GCK
entrez
2645
canonical
uniprot
P35557
canonical
ensembl
ENSG00000106633
resolver
ensp
ENSP00000223366
resolver
ensp
ENSP00000338009
resolver
ensp
ENSP00000384247
resolver
ensp
ENSP00000499852
resolver
enst
ENST00000336642
resolver
enst
ENST00000673284
resolver
genesymbol
GCK
resolver
hgnc
HGNC:4195
resolver
uniprot
A0A5F9ZGW4
resolver
uniprot
A4D2J2
resolver
uniprot
A4D2J3
resolver
uniprot
H7BXV0
resolver
uniprot
Q05810
resolver
uniprot
Q53Y25
resolver
uniprot_entry
A0A5F9ZGW4_HUMAN
resolver
uniprot_entry
H7BXV0_HUMAN
resolver
uniprot_entry
HXK4_HUMAN
resolver
uniprot_entry
Q53Y25_HUMAN
resolver
uniprot_sec
A4D2J2
resolver
uniprot_sec
A4D2J3
resolver
uniprot_sec
Q05810
resolver
activity_regulation
ACTIVITY REGULATION: Subject to allosteric regulation (PubMed:15016359). Low glucose and high fructose-6-phosphate triggers association with the inhibitor GCKR followed by sequestration in the nucleus (PubMed:10456334). {ECO:0000269|PubMed:10456334, ECO:0000269|PubMed:15016359}.
uniprot
proteins
amino_acid_sequence
MLDDRARMEAAKKEKVEQILAEFQLQEEDLKKVMRRMQKEMDRGLRLETHEEASVKMLPTYVRSTPEGSEVGDFLSLDLGGTNFRVMLVKVGEGEEGQWSVKTKHQMYSIPEDAMTGTAEMLFDYISECISDFLDKHQMKHKKLPLGFTFSFPVRHEDIDKGILLNWTKGFKASGAEGNNVVGLLRDAIKRRGDFEMDVVAMVNDTVATMISCYYEDHQCEVGMIVGTGCNACYMEEMQNVELVEGDEGRMCVNTEWGAFGDSGELDEFLLEYDRLVDESSANPGQQLYEKLIGGKYMGELVRLVLLRLVDENLLFHGEASEQLRTRGAFETRFVSQVESDTGDRKQIYNILSTLGLRPSTTDCDIVRRACESVSTRAAHMCSAGLAGVINRMRESRSEDVMRITVGVDGSVYKLHPSFKERFHASVRRLTPSCEITFIESEEGSGRGAALVSAVACKKACMLGQ
uniprot
proteins
disease_involvement
DISEASE: Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. {ECO:0000269|PubMed:10588527, ECO:0000269|PubMed:10694920, ECO:0000269|PubMed:11106831, ECO:0000269|PubMed:11372010, ECO:0000269|PubMed:1303265, ECO:0000269|PubMed:1464666, ECO:0000269|PubMed:1502186, ECO:0000269|PubMed:16965331, ECO:0000269|PubMed:17573900, ECO:0000269|PubMed:18322640, ECO:0000269|PubMed:19884385, ECO:0000269|PubMed:22611063, ECO:0000269|PubMed:25015100, ECO:0000269|PubMed:8168652, ECO:0000269|PubMed:8325892, ECO:0000269|PubMed:8433729, ECO:0000269|PubMed:8446612, ECO:0000269|PubMed:8495817, ECO:0000269|PubMed:8878425, ECO:0000269|PubMed:9049484, ECO:0000269|PubMed:9662401}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hyperinsulinemic hypoglycemia, familial, 3 (HHF3) [MIM:602485]: A form of hyperinsulinemic hypoglycemia, a clinically and genetically heterogeneous disorder characterized by inappropriate insulin secretion from the pancreatic beta-cells in the presence of low blood glucose levels. HHF3 clinical features include loss of consciousness due to hypoglycemia, hypoglycemic coma, mental retardation due to repeated episodes of hypoglycemia, and seizures. HHF3 inheritance is autosomal dominant. {ECO:0000269|PubMed:11916951, ECO:0000269|PubMed:12941786, ECO:0000269|PubMed:15277402, ECO:0000269|PubMed:17082186, ECO:0000269|PubMed:19884385, ECO:0000269|PubMed:20375417, ECO:0000269|PubMed:28247534, ECO:0000269|PubMed:9435328}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:1360036}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Diabetes mellitus, permanent neonatal, 1 (PNDM1) [MIM:606176]: An autosomal recessive form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. {ECO:0000269|PubMed:11372010, ECO:0000269|PubMed:25015100}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.1.1
uniprot
proteins
function
FUNCTION: Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate, D-fructose 6-phosphate and D-mannose 6-phosphate, respectively) (PubMed:11916951, PubMed:15277402, PubMed:17082186, PubMed:18322640, PubMed:19146401, PubMed:25015100, PubMed:7742312, PubMed:8325892). Compared to other hexokinases, has a weak affinity for D-glucose, and is effective only when glucose is abundant (By similarity). Mainly expressed in pancreatic beta cells and the liver and constitutes a rate-limiting step in glucose metabolism in these tissues (PubMed:11916951, PubMed:15277402, PubMed:18322640, PubMed:25015100, PubMed:8325892). Since insulin secretion parallels glucose metabolism and the low glucose affinity of GCK ensures that it can change its enzymatic activity within the physiological range of glucose concentrations, GCK acts as a glucose sensor in the pancreatic beta cell (By similarity). In pancreas, plays an important role in modulating insulin secretion (By similarity). In liver, helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage (By similarity). Required to provide D-glucose 6-phosphate for the synthesis of glycogen (PubMed:8878425). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (PubMed:7742312). {ECO:0000250|UniProtKB:P17712, ECO:0000250|UniProtKB:P52792, ECO:0000269|PubMed:11916951, ECO:0000269|PubMed:15277402, ECO:0000269|PubMed:17082186, ECO:0000269|PubMed:18322640, ECO:0000269|PubMed:19146401, ECO:0000269|PubMed:25015100, ECO:0000269|PubMed:7742312, ECO:0000269|PubMed:8325892, ECO:0000269|PubMed:8878425}.
