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Entry version 209 (16 Oct 2019)
Sequence version 1 (01 Jun 1994)
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Protein

Hexokinase-4

Gene

GCK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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:7742312, PubMed:11916951, PubMed:15277402, PubMed:17082186, PubMed:18322640, PubMed:19146401, PubMed:25015100, 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:18322640, PubMed:25015100, PubMed:8325892, PubMed:11916951, PubMed:15277402). 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).By similarity9 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

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).2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: hexose metabolism

This protein is involved in the pathway hexose metabolism, which is part of Carbohydrate metabolism.1 Publication
View all proteins of this organism that are known to be involved in the pathway hexose metabolism and in Carbohydrate metabolism.

Pathwayi: glycolysis

This protein is involved in step 1 of the subpathway that synthesizes D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose.1 Publication
Proteins known to be involved in the 4 steps of the subpathway in this organism are:
  1. Hexokinase 3 (White cell), isoform CRA_b (HK3), Hexokinase 3 variant, Hexokinase-3 (HK3), cDNA FLJ77931, Hexokinase-4 (GCK), cDNA FLJ46359 fis, clone TESTI4049786, highly similar to Hexokinase-1, Phosphotransferase (GCK), Phosphotransferase (HK2), Hexokinase-2 (HK2), Phosphotransferase (GCK), Hexokinase 1 isoform HKI variant, Phosphotransferase (GCK), Phosphotransferase, cDNA FLJ37767 fis, clone BRHIP2024911, highly similar to Homo sapiens hexokinase domain containing 1 (HKDC1), mRNA, Phosphotransferase, Hexokinase HKDC1 (HKDC1), Hexokinase-1 (HK1), cDNA FLJ56506, highly similar to Hexokinase-1, Phosphotransferase (HK1), Hexokinase-2 (HK2), Phosphotransferase (HK2), cDNA FLJ57348, highly similar to Homo sapiens hexokinase domain containing 1 (HKDC1), mRNA, Hexokinase 1, isoform CRA_c (HK1), cDNA FLJ78173, highly similar to Homo sapiens hexokinase 1 (HK1) mRNA, Phosphotransferase (GCK), cDNA FLJ75392, highly similar to Homo sapiens hexokinase II (HKII) mRNA, Uncharacterized protein DKFZp686M1669 (DKFZp686M1669), Phosphotransferase (HK3)
  2. Glucose-6-phosphate isomerase (GPI), Glucose-6-phosphate isomerase (GPI), Glucose-6-phosphate isomerase (GPI), Glucose-6-phosphate isomerase, Glucose-6-phosphate isomerase, Glucose-6-phosphate isomerase, Glucose-6-phosphate isomerase (GPI), Glucose-6-phosphate isomerase (GPI)
  3. ATP-dependent 6-phosphofructokinase, muscle type (PFKM), ATP-dependent 6-phosphofructokinase, platelet type (PFKP), ATP-dependent 6-phosphofructokinase (PFKM), ATP-dependent 6-phosphofructokinase, liver type (PFKL), ATP-dependent 6-phosphofructokinase (PFKM)
  4. Fructose-bisphosphate aldolase (ALDOC), Fructose-bisphosphate aldolase (ALDOB), Fructose-bisphosphate aldolase, Fructose-bisphosphate aldolase, Fructose-bisphosphate aldolase (ALDOB), Fructose-bisphosphate aldolase, Fructose-bisphosphate aldolase (ALDOB), Fructose-bisphosphate aldolase (ALDOA), Fructose-bisphosphate aldolase, Fructose-bisphosphate aldolase, Fructose-bisphosphate aldolase, Fructose-bisphosphate aldolase, Fructose-bisphosphate aldolase, Fructose-bisphosphate aldolase (ALDOA), Fructose-bisphosphate aldolase (ALDOA), Fructose-bisphosphate aldolase B (ALDOB), Fructose-bisphosphate aldolase C (ALDOC), Fructose-bisphosphate aldolase A (ALDOA), Fructose-bisphosphate aldolase (ALDOC), Fructose-bisphosphate aldolase, Fructose-bisphosphate aldolase (HEL-S-87p), Fructose-bisphosphate aldolase, Fructose-bisphosphate aldolase (ALDOA)
This subpathway is part of the pathway glycolysis, which is itself part of Carbohydrate degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose, the pathway glycolysis and in Carbohydrate degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei228ATPCombined sources1 Publication1
Binding sitei231Substrate1 Publication1
Binding sitei256Substrate1 Publication1
Binding sitei290Substrate1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi78 – 83ATPBy similarity6
Nucleotide bindingi295 – 296ATPCombined sources1 Publication2
Nucleotide bindingi332 – 336ATPCombined sources1 Publication5
Nucleotide bindingi411 – 415ATPCombined sources1 Publication5

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionAllosteric enzyme, Kinase, Transferase
Biological processGlycolysis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

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BioCyci
MetaCyc:HS02935-MONOMER

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.1.1 2681
2.7.1.2 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-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
R-HSA-9615017 FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes

SABIO-RK: Biochemical Reaction Kinetics Database

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SABIO-RKi
P35557

SIGNOR Signaling Network Open Resource

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SIGNORi
P35557

UniPathway: a resource for the exploration and annotation of metabolic pathways

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UniPathwayi
UPA00109;UER00180
UPA00242

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Hexokinase-4Curated (EC:2.7.1.17 Publications)
Short name:
HK4Curated
Alternative name(s):
Glucokinase1 Publication
Hexokinase type IVBy similarity
Short name:
HK IVBy similarity
Hexokinase-DBy similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:GCK1 PublicationImported
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 7

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:4195 GCK

Online Mendelian Inheritance in Man (OMIM)

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MIMi
138079 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P35557

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Maturity-onset diabetes of the young 2 (MODY2)20 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>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:rs762263694EnsemblClinVar.1
Natural variantiVAR_07522043R → H in MODY2; unknown pathological significance; no change in glucokinase activity. 1 PublicationCorresponds to variant dbSNP:rs764232985EnsemblClinVar.1
Natural variantiVAR_07943543R → S in MODY2. 1 Publication1
Natural variantiVAR_07943644G → S in MODY2. 1 PublicationCorresponds to variant dbSNP:rs267601516Ensembl.1
Natural variantiVAR_01058553A → S in MODY2. 1 Publication1
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 PublicationsCorresponds to variant dbSNP:rs193922289EnsemblClinVar.1
Natural variantiVAR_07944177L → P in MODY2. 1 Publication1
Natural variantiVAR_07944278D → E in MODY2. 1 Publication1
Natural variantiVAR_00369480G → A in MODY2. 1 Publication1
Natural variantiVAR_07944380G → D in MODY2. 1 Publication1
Natural variantiVAR_00369580G → S in MODY2. 1 PublicationCorresponds to variant dbSNP:rs1554335761EnsemblClinVar.1
Natural variantiVAR_07944482T → I in MODY2. 1 Publication1
Natural variantiVAR_010586108Y → H in MODY2. 2 Publications1
Natural variantiVAR_012352110I → T in MODY2. 1 PublicationCorresponds to variant dbSNP:rs1338970607Ensembl.1
Natural variantiVAR_079445116T → P in MODY2. 1 Publication1
Natural variantiVAR_012353119A → D in MODY2. 1 PublicationCorresponds to variant dbSNP:rs1176659689Ensembl.1
Natural variantiVAR_078246129C → Y in MODY2. 1 Publication1
Natural variantiVAR_003697131S → P in MODY2; decreased affinity for glucose. 2 PublicationsCorresponds to variant dbSNP:rs104894010EnsemblClinVar.1
Natural variantiVAR_010587137H → R in MODY2. 1 Publication1
Natural variantiVAR_010588150F → S in MODY2. 1 PublicationCorresponds to variant dbSNP:rs193922297EnsemblClinVar.1
Natural variantiVAR_078247152F → L in MODY2; unknown pathological significance. 1 Publication1
Natural variantiVAR_079447160D → N in MODY2; decreased glucokinase activity; decreased affinity for glucose. 1 PublicationCorresponds to variant dbSNP:rs1554335566EnsemblClinVar.1
Natural variantiVAR_012350164L → P in MODY2 and PNDM. 2 Publications1
Natural variantiVAR_010589168T → P in MODY2. 1 Publication1
Natural variantiVAR_003698175G → R in MODY2. Corresponds to variant dbSNP:rs587780344EnsemblClinVar.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:rs587780345EnsemblClinVar.1
Natural variantiVAR_079451186 – 465Missing in MODY2 and NIDDM. 3 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:rs193922307EnsemblClinVar.1
Natural variantiVAR_078249191R → W in MODY2. 2 PublicationsCorresponds to variant dbSNP:rs1085307455EnsemblClinVar.1
Natural variantiVAR_079453200V → L in MODY2. 1 Publication1
Natural variantiVAR_078250202M → R in MODY2. 1 Publication1
Natural variantiVAR_079454202M → T in MODY2. 1 PublicationCorresponds to variant dbSNP:rs193922311EnsemblClinVar.1
Natural variantiVAR_003701203V → A in MODY2. 1
Natural variantiVAR_079455206T → M in MODY2. 1 PublicationCorresponds to variant dbSNP:rs1441649062Ensembl.1
Natural variantiVAR_010590209T → M in MODY2. 2 Publications1
Natural variantiVAR_012351210M → K in MODY2 and PNDM. 1 PublicationCorresponds to variant dbSNP:rs80356654EnsemblClinVar.1
Natural variantiVAR_010591210M → T in MODY2. 1 PublicationCorresponds to variant dbSNP:rs80356654EnsemblClinVar.1
Natural variantiVAR_010592213C → R in MODY2. 1 Publication1
