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This gene encodes a protein belonging to the GCKR subfamily of the SIS (Sugar ISomerase) family of proteins. The gene product is a regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. This gene is considered a susceptibility gene candidate for a form of maturity-onset diabetes of the young (MODY). [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: HAD, Insulin, CAN, ACID, AGE
Papers on GCKR
Theoretical investigations on the interactions of glucokinase regulatory protein with fructose phosphates.
Bi et al., Qufu, China. In Comput Biol Chem, Feb 2016
In the liver, the activity of GK is modulated by the glucokinase regulatory protein (GKRP) which functions as a competitive inhibitor of glucose to bind to GK.
Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs.
Valladares-Salgado et al., Houston, United States. In Sci Rep, Dec 2015
Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides.
Genes associated with diabetes: potential for novel therapeutic targets?
Odawara et al., Tokyo, Japan. In Expert Opin Ther Targets, Nov 2015
This paper also reviews the current status of the compounds targeting the T2D-associated genes GCK, GKRP, ADIPOQ, and ADRA2A in clinical and preclinical phases.
Modulation of Glucokinase Regulatory Protein: A Double-Edged Sword?
Schaper et al., Maastricht, Netherlands. In Trends Mol Med, Oct 2015
The continuous search for drugs targeting type 2 diabetes mellitus (T2DM) has led to the identification of small molecules that disrupt the binding between glucokinase and glucokinase regulatory protein (GKRP).
Glucokinase regulatory protein: complexity at the crossroads of triglyceride and glucose metabolism.
Gloyn et al., Cambridge, United States. In Curr Opin Lipidol, Apr 2015
PURPOSE OF REVIEW: Glucokinase regulator (GCKR) encodes glucokinase regulatory protein (GKRP), a hepatocyte-specific inhibitor of the glucose-metabolizing enzyme glucokinase (GCK).
Molecular targeting of the GK-GKRP pathway in diabetes.
Véniant et al., Thousand Oaks, United States. In Expert Opin Ther Targets, 2015
AREAS COVERED: This review summarizes the roles of GK and its key partner glucokinase regulatory protein in glucose metabolism and describes approaches that may alleviate hypoglycemic risk observed with GKAs.
Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity.
Ahn et al., Seoul, South Korea. In Sci Rep, 2014
Post-translationally, GK is regulated by binding the glucokinase regulatory protein (GKRP), resulting in GK retention in the nucleus and its inability to participate in cytosolic glycolysis.
The Association of Type 2 Diabetes Loci Identified in Genome-Wide Association Studies with Metabolic Syndrome and Its Components in a Chinese Population with Type 2 Diabetes.
Yang et al., Beijing, China. In Plos One, 2014
The T2D risk alleles of rs972283 near KLF14 and rs11634397 near ZFAND6 were associated with a higher risk for elevated triglycerides (rs972283: 1.11 (1.02, 1.24), P = 1.46 × 10-2; rs11634397: 1.14 (1.00, 1.29), P = 4.66 × 10-2), while the T2D risk alleles of rs780094 in GCKR and rs7903146 in TCF7L2 were related to a lower risk of elevated triglycerides (rs780094: 0.86 (0.80, 0.93), P = 1.35 × 10-4; rs7903146: 0.82 (0.69, 0.98), P = 3.18 × 10-2).
Expression analysis of innate immunity related genes in the true/field blast resistance gene-mediated defence response.
Liu et al., Wuhan, China. In Biotechnol Biotechnol Equip, 2014
And, JAmyb (marker gene of jasmonic acid signalling) showed higher upregulation in the resistance lines with nucleotide-binding sites and leucine-rich repeat (NBS-LRR) R genes Pib, Pizt, Pik, Pita2 and Pikahei than in NB and KHS.
A patent review of glucokinase activators and disruptors of the glucokinase--glucokinase regulatory protein interaction: 2011-2014.
Pfefferkorn et al., Cambridge, United States. In Expert Opin Ther Pat, 2014
AREAS COVERED: This manuscript reviews small molecule patent disclosures between late 2011 and February 2014 for both GK activators (GKAs) and GK-glucokinase regulatory protein (GK-GKRP) disruptors.
Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors.
Hale et al., Thousand Oaks, United States. In Nature, 2014
Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes.
Association between gout and polymorphisms in GCKR in male Han Chinese.
Ma et al., Beijing, China. In Hum Genet, 2012
2 SNPs, rs780093 and rs780094, located in intronic regions of the GCKR gene were found to be significantly associated with the development of gout in male Han Chinese; GCKR was identified as a novel candidate gene associated with gout
Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men.
Laakso et al., Kuopio, Finland. In Diabetes, 2012
Only one single nucleotide polymorphism of GCKR hyperglycemia was significantly associated with amino acid blood levels, hyperglycemia, and risk for type 2 diabetes.
Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents.
Caprio et al., New Haven, United States. In Hepatology, 2012
The rs1260326 in GCKR is associated with hepatic fat accumulation along with large VLDL and triglyceride levels. GCKR and PNPLA3 act together to convey susceptibility to fatty liver in obese youths.
Modulation of glucokinase by glucose, small-molecule activator and glucokinase regulatory protein: steady-state kinetic and cell-based analysis.
Landro et al., United States. In Biochem J, 2012
When GK is pre-incubated with glucose and compound A, the inhibition observed by GKRP is time dependent, but independent of GKRP concentration, reflecting the GKA-controlled transition between closed and open GK conformations.
Correlation of rare coding variants in the gene encoding human glucokinase regulatory protein with phenotypic, cellular, and kinetic outcomes.
Collins et al., Bethesda, United States. In J Clin Invest, 2012
Defects were observed for the majority of rare variants after assessment of cellular localization, ability to interact with GCK, and kinetic activity of the encoded proteins. Functional rare variants showed associations with lipid phenotypes.
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
Kooner et al., London, United Kingdom. In Nat Genet, 2011
We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827).
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Barroso et al., Boston, United States. In Nat Genet, 2010
We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes.
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
Purcell et al., Cambridge, United States. In Science, 2007
We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides.
A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2.
Blangero et al., San Antonio, United States. In Nat Genet, 1997
This region contains several potential candidate genes for obesity, including glucokinase regulatory protein (GCKR) and pro-opiomelanocortin (POMC).
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