uniprot
proteins
mass_dalton
52191
uniprot
proteins
mutagenesis
MUTAGEN 64; /note="S->P: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose."; /evidence="ECO:0000269|PubMed:19146401"; MUTAGEN 177; /note="E->K: Small change in glucokinase activity."; /evidence="ECO:0000269|PubMed:8325892"; MUTAGEN 197; /note="M->V: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose."; /evidence="ECO:0000269|PubMed:19146401"; MUTAGEN 211; /note="I->F: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose."; /evidence="ECO:0000269|PubMed:19146401"; MUTAGEN 214; /note="Y->A: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose. No effect on affinity for ATP."; /evidence="ECO:0000269|PubMed:17082186"; MUTAGEN 215; /note="Y->A: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose. Loss of inhibition by GCKR. No effect on affinity for ATP."; /evidence="ECO:0000269|PubMed:17082186"; MUTAGEN 256; /note="E->A: Inactive enzyme with no glucokinase activity."; /evidence="ECO:0000269|PubMed:8325892"; MUTAGEN 414; /note="K->A: Small change in glucokinase activity."; /evidence="ECO:0000269|PubMed:8325892"; MUTAGEN 453; /note="S->A: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose."; /evidence="ECO:0000269|PubMed:19146401
uniprot
proteins
pathway_participation
PATHWAY: Carbohydrate metabolism; hexose metabolism. {ECO:0000305|PubMed:7742312}.; PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 1/4. {ECO:0000305|PubMed:7742312}.
uniprot
proteins
protein_family
Hexokinase family
uniprot
proteins
pubmed
10456334
uniprot
proteins
pubmed
10588527
uniprot
proteins
pubmed
10694920
uniprot
proteins
pubmed
11106831
uniprot
proteins
pubmed
11372010
uniprot
proteins
pubmed
11916951
uniprot
proteins
pubmed
12690205
uniprot
proteins
pubmed
12941786
uniprot
proteins
pubmed
1303265
uniprot
proteins
pubmed
1354840
uniprot
proteins
pubmed
1360036
uniprot
proteins
pubmed
1464666
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15016359
uniprot
proteins
pubmed
1502186
uniprot
proteins
pubmed
1511800
uniprot
proteins
pubmed
15277402
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1612194
uniprot
proteins
pubmed
16965331
uniprot
proteins
pubmed
17082186
uniprot
proteins
pubmed
17573900
uniprot
proteins
pubmed
18322640
uniprot
proteins
pubmed
1871135
uniprot
proteins
pubmed
19146401
uniprot
proteins
pubmed
19362831
uniprot
proteins
pubmed
19884385
uniprot
proteins
pubmed
20375417
uniprot
proteins
pubmed
21604084
uniprot
proteins
pubmed
22101819
uniprot
proteins
pubmed
22611063
uniprot
proteins
pubmed
23957911
uniprot
proteins
pubmed
24187134
uniprot
proteins
pubmed
25015100
uniprot
proteins
pubmed
28247534
uniprot
proteins
pubmed
7742312
uniprot
proteins
pubmed
8168652
uniprot
proteins
pubmed
8194664
uniprot
proteins
pubmed
8325892
uniprot
proteins
pubmed
8433729
uniprot
proteins
pubmed
8446612
uniprot
proteins
pubmed
8454109
uniprot
proteins
pubmed
8495817
uniprot
proteins
pubmed
8878425
uniprot
proteins
pubmed
9049484
uniprot
proteins
pubmed
9435328
uniprot
proteins
pubmed
9662401
uniprot
proteins
sequence_length
465
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10456334, ECO:0000269|PubMed:24187134}. Nucleus {ECO:0000269|PubMed:10456334, ECO:0000269|PubMed:24187134}. Mitochondrion {ECO:0000250|UniProtKB:P17712}. Note=Under low glucose concentrations, GCK associates with GCKR and the inactive complex is recruited to the hepatocyte nucleus. {ECO:0000269|PubMed:10456334}.
uniprot
proteins