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Protein

Glucokinase

Gene

GCK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.7 Publications

Miscellaneous

In vertebrates there are four major glucose-phosphorylating isoenzymes, designated hexokinase I, II, III and IV (glucokinase).

Catalytic activityi

ATP + D-glucose = ADP + D-glucose 6-phosphate.7 Publications

Enzyme regulationi

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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei104ATPSequence analysis1
Binding sitei228ATPBy similarity1
Binding sitei231Substrate1
Binding sitei256Substrate1
Binding sitei290Substrate1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi78 – 83ATPBy similarity6
Nucleotide bindingi295 – 296ATPBy similarity2
Nucleotide bindingi332 – 336ATPBy similarity5
Nucleotide bindingi411 – 415ATPBy similarity5

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • glucokinase activity Source: UniProtKB
  • glucose binding Source: UniProtKB

GO - Biological processi

  • calcium ion import Source: Ensembl
  • canonical glycolysis Source: Reactome
  • cellular glucose homeostasis Source: GO_Central
  • cellular response to insulin stimulus Source: BHF-UCL
  • cellular response to leptin stimulus Source: BHF-UCL
  • detection of glucose Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • glycolytic process Source: GO_Central
  • NADP metabolic process Source: Ensembl
  • negative regulation of gluconeogenesis Source: UniProtKB
  • positive regulation of glycogen biosynthetic process Source: UniProtKB
  • positive regulation of insulin secretion Source: UniProtKB
  • regulation of glycolytic process Source: Reactome
  • regulation of insulin secretion Source: BHF-UCL
  • regulation of potassium ion transport Source: Ensembl

Keywordsi

Molecular functionKinase, Transferase
Biological processGlycolysis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS02935-MONOMER.
BRENDAi2.7.1.1. 2681.
2.7.1.2. 2681.
ReactomeiR-HSA-170822. Regulation of Glucokinase by Glucokinase Regulatory Protein.
R-HSA-210745. Regulation of gene expression in beta cells.
R-HSA-5619073. Defective GCK causes maturity-onset diabetes of the young 2 (MODY2).
R-HSA-5619107. Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC).
R-HSA-70171. Glycolysis.
SABIO-RKiP35557.

Names & Taxonomyi

Protein namesi
Recommended name:
Glucokinase (EC:2.7.1.27 Publications)
Alternative name(s):
Hexokinase type IV
Short name:
HK IV
Hexokinase-4
Short name:
HK4
Hexokinase-D
Gene namesi
Name:GCK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000106633.15.
HGNCiHGNC:4195. GCK.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Maturity-onset diabetes of the young 2 (MODY2)19 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:125851
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07943016V → E in MODY2. 1 Publication1
Natural variantiVAR_07943119I → N in MODY2. 1 Publication1
Natural variantiVAR_07943220L → P in MODY2. 1 Publication1
Natural variantiVAR_01058436R → W in MODY2. 3 PublicationsCorresponds to variant dbSNP:rs762263694Ensembl.1
Natural variantiVAR_07522043R → H in MODY2; unknown pathological significance; no change in glucokinase activity. 1 PublicationCorresponds to variant dbSNP:rs764232985Ensembl.1
Natural variantiVAR_07943543R → S in MODY2. 1 Publication1
Natural variantiVAR_07943644G → S in MODY2. 1 Publication1
Natural variantiVAR_01058553A → S in MODY2. 1
Natural variantiVAR_07943861 – 465Missing in MODY2. 1 PublicationAdd BLAST405
Natural variantiVAR_07943961Y → S in MODY2; decreased glucokinase activity; decreased affinity for glucose; increased affinity for ATP. 2 Publications1
Natural variantiVAR_07522168G → D in MODY2; unknown pathological significance; mildly increases glucokinase activity. 1 PublicationCorresponds to variant dbSNP:rs373418736Ensembl.1
Natural variantiVAR_00369370E → K in MODY2; decreased affinity for glucose. 2 Publications1
Natural variantiVAR_07944072G → R in MODY2 and PNDM; decreased stability; no effect on glucokinase activity; no effect on affinity for glucose. 2 Publications1
Natural variantiVAR_07944177L → P in MODY2. 1 Publication1
Natural variantiVAR_07944278D → E in MODY2. 1 Publication1
Natural variantiVAR_00369480G → A in MODY2. 1
Natural variantiVAR_07944380G → D in MODY2. 1 Publication1
Natural variantiVAR_00369580G → S in MODY2. 1 Publication1
Natural variantiVAR_07944482T → I in MODY2. 1 Publication1
Natural variantiVAR_010586108Y → H in MODY2. 2 Publications1
Natural variantiVAR_012352110I → T in MODY2. 1 Publication1
Natural variantiVAR_079445116T → P in MODY2. 1 Publication1
Natural variantiVAR_012353119A → D in MODY2. 1 Publication1
Natural variantiVAR_078246129C → Y in MODY2. 1 Publication1
Natural variantiVAR_003697131S → P in MODY2; decreased affinity for glucose. 2 PublicationsCorresponds to variant dbSNP:rs104894010Ensembl.1
Natural variantiVAR_010587137H → R in MODY2. 1
Natural variantiVAR_010588150F → S in MODY2. 1 PublicationCorresponds to variant dbSNP:rs193922297Ensembl.1
Natural variantiVAR_078247152F → L in MODY2; unknown pathological significance. 1 Publication1
Natural variantiVAR_079447160D → N in MODY2; no effect on stability; decreased glucokinase activity; decreased affinity for glucose. 1 Publication1
Natural variantiVAR_012350164L → P in MODY2 and PNDM. 2 Publications1
Natural variantiVAR_010589168T → P in MODY2. 1
Natural variantiVAR_003698175G → R in MODY2. Corresponds to variant dbSNP:rs587780344Ensembl.1
Natural variantiVAR_079450182V → L in MODY2; decreased glucokinase activity; decreased affinity for glucose; increased affinity for ATP. 2 Publications1
Natural variantiVAR_003699182V → M in MODY2. Corresponds to variant dbSNP:rs587780345Ensembl.1
Natural variantiVAR_079451186 – 465Missing in MODY2 and NIDDM. 2 PublicationsAdd BLAST280
Natural variantiVAR_079452187D → Y in MODY2. 1 Publication1
Natural variantiVAR_003700188A → T in MODY2; decreased affinity for glucose. 1 PublicationCorresponds to variant dbSNP:rs751279776Ensembl.1
Natural variantiVAR_078248188A → V in MODY2. 1 PublicationCorresponds to variant dbSNP:rs193922307Ensembl.1
Natural variantiVAR_078249191R → W in MODY2. 2 Publications1
Natural variantiVAR_079453200V → L in MODY2. 1 Publication1
Natural variantiVAR_078250202M → R in MODY2. 1 Publication1
Natural variantiVAR_079454202M → T in MODY2. 1 Publication1
Natural variantiVAR_003701203V → A in MODY2. 1
Natural variantiVAR_079455206T → M in MODY2. 1 Publication1
Natural variantiVAR_010590209T → M in MODY2. 2 Publications1
Natural variantiVAR_012351210M → K in MODY2 and PNDM. 1 PublicationCorresponds to variant dbSNP:rs80356654Ensembl.1
Natural variantiVAR_010591210M → T in MODY2. 1
Natural variantiVAR_010592213C → R in MODY2. 1
Natural variantiVAR_075222217D → N in MODY2; associated in cis with R-261 in some patients; mildly increased glucokinase activity; loss of glucokinase activity when associated with R-261. 1 PublicationCorresponds to variant dbSNP:rs147065275Ensembl.1
