MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP001178

UniProt Annotations

Entry Information
Gene Nameglucokinase (hexokinase 4)
Protein EntryHXK4_HUMAN
UniProt IDP35557
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=P35557-1; Sequence=Displayed; Name=2; IsoId=P35557-2; Sequence=VSP_002074; Name=3; IsoId=P35557-3; Sequence=VSP_002075;
Catalytic ActivityATP + D-glucose = ADP + D-glucose 6-phosphate.
DiseaseFamilial hyperinsulinemic hypoglycemia 3 (HHF3) [MIM:602485]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. {ECO:0000269|PubMed:9435328}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseMaturity-onset diabetes of the young 2 (MODY2) [MIM:125851]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. {ECO:0000269|PubMed:10588527, ECO:0000269|PubMed:10694920, ECO:0000269|PubMed:11106831, ECO:0000269|PubMed:11372010, ECO:0000269|PubMed:1303265, ECO:0000269|PubMed:1464666, ECO:0000269|PubMed:1502186, ECO:0000269|PubMed:8168652, ECO:0000269|PubMed:8325892, ECO:0000269|PubMed:8495817, ECO:0000269|PubMed:9049484, ECO:0000269|PubMed:9662401}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme RegulationThe use of alternative promoters apparently enables the type IV hexokinase gene to be regulated by insulin in the liver and glucose in the beta cell. This may constitute an important feedback loop for maintaining glucose homeostasis. Subject to allosteric regulation. Low glucose and high fructose-6- phosphate triggers association with the inhibitor GKRP followed by sequestration in the nucleus. {ECO:0000269|PubMed:10456334, ECO:0000269|PubMed:15016359}.
FunctionCatalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose concentration. Glucokinase has a high Km for glucose, and so it is effective only when glucose is abundant. The role of GCK is to provide G6P for the synthesis of glycogen. Pancreatic glucokinase plays an important role in modulating insulin secretion. Hepatic glucokinase helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage.
InteractionQ14397:GCKR; NbExp=2; IntAct=EBI-709928, EBI-709948; P16118:PFKFB1; NbExp=2; IntAct=EBI-709928, EBI-709807;
MiscellaneousIn vertebrates there are four major glucose- phosphorylating isoenzymes, designated hexokinase I, II, III and IV (glucokinase).
SimilarityBelongs to the hexokinase family. {ECO:0000305}.
SimilarityContains 1 hexokinase type-1 domain. {ECO:0000305}.
SimilarityContains 1 hexokinase type-2 domain. {ECO:0000305}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:10456334}. Nucleus {ECO:0000269|PubMed:10456334}. Note=Under low glucose concentrations, GCK associates with GKRP and the inactive complex is recruited to the hepatocyte nucleus.
SubunitMonomer. {ECO:0000269|PubMed:15016359, ECO:0000269|PubMed:19362831, ECO:0000269|PubMed:23957911}.
Tissue SpecificityIsoform 1 is expressed in pancreas. Isoform 2 and isoform 3 is expressed in liver.
Web ResourceName=Wikipedia; Note=Glucokinase entry; URL="http://en.wikipedia.org/wiki/Glucokinase";
  logo