Glucokinase regulator
| Glucokinase regulator | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 624 amino acids | |
| Identifier | ||
| Gene name | GCKR | |
| External IDs | ||
| Occurrence | ||
| Homology family | Glucokinase regulator | |
| Parent taxon | Euteleostomi | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 2646 | 231103 |
| Ensemble | ENSG00000084734 | ENSMUSG00000059434 |
| UniProt | Q14397 | Q91X44 |
| Refseq (mRNA) | NM_001486 | NM_144909 |
| Refseq (protein) | NP_001477 | NP_659158 |
| Gene locus | Chr 2: 27.5 - 27.52 Mb | Chr 5: 31.3 - 31.33 Mb |
| PubMed search | 2646 |
231103
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The protein called glucokinase regulator (GCKR) is produced in the liver and pancreas in humans and all vertebrates . GCKR binds reversibly to the enzyme glucokinase . After translocation into the cell nucleus , the complex is separated when the glucose level is high and the glucokinase is returned to the cytosol . The effect is that when the glucose level is low, a pool of GK: GCKR is available in the nucleus in order to quickly intercept increased glucose levels after ingestion of food.
Binding is stimulated by fructose-6-phosphate and sorbitol-6-phosphate , but hindered by fructose-1-phosphate . The latter thus increases the glucokinase activity.
A genetic variant of the protein that occurs in 34 percent of non-Europeans is associated with increased CRP and triglycerides, as well as decreased glucose during fasting. Another study with Canadians of European descent associated increased triglycerides during fasting with a GCKR variant. A French study produced identical results.
Individual evidence
- ↑ UniProt Q14397
- ↑ a b reactome.org: Negative Regulation of Glucokinase by Glucokinase Regulatory Protein
- ↑ Anderka O, Boyken J, Aschenbach U, Batzer A, Boscheinen O, Schmoll D: Biophysical characterization of the interaction between hepatic glucokinase and its regulatory protein: impact of physiological and pharmacological effectors . In: J. Biol. Chem. . 283, No. 46, November 2008, pp. 31333-40. doi : 10.1074 / jbc.M805434200 . PMID 18809676 .
- ↑ Orho-Melander M, Melander O, Guiducci C, et al : Common missense variant in the glucokinase regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein but lower fasting glucose concentrations . In: Diabetes . 57, No. 11, November 2008, pp. 3112-21. doi : 10.2337 / db08-0516 . PMID 18678614 .
- ↑ Wang J, Ban MR, Zou GY, et al : Polygenic determinants of severe hypertriglyceridemia . In: Hum. Mol. Genet. . 17, No. 18, September 2008, pp. 2894-9. doi : 10.1093 / hmg / ddn188 . PMID 18596051 .
- ↑ Vaxillaire M, Cavalcanti-Proença C, Dechaume A, et al : The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population . In: Diabetes . 57, No. 8, August 2008, pp. 2253-7. doi : 10.2337 / db07-1807 . PMID 18556336 .
- ↑ Ridker PM, Pare G, Parker A, et al : Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study . In: Am. J. Hum. Genet. . 82, No. 5, May 2008, pp. 1185-92. doi : 10.1016 / j.ajhg.2008.03.015 . PMID 18439548 .
- ↑ Sparsø T, Andersen G, Nielsen T, et al : The GCKR rs780094 polymorphism is associated with elevated fasting serum triacylglycerol, reduced fasting and OGTT-related insulinaemia, and reduced risk of type 2 diabetes . In: Diabetologia . 51, No. 1, January 2008, pp. 70-5. doi : 10.1007 / s00125-007-0865-z . PMID 18008060 .