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Protein

Vitamin K-dependent gamma-carboxylase

Gene

GGCX

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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.

Caution

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

Keywordsi

Molecular functionLyase

Enzyme and pathway databases

BioCyciMetaCyc: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

EuPathDBiHostDB:ENSG00000115486.11
HGNCiHGNC:4247 GGCX
MIMi137167 gene
neXtProtiNX_P38435

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Combined deficiency of vitamin K-dependent clotting factors 1 (VKCFD1)4 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 dbSNP:rs121909675Ensembl.1
Natural variantiVAR_021826485R → P in VKCFD1. 1 PublicationCorresponds to variant dbSNP:rs121909676Ensembl.1
Natural variantiVAR_015218501W → S in VKCFD1. 1 PublicationCorresponds to variant dbSNP:rs28928872Ensembl.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 dbSNP:rs121909677Ensembl.1
Natural variantiVAR_032980476R → C in PXEL-MCFD. 1 PublicationCorresponds to variant dbSNP:rs121909681Ensembl.1
Natural variantiVAR_032981476R → H in PXEL-MCFD. 1 PublicationCorresponds to variant dbSNP:rs121909682Ensembl.1
Natural variantiVAR_032982493W → S in PXEL-MCFD. 1 PublicationCorresponds to variant dbSNP:rs121909679Ensembl.1
Natural variantiVAR_032983558G → R in PXEL-MCFD. 1 PublicationCorresponds to variant dbSNP:rs121909678Ensembl.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 (Recombinant)
DB00036 Coagulation factor VIIa Recombinant Human
DB00055 Drotrecogin alfa
DB00142 L-Glutamic Acid
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...) asparagine1 Publication1
Glycosylationi550N-linked (GlcNAc...) asparagine1 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

BioGridi10894516 interactors.
IntActiP38435 20 interactors.
MINTiP38435
STRINGi9606.ENSP00000233838

Structurei

3D structure databases

ProteinModelPortaliP38435
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

InterProiView protein in InterPro
IPR011020 HTTM
IPR011051 RmlC_Cupin_sf
IPR007782 VKG_COase
PANTHERiPTHR12639 PTHR12639, 1 hit
PfamiView protein in Pfam
PF05090 VKG_Carbox, 1 hit
SMARTiView protein in SMART
SM00752 HTTM, 1 hit
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 dbSNP:rs121909677Ensembl.1
Natural variantiVAR_005780325R → Q1 PublicationCorresponds to variant dbSNP:rs699664Ensembl.1
Natural variantiVAR_005781394L → R in VKCFD1; affects glutamate binding. 2 PublicationsCorresponds to variant dbSNP:rs121909675Ensembl.1
Natural variantiVAR_032980476R → C in PXEL-MCFD. 1 PublicationCorresponds to variant dbSNP:rs121909681Ensembl.1
Natural variantiVAR_032981476R → H in PXEL-MCFD. 1 PublicationCorresponds to variant dbSNP:rs121909682Ensembl.1
Natural variantiVAR_021826485R → P in VKCFD1. 1 PublicationCorresponds to variant dbSNP:rs121909676Ensembl.1
Natural variantiVAR_032982493W → S in PXEL-MCFD. 1 PublicationCorresponds to variant dbSNP:rs121909679Ensembl.1
Natural variantiVAR_015218501W → S in VKCFD1. 1 PublicationCorresponds to variant dbSNP:rs28928872Ensembl.1
Natural variantiVAR_032983558G → R in PXEL-MCFD. 1 PublicationCorresponds to variant dbSNP:rs121909678Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiVKGC_HUMAN
AccessioniPrimary (citable) accession number: P38435
Secondary accession number(s): B4DMC5
, E9PEE1, Q14415, Q6GU45
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: December 20, 2005
Last modified: April 25, 2018
This is version 166 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome