GCK glucokinase (hexokinase 4) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: GCKprovided by HGNC
Official Full Name: glucokinase (hexokinase 4)provided by HGNC
Primary source: HGNC:4195
See related: Ensembl:ENSG00000106633; HPRD:00680; MIM:138079; Vega:OTTHUMG00000022903
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GK; GLK; HK4; HHF3; HKIV; HXKP; LGLK; MODY2; FGQTL3
Summary: Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. Alternative splicing of this gene results in three tissue-specific forms of glucokinase, one found in pancreatic islet beta cells and two found in liver. The protein localizes to the outer membrane of mitochondria. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. Mutations in this gene have been associated with non-insulin dependent diabetes mellitus (NIDDM), maturity onset diabetes of the young, type 2 (MODY2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). [provided by RefSeq, Apr 2009]

Genomic context

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Location :: 7p15.3-p15.1

Sequence :: Chromosome: 7; NC_000007.13 (44183870..44229022, complement)

See GCK in Epigenomics, MapViewer

Chromosome 7 - NC_000007.13 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

study identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene
Title: MODY 2: mutation identification and molecular ancestry in a Brazilian family.
The results show that mutations in glucokinase resulting in maturity-onset diabetes of the young 2 yield a metabolically normal condition, which may contribute to the lack of late complications and the nonprogressive nature of the disease.
Title: Metabolite profiling reveals normal metabolic control in carriers of mutations in the glucokinase gene (MODY2).
Glucokinase mutations are associated with Type 2 Maturity Onset Diabetes of the Young.
Title: Glucokinase (GCK) mutations and their characterization in MODY2 children of southern Italy.
Sequences downstream of the liver-specific mRNA start site have important roles in the regulation of liver-specific glucokinase gene expression.
Title: Expression of the human glucokinase gene: important roles of the 5' flanking and intron 1 sequences.
report of a family with MODY2 caused by a novel NM_000162.3:c.878T>C mutation in exon 8 of the GCK gene
Title: MODY2 caused by a novel mutation of GCK gene.
The large proportion of families carrying three ancestral mutations in GCK indicates that the previously assumed rarity of the founder effect with regard to GCK-maturity onset diabetes of the young (MODY) should be reconsidered.
Title: Ancestral mutations may cause a significant proportion of GCK-MODY.
The high incidence of the mutant allele in GCK-MODY patients of Jewish-Ashkenazi descent suggests a founder effect.
Title: The glucokinase mutation p.T206P is common among MODY patients of Jewish Ashkenazi descent.
Essential roles of the polymorphisms of the APOA5, GCK and GCKR in the lipid or glucose metabolism disorders.
Title: Associations of apolipoprotein A5 (APOA5), glucokinase (GCK) and glucokinase regulatory protein (GCKR) polymorphisms and lifestyle factors with the risk of dyslipidemia and dysglycemia in Japanese - a cross-sectional data from the J-MICC Study.
similar properties may represent the molecular mechanisms for additional unexplained GCK-MODY mutations, and may also contribute to the disease mechanism in other previously characterized GCK-MODY inactivating mutations
Title: GCK-MODY diabetes associated with protein misfolding, cellular self-association and degradation.
R43H-GCK appeared to have similar basic kinetic characteristics to WT-GCK, there was in vitro evidence of protein instability, indicating that this variant is pathogenic. For G68D-GCK, there was no evidence of protein instability
Title: Insights into the pathogenicity of rare missense GCK variants from the identification and functional characterization of compound heterozygous and double mutations inherited in cis.

Submit: New GeneRIF Correction See all (143)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Hyperinsulinemic hypoglycemia familial 3

