboxylase
BRITE hierarchy
Other DBs
Genes
HSA: 
2677(GGCX)
PTR: 
459364(GGCX)
PPS: 
100979139(GGCX)
GGO: 
101133597(GGCX)
PON: 
100171564(GGCX)
NLE: 
100605566(GGCX)
MCC: 
695628(GGCX)
MCF: 
102116153(GGCX)
CSAB: 
103219944(GGCX)
RRO: 
104677047(GGCX)
CJC: 
100412061(GGCX)
SBQ: 
101035344(GGCX)
MMU: 
56316(Ggcx)
RNO: 
81716(Ggcx)
CGE: 
100774482(Ggcx)
NGI: 
103739792(Ggcx)
HGL: 
101703456(Ggcx)
CCAN: 
109686177(Ggcx)
OCU: 
100346091(GGCX)
TUP: 
102479702(GGCX)
CFA: 
475769(GGCX)
AML: 
100477985(GGCX)
UMR: 
103671848(GGCX)
FCA: 
101085622(GGCX)
PTG: 
102962433(GGCX)
AJU: 
106978202(GGCX)
BTA: 
281190(GGCX)
BOM: 
102277857(GGCX)
BIU: 
109566174(GGCX)
PHD: 
102319966(GGCX)
CHX: 
102170242(GGCX)
OAS: 
443129(GGCX)
SSC: 
100620337(GGCX)
CFR: 
102506387(GGCX)
BACU: 
103007146(GGCX)
LVE: 
103089680(GGCX)
ECB: 
100067312(GGCX)
MYB: 
102242720(GGCX)
MYD: 
102767774(GGCX)
HAI: 
109371334(GGCX)
RSS: 
109436168(GGCX)
PALE: 
102898204(GGCX)
LAV: 
100675417(GGCX)
MDO: 
100030057(GGCX)
OAA: 
100077833
MGP: 
104916860(GGCX)
CJO: 
107323599(GGCX)
TGU: 
100221126(GGCX)
FAB: 
101818545(GGCX)
PHI: 
102110670(GGCX)
CCW: 
104683151(GGCX)
CLV: 
102090925(GGCX)
AAM: 
106493802(GGCX)
ASN: 
102383382(GGCX)
AMJ: 
106737680 109282852(GGCX)
PSS: 
102449866(GGCX)
CMY: 
102930896(GGCX)
CPIC: 
101940387(GGCX)
ACS: 
100555036(ggcx)
PBI: 
103064362(GGCX)
GJA: 
107120342(GGCX)
XLA: 
444473(ggcx.L)
XTR: 
100144666(ggcx)
DRE: 
557240(ggcx)
IPU: 
108276729(ggcx)
TRU: 
101067681(ggcx)
TNG: 
GSTEN00017326G001
LCO: 
104923320(ggcx)
MZE: 
101484617(ggcx)
OLA: 
101172424(ggcx)
XMA: 
102224466(ggcx)
CSEM: 
103390489(ggcx)
SASA: 
106563193
LCM: 
102360484(GGCX)
CMK: 
103187831(ggcx)
BFO: 
BRAFLDRAFT_124426 BRAFLDRAFT_92865
CIN: 
780874(ggcx)
SPU: 
764318
SKO: 
102801874
DME: 
Dmel_CG13927(GC)
DPO: 
Dpse_GA12632
DAN: 
Dana_GF24021
DER: 
Dere_GG14584
DPE: 
Dper_GL20734
DSE: 
Dsec_GM14197
DSI: 
Dsimw501_GD13462(Dsim_GD13462)
DWI: 
Dwil_GK23671
DYA: 
Dyak_GE20943
DGR: 
Dgri_GH14871
DMO: 
Dmoj_GI12843
DVI: 
Dvir_GJ12988
MDE: 
101889022
AGA: 
AgaP_AGAP006363
AAG: 
AaeL_AAEL002622
CQU: 
CpipJ_CPIJ007343
AME: 
551869(GC)
BIM: 
100749841
BTER: 
100645769
SOC: 
105204060
AEC: 
105149615
PBAR: 
105421986
HST: 
105191645
CFO: 
105250361
NVI: 
100123716
TCA: 
659418
PXY: 
105388304
API: 
100161672
PHU: 
Phum_PHUM216730
DPX: 
DAPPUDRAFT_301381
ISC: 
IscW_ISCW020854 IscW_ISCW020855
LGI: 
LOTGIDRAFT_182855
CRG: 
105332560
OBI: 
106881997
NVE: 
NEMVE_v1g187853
ADF: 
107336790
HMG: 
100204648 101241467
TAD: 
TRIADDRAFT_30063
FCY: 
FRACYDRAFT_249245
 » show all
TaxonomyKoalaUniProt
Reference
  Authors
Tie JK, Jin DY, Straight DL, Stafford DW
  Title
Functional study of the vitamin K cycle in mammalian cells.
