Gamma-glutamyl carboxylase

Gamma-glutamyl carboxylase is an enzyme that in humans is encoded by the GGCX gene, located on chromosome 2 at 2p12.[4]

GGCX
Identifiers
AliasesGGCX, VKCFD1, gamma-glutamyl carboxylase, Gamma-glutamyl carboxylase; GGCX
External IDsOMIM: 137167 MGI: 1927655 HomoloGene: 639 GeneCards: GGCX
Gene location (Human)
Chr.Chromosome 2 (human)[1]
Band2p11.2Start85,544,720 bp[1]
End85,561,547 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

2677

56316

Ensembl

ENSG00000115486

n/a

UniProt

P38435

Q9QYC7

RefSeq (mRNA)

NM_000821
NM_001142269
NM_001311312

NM_019802

RefSeq (protein)

NP_000812
NP_001135741
NP_001298241

NP_062776

Location (UCSC)Chr 2: 85.54 – 85.56 Mbn/a
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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.[5] Most gla domain-containing proteins depend on this carboxylation reaction for posttranslational modification.[6] In humans, the gamma-glutamyl carboxylase enzyme is most highly expressed in the liver.

Catalytic reaction

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). Presence of two carboxylate groups causes chelation of Ca2+ , resulting in change in tertiary structure of protein and its activation. 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.[7][8][9]

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
2O

Clinical significance

Mutations in this gene are associated with vitamin K-dependent coagulation defect and PXE-like disorder with multiple coagulation factor deficiency.[5][10]

gollark: Complex analysis is quite hard, I believe.
gollark: Basic definition, arithmetic operations, conjugates, geometric form, Euler's relation, applications to weird serieseseses, roots of unity, roots of polynomials, sort of thing.
gollark: You could go through it in maybe 15 minutes, but not *teach* it that well.
gollark: A-level calculus is just a few differentiation rules and ææææ integration.
gollark: I guess it's fairly okay a s long as you don't mind being remembered for it in a ridiculously specific niche.

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000115486 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. 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.
  5. "Entrez Gene: GGCX".
  6. 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.
  7. Suttie JW (1985). "Vitamin K-dependent carboxylase". Annu. Rev. Biochem. 54 (1): 459–77. doi:10.1146/annurev.bi.54.070185.002331. PMID 3896125.
  8. Presnell SR, Stafford DW (2002). "The vitamin K-dependent carboxylase". Thromb. Haemost. 87 (6): 937–46. doi:10.1055/s-0037-1613115. PMID 12083499.
  9. 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.
  10. 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
  • Bandyopadhyay PK (2008). "Vitamin K-dependent gamma-glutamylcarboxylation: an ancient posttranslational modification". Vitam. Horm. Vitamins & Hormones. 78: 157–84. doi:10.1016/S0083-6729(07)00008-8. ISBN 9780123741134. PMID 18374194.
  • Berkner KL (2008). "Vitamin K-dependent carboxylation". Vitam. Horm. Vitamins & Hormones. 78: 131–56. doi:10.1016/S0083-6729(07)00007-6. ISBN 9780123741134. PMID 18374193.
  • Oldenburg J, Marinova M, Müller-Reible C, Watzka M (2008). "The vitamin K cycle". Vitam. Horm. Vitamins & Hormones. 78: 35–62. doi:10.1016/S0083-6729(07)00003-9. ISBN 9780123741134. PMID 18374189.
  • Berkner KL (2005). "The vitamin K-dependent carboxylase". Annu. Rev. Nutr. 25 (1): 127–49. doi:10.1146/annurev.nutr.25.050304.092713. PMID 16011462.
  • Zhang B, Ginsburg D (September 2004). "Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disorders". J. Thromb. Haemost. 2 (9): 1564–72. doi:10.1111/j.1538-7836.2004.00857.x. hdl:2027.42/74529. PMID 15333032.
  • Wallin R, Hutson SM (July 2004). "Warfarin and the vitamin K-dependent gamma-carboxylation system". Trends Mol Med. 10 (7): 299–302. doi:10.1016/j.molmed.2004.05.003. PMID 15242675.
  • Berkner KL (August 2000). "The vitamin K-dependent carboxylase". J. Nutr. 130 (8): 1877–80. doi:10.1093/jn/130.8.1877. PMID 10917896.
  • Presnell SR, Stafford DW (June 2002). "The vitamin K-dependent carboxylase". Thromb. Haemost. 87 (6): 937–46. doi:10.1055/s-0037-1613115. PMID 12083499.
  • Bender, David A. (2003). Nutritional biochemistry of the vitamins. Cambridge, UK: Cambridge University Press. ISBN 0-521-80388-8.
  • Ball, George E. (2004). Vitamins: their role in the human body. Oxford: Blackwell Science. ISBN 0-632-06478-1.
  • Combs, Gerald F. (1998). The vitamins: fundamental aspects in nutrition and health. Boston: Academic Press. ISBN 0-12-183492-1.

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