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:rs193922317EnsemblClinVar.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. 3 PublicationsCorresponds to variant dbSNP:rs148311934EnsemblClinVar.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:rs80356655EnsemblClinVar.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_081975248 – 465Missing in MODY2. 1 PublicationAdd BLAST218
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:rs769268803EnsemblClinVar.1
Natural variantiVAR_003707257W → R in MODY2; almost complete loss of glucokinase activity. 1 PublicationCorresponds to variant dbSNP:rs1554335135EnsemblClinVar.1
Natural variantiVAR_010593259A → T in MODY2. 1 PublicationCorresponds to variant dbSNP:rs1375656631EnsemblClinVar.1
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. 6 PublicationsCorresponds to variant dbSNP:rs104894008EnsemblClinVar.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:rs104894005EnsemblClinVar.1
Natural variantiVAR_079464298M → K in MODY2. 1 Publication1
Natural variantiVAR_003710299G → R in MODY2. 2 PublicationsCorresponds to variant dbSNP:rs104894009EnsemblClinVar.1
Natural variantiVAR_003712300E → K in MODY2. Corresponds to variant dbSNP:rs1255911887Ensembl.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 Publication1
Natural variantiVAR_081976360 – 465Missing in MODY2. 1 PublicationAdd BLAST106
Natural variantiVAR_010596367V → M in MODY2. 1 PublicationCorresponds to variant dbSNP:rs1057521092EnsemblClinVar.1
Natural variantiVAR_079466377R → H in MODY2. 1 PublicationCorresponds to variant dbSNP:rs193922264EnsemblClinVar.1
Natural variantiVAR_078254378A → T in MODY2. 1 PublicationCorresponds to variant dbSNP:rs104894016EnsemblClinVar.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 PublicationCorresponds to variant dbSNP:rs777870079EnsemblClinVar.1
Natural variantiVAR_010598384A → T in MODY2. 1 PublicationCorresponds to variant dbSNP:rs1376620210Ensembl.1
Natural variantiVAR_012354385G → V in MODY2. 1 Publication1
Natural variantiVAR_010599392R → C in MODY2. 1 PublicationCorresponds to variant dbSNP:rs1167124132EnsemblClinVar.1
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:rs193922272EnsemblClinVar.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 PublicationCorresponds to variant dbSNP:rs1131691416EnsemblClinVar.1
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.
Related information in OMIM
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 GCKR; 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 GCKR. 2 PublicationsCorresponds to variant dbSNP:rs104894015EnsemblClinVar.1
Natural variantiVAR_078257442E → K in HHF3; increased affinity for glucose. 2 PublicationsCorresponds to variant dbSNP:rs758737171EnsemblClinVar.1
Natural variantiVAR_003715455V → M in HHF3; increased glucokinase activity based on measure of catalytic efficiency; increased affinity for glucose; decreased inhibition by GCKR; no effect on affinity for ATP. 2 PublicationsCorresponds to variant dbSNP:rs104894012EnsemblClinVar.1
Natural variantiVAR_079477456A → V in HHF3; increased glucokinase activity based on measure of catalytic efficiency; increased affinity for glucose; loss of inhibition by GCKR; no effect on affinity for ATP. 2 PublicationsCorresponds to variant dbSNP:rs104894014EnsemblClinVar.1
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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079451186 – 465Missing in MODY2 and NIDDM. 3 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07943340E → K in PNDM; decreased stability; decreased glucokinase activity; decreased affinity for glucose. 1 PublicationCorresponds to variant dbSNP:rs794727236EnsemblClinVar.1
Natural variantiVAR_07943443R → C in PNDM; decreased stability; decreased glucokinase activity; no effect on affinity for glucose. 1 PublicationCorresponds to variant dbSNP:rs1486280029EnsemblClinVar.1
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 PublicationsCorresponds to variant dbSNP:rs193922289EnsemblClinVar.1
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:rs80356654EnsemblClinVar.1
Natural variantiVAR_003705228T → M in MODY2 and PNDM. 3 PublicationsCorresponds to variant dbSNP:rs80356655EnsemblClinVar.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. 6 PublicationsCorresponds to variant dbSNP:rs104894008EnsemblClinVar.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 PublicationCorresponds to variant dbSNP:rs193929375EnsemblClinVar.1
Natural variantiVAR_079475441S → L in PNDM; decreased stability; decreased glucokinase activity; no effect on affinity for glucose. 1 PublicationCorresponds to variant dbSNP:rs1286804191EnsemblClinVar.1
Natural variantiVAR_079476449A → T in PNDM; decreased stability; increased glucokinase activity; increased affinity for glucose. 1 PublicationCorresponds to variant dbSNP:rs193922282EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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 GCKR. 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