Natural variantiVAR_003702221E → K in MODY2. 1 PublicationCorresponds to variant dbSNP:rs193922317Ensembl.1
Natural variantiVAR_078251223G → S in MODY2. 2 Publications1
Natural variantiVAR_079457224M → R in MODY2. 1 Publication1
Natural variantiVAR_075223225I → M in MODY2; associated in cis with K-248; highly decreased glucokinase activity; loss of glucokinase activity when associated with K-248. 1 Publication1
Natural variantiVAR_003703226V → M in MODY2; no effect on stability; decreased glucokinase activity; decreased affinity for glucose. 2 PublicationsCorresponds to variant dbSNP:rs148311934Ensembl.1
Natural variantiVAR_003704227G → C in MODY2. 1 Publication1
Natural variantiVAR_079458227G → S in MODY2. 1 Publication1
Natural variantiVAR_003705228T → M in MODY2 and PNDM. 3 PublicationsCorresponds to variant dbSNP:rs80356655Ensembl.1
Natural variantiVAR_078252231N → H in MODY2; unknown pathological significance. 1 Publication1
Natural variantiVAR_079459233C → R in MODY2; loss of glucokinase activity; loss of affinity for glucose; loss of affinity for ATP. 2 Publications1
Natural variantiVAR_079460234 – 465Missing in MODY2. 1 PublicationAdd BLAST232
Natural variantiVAR_075224248E → K in MODY2; associated in cis with M-225; highly decreased glucokinase activity; loss of glucokinase activity when associated with M-225. 1 PublicationCorresponds to variant dbSNP:rs759421263Ensembl.1
Natural variantiVAR_079461252C → G in MODY2. 1 Publication1
Natural variantiVAR_079462255T → A in MODY2. 1 Publication1
Natural variantiVAR_003706256E → K in MODY2. 1 PublicationCorresponds to variant dbSNP:rs769268803Ensembl.1
Natural variantiVAR_003707257W → R in MODY2; almost complete loss of glucokinase activity. 1 Publication1
Natural variantiVAR_010593259A → T in MODY2. 1 Publication1
Natural variantiVAR_010594261G → E in MODY2. 1 Publication1
Natural variantiVAR_003708261G → R in MODY2 and PNDM; associated in cis with N-217 in some patients; highly decreased glucokinase activity; loss of glucokinase activity when associated with N-217; decreased affinity for glucose. 5 PublicationsCorresponds to variant dbSNP:rs104894008Ensembl.1
Natural variantiVAR_079463265E → K in MODY2; decreased glucokinase activity; decreased affinity for glucose; no effect on affinity for ATP. 2 Publications1
Natural variantiVAR_003709279E → Q in MODY2. Corresponds to variant dbSNP:rs104894005Ensembl.1
Natural variantiVAR_079464298M → K in MODY2. 1 Publication1
Natural variantiVAR_003710299G → R in MODY2. 2 PublicationsCorresponds to variant dbSNP:rs104894009Ensembl.1
Natural variantiVAR_003712300E → K in MODY2. 1
Natural variantiVAR_003711300E → Q in MODY2. 1
Natural variantiVAR_079465308R → W in MODY2. 1 Publication1
Natural variantiVAR_003713309L → P in MODY2. 1
Natural variantiVAR_078253315L → F in MODY2; unknown pathological significance. 1 Publication1
Natural variantiVAR_010595336S → L in MODY2. 1
Natural variantiVAR_010596367V → M in MODY2. 1
Natural variantiVAR_079466377R → H in MODY2. 1 Publication1
Natural variantiVAR_078254378A → T in MODY2. 1 PublicationCorresponds to variant dbSNP:rs104894016Ensembl.1
Natural variantiVAR_079467379A → V in MODY2; decreased glucokinase activity; decreased affinity for glucose; decreased affinity for ATP. 2 Publications1
Natural variantiVAR_010597382C → Y in MODY2. 1 Publication1
Natural variantiVAR_079468383S → L in MODY2. 1 Publication1
Natural variantiVAR_010598384A → T in MODY2. 1 Publication1
Natural variantiVAR_012354385G → V in MODY2. 1 Publication1
Natural variantiVAR_010599392R → C in MODY2. 1 Publication1
Natural variantiVAR_079471399 – 465Missing in MODY2. 1 PublicationAdd BLAST67
Natural variantiVAR_079472411S → F in MODY2. 1 Publication1
Natural variantiVAR_003714414K → E in MODY2; decreased affinity for glucose. 1 PublicationCorresponds to variant dbSNP:rs193922272Ensembl.1
Natural variantiVAR_079473416H → P in MODY2. 1 Publication1
Natural variantiVAR_079474420K → E in MODY2; no effect on glucokinase activity; decreased affinity for glucose; no effect on affinity for ATP. 2 Publications1
Natural variantiVAR_078255434C → F in MODY2; unknown pathological significance. 1 Publication1
Natural variantiVAR_078256441S → W in MODY2; decreased affinity for glucose. 3 Publications1
Natural variantiVAR_078258447R → Q in MODY2. 1 Publication1
Familial hyperinsulinemic hypoglycemia 3 (HHF3)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMost common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.
See also OMIM:602485