MIM: 602485

Genetic Testing Registry

Summary from GeneReviews: Familial Hyperinsulinism

Familial hyperinsulinism (referred to as FHI in this GeneReview) is characterized by hypoglycemia that ranges from severe neonatal-onset, difficult-to-manage disease to childhood-onset disease with mild symptoms and difficult-to-diagnose hypoglycemia. Neonatal-onset disease manifests within hours to two days after birth. Childhood-onset disease manifests during the first months or years of life. In the newborn period, presenting symptoms may be nonspecific, including seizures, hypotonia, poor feeding, and apnea. In severe cases, serum glucose concentrations are typically extremely low and thus easily recognized, whereas in milder cases, variable and mild hypoglycemia may make the diagnosis more difficult. Even within the same family, disease manifestations can range from mild to severe. Individuals with autosomal recessive familial hyperinsulinism, caused by mutations in either ABCC8 or KCNJ11 (FHI-KATP), tend to be large for gestational age and usually present with severe refractory hypoglycemia in the first 48 hours of life; affected infants usually respond only partially to diet or medical management (i.e., diazoxide therapy) and thus may require pancreatic resection. Individuals with autosomal dominant FHI-KATP tend to be appropriate for gestational age at birth, to present at approximately age one year (range: 2 days - 30 years), and to respond to diet and diazoxide therapy. Exceptions to both of these generalities have been reported. FHI-GCK, caused by mutations in GCK, may be much milder than FHI-KATP; however, some persons have severe, diazoxide-unresponsive hypoglycemia. FHI-HADH, caused by mutations in HADH, tends to be relatively mild, although severe cases have been reported. Individuals with FHI-HNF4A, caused by mutations in HNF4A, are typically born large for gestational age and have mild features that respond to diazoxide treatment. FHI-UCP2, caused by mutations in UCP2, is a rare cause of diazoxide-responsive FH1. Hyperammonemia/hyperinsulinism (HA/HI) is associated with mild-to-moderate hyperammonemia and with relatively mild, late-onset hypoglycemia; most but not all affected individuals have mutations in GLUD1.

Diagnosis Testing

Approximately 45% of affected individuals have mutations in either ABCC8, which encodes the protein SUR1, or KCNJ11, which encodes the protein Kir6.2. In the Ashkenazi Jewish population, two ABCC8 founder mutations are responsible for approximately 97% of FHI. Other ABCC8 founder mutations are present in the Finnish population (p.Val187Asp and p.Asp1506Lys). Mutations in GLUD1 and HNF4A each account for approximately 5% of individuals with FHI. Activating mutations in GCK or inactivating mutations in HADH occur in fewer than 1% of individuals with FHI. Mutations in UCP2 have been reported in only two families to date. Approximately 40% of individuals with FHI do not have an identifiable mutation in any of the genes known to be associated with FHI. Molecular genetic testing of ABCC8, KCNJ11, GLUD1, GCK, HADH and HNF4A is available on a clinical basis.

Genetic Counseling

FHI-KATP, caused by mutations in either ABCC8 or KCNJ11, is most commonly inherited in an autosomal recessive manner and less commonly in an autosomal dominant manner, although de novo mutations have been reported. FHI-GCK, caused by mutations in GCK, and HA/HI, caused by mutations in GLUD1, are inherited in an autosomal dominant manner; de novo mutations are not rare. FHI-HADH, caused by mutations in HADH, is inherited in an autosomal recessive manner. The focal form of FHI, caused by biallelic mutations of ABCC8 or KCNJ11, is inherited in an autosomal dominant manner, but only manifests when the mutation occurs on the paternally derived allele and a somatic event results in the loss of the maternal allele in a beta cell precursor. Risk to sibs of a proband depends on the underlying genetic mechanism. Carrier testing for relatives at risk for the autosomal recessive forms of FHI and prenatal diagnosis for pregnancies at increased risk for the diffuse form of FHI are possible if the family-specific mutation(s) are known. Prenatal or preimplantation genetic diagnosis for focal FHI is not possible, as a somatic mutation in the pancreas is required for clinical disease.

Summary from GeneReviews: Permanent Neonatal Diabetes Mellitus

Disease Characteristics

Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life (mean age: 7 weeks; range: birth to 26 weeks) that does not resolve over time. Clinical manifestations at the time of diagnosis include intrauterine growth retardation (IUGR); hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Therapy with insulin corrects the hyperglycemia and allows for catch-up growth. The course of PNDM varies by genotype. Approximately 20% of individuals with mutations in KCNJ11 have associated neurologic findings, called the DEND syndrome (developmental delay, epilepsy, and neonatal diabetes mellitus); a milder form without seizures and with less severe developmental delay is called intermediate DEND syndrome. Pancreatic hypoplasia caused by homozygous PDX1 mutations results in severe insulin deficiency and exocrine pancreatic insufficiency.

Diagnosis Testing

Persistent hyperglycemia (plasma glucose concentration >150-200 mg/dL) in infants younger than age six months establishes the diagnosis of PNDM. The five genes currently known to be associated with nonsyndromic PNDM are KCNJ11 (~30% of PNDM), ABCC8 (~19%), INS (~20%), GCK (~4%), and PDX1 (<1%). Molecular genetic testing is available on a clinical basis for all genes.

