Gamma-glutamyl carboxylase: Difference between revisions

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{{protein
{{Infobox_gene}}
|Name=gamma-glutamyl carboxylase
'''Gamma-glutamyl carboxylase''' is an [[enzyme]] that in humans is encoded by the ''GGCX'' [[gene]], located on [[chromosome 2]] at 2p12.<ref name="pmid1749935">{{cite journal |vauthors=Wu SM, Cheung WF, Frazier D, Stafford DW | title = Cloning and expression of the cDNA for human gamma-glutamyl carboxylase | journal = Science | volume = 254 | issue = 5038 | pages = 1634–6 |date=December 1991 | pmid = 1749935 | doi = 10.1126/science.1749935 | url = | issn = }}</ref>
|caption=
 
|image=
==Function==
|width=
 
|HGNCid=4247
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.<ref name="entrez">{{cite web | title = Entrez Gene: GGCX | url =https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2677| accessdate = }}</ref>  Most [[gla domain]]-containing proteins depend on this carboxylation reaction for [[posttranslational modification]].<ref name="pmid2145029">{{cite journal |vauthors=Brenner B, Tavori S, Zivelin A, Keller CB, Suttie JW, Tatarsky I, Seligsohn U | title = Hereditary deficiency of all vitamin K-dependent procoagulants and anticoagulants | journal = Br. J. Haematol. | volume = 75 | issue = 4 | pages = 537–42 |date=August 1990 | pmid = 2145029 | doi = 10.1111/j.1365-2141.1990.tb07795.x| url = | issn = }}</ref>  In humans, the gamma-glutamyl carboxylase enzyme is most highly expressed in the liver.
|Symbol=GGCX
 
|AltSymbols=
==Catalytic reaction==
|EntrezGene=2677
Gamma-glutamyl carboxylase oxidizes [[Vitamin K]] hydroquinone to Vitamin K 2,3 epoxide, while simultaneously adding CO<sub>2</sub> 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.<ref name="pmid3896125">{{cite journal | author = Suttie JW | title = Vitamin K-dependent carboxylase | journal = Annu. Rev. Biochem. | volume = 54 | issue = 1| pages = 459–77 | year = 1985 | pmid = 3896125 | doi = 10.1146/annurev.bi.54.070185.002331 | issn = }}</ref><ref name="pmid12083499">{{cite journal |vauthors=Presnell SR, Stafford DW | title = The vitamin K-dependent carboxylase | journal = Thromb. Haemost. | volume = 87 | issue = 6 | pages = 937–46 | year = 2002 | pmid = 12083499 | doi = | issn = }}</ref><ref name="pmid17935315">{{cite journal |vauthors=Silva PJ, Ramos MJ | title = Reaction mechanism of the vitamin K-dependent glutamate carboxylase: a computational study | journal = J Phys Chem B | volume = 111 | issue = 44 | pages = 12883–7 | year = 2007 | pmid = 17935315 | doi = 10.1021/jp0738208 | issn = }}</ref>
|OMIM=137167
 
|RefSeq=NM_000821
[[File:Gamma-glutamyl carboxylase.svg|center|600px]]
|UniProt=P38435
 
|PDB=
<center>a [protein]-α-L-glutamate (Glu) + phylloquinol ({{chem|KH|2}}) + {{chem|CO|2}} + oxygen →
|ECnumber=
a [protein] 4-carboxy-L-glutamate (Gla) + vitamin K 2,3-epoxide (KO) + {{chem|H|+}} + {{chem|H|2|O}}</center>
|Chromosome=2
|Arm=p
|Band=12
|LocusSupplementaryData=
}}
'''Gamma-glutamyl carboxylase''' is an enzyme which oxidizes [[Vitamin K]] hydroquinone to Vitamin K 2,3 epoxide, while simultaneously adding CO<sub>2</sub> 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.<ref name="Suttie">{{cite journal |author=Suttie JW |title=Vitamin K-dependent carboxylase |journal=Annu. Rev. Biochem. |volume=54 |issue= |pages=459–77 |year=1985 |pmid=3896125 |doi=10.1146/annurev.bi.54.070185.002331}}</ref><ref name="Presnell">{{cite journal |author=Presnell SR, Stafford DW |title=The vitamin K-dependent carboxylase |journal=Thromb. Haemost. |volume=87 |issue=6 |pages=937–46 |year=2002 |pmid=12083499 |doi=}}</ref> [[Gla domain]]-containing proteins depend on the carboxylation reaction for [[posttranslational modification]].