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07824365T → I in HHF3; increased glucokinase activity based on measure of catalytic efficiency; increased affinity for glucose; loss of inhibition by GKRP; unchanged affinity for ATP. 3 Publications1
Natural variantiVAR_07824491V → L in HHF3; increased glucokinase activity; increased affinity for glucose. 2 Publications1
Natural variantiVAR_07824599W → C in HHF3; increased glucokinase activity; increased affinity for glucose; increased affinity for ATP. 1 Publication1
Natural variantiVAR_079456214Y → C in HHF3; increased glucokinase activity based on measure of catalytic efficiency; increased affinity for glucose; decreased inhibition by GKRP. 2 Publications1
Natural variantiVAR_078257442E → K in HHF3; increased affinity for glucose. 2 PublicationsCorresponds to variant dbSNP:rs758737171Ensembl.1
Natural variantiVAR_003715455V → M in HHF3; increased glucokinase activity based on measure of catalytic efficiency; increased affinity for glucose; decreased inhibition by GKRP; no effect on affinity for ATP. 2 PublicationsCorresponds to variant dbSNP:rs104894012Ensembl.1
Natural variantiVAR_079477456A → V in HHF3; increased glucokinase activity based on measure of catalytic efficiency; increased affinity for glucose; loss of inhibition by GKRP; no effect on affinity for ATP. 2 Publications1
Diabetes mellitus, non-insulin-dependent (NIDDM)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own 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.
See also OMIM:125853
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079451186 – 465Missing in MODY2 and NIDDM. 2 PublicationsAdd BLAST280
Diabetes mellitus, permanent neonatal (PNDM)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.
See also OMIM:606176
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07943340E → K in PNDM; decreased stability; decreased glucokinase activity; decreased affinity for glucose. 1 Publication1
Natural variantiVAR_07943443R → C in PNDM; decreased stability; decreased glucokinase activity; no effect on affinity for glucose. 1 Publication1
Natural variantiVAR_07943750H → D in PNDM; loss of stability; loss of glucokinase activity; decreased affinity for glucose. 1 Publication1
Natural variantiVAR_07944072G → R in MODY2 and PNDM; decreased stability; no effect on glucokinase activity; no effect on affinity for glucose. 2 Publications1
Natural variantiVAR_079446151S → T in PNDM. 1 Publication1
Natural variantiVAR_012350164L → P in MODY2 and PNDM. 2 Publications1
Natural variantiVAR_079448168T → A in PNDM; decreased glucokinase activity; decreased affinity for glucose. 1 Publication1
Natural variantiVAR_079449169K → R in PNDM. 1 Publication1
Natural variantiVAR_012351210M → K in MODY2 and PNDM. 1 PublicationCorresponds to variant dbSNP:rs80356654Ensembl.1
Natural variantiVAR_003705228T → M in MODY2 and PNDM. 3 PublicationsCorresponds to variant dbSNP:rs80356655Ensembl.1
Natural variantiVAR_003708261G → R in MODY2 and PNDM; associated in cis with N-217 in some patients; highly decreased glucokinase activity; loss of glucokinase activity when associated with N-217; decreased affinity for glucose. 5 PublicationsCorresponds to variant dbSNP:rs104894008Ensembl.1
Natural variantiVAR_079469393M → T in PNDM; decreased stability; increased glucokinase activity; no effect on affinity for glucose. 1 Publication1
Natural variantiVAR_079470397R → L in PNDM; decreased stability; increased glucokinase activity; no effect on affinity for glucose. 1 Publication1
Natural variantiVAR_079475441S → L in PNDM; decreased stability; decreased glucokinase activity; no effect on affinity for glucose. 1 Publication1
Natural variantiVAR_079476449A → T in PNDM; decreased stability; increased glucokinase activity; increased affinity for glucose. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi64S → P: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose. 1 Publication1
Mutagenesisi177E → K: Small change in glucokinase activity. 1 Publication1
Mutagenesisi197M → V: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose. 1 Publication1
Mutagenesisi211I → F: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose. 1 Publication1
Mutagenesisi214Y → A: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose. No effect on affinity for ATP. 1 Publication1
Mutagenesisi215Y → A: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose. Loss of inhibition by GKRP. No effect on affinity for ATP. 1 Publication1
Mutagenesisi256E → A: Inactive enzyme with no glucokinase activity. 1 Publication1
Mutagenesisi414K → A: Small change in glucokinase activity. 1 Publication1
Mutagenesisi453S → A: Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose. 1 Publication1

