Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

GCK

contributors: mct - updated : 12-06-2013

HGNC name	glucokinase (hexokinase 4)
HGNC id	4195

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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)

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000162 10 - 2741 NP_000153 - 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 NM_033507 10 - 2442 NP_277042 - 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 NM_033508 11 - 2566 NP_277043 - 464 minor form expressed in liver 2012 23297408

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Homo sapiens Adult NM_033507 Endocrine pancreas         Lymphoid/Immune lymph node         Nervous brain midbrain hypothalamus     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine

cells

System Cell Pubmed Species Stage Rna symbol Digestive hepatocyte Homo sapiens Endocrine islet cell (alpha,beta...) Homo sapiens NM_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
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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