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FLASH GENE

Symbol

GCKR

contributors: mct - updated : 12-06-2015

HGNC name	glucokinase (hexokinase 4) regulatory protein
HGNC id	4196

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	2p23.3      Physical location : 27.719.705 - 27.746.548
Synonym symbol(s)	FGQTL5, GKRP
EC.number	2.7.1.2

DNA

TYPE	functioning gene
STRUCTURE	26.84 kb     19 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

Map	pter - PPP1CB - D2S1237 - D2S220 - KHK KHK - GCKR - D2S165 - cen
Authors	Hayward (97)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001486 19 - 2197 NP_001477 - 625 - 1998 9570959

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         Endocrine pancreas         Reproductive male system testis

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	liver testis

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

one sis domain

HOMOLOGY

Homologene

FAMILY

CATEGORY

enzyme , regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	controling the activity of glucokinase in liver but possibly also in some areas of the central nervous system, suggesting that it could play a role in body mass control
	inhibiting glucokinase by forming an inactive complex with this enzyme
	GCK and GCKR function as key glucose sensors (
	is the most important post-transcriptional regulator of GCK in the liver, and participates in the modulation of GCK activity and location depending upon changes in glucose levels
	releases GCK in a sigmoidal manner in response to glucose concentration by restricting a structural rearrangement of the GCK small domain via a single ion pair

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

carbohydrate

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting non-covalently with GCR and inhibiting it in presence of fructose-6-phosphate
	GCK regulates glucose storage and disposal in the liver where its activity is regulated by glucokinase regulatory protein, GCKR
	binds to a super-open conformation of GCK mainly through hydrophobic interaction, inhibiting the GCK activity by locking a small domain of GCK
	SIRT2-dependent GCKR deacetylation improves impaired hepatic glucose uptake (HGU)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       that may play a role in regulating HDLc levels '

Susceptibility

to hepatic fat accumulation along with large VLDL and triglyceride levels to familial type 2 diabetes

Variant & Polymorphism SNP	rs1260326 in GCKR is associated with hepatic fat accumulation along with large VLDL and triglyceride levels

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