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Protein

Vitamin K-dependent gamma-carboxylase

Gene

GGCX

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide.1 Publication

Catalytic activityi

[Peptidyl]-4-carboxyglutamate + 2,3-epoxyphylloquinone + H2O = [peptidyl]-glutamate + CO2 + O2 + phylloquinol.1 Publication

pH dependencei

Optimum pH is 7.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei218Proton acceptor1 Publication1

GO - Molecular functioni

GO - Biological processi

  • blood coagulation Source: ProtInc
  • cellular protein modification process Source: ProtInc
  • peptidyl-glutamic acid carboxylation Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Enzyme and pathway databases

BioCyciMetaCyc:HS03897-MONOMER.
ZFISH:HS03897-MONOMER.
BRENDAi4.1.1.90. 2681.
ReactomeiR-HSA-159740. Gamma-carboxylation of protein precursors.

Names & Taxonomyi

Protein namesi
Recommended name:
Vitamin K-dependent gamma-carboxylase (EC:4.1.1.901 Publication)
Alternative name(s):
Gamma-glutamyl carboxylase
Peptidyl-glutamate 4-carboxylase
Vitamin K gamma glutamyl carboxylase
Gene namesi
Name:GGCX
Synonyms:GC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:4247. GGCX.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 60CytoplasmicSequence analysisAdd BLAST59
Transmembranei61 – 81HelicalSequence analysisAdd BLAST21
Topological domaini82 – 113LumenalSequence analysisAdd BLAST32
Transmembranei114 – 134HelicalSequence analysisAdd BLAST21
Topological domaini135 – 136CytoplasmicSequence analysis2
Transmembranei137 – 157HelicalSequence analysisAdd BLAST21
Topological domaini158 – 292LumenalSequence analysisAdd BLAST135
Transmembranei293 – 313HelicalSequence analysisAdd BLAST21
Topological domaini314 – 361CytoplasmicSequence analysisAdd BLAST48
Transmembranei362 – 382HelicalSequence analysisAdd BLAST21
Topological domaini383 – 758LumenalSequence analysisAdd BLAST376

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: Reactome
  • integral component of membrane Source: ProtInc
  • membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Combined deficiency of vitamin K-dependent clotting factors 1 (VKCFD1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionVKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K.
See also OMIM:277450
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_005781394L → R in VKCFD1; affects glutamate binding. 2 PublicationsCorresponds to variant rs121909675dbSNPEnsembl.1
Natural variantiVAR_021826485R → P in VKCFD1. 1 PublicationCorresponds to variant rs121909676dbSNPEnsembl.1
Natural variantiVAR_015218501W → S in VKCFD1. 1 PublicationCorresponds to variant rs28928872dbSNPEnsembl.1
Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency (PXEL-MCFD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized by hyperlaxity of the skin involving the entire body. Important phenotypic differences with classical PXE include much more severe skin laxity with spreading toward the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. Moreover, detailed electron microscopic analyzes revealed that alterations of elastic fibers as well as their mineralization are slightly different from those in classic PXE.
See also OMIM:610842
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032979299F → S in PXEL-MCFD. 1 PublicationCorresponds to variant rs121909677dbSNPEnsembl.1
Natural variantiVAR_032980476R → C in PXEL-MCFD. 1 PublicationCorresponds to variant rs121909681dbSNPEnsembl.1
Natural variantiVAR_032981476R → H in PXEL-MCFD. 1 PublicationCorresponds to variant rs121909682dbSNPEnsembl.1
Natural variantiVAR_032982493W → S in PXEL-MCFD. 1 PublicationCorresponds to variant rs121909679dbSNPEnsembl.1
Natural variantiVAR_032983558G → R in PXEL-MCFD. 1 PublicationCorresponds to variant rs121909678dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi160H → A: No effect on activity. 1 Publication1
Mutagenesisi218K → A: No activity. 1 Publication1
Mutagenesisi287H → A: No effect on activity. 1 Publication1
Mutagenesisi381H → A: No effect on activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2677.
MalaCardsiGGCX.
MIMi277450. phenotype.
610842. phenotype.
OpenTargetsiENSG00000115486.
Orphaneti91135. Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency.
98434. Hereditary combined deficiency of vitamin K-dependent clotting factors.
PharmGKBiPA28660.