DisGeNET

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DisGeNETi
2645

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
GCK

MalaCards human disease database

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MalaCardsi
GCK
MIMi125851 phenotype
125853 phenotype
602485 phenotype
606176 phenotype
606391 phenotype

Open Targets

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OpenTargetsi
ENSG00000106633

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
79299 Hyperinsulinism due to glucokinase deficiency
552 MODY
99885 Permanent neonatal diabetes mellitus

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA28610

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
P35557

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL3820

Drug and drug target database

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DrugBanki
DB08118 2-(methylamino)-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide
DB08210 2-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDE
DB07358 2-amino-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide
DB07359 3-[(4-fluorophenyl)sulfanyl]-N-(4-methyl-1,3-thiazol-2-yl)-6-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carboxamide
DB02379 Beta-D-Glucose
DB01914 D-glucose
DB09341 Dextrose, unspecified form
DB09344 Invert sugar

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2798

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
GCK

Domain mapping of disease mutations (DMDM)

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DMDMi
547696

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001975931 – 465Hexokinase-4Add BLAST465

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P35557

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
P35557

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P35557

PeptideAtlas

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PeptideAtlasi
P35557

PRoteomics IDEntifications database

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PRIDEi
P35557

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
55084 [P35557-1]
55085 [P35557-2]
55086 [P35557-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P35557

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P35557

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000106633 Expressed in 96 organ(s), highest expression level in liver

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P35557 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P35557 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA007034
HPA007093

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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 hexokinase activity (PubMed:24187134).

Interacts with GCKR; leading to sequestration in the nucleus (PubMed:10456334).

5 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
108915, 13 interactors

Protein interaction database and analysis system

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IntActi
P35557, 6 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000223366

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P35557

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
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3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P35557

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P35557

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini10 – 454HexokinasePROSITE-ProRule annotation