Glucokinase (GCK)

GK; GLK; HHF3; HK4; HKIV; HXKP; MODY2; Hexokinase-D; Hexokinase 4; Maturity Onset Diabetes Of The Young 2

SPN	W145
HGNC	4195
MGI	1270854
PubMed	19790256
RGD	2670
UniProt	P35557
Wiki	Glucokinase

Glucokinase (GK) is a hexokinase isozyme, related homologously and by evolution to at least three other hexokinases. All of the hexokinases can mediate phosphorylation of glucose to glucose-6-phosphate (G6P), which is the first step of both glycogen synthesis and glycolysis. However, glucokinase is coded by a separate gene and its distinctive kinetic properties allow it to serve a different set of functions. Glucokinase has a lower affinity for glucose than the other hexokinases do, and its activity is localized to a few cell types, leaving the other three hexokinases as more important preparers of glucose for glycolysis and glycogen synthesis for most tissues and organs. Because of this reduced affinity, the activity of glucokinase, under usual physiological conditions, varies substantially according to the concentration of glucose.

Reference

"Human glucokinase gene: isolation, structural characterization, and identification of a microsatellite repeat polymorphism."
Mol. Endocrinol. 6:1070-1081(1992) [PubMed] [Europe PMC] [Abstract]

"Human liver glucokinase gene: cloning and sequence determination of two alternatively spliced cDNAs."
Proc. Natl. Acad. Sci. U.S.A. 88:7294-7297(1991) [PubMed] [Europe PMC] [Abstract]

"Human pancreatic beta-cell glucokinase: cDNA sequence and localization of the polymorphic gene to chromosome 7, band p13."
Diabetologia 35:743-747(1992) [PubMed] [Europe PMC] [Abstract]

"Human islet glucokinase gene. Isolation and sequence analysis of full-length cDNA."
Diabetes 41:807-811(1992) [PubMed] [Europe PMC] [Abstract]

"Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus."
Proc. Natl. Acad. Sci. U.S.A. 89:7698-7702(1992) [PubMed] [Europe PMC] [Abstract]

Erratum
Proc. Natl. Acad. Sci. U.S.A. 89:10562-10562(1992)

"Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus."
J. Clin. Endocrinol. Metab. 75:1571-1573(1992) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"Human chromosome 7: DNA sequence and biology."
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Glucokinase regulatory protein is essential for the proper subcellular localisation of liver glucokinase."
FEBS Lett. 456:332-338(1999) [PubMed] [Europe PMC] [Abstract]

"Molecular model of human beta-cell glucokinase built by analogy to the crystal structure of yeast hexokinase B."
Diabetes 43:784-791(1994) [PubMed] [Europe PMC] [Abstract]

"Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase."
Structure 12:429-438(2004) [PubMed] [Europe PMC] [Abstract]

"Discovery of novel 3,6-disubstituted 2-pyridinecarboxamide derivatives as GK activators."
Bioorg. Med. Chem. Lett. 19:2718-2721(2009) [PubMed] [Europe PMC] [Abstract]

"Structural basis for regulation of human glucokinase by glucokinase regulatory protein."
Biochemistry 52:6232-6239(2013) [PubMed] [Europe PMC] [Abstract]

"Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes."
Nat. Genet. 2:153-156(1992) [PubMed] [Europe PMC] [Abstract]

"Glucokinase gene variants in the common form of NIDDM."
Diabetes 42:579-582(1993) [PubMed] [Europe PMC] [Abstract]

"Identification of glucokinase mutations in subjects with gestational diabetes mellitus."
Diabetes 42:937-940(1993) [PubMed] [Europe PMC] [Abstract]

"Structure/function studies of human beta-cell glucokinase. Enzymatic properties of a sequence polymorphism, mutations associated with diabetes, and other site-directed mutants."
J. Biol. Chem. 268:15200-15204(1993) [PubMed] [Europe PMC] [Abstract]

"Glucokinase mutations associated with non-insulin-dependent (type 2) diabetes mellitus have decreased enzymatic activity: implications for structure/function relationships."
Proc. Natl. Acad. Sci. U.S.A. 90:1932-1936(1993) [PubMed] [Europe PMC] [Abstract]

"Six mutations in the glucokinase gene identified in MODY by using a nonradioactive sensitive screening technique."
Diabetes 43:730-733(1994) [PubMed] [Europe PMC] [Abstract]

"Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families."
Diabetologia 40:217-224(1997) [PubMed] [Europe PMC] [Abstract]

"Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity-onset diabetes of the young (MODY)."
Hum. Mutat. 12:136-136(1998) [PubMed] [Europe PMC] [Abstract]

"Mutations in the glucokinase gene of the fetus result in reduced birth weight."
Nat. Genet. 19:268-270(1998) [PubMed] [Europe PMC] [Abstract]

"Familial hyperinsulinism caused by an activating glucokinase mutation."
N. Engl. J. Med. 338:226-230(1998) [PubMed] [Europe PMC] [Abstract]

"Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY."
Diabet. Med. 16:956-963(1999) [PubMed] [Europe PMC] [Abstract]

"Identification of glucokinase mutation in subjects with post-renal transplantation diabetes mellitus."
Diabetes Res. Clin. Pract. 50:169-176(2000) [PubMed] [Europe PMC] [Abstract]

"Neonatal diabetes mellitus due to complete glucokinase deficiency."
N. Engl. J. Med. 344:1588-1592(2001) [PubMed] [Europe PMC] [Abstract]

"The previously reported T342P GCK missense variant is not a pathogenic mutation causing MODY."
Diabetologia 54:2202-2205(2011) [PubMed] [Europe PMC] [Abstract]