==References==
==Clinical significance==
<div class="references-small">
{{reflist|2}}
</div>


==Further reading==
Mutations in this gene are associated with vitamin K-dependent coagulation defect and [[Pseudoxanthoma elasticum|PXE]]-like disorder with multiple coagulation factor deficiency.<ref name="entrez"/><ref name="pmid17110937">{{cite journal |vauthors=Vanakker OM, Martin L, Gheduzzi D, Leroy BP, Loeys BL, Guerci VI, Matthys D, Terry SF, Coucke PJ, Pasquali-Ronchetti I, De Paepe A | title = Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity | journal = J. Invest. Dermatol. | volume = 127 | issue = 3 | pages = 581–7 |date=March 2007 | pmid = 17110937 | doi = 10.1038/sj.jid.5700610 | url = | issn = }}</ref>
* David A. Bender, ''Nutritional biochemistry of the vitamins'', Cambridge University Press, 2003
* G. F. M. Ball, ''Vitamins: their role in the human body'', Blackwell Science, 2004
* Gerald F. Combs, ''The vitamins: fundamental aspects in nutrition and health'', Academic Press, 1998


==See also==
==See also==
* [[Carboxyglutamate]]
* [[Carboxyglutamate]]
==References==
{{Reflist|2}}
==Further reading==
{{refbegin | 2}}
* {{cite journal | author = Bandyopadhyay PK | title = Vitamin K-dependent gamma-glutamylcarboxylation: an ancient posttranslational modification | journal = Vitam. Horm. | volume = 78 | issue = | pages = 157–84 | year = 2008 | pmid = 18374194 | doi = 10.1016/S0083-6729(07)00008-8 | url = | issn = }}
* {{cite journal | author = Berkner KL | title = Vitamin K-dependent carboxylation | journal = Vitam. Horm. | volume = 78 | issue = | pages = 131–56 | year = 2008 | pmid = 18374193 | doi = 10.1016/S0083-6729(07)00007-6 | url = | issn = }}
* {{cite journal |vauthors=Oldenburg J, Marinova M, Müller-Reible C, Watzka M | title = The vitamin K cycle | journal = Vitam. Horm. | volume = 78 | issue = | pages = 35–62 | year = 2008 | pmid = 18374189 | doi = 10.1016/S0083-6729(07)00003-9 | url = | issn = }}
* {{cite journal | author = Berkner KL | title = The vitamin K-dependent carboxylase | journal = Annu. Rev. Nutr. | volume = 25 | issue = 1| pages = 127–49 | year = 2005 | pmid = 16011462 | doi = 10.1146/annurev.nutr.25.050304.092713 | url = | issn = }}
* {{cite journal |vauthors=Zhang B, Ginsburg D | title = Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disorders | journal = J. Thromb. Haemost. | volume = 2 | issue = 9 | pages = 1564–72 |date=September 2004 | pmid = 15333032 | doi = 10.1111/j.1538-7836.2004.00857.x | url = | issn = }}
* {{cite journal |vauthors=Wallin R, Hutson SM | title = Warfarin and the vitamin K-dependent gamma-carboxylation system | journal = Trends Mol Med | volume = 10 | issue = 7 | pages = 299–302 |date=July 2004 | pmid = 15242675 | doi = 10.1016/j.molmed.2004.05.003 | url = | issn = }}
* {{cite journal | author = Berkner KL | title = The vitamin K-dependent carboxylase | journal = J. Nutr. | volume = 130 | issue = 8 | pages = 1877–80 |date=August 2000 | pmid = 10917896 | doi = | url = http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=10917896 | issn = }}
* {{cite journal |vauthors=Presnell SR, Stafford DW | title = The vitamin K-dependent carboxylase | journal = Thromb. Haemost. | volume = 87 | issue = 6 | pages = 937–46 |date=June 2002 | pmid = 12083499 | doi = | url = | issn = }}
* {{cite book | author = Bender, David A. | title = Nutritional biochemistry of the vitamins | publisher = Cambridge University Press | location = Cambridge, UK | year = 2003 | pages = | isbn = 0-521-80388-8 | oclc = | doi = }}
* {{cite book | author = Ball, George E. | title = Vitamins: their role in the human body | publisher = Blackwell Science | location = Oxford | year = 2004 | pages = | isbn = 0-632-06478-1 | oclc = | doi = }}
* {{cite book | author = Combs, Gerald F. | title = The vitamins: fundamental aspects in nutrition and health | publisher = Academic Press | location = Boston | year = 1998 | pages = | isbn = 0-12-183492-1 | oclc = | doi = }}
{{refend}}


==External links==
==External links==
* {{MeshName|glutamyl+carboxylase}}
* {{MeshName|glutamyl+carboxylase}}


{{biochemistry-stub}}
{{NLM content}}
{{Carbon-carbon ligases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}
 
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[[Category:EC 6.4]]
[[Category:EC 6.4]]
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{{biochemistry-stub}}

Latest revision as of 13:29, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Wikidata
View/Edit Human

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

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.[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

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]

File: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
2O

Clinical significance

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

References

  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. ↑ 2.0 2.1 "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

External links

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


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