Genetic Counseling

The mode of inheritance of PNDM is autosomal dominant for mutations in KCNJ11, autosomal dominant or autosomal recessive for mutations in ABCC8 and INS, and autosomal recessive for mutations in GCK and PDX1. Individuals with autosomal dominant PNDM may have an affected parent or may have a de novo mutation. Each child of an individual with PNDM inherited in an autosomal dominant manner has a 50% chance of inheriting the mutation. The parents of a child with autosomal recessive PNDM are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes (carriers) for mutations in GCK and PDX1 have a mild form of diabetes mellitus known as GCK-familial monogenic diabetes (formerly known as MODY2) and PDX1-familial monogenic diabetes (formerly known as MODY4). At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier (or of having familial monogenic diabetes), and a 25% chance of being unaffected and not a carrier. Prenatal diagnosis for pregnancies at increased risk for most forms of PNDM is available if the disease-causing mutation(s) in the family are known.

References

PMID: 20301620

NHGRI GWAS Catalog

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Common variants at 10 genomic loci influence hemoglobin A&#x02081;(C) levels via glycemic and nonglycemic pathways.

Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits.

Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits.

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P35557	Q14397	GCKR	HPRD	PubMed
P35557	P01308	INS	HPRD	PubMed
P35557	O60825	PFKFB2	HPRD	PubMed
BioGRID:108915	BioGRID:108916	GCKR	BioGRID	PubMed	Two-hybrid
BioGRID:108915	BioGRID:33212	MIG1	BioGRID	PubMed	Two-hybrid
BioGRID:108915	BioGRID:111142	PCNA	BioGRID	PubMed	Reconstituted Complex
BioGRID:108915	BioGRID:111229	PFKFB2	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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Amino sugar and nucleotide sugar metabolism, organism-specific biosystem (from KEGG)
Amino sugar and nucleotide sugar metabolism, organism-specific biosystem
Amino sugar and nucleotide sugar metabolism
Amino sugar and nucleotide sugar metabolism, conserved biosystem (from KEGG)
Amino sugar and nucleotide sugar metabolism, conserved biosystem
Amino sugar and nucleotide sugar metabolism
Butirosin and neomycin biosynthesis, organism-specific biosystem (from KEGG)
Butirosin and neomycin biosynthesis, organism-specific biosystem
Butirosin and neomycin biosynthesis
Butirosin and neomycin biosynthesis, conserved biosystem (from KEGG)
Butirosin and neomycin biosynthesis, conserved biosystem
Butirosin and neomycin biosynthesis
Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
FOXA2 and FOXA3 transcription factor networks, organism-specific biosystem (from Pathway Interaction Database)
FOXA2 and FOXA3 transcription factor networks, organism-specific biosystem
FOXA2 and FOXA3 transcription factor networks
GDP-glucose biosynthesis, organism-specific biosystem (from BIOCYC)
GDP-glucose biosynthesis, organism-specific biosystemAbout 50 different nucleoside diphosphate sugars have been isolated, and many of these have been shown to be intermediates in the biosynthesis of various types of complex carbohydrates . These substa...
GDP-glucose biosynthesis, conserved biosystem (from BIOCYC)
GDP-glucose biosynthesis, conserved biosystemAbout 50 different nucleoside diphosphate sugars have been isolated, and many of these have been shown to be intermediates in the biosynthesis of various types of complex carbohydrates |CITS: [110821...
Galactose metabolism, organism-specific biosystem (from KEGG)
Galactose metabolism, organism-specific biosystem
Galactose metabolism
Galactose metabolism, conserved biosystem (from KEGG)
Galactose metabolism, conserved biosystem
Galactose metabolism
Glucose transport, organism-specific biosystem (from REACTOME)
Glucose transport, organism-specific biosystemCells take up glucose by facilitated diffusion, via glucose transporters (GLUTs) associated with the plasma membrane, a reversible reaction (Joost and Thorens 2001). Four tissue-specific GLUT isoform...
Glycolysis (Embden-Meyerhof pathway), glucose => pyruvate, organism-specific biosystem (from KEGG)
Glycolysis (Embden-Meyerhof pathway), glucose => pyruvate, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Glycolysis (Embden-Meyerhof pathway), glucose => pyruvate, conserved biosystem (from KEGG)
Glycolysis (Embden-Meyerhof pathway), glucose => pyruvate, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Glycolysis / Gluconeogenesis, organism-specific biosystem (from KEGG)
Glycolysis / Gluconeogenesis, organism-specific biