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FLASH GENE
Symbol GCK contributors: mct - updated : 12-06-2013
HGNC name glucokinase (hexokinase 4)
HGNC id 4195
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
Homologene
FAMILY
CATEGORY enzyme
SUBCELLULAR LOCALIZATION     intracellular
intracellular,cytoplasm,organelle,mitochondria,outer
intracellular,cytoplasm,organelle,membrane
intracellular,cytoplasm,cytosolic,granule
intracellular,nucleus,nucleoplasm
basic FUNCTION
  • provide G6P for the synthesis of glycogen
  • pancreatic glucokinase plays an important role in modulating insulin secretion
  • glucose specific, primary regulator of glucose-controlled insulin secretion, catalyzing the first step of glycolysis, energy pathway
  • regulates glucose storage and disposal in the liver where its activity is regulated by glucokinase regulatory protein, GCKR
  • role for posttranslational regulation of GCK S-nitrosylation as a vital regulatory mechanism for glucose-stimulated insulin secretion
  • acts as a sensor of blood glucose levels in the pancreas, and a few other cells of the gut and brain, and as the rate-limiting step in glucose metabolism in the liver
  • maintains glucose homeostasis by displaying a sigmoidal kinetic response to increasing blood glucose levels (
  • GCK and GCKR function as key glucose sensors (
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • post-translational activation of GCK is an important mechanism for mediating the insulinotropic effects of GCG
  • KLF6 regulation of GCK contributes to the development of hepatic insulin resistance
  • IRS2 signalling is important for maintaining the activity of liver GCK
  • GCKR acts as an allosteric switch for GCK in blood glucose control by the liver
  • cell & other
    REGULATION
    repressed by palmitate
    Other regulated by GK regulatory protein (GCKR), and indirectly by allosteric effectors of GCKR
    ASSOCIATED DISORDERS
    corresponding disease(s) GCK , MODY2 , PNDM1
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    altered GCK regulation in liver is predicted to enhance glycolytic flux, promoting hepatic glucose metabolism and elevating concentrations of malonyl-CoA, a substrate for de novo lipogenesis, providing a mutational mechanism for the reported association of this variant with raised triglycerides and lower glucose levels
    Susceptibility
  • to NIDDM1
  • to sudden and unexpected death
  • Variant & Polymorphism other polymorphisms increasing the risk of sudden and unexpected death
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • liver content of GCK was reduced in Irs2(-/-) mice as compared with controls, although GCKR levels were similar
  • Gck+/- Ucp2-/- mice had improved glucose tolerance compared with Gck+/- mice