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

DisGeNETi2645.
GeneReviewsiGCK.
MalaCardsiGCK.
MIMi125851. phenotype.
125853. phenotype.
602485. phenotype.
606176. phenotype.
606391. phenotype.
OpenTargetsiENSG00000106633.
Orphaneti79299. Hyperinsulinism due to glucokinase deficiency.
552. MODY.
99885. Permanent neonatal diabetes mellitus.
PharmGKBiPA28610.

Chemistry databases

ChEMBLiCHEMBL3820.
DrugBankiDB02379. Beta-D-Glucose.
GuidetoPHARMACOLOGYi2798.

Polymorphism and mutation databases

BioMutaiGCK.
DMDMi547696.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001975931 – 465GlucokinaseAdd BLAST465

Proteomic databases

PaxDbiP35557.
PeptideAtlasiP35557.
PRIDEiP35557.

PTM databases

iPTMnetiP35557.
PhosphoSitePlusiP35557.

Expressioni

Tissue specificityi

Isoform 1 is expressed in pancreas. Isoform 2 and isoform 3 is expressed in liver.

Gene expression databases

BgeeiENSG00000106633.
CleanExiHS_GCK.
ExpressionAtlasiP35557. baseline and differential.
GenevisibleiP35557. HS.

Organism-specific databases

HPAiHPA007034.
HPA007093.

Interactioni

Subunit structurei

Monomer (PubMed:15016359, PubMed:19362831, PubMed:23957911). Interacts with MIDN; the interaction occurs preferentially at low glucose levels and results in inhibition of GCK activity (PubMed:24187134).4 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi108915. 9 interactors.
IntActiP35557. 6 interactors.
STRINGi9606.ENSP00000223366.

Chemistry databases

BindingDBiP35557.

Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi12 – 20Combined sources9
Helixi21 – 23Combined sources3
Helixi27 – 45Combined sources19
Turni47 – 52Combined sources6
Beta strandi58 – 65Combined sources8
Turni66 – 68Combined sources3
Beta strandi72 – 92Combined sources21
Beta strandi95 – 97Combined sources3
Beta strandi99 – 109Combined sources11
Helixi112 – 115Combined sources4
Beta strandi116 – 118Combined sources3
Helixi119 – 136Combined sources18
Beta strandi140 – 142Combined sources3
Beta strandi145 – 150Combined sources6
Beta strandi154 – 158Combined sources5
Beta strandi161 – 164Combined sources4
Helixi181 – 192Combined sources12
Beta strandi198 – 203Combined sources6
Helixi205 – 214Combined sources10
Beta strandi220 – 237Combined sources18
Helixi238 – 240Combined sources3
Beta strandi248 – 254Combined sources7
Helixi257 – 259Combined sources3
Turni260 – 263Combined sources4
Beta strandi264 – 266Combined sources3
Helixi267 – 269Combined sources3
Helixi272 – 280Combined sources9
Beta strandi281 – 283Combined sources3
Helixi288 – 291Combined sources4
Helixi295 – 311Combined sources17
Helixi316 – 318Combined sources3
Turni322 – 325Combined sources4
Helixi332 – 339Combined sources8
Beta strandi340 – 342Combined sources3
Beta strandi343 – 345Combined sources3
Helixi346 – 354Combined sources9
Helixi361 – 396Combined sources36
Beta strandi400 – 409Combined sources10
Helixi411 – 415Combined sources5
Beta strandi416 – 418Combined sources3
Helixi419 – 430Combined sources12
Beta strandi434 – 440Combined sources7
Helixi444 – 456Combined sources13
Turni457 – 459Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GLKmodel-A1-465[»]
1V4SX-ray2.30A16-465[»]
1V4TX-ray3.40A16-465[»]
3A0IX-ray2.20X16-465[»]
3F9MX-ray1.50A12-465[»]
3FGUX-ray2.15A12-465[»]
3FR0X-ray2.70A16-465[»]
3GOIX-ray2.52A16-465[»]
3H1VX-ray2.11X16-465[»]
3ID8X-ray2.40A12-465[»]
3IDHX-ray2.14A12-465[»]
3IMXX-ray2.00A16-465[»]
3QICX-ray2.20A12-465[»]
3S41X-ray2.18A12-465[»]
3VEVX-ray1.80A12-465[»]
3VEYX-ray2.25A16-465[»]
3VF6X-ray1.86A12-465[»]
4DCHX-ray1.79A1-465[»]
4DHYX-ray2.38A12-465[»]
4ISEX-ray1.78A16-465[»]
4ISFX-ray2.09A16-465[»]
4ISGX-ray2.64A16-465[»]
4IWVX-ray2.10A16-465[»]
4IXCX-ray2.00A16-465[»]
4L3QX-ray2.70A16-465[»]
4LC9X-ray3.40B3-465[»]
4MLEX-ray2.60A16-465[»]
4MLHX-ray2.90A16-465[»]
4NO7X-ray1.70A12-465[»]
4RCHX-ray2.30A16-465[»]
5V4WX-ray2.39A16-465[»]
5V4XX-ray2.08A16-465[»]
ProteinModelPortaliP35557.
SMRiP35557.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35557.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 454HexokinasePROSITE-ProRule annotationAdd BLAST445

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni67 – 203Hexokinase small subdomainPROSITE-ProRule annotationAdd BLAST137
Regioni151 – 152Substrate binding2
Regioni168 – 169Substrate binding2
Regioni204 – 443Hexokinase large subdomainPROSITE-ProRule annotationAdd BLAST240
Regioni204 – 205Substrate binding2

Sequence similaritiesi

Belongs to the hexokinase family.PROSITE-ProRule annotationCurated

Phylogenomic databases

eggNOGiKOG1369. Eukaryota.
COG5026. LUCA.
GeneTreeiENSGT00390000017159.
HOGENOMiHOG000162670.
HOVERGENiHBG000142.
InParanoidiP35557.
KOiK12407.
OMAiERQFFRA.
OrthoDBiEOG091G08MD.
PhylomeDBiP35557.
TreeFamiTF314238.

Family and domain databases

InterProiView protein in InterPro
IPR001312. Hexokinase.
IPR019807. Hexokinase_BS.
IPR022673. Hexokinase_C.
IPR022672. Hexokinase_N.
PANTHERiPTHR19443. PTHR19443. 1 hit.
PfamiView protein in Pfam
PF00349. Hexokinase_1. 1 hit.
PF03727. Hexokinase_2. 1 hit.
PROSITEiView protein in PROSITE
PS00378. HEXOKINASE_1. 1 hit.
PS51748. HEXOKINASE_2. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35557-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MLDDRARMEA AKKEKVEQIL AEFQLQEEDL KKVMRRMQKE MDRGLRLETH
60 70 80 90 100
EEASVKMLPT YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEEGQWS
110 120 130 140 150
VKTKHQMYSI PEDAMTGTAE MLFDYISECI SDFLDKHQMK HKKLPLGFTF
160 170 180 190 200
SFPVRHEDID KGILLNWTKG FKASGAEGNN VVGLLRDAIK RRGDFEMDVV
210 220 230 240 250
AMVNDTVATM ISCYYEDHQC EVGMIVGTGC NACYMEEMQN VELVEGDEGR
260 270 280 290 300
MCVNTEWGAF GDSGELDEFL LEYDRLVDES SANPGQQLYE KLIGGKYMGE
310 320 330 340 350
LVRLVLLRLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DTGDRKQIYN
360 370 380 390 400
ILSTLGLRPS TTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED
410 420 430 440 450
VMRITVGVDG SVYKLHPSFK ERFHASVRRL TPSCEITFIE SEEGSGRGAA
460
LVSAVACKKA CMLGQ
Length:465
Mass (Da):52,191
Last modified:June 1, 1994 - v1
Checksum:i094D4A2F78096724
GO
Isoform 2 (identifier: P35557-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MLDDRARMEAAKKEK → MAMDVTRSQAQTALTL

