Gamma-glutamyl carboxylase

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GGCX
Identifiers
Aliases GGCX, VKCFD1, gamma-glutamyl carboxylase
External IDs OMIM: 137167 MGI: 1927655 HomoloGene: 639 GeneCards: 2677
RNA expression pattern
PBB GE GGCX 205351 at tn.png

PBB GE GGCX 214006 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000821
NM_001142269
NM_001311312

NM_019802

RefSeq (protein)

NP_000812.2
NP_001135741.1

NP_062776.1

Location (UCSC) Chr 2: 85.54 – 85.56 Mb Chr 6: 72.41 – 72.43 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Gamma-glutamyl carboxylase is an enzyme that in humans is encoded by the GGCX gene, located on chromosome 2 at 2p12.[1]

Function[edit]

Gamma-glutamyl carboxylase is an enzyme that catalyzes the posttranslational modification of vitamin K-dependent proteins. Many of these vitamin K-dependent proteins are involved in coagulation so the function of the encoded enzyme is essential for hemostasis.[2] Most gla domain-containing proteins depend on this carboxylation reaction for posttranslational modification.[3] In humans, the gamma-glutamyl carboxylase enzyme is most highly expressed in the liver.

Catalytic reaction[edit]

Gamma-glutamyl carboxylase oxidizes Vitamin K hydroquinone to Vitamin K 2,3 epoxide, while simultaneously adding CO2 to protein-bound glutamic acid (abbreviation = Glu) to form gamma-carboxyglutamic acid (also called gamma-carboxyglutamate, abbreviation = Gla). The carboxylation reaction will only proceed if the carboxylase enzyme is able to oxidize vitamin K hydroquinone to vitamin K epoxide at the same time; the carboxylation and epoxidation reactions are said to be coupled reactions.[4][5][6]

Gamma-glutamyl carboxylase.svg
a [protein]-α-L-glutamate (Glu) + phylloquinol (KH
2
) + CO
2
+ oxygen → a [protein] 4-carboxy-L-glutamate (Gla) + vitamin K 2,3-epoxide (KO) + H+
+ H
2
O

Clinical significance[edit]

Mutations in this gene are associated with vitamin K-dependent coagulation defect and PXE-like disorder with multiple coagulation factor deficiency.[2][7]

See also[edit]

References[edit]

  1. ^ Wu SM, Cheung WF, Frazier D, Stafford DW (December 1991). "Cloning and expression of the cDNA for human gamma-glutamyl carboxylase". Science 254 (5038): 1634–6. doi:10.1126/science.1749935. PMID 1749935. 
  2. ^ a b "Entrez Gene: GGCX". 
  3. ^ Brenner B, Tavori S, Zivelin A, Keller CB, Suttie JW, Tatarsky I, Seligsohn U (August 1990). "Hereditary deficiency of all vitamin K-dependent procoagulants and anticoagulants". Br. J. Haematol. 75 (4): 537–42. doi:10.1111/j.1365-2141.1990.tb07795.x. PMID 2145029. 
  4. ^ Suttie JW (1985). "Vitamin K-dependent carboxylase". Annu. Rev. Biochem. 54 (1): 459–77. doi:10.1146/annurev.bi.54.070185.002331. PMID 3896125. 
  5. ^ Presnell SR, Stafford DW (2002). "The vitamin K-dependent carboxylase". Thromb. Haemost. 87 (6): 937–46. PMID 12083499. 
  6. ^ Silva PJ, Ramos MJ (2007). "Reaction mechanism of the vitamin K-dependent glutamate carboxylase: a computational study". J Phys Chem B 111 (44): 12883–7. doi:10.1021/jp0738208. PMID 17935315. 
  7. ^ Vanakker OM, Martin L, Gheduzzi D, Leroy BP, Loeys BL, Guerci VI, Matthys D, Terry SF, Coucke PJ, Pasquali-Ronchetti I, De Paepe A (March 2007). "Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity". J. Invest. Dermatol. 127 (3): 581–7. doi:10.1038/sj.jid.5700610. PMID 17110937. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.