  Journal
Blood 117:2967-74 (2011)
DOI:10.1182/blood-2010-08-304303
KEGG   ENZYME: 4.1.1.90Help
Entry
EC 4.1.1.90                 Enzyme                                 

Name
peptidyl-glutamate 4-carboxylase;
vitamin K-dependent carboxylase;
gamma-glutamyl carboxylase;
peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinone-epoxidizing)
Class
Lyases;
Carbon-carbon lyases;
Carboxy-lyases
BRITE hierarchy
Sysname
peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinol-epoxidizing)
Reaction(IUBMB)
peptidyl-4-carboxyglutamate + 2,3-epoxyphylloquinone + H2O = peptidyl-glutamate + CO2 + O2 + phylloquinol [RN:R05144]
Reaction(KEGG)
R05144;
(other) R09991
Show
Substrate
peptidyl-4-carboxyglutamate [CPD:C06246];
2,3-epoxyphylloquinone [CPD:C05849];
H2O [CPD:C00001]
Product
peptidyl-glutamate [CPD:C06247];
CO2 [CPD:C00011];
O2 [CPD:C00007];
phylloquinol [CPD:C03313]
Comment
The enzyme can use various vitamin-K derivatives, including menaquinol, but does not contain iron. The mechanism appears to involve the generation of a strong base by oxygenation of vitamin K. It catalyses the post-translational carboxylation of glutamate residues of several proteins of the blood-clotting system. 9--12 glutamate residues are converted to 4-carboxyglutamate (Gla) in a specific domain of the target protein. The 4-pro-S hydrogen of the glutamate residue is removed [5] and there is an inversion of stereochemistry at this position [6].
History
EC 4.1.1.90 created 2009, modified 2011
Pathway
Ubiquinone and other terpenoid-quinone biosynthesis
Biosynthesis of secondary metabolites
Orthology
K10106  
vitamin K-dependent gamma-carboxylase
Genes
HSA: 
2677(GGCX)
PTR: 
459364(GGCX)
PPS: 
100979139(GGCX)
GGO: 
101133597(GGCX)
PON: 
100171564(GGCX)
NLE: 
100605566(GGCX)
MCC: 
695628(GGCX)
MCF: 
102116153(GGCX)
CSAB: 
103219944(GGCX)
RRO: 
104677047(GGCX)
CJC: 
100412061(GGCX)
SBQ: 
101035344(GGCX)
MMU: 
56316(Ggcx)
RNO: 
81716(Ggcx)
CGE: 
100774482(Ggcx)
NGI: 
103739792(Ggcx)
HGL: 
101703456(Ggcx)
CCAN: 
109686177(Ggcx)
OCU: 
100346091(GGCX)
TUP: 
102479702(GGCX)
CFA: 
475769(GGCX)
AML: 
100477985(GGCX)
UMR: 
103671848(GGCX)
FCA: 
101085622(GGCX)
PTG: 
102962433(GGCX)
AJU: 
106978202(GGCX)
BTA: 
281190(GGCX)
BOM: 
102277857(GGCX)
BIU: 
109566174(GGCX)
PHD: 
102319966(GGCX)
CHX: 
102170242(GGCX)
OAS: 
443129(GGCX)
SSC: 
100620337(GGCX)
CFR: 
102506387(GGCX)
BACU: 
103007146(GGCX)
LVE: 
103089680(GGCX)
ECB: 
100067312(GGCX)
MYB: 
102242720(GGCX)
MYD: 
102767774(GGCX)
HAI: 
109371334(GGCX)
RSS: 
109436168(GGCX)
PALE: 
102898204(GGCX)
LAV: 
100675417(GGCX)
MDO: 
100030057(GGCX)
OAA: 
100077833
MGP: 
104916860(GGCX)
CJO: 
107323599(GGCX)
TGU: 
100221126(GGCX)
FAB: 
101818545(GGCX)
PHI: 
102110670(GGCX)
CCW: 
104683151(GGCX)
CLV: 
102090925(GGCX)
AAM: 
106493802(GGCX)
ASN: 
102383382(GGCX)
AMJ: 
106737680 109282852(GGCX)
PSS: 
102449866(GGCX)
CMY: 
102930896(GGCX)
CPIC: 
101940387(GGCX)
ACS: 
100555036(ggcx)
PBI: 
103064362(GGCX)
GJA: 
107120342(GGCX)
XLA: 
444473(ggcx.L)
XTR: 
100144666(ggcx)
DRE: 
557240(ggcx)
IPU: 
108276729(ggcx)
TRU: 
101067681(ggcx)
TNG: 
GSTEN00017326G001
LCO: 
104923320(ggcx)
MZE: 
101484617(ggcx)
OLA: 
101172424(ggcx)
XMA: 
102224466(ggcx)
CSEM: 
103390489(ggcx)
SASA: 
106563193
LCM: 
102360484(GGCX)