Chemistry databases

ChEMBLiCHEMBL2012.
DrugBankiDB01125. Anisindione.
DB00100. Coagulation Factor IX.
DB00036. Coagulation factor VIIa.
DB00055. Drotrecogin alfa.
DB00170. Menadione.
DB01022. Phylloquinone.

Polymorphism and mutation databases

BioMutaiGGCX.
DMDMi84028279.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001918232 – 758Vitamin K-dependent gamma-carboxylaseAdd BLAST757

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Disulfide bondi99 ↔ 4501 Publication
Glycosylationi459N-linked (GlcNAc...)1 Publication1
Glycosylationi550N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein

Proteomic databases

EPDiP38435.
MaxQBiP38435.
PaxDbiP38435.
PeptideAtlasiP38435.
PRIDEiP38435.

PTM databases

iPTMnetiP38435.
PhosphoSitePlusiP38435.

Expressioni

Gene expression databases

BgeeiENSG00000115486.
CleanExiHS_GC.
HS_GGCX.
ExpressionAtlasiP38435. baseline and differential.
GenevisibleiP38435. HS.

Organism-specific databases

HPAiHPA018284.

Interactioni

Subunit structurei

Monomer. May interact with CALU (By similarity).By similarity

Protein-protein interaction databases

BioGridi108945. 15 interactors.
IntActiP38435. 16 interactors.
STRINGi9606.ENSP00000233838.

Structurei

3D structure databases

ProteinModelPortaliP38435.
SMRiP38435.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHG2. Eukaryota.
ENOG410XR5Q. LUCA.
GeneTreeiENSGT00390000014909.
HOGENOMiHOG000007593.
HOVERGENiHBG012798.
InParanoidiP38435.
KOiK10106.
OMAiSPSCYMY.
OrthoDBiEOG091G07P8.
PhylomeDBiP38435.
TreeFamiTF323879.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR011020. HTTM.
IPR014710. RmlC-like_jellyroll.
IPR011051. RmlC_Cupin.
IPR007782. VKG_COase.
[Graphical view]
PANTHERiPTHR12639. PTHR12639. 1 hit.
PfamiPF05090. VKG_Carbox. 1 hit.
[Graphical view]
SMARTiSM00752. HTTM. 1 hit.
[Graphical view]
SUPFAMiSSF51182. SSF51182. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P38435-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAVSAGSART SPSSDKVQKD KAELISGPRQ DSRIGKLLGF EWTDLSSWRR
60 70 80 90 100
LVTLLNRPTD PASLAVFRFL FGFLMVLDIP QERGLSSLDR KYLDGLDVCR
110 120 130 140 150
FPLLDALRPL PLDWMYLVYT IMFLGALGMM LGLCYRISCV LFLLPYWYVF
160 170 180 190 200
LLDKTSWNNH SYLYGLLAFQ LTFMDANHYW SVDGLLNAHR RNAHVPLWNY
210 220 230 240 250
AVLRGQIFIV YFIAGVKKLD ADWVEGYSME YLSRHWLFSP FKLLLSEELT
260 270 280 290 300
SLLVVHWGGL LLDLSAGFLL FFDVSRSIGL FFVSYFHCMN SQLFSIGMFS
310 320 330 340 350
YVMLASSPLF CSPEWPRKLV SYCPRRLQQL LPLKAAPQPS VSCVYKRSRG
360 370 380 390 400
KSGQKPGLRH QLGAAFTLLY LLEQLFLPYS HFLTQGYNNW TNGLYGYSWD
410 420 430 440 450
MMVHSRSHQH VKITYRDGRT GELGYLNPGV FTQSRRWKDH ADMLKQYATC
460 470 480 490 500
LSRLLPKYNV TEPQIYFDIW VSINDRFQQR IFDPRVDIVQ AAWSPFQRTS
510 520 530 540 550
WVQPLLMDLS PWRAKLQEIK SSLDNHTEVV FIADFPGLHL ENFVSEDLGN
560 570 580 590 600
TSIQLLQGEV TVELVAEQKN QTLREGEKMQ LPAGEYHKVY TTSPSPSCYM
610 620 630 640 650
YVYVNTTELA LEQDLAYLQE LKEKVENGSE TGPLPPELQP LLEGEVKGGP
660 670 680 690 700
EPTPLVQTFL RRQQRLQEIE RRRNTPFHER FFRFLLRKLY VFRRSFLMTC
710 720 730 740 750
ISLRNLILGR PSLEQLAQEV TYANLRPFEA VGELNPSNTD SSHSNPPESN

