GCK - Glucokinase - human protein (Function)
 
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GCK »  Glucokinase   [ EC 2.7.1.2 ]
 
Protein also known as:  Hexokinase type IV (HK IV).
Gene name:  GCK
Family name: Hexokinase
Entry whose protein(s) existence is based on evidence at protein level
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1 190 3
GENE REF ISO

Function

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Overview 
Catalyzes 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.  
1
  • UniProtKB
GO molecular function 
ADP bindingdefinition[GO:0043531] silver  
1
  • Ortholog Compara
ATP bindingdefinition[GO:0005524]  
3
  • UniProtKB
Not  Fructokinase activitydefinition[GO:0008865]  
1
  • RefGenome
Glucokinase activitydefinition[GO:0004340]  
3
  • UniProtKB
Glucose bindingdefinition[GO:0005536]  
3
  • UniProtKB
Magnesium ion bindingdefinition[GO:0000287] silver  
1
  • Ortholog Compara
Not  Mannokinase activitydefinition[GO:0019158]  
1
  • RefGenome
Protein bindingdefinition[GO:0005515]  
2
  • UniProtKB
  • IntAct
Protein phosphatase bindingdefinition[GO:0019903] silver  
1
  • Ortholog Compara
GO biological process 
Calcium ion importdefinition[GO:0070509] silver  
1
  • Ortholog Compara
Carbohydrate phosphorylationdefinition[GO:0046835] silver  
1
  • Ortholog Compara
Cellular glucose homeostasisdefinition[GO:0001678]  
1
  • RefGenome
Cellular response to glucose starvationdefinition[GO:0042149] silver  
1
  • Ortholog Compara
Cellular response to insulin stimulusdefinition[GO:0032869]  
1
  • Ortholog Curator
Cellular response to leptin stimulusdefinition[GO:0044320]  
1
  • Ortholog Curator
Detection of glucosedefinition[GO:0051594]  
1
  • UniProtKB
Fructose 2,6-bisphosphate metabolic processdefinition[GO:0006003] silver  
1
  • Ortholog Compara
Glucose 6-phosphate metabolic processdefinition[GO:0051156] silver  
1
  • Ortholog Compara
Glucose homeostasisdefinition[GO:0042593]  
2
  • BHF-UCL
  • UniProtKB
Glycogen biosynthetic processdefinition[GO:0005978] silver  
1
  • Ortholog Compara
Lipid homeostasisdefinition[GO:0055088] silver  
1
  • Ortholog Compara
NADP metabolic processdefinition[GO:0006739] silver  
1
  • Ortholog Compara
Negative regulation of epinephrine secretiondefinition[GO:0032811] silver  
1
  • Ortholog Compara
Negative regulation of gluconeogenesisdefinition[GO:0045721]  
1
  • UniProtKB
Positive regulation of cytosolic calcium ion concentrationdefinition[GO:0007204] silver  
1
  • Ortholog Compara
Positive regulation of glycogen biosynthetic processdefinition[GO:0045725]  
1
  • UniProtKB
Positive regulation of glycolytic processdefinition[GO:0045821] silver  
1
  • Ortholog Compara
Positive regulation of insulin secretiondefinition[GO:0032024]  
2
  • UniProtKB
Positive regulation of phosphorylationdefinition[GO:0042327] silver  
1
  • Ortholog Compara
Regulation of glycolytic processdefinition[GO:0006110]  
1
  • BHF-UCL
Regulation of insulin secretiondefinition[GO:0050796]  
1
  • BHF-UCL
Regulation of potassium ion transportdefinition[GO:0043266] silver  
1
  • Ortholog Compara
Second-messenger-mediated signalingdefinition[GO:0019932] silver  
1
  • Ortholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.1.2: ATP + D-glucose ADP + D-glucose 6-phosphate.  
1
  • UniProtKB
It is regulated in the following manner
The 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.  
3
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Amino sugar and nucleotide sugar metabolism  hsa00520+2645  
Butirosin and neomycin biosynthesis  hsa00524+2645  
Galactose metabolism  hsa00052+2645  
Glycolysis / Gluconeogenesis  hsa00010+2645  
Insulin signaling pathway  hsa04910+2645  
Maturity onset diabetes of the young  hsa04950+2645  
Metabolic pathways  hsa01100+2645  
Starch and sucrose metabolism  hsa00500+2645  
Type II diabetes mellitus  hsa04930+2645  
According to Reactome, this protein belongs to the following pathways:
Glucose transport  REACT_212  
Regulation of gene expression in beta cells  REACT_13819  
Regulation of Glucokinase by Glucokinase Regulatory Protein  REACT_6804  
 
More information is available from:
Note 
In vertebrates there are four major glucose-phosphorylating isoenzymes, designated hexokinase I, II, III and IV (glucokinase).  
1
  • UniProtKB
 

Keywords

Biological process 
Glycolysis  definition   [KW-0324]
Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Technical term 
Allosteric enzyme  definition   [KW-0021]
Reference proteome  definition   [KW-1185]
 

Further external links

Enzyme and pathway databases
SABIO-RK: P35557
Other
GeneWiki: Glucokinase
GenomeRNAi: 2645
PRO: PR:P35557
Chemistry
GuidetoPHARMACOLOGY: 2798