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Length:466
Mass (Da):52,136
Checksum:iA44B768452105627
GO
Isoform 3 (identifier: P35557-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MLDDRARMEAAKKEK → MPRPRSQLPQPNSQ

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Length:464
Mass (Da):52,035
Checksum:i5FA1020BBF98A4E9
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0036924D → N1 PublicationCorresponds to variant dbSNP:rs202091228Ensembl.1
Natural variantiVAR_01058311A → T1 PublicationCorresponds to variant dbSNP:rs116093166Ensembl.1
Natural variantiVAR_07943016V → E in MODY2. 1 Publication1
Natural variantiVAR_07943119I → N in MODY2. 1 Publication1
Natural variantiVAR_07943220L → P in MODY2. 1 Publication1
Natural variantiVAR_01058436R → W in MODY2. 3 PublicationsCorresponds to variant dbSNP:rs762263694Ensembl.1
Natural variantiVAR_07943340E → K in PNDM; decreased stability; decreased glucokinase activity; decreased affinity for glucose. 1 Publication1
Natural variantiVAR_07943443R → C in PNDM; decreased stability; decreased glucokinase activity; no effect on affinity for glucose. 1 Publication1
Natural variantiVAR_07522043R → H in MODY2; unknown pathological significance; no change in glucokinase activity. 1 PublicationCorresponds to variant dbSNP:rs764232985Ensembl.1
Natural variantiVAR_07943543R → S in MODY2. 1 Publication1
Natural variantiVAR_07943644G → S in MODY2. 1 Publication1
Natural variantiVAR_07943750H → D in PNDM; loss of stability; loss of glucokinase activity; decreased affinity for glucose. 1 Publication1
Natural variantiVAR_01058553A → S in MODY2. 1
Natural variantiVAR_07943861 – 465Missing in MODY2. 1 PublicationAdd BLAST405
Natural variantiVAR_07943961Y → S in MODY2; decreased glucokinase activity; decreased affinity for glucose; increased affinity for ATP. 2 Publications1
Natural variantiVAR_07824365T → I in HHF3; increased glucokinase activity based on measure of catalytic efficiency; increased affinity for glucose; loss of inhibition by GKRP; unchanged affinity for ATP. 3 Publications1
Natural variantiVAR_07522168G → D in MODY2; unknown pathological significance; mildly increases glucokinase activity. 1 PublicationCorresponds to variant dbSNP:rs373418736Ensembl.1
Natural variantiVAR_00369370E → K in MODY2; decreased affinity for glucose. 2 Publications1
Natural variantiVAR_07944072G → R in MODY2 and PNDM; decreased stability; no effect on glucokinase activity; no effect on affinity for glucose. 2 Publications1
Natural variantiVAR_07944177L → P in MODY2. 1 Publication1
Natural variantiVAR_07944278D → E in MODY2. 1 Publication1
Natural variantiVAR_00369480G → A in MODY2. 1
Natural variantiVAR_07944380G → D in MODY2. 1 Publication1
Natural variantiVAR_00369580G → S in MODY2. 1 Publication1
Natural variantiVAR_07944482T → I in MODY2. 1 Publication1
Natural variantiVAR_07824491V → L in HHF3; increased glucokinase activity; increased affinity for glucose. 2 Publications1
Natural variantiVAR_07824599W → C in HHF3; increased glucokinase activity; increased affinity for glucose; increased affinity for ATP. 1 Publication1
Natural variantiVAR_003696107M → T2 Publications