PDPVHSEF
Length:758
Mass (Da):87,561
Last modified:December 20, 2005 - v2
Checksum:i720D5B08E9B558C8
GO
Isoform 2 (identifier: P38435-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     15-71: Missing.

Note: No experimental confirmation available.
Show »
Length:701
Mass (Da):80,989
Checksum:iCA7D806186E791B5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti400D → N in AAA91834 (Ref. 3) Curated1
Sequence conflicti659F → S in BAG59837 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032979299F → S in PXEL-MCFD. 1 PublicationCorresponds to variant rs121909677dbSNPEnsembl.1
Natural variantiVAR_005780325R → Q.1 PublicationCorresponds to variant rs699664dbSNPEnsembl.1
Natural variantiVAR_005781394L → R in VKCFD1; affects glutamate binding. 2 PublicationsCorresponds to variant rs121909675dbSNPEnsembl.1
Natural variantiVAR_032980476R → C in PXEL-MCFD. 1 PublicationCorresponds to variant rs121909681dbSNPEnsembl.1
Natural variantiVAR_032981476R → H in PXEL-MCFD. 1 PublicationCorresponds to variant rs121909682dbSNPEnsembl.1
Natural variantiVAR_021826485R → P in VKCFD1. 1 PublicationCorresponds to variant rs121909676dbSNPEnsembl.1
Natural variantiVAR_032982493W → S in PXEL-MCFD. 1 PublicationCorresponds to variant rs121909679dbSNPEnsembl.1
Natural variantiVAR_015218501W → S in VKCFD1. 1 PublicationCorresponds to variant rs28928872dbSNPEnsembl.1
Natural variantiVAR_032983558G → R in PXEL-MCFD. 1 PublicationCorresponds to variant rs121909678dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04617915 – 71Missing in isoform 2. 1 PublicationAdd BLAST57

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81592 mRNA. Translation: AAA58643.1.
U65896 Genomic DNA. Translation: AAB39832.1.
L17128 mRNA. Translation: AAA91834.1.
AK297397 mRNA. Translation: BAG59837.1.
AC016753 Genomic DNA. Translation: AAY24340.1.
BC013979 mRNA. Translation: AAH13979.1.
CCDSiCCDS1978.1. [P38435-1]
CCDS46353.1. [P38435-2]
PIRiA39283.
RefSeqiNP_000812.2. NM_000821.6. [P38435-1]
NP_001135741.1. NM_001142269.3. [P38435-2]
UniGeneiHs.77719.

Genome annotation databases

EnsembliENST00000233838; ENSP00000233838; ENSG00000115486. [P38435-1]
ENST00000430215; ENSP00000408045; ENSG00000115486. [P38435-2]
GeneIDi2677.
KEGGihsa:2677.
UCSCiuc002sps.4. human. [P38435-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81592 mRNA. Translation: AAA58643.1.
U65896 Genomic DNA. Translation: AAB39832.1.
L17128 mRNA. Translation: AAA91834.1.
AK297397 mRNA. Translation: BAG59837.1.
AC016753 Genomic DNA. Translation: AAY24340.1.
BC013979 mRNA. Translation: AAH13979.1.
CCDSiCCDS1978.1. [P38435-1]
CCDS46353.1. [P38435-2]
PIRiA39283.
RefSeqiNP_000812.2. NM_000821.6. [P38435-1]
NP_001135741.1. NM_001142269.3. [P38435-2]
UniGeneiHs.77719.

