GGCX

Protein identityUniProt · HPA

UniProt accession

P38435

Gene

GGCX

Ensembl

ENSG00000115486

Chromosome

2

Canonical length

758 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

This gene encodes an integral membrane protein of the rough endoplasmic reticulum that carboxylates glutamate residues of vitamin K-dependent proteins to gamma carboxyl glutamate, a modification that is required for their activity. The vitamin K-dependent protein substrates have a propeptide that binds the enzyme, with carbon dioxide, dioxide, and reduced vitamin K acting as co-substrates. Vitamin K-dependent proteins affect a number of physiologic processes including blood coagulation, prevention of vascular calcification, and inflammation. Allelic variants of this gene have been associated with pseudoxanthoma elasticum-like disorder with associated multiple coagulation factor deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

Canonical amino-acid sequenceUniProt

758 residues, UniProt reviewed canonical sequence.

>P38435|GGCX
     1  MAVSAGSART SPSSDKVQKD KAELISGPRQ DSRIGKLLGF EWTDLSSWRR LVTLLNRPTD
    61  PASLAVFRFL FGFLMVLDIP QERGLSSLDR KYLDGLDVCR FPLLDALRPL PLDWMYLVYT
   121  IMFLGALGMM LGLCYRISCV LFLLPYWYVF LLDKTSWNNH SYLYGLLAFQ LTFMDANHYW
   181  SVDGLLNAHR RNAHVPLWNY AVLRGQIFIV YFIAGVKKLD ADWVEGYSME YLSRHWLFSP
   241  FKLLLSEELT SLLVVHWGGL LLDLSAGFLL FFDVSRSIGL FFVSYFHCMN SQLFSIGMFS
   301  YVMLASSPLF CSPEWPRKLV SYCPRRLQQL LPLKAAPQPS VSCVYKRSRG KSGQKPGLRH
   361  QLGAAFTLLY LLEQLFLPYS HFLTQGYNNW TNGLYGYSWD MMVHSRSHQH VKITYRDGRT
   421  GELGYLNPGV FTQSRRWKDH ADMLKQYATC LSRLLPKYNV TEPQIYFDIW VSINDRFQQR
   481  IFDPRVDIVQ AAWSPFQRTS WVQPLLMDLS PWRAKLQEIK SSLDNHTEVV FIADFPGLHL
   541  ENFVSEDLGN TSIQLLQGEV TVELVAEQKN QTLREGEKMQ LPAGEYHKVY TTSPSPSCYM
   601  YVYVNTTELA LEQDLAYLQE LKEKVENGSE TGPLPPELQP LLEGEVKGGP EPTPLVQTFL
   661  RRQQRLQEIE RRRNTPFHER FFRFLLRKLY VFRRSFLMTC ISLRNLILGR PSLEQLAQEV
   721  TYANLRPFEA VGELNPSNTD SSHSNPPESN PDPVHSEF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GGCX can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

9

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

101 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GGCX.

Disease | AllUniProt

Conditions GGCX is implicated in, by any mechanism.

• Combined deficiency of vitamin K-dependent clotting factors 1 (VKCFD1) MIM:277450
• Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency (PXEL-MCFD) MIM:610842

Disease | GeneticClinVar

54 pathogenic / likely-pathogenic of 615 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Vitamin K-dependent clotting factors, combined deficiency of, type 1
• Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency
• GGCX-related disorder
• Hepatocellular carcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.93

gnomAD pLI

0

gnomAD missense Z

0.88

DepMap mean gene effect

-0.21

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood coagulation
• cellular response to insulin stimulus
• glucose homeostasis
• negative regulation of bone development
• negative regulation of neurotransmitter secretion
• negative regulation of testosterone biosynthetic process
• protein maturation
• protein modification process
• type B pancreatic cell proliferation
• vitamin K metabolic process

Molecular functions

• vitamin binding
• gamma-glutamyl carboxylase activity

Cellular components

• endoplasmic reticulum lumen
• endoplasmic reticulum membrane
• membrane

Protein domainsUniProt · Pfam · InterPro

• RmlC-like cupin domain superfamily
• RmlC-like jelly roll fold
• Vitamin K-dependent gamma-carboxylase
• HTTM-like
• HTTM domain
• Vitamin K-dependent gamma-carboxylase, lumenal domain
• HTTM domain
• Vitamin K-dependent gamma-carboxylase, lumenal domain

KeywordsUniProt

• Acetylation
• Disulfide bond
• Endoplasmic reticulum
• Glycoprotein
• Lipid-binding
• Lyase
• Membrane
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of GGCX in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CALU
• FBXO6