CMK: 
103187831(ggcx)
BFO: 
BRAFLDRAFT_124426 BRAFLDRAFT_92865
CIN: 
780874(ggcx)
SPU: 
764318
SKO: 
102801874
DME: 
Dmel_CG13927(GC)
DPO: 
Dpse_GA12632
DAN: 
Dana_GF24021
DER: 
Dere_GG14584
DPE: 
Dper_GL20734
DSE: 
Dsec_GM14197
DSI: 
Dsimw501_GD13462(Dsim_GD13462)
DWI: 
Dwil_GK23671
DYA: 
Dyak_GE20943
DGR: 
Dgri_GH14871
DMO: 
Dmoj_GI12843
DVI: 
Dvir_GJ12988
MDE: 
101889022
AGA: 
AgaP_AGAP006363
AAG: 
AaeL_AAEL002622
CQU: 
CpipJ_CPIJ007343
AME: 
551869(GC)
BIM: 
100749841
BTER: 
100645769
SOC: 
105204060
AEC: 
105149615
PBAR: 
105421986
HST: 
105191645
CFO: 
105250361
NVI: 
100123716
TCA: 
659418
PXY: 
105388304
API: 
100161672
PHU: 
Phum_PHUM216730
DPX: 
DAPPUDRAFT_301381
ISC: 
IscW_ISCW020854 IscW_ISCW020855
LGI: 
LOTGIDRAFT_182855
CRG: 
105332560
OBI: 
106881997
NVE: 
NEMVE_v1g187853
ADF: 
107336790
HMG: 
100204648 101241467
TAD: 
TRIADDRAFT_30063
FCY: 
FRACYDRAFT_249245
 » show all
Taxonomy
Reference
1  [PMID:7569894]
  Authors
Dowd P, Hershline R, Ham SW, Naganathan S
  Title
Vitamin K and energy transduction: a base strength amplification mechanism.
  Journal
Science. 269 (1995) 1684-91.
Reference
2  [PMID:10068650]
  Authors
Furie B, Bouchard BA, Furie BC
  Title
Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid.
  Journal
Blood. 93 (1999) 1798-808.
Reference
3  [PMID:17073445]
  Authors
Rishavy MA, Hallgren KW, Yakubenko AV, Shtofman RL, Runge KW, Berkner KL
  Title
Bronsted analysis reveals Lys218 as the carboxylase active site base that deprotonates vitamin K hydroquinone to initiate vitamin K-dependent protein carboxylation.
  Journal
Biochemistry. 45 (2006) 13239-48.
  Sequence
[hsa:2677]
Reference
4  [PMID:17935315]
  Authors
Silva PJ, Ramos MJ
  Title
Reaction mechanism of the vitamin K-dependent glutamate carboxylase: a computational study.
  Journal
J. Phys. Chem. B. 111 (2007) 12883-7.
Reference
5  [PMID:6150930]
  Authors
Decottignies-Le Marechal P, Ducrocq C, Marquet A, Azerad R
  Title
The stereochemistry of hydrogen abstraction in vitamin K-dependent carboxylation.
  Journal
J. Biol. Chem. 259 (1984) 15010-2.
Reference
6  [PMID:1931973]
  Authors
Dubois J, Dugave C, Foures C, Kaminsky M, Tabet JC, Bory S, Gaudry M, Marquet A
  Title
Vitamin K dependent carboxylation: determination of the stereochemical course using 4-fluoroglutamyl-containing substrate.
  Journal
Biochemistry. 30 (1991) 10506-12.
Reference
7  [PMID:22516721]
  Authors
Rishavy MA, Berkner KL
  Title
Vitamin K oxygenation, glutamate carboxylation, and processivity: defining the three critical facets of catalysis by the vitamin K-dependent carboxylase.
  Journal
Adv. Nutr. 3 (2012) 135-48.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
KEGG   REACTION: R05144Help
Entry
R05144                      Reaction                               

Name
peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinone-epoxidizing)
Definition
Gla protein + Vitamin K1 epoxide + H2O <=> Gla protein precursor + Phylloquinol + CO2 + Oxygen
Equation
Reaction class
C03313_C05849
C06246_C06247
Enzyme
Pathway
Ubiquinone and other terpenoid-quinone biosynthesis
Biosynthesis of secondary metabolites
Orthology
K10106  
vitamin K-dependent gamma-carboxylase [EC:4.1.1.90]
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