3D structure databases

ProteinModelPortaliP38435.
SMRiP38435.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108945. 15 interactors.
IntActiP38435. 16 interactors.
STRINGi9606.ENSP00000233838.

Chemistry databases

ChEMBLiCHEMBL2012.
DrugBankiDB01125. Anisindione.
DB00100. Coagulation Factor IX.
DB00036. Coagulation factor VIIa.
DB00055. Drotrecogin alfa.
DB00170. Menadione.
DB01022. Phylloquinone.

PTM databases

iPTMnetiP38435.
PhosphoSitePlusiP38435.

Polymorphism and mutation databases

BioMutaiGGCX.
DMDMi84028279.

Proteomic databases

EPDiP38435.
MaxQBiP38435.
PaxDbiP38435.
PeptideAtlasiP38435.
PRIDEiP38435.

Protocols and materials databases

DNASUi2677.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000233838; ENSP00000233838; ENSG00000115486. [P38435-1]
ENST00000430215; ENSP00000408045; ENSG00000115486. [P38435-2]
GeneIDi2677.
KEGGihsa:2677.
UCSCiuc002sps.4. human. [P38435-1]

Organism-specific databases

CTDi2677.
DisGeNETi2677.
GeneCardsiGGCX.
HGNCiHGNC:4247. GGCX.
HPAiHPA018284.
MalaCardsiGGCX.
MIMi137167. gene.
277450. phenotype.
610842. phenotype.
neXtProtiNX_P38435.
OpenTargetsiENSG00000115486.
Orphaneti91135. Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency.
98434. Hereditary combined deficiency of vitamin K-dependent clotting factors.
PharmGKBiPA28660.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHG2. Eukaryota.
ENOG410XR5Q. LUCA.
GeneTreeiENSGT00390000014909.
HOGENOMiHOG000007593.
HOVERGENiHBG012798.
InParanoidiP38435.
KOiK10106.
OMAiSPSCYMY.
OrthoDBiEOG091G07P8.
PhylomeDBiP38435.
TreeFamiTF323879.

Enzyme and pathway databases

BioCyciMetaCyc:HS03897-MONOMER.
ZFISH:HS03897-MONOMER.
BRENDAi4.1.1.90. 2681.
ReactomeiR-HSA-159740. Gamma-carboxylation of protein precursors.

Miscellaneous databases

ChiTaRSiGGCX. human.
GeneWikiiGamma-glutamyl_carboxylase.
GenomeRNAii2677.
PROiP38435.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115486.
CleanExiHS_GC.
HS_GGCX.
ExpressionAtlasiP38435. baseline and differential.
GenevisibleiP38435. HS.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR011020. HTTM.
IPR014710. RmlC-like_jellyroll.
IPR011051. RmlC_Cupin.
IPR007782. VKG_COase.
[Graphical view]
PANTHERiPTHR12639. PTHR12639. 1 hit.
PfamiPF05090. VKG_Carbox. 1 hit.
[Graphical view]
SMARTiSM00752. HTTM. 1 hit.
[Graphical view]
SUPFAMiSSF51182. SSF51182. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiVKGC_HUMAN
AccessioniPrimary (citable) accession number: P38435
Secondary accession number(s): B4DMC5
, E9PEE1, Q14415, Q6GU45
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: December 20, 2005
Last modified: November 2, 2016
This is version 157 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

The vitamin K-dependent protein substrates of carboxylase have usually a propeptide that binds to a high-affinity site on the carboxylase. CO2, O2 and reduced vitamin K are cosubstrates.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.