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FLASH GENE
Symbol GCK contributors: mct - updated : 12-06-2013
HGNC name glucokinase (hexokinase 4)
HGNC id 4195
Corresponding disease
GCK familial hyperinsulinism
MODY2 maturity onset diabetes of the young, type II
PNDM1 permanent neonatal diabetes mellitus 1
Location 7p13      Physical location : 44.183.869 - 44.229.022
Synonym name
  • glucokinase (hexokinase 4, maturity onset diabetes of the young 2)
  • ATP:D-hexose 6-phosphotransferase
  • hexokinase D, pancreatic isozyme
  • Synonym symbol(s) HK4, GK, GLK, HHF3, HKIV, HXKP, FGQTL3, HKIV, HXKP, LGLK, MODY2
    EC.number 2.7.1.2
    DNA
    TYPE functioning gene
    STRUCTURE 45.15 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status provisional
    Map pter - TRGC1 ,TRGC2 - D7S65 - GCK GCK - D7S57 - D7S74 - D7S9 - cen
    Authors Mishra (92)
    Physical map
    HIP-55 7p13 src homology 3 domain-containing protein HIP-55 LOC393058 7 similar to OG-2 homeodomain protein-like; similar to U65067 (PID:g1575526) PGAM2 7p13-p12 phosphoglycerate mutase 2 (muscle) POLM 7p13 polymerase (DNA directed), mu LOC393059 7 similar to peptidyl-Pro cis trans isomerase AEBP1 7p15.1 AE binding protein 1 TPK1 7q34 thiamin pyrophosphokinase 1 POLD2 7p15.1 polymerase (DNA directed), delta 2, regulatory subunit 50kDa BLVRA 7p14-cen biliverdin reductase A MYL7 7p21-p11.2 myosin, light polypeptide 7, regulatory GCK 7p14-p13 glucokinase (hexokinase 4, maturity onset diabetes of the young 2) YKT6 7p15.1 SNARE protein Ykt6 CAMK2B 7p13 calcium/calmodulin-dependent protein kinase (CaM kinase) II beta MRPS24 7p14 mitochondrial ribosomal protein S24 URG4 7p13 up-regulated gene 4 LOC51619 7p13 ubiquitin-conjugating enzyme HBUCE1 LOC389486 7 similar to RAS p21 protein activator 4; GTPase activating protein-like; Ca2+-promoted Ras inactivator; calcium-promoted Ras inactivator WBSCR19 7q11.23 Williams Beuren syndrome chromosome region 19 KIAA1068 7p13-p12 Williams Beuren syndrome chromosome region 19 LOC392023 7 similar to RasGAP-activating-like protein 2 (Calcium-promoted Ras inactivator) HIP-55 7p13 src homology 3 domain-containing protein HIP-55 PGAM2 7p13-p12 phosphoglycerate mutase 2 (muscle) POLM 7p13 polymerase (DNA directed), mu AEBP1 7p15.1 AE binding protein 1 POLD2 7p15.1 polymerase (DNA directed), delta 2, regulatory subunit 50kDa MYL7 7p21-p11.2 myosin, light polypeptide 7, regulatory NPC1L1 7p13 NPC1 (Niemann-Pick disease, type C1, gene)-like 1 GCK 7p14-p13 glucokinase (hexokinase 4, maturity onset diabetes of the young 2) DDX56 7p13 DEAD (Asp-Glu-Ala-Asp) box polypeptide 56 YKT6 7p15.1 SNARE protein Ykt6 HNLF 7p13 putative NFkB activating protein HNLF CAMK2B 7p13 calcium/calmodulin-dependent protein kinase (CaM kinase) II beta OGDH 7p14-p13 oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide) LOC393060 7 similar to Importin alpha-2 subunit (Karyopherin alpha-2 subunit) (SRP1-alpha) (RAG cohort protein 1) LOC393061 7 similar to ribosomal protein L7 DKFZp761I2123 7p13 hypothetical protein DKFZp761I2123 KIAA1068 7p13-p12 hypothetical protein DKFZp761I2123 PPIA 7p13-p11.2 peptidylprolyl isomerase A (cyclophilin A) H2AV 7p13 H2A histone family, member V NPC1L1 7p13 NPC1 (Niemann-Pick disease, type C1, gene)-like 1 PURB 7p13 purine-rich element binding protein B DDX56 7p13 DEAD (Asp-Glu-Ala-Asp) box polypeptide 56
    RNA
    TRANSCRIPTS type messenger
    text
  • 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
  • constituting an important feedback loop for maintaining
  • glucose homeostasis
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2741 - 465 expressed specifically in pancreatic islet beta cells 2012 23297408
  • 3 N-terminal lysines unique for the pancreatic isoform (Lys-12/Lys-13 and/or Lys-15) may represent one SUMOylation site, with an additional site (Lys-346) common for the pancreatic and the liver isoform
  • 10 - 2442 - 466 major in liver 2012 23297408
  • 3 N-terminal lysines unique for the pancreatic isoform (Lys-12/Lys-13 and/or Lys-15) may represent one SUMOylation site, with an additional site (Lys-346) common for the pancreatic and the liver isoform
  • 11 - 2566 - 464 minor form expressed in liver 2012 23297408
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver     Homo sapiensAdultNM_033507
    Endocrinepancreas    
    Lymphoid/Immunelymph node    
    Nervousbrainmidbrainhypothalamus   Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestivehepatocyte Homo sapiens
    Endocrineislet cell (alpha,beta...) Homo sapiensNM_000162
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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
  • 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