Names & Taxonomy

Uniprot ID:
P35557
Entry Name:
HXK4_HUMAN
Status:
reviewed
Protein Names:
Glucokinase (EC 2.7.1.2) (Hexokinase type IV) (HK IV) (Hexokinase-4) (HK4) (Hexokinase-D)
Gene Names:
GCK
Gene Names Primary:
GCK
Organism:
Homo sapiens (Human)

Structure

Length:
465
Sequence:
MLDDRARMEAAKKEKVEQILAEFQLQEEDLKKVMRRMQKEMDRGLRLETHEEASVKMLPTYVRSTPEGSEVGDFLSLDLGGTNFRVMLVKVGEGEEGQWSVKTKHQMYSIPEDAMTGTAEMLFDYISECISDFLDKHQMKHKKLPLGFTFSFPVRHEDIDKGILLNWTKGFKASGAEGNNVVGLLRDAIKRRGDFEMDVVAMVNDTVATMISCYYEDHQCEVGMIVGTGCNACYMEEMQNVELVEGDEGRMCVNTEWGAFGDSGELDEFLLEYDRLVDESSANPGQQLYEKLIGGKYMGELVRLVLLRLVDENLLFHGEASEQLRTRGAFETRFVSQVESDTGDRKQIYNILSTLGLRPSTTDCDIVRRACESVSTRAAHMCSAGLAGVINRMRESRSEDVMRITVGVDGSVYKLHPSFKERFHASVRRLTPSCEITFIESEEGSGRGAALVSAVACKKACMLGQ
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm

Function

Function:
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.
Catalytic Activity:
ATP + D-glucose = ADP + D-glucose 6-phosphate.
Enzyme Regulation:
ENZYME REGULATION: 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.
Gene Ontology Go:
actin filament
basal cortex
cytosol
mitochondrion
nucleoplasm
secretory granule
ADP binding
ATP binding
glucokinase activity
glucose binding
magnesium ion binding
calcium ion import
canonical glycolysis
carbohydrate metabolic process
cellular glucose homeostasis
cellular response to glucose starvation
cellular response to insulin stimulus
cellular response to leptin stimulus
detection of glucose
endocrine pancreas development
fructose 2,6-bisphosphate metabolic process
glucose homeostasis
glucose metabolic process
glucose transport
glycogen biosynthetic process
glycolytic process
hexose transport
lipid homeostasis
NADP metabolic process
negative regulation of epinephrine secretion
negative regulation of gluconeogenesis
positive regulation of cytosolic calcium ion concentration
positive regulation of glycogen biosynthetic process
positive regulation of glycolytic process
positive regulation of insulin secretion
regulation of glucose transport
regulation of glycolytic process
regulation of insulin secretion
regulation of potassium ion transport
second-messenger-mediated signaling
small molecule metabolic process
transmembrane transport
Gene Ontology Biological Process:
calcium ion import
canonical glycolysis
carbohydrate metabolic process
cellular glucose homeostasis
cellular response to glucose starvation
cellular response to insulin stimulus
cellular response to leptin stimulus
detection of glucose
endocrine pancreas development
fructose 2,6-bisphosphate metabolic process
glucose homeostasis
glucose metabolic process
glucose transport
glycogen biosynthetic process
glycolytic process
hexose transport
lipid homeostasis
NADP metabolic process
negative regulation of epinephrine secretion
negative regulation of gluconeogenesis
positive regulation of cytosolic calcium ion concentration
positive regulation of glycogen biosynthetic process
positive regulation of glycolytic process
positive regulation of insulin secretion
regulation of glucose transport
regulation of glycolytic process
regulation of insulin secretion
regulation of potassium ion transport
second-messenger-mediated signaling
small molecule metabolic process
transmembrane transport
Gene Ontology Molecular Function:
ADP binding
ATP binding
glucokinase activity
glucose binding
magnesium ion binding
Gene Ontology Cellular Component:
actin filament
basal cortex
cytosol
mitochondrion
nucleoplasm
secretory granule
Keywords:
3D-structure
ATP-binding
Allosteric enzyme
Alternative splicing
Complete proteome
Cytoplasm
Diabetes mellitus
Disease mutation
Glycolysis
Kinase
Nucleotide-binding
Nucleus
Polymorphism
Reference proteome
Transferase
Interacts With:
Q14397; P16118

Publication

PubMed ID:
1354840 1871135 1511800 1612194 1502186 1464666 14702039 12690205 15489334 10456334 8194664 15016359 19362831 23957911 1303265 8454109 8495817 8325892 8446612 8168652 9049484 10694920 9662401 9435328 10588527 11106831 11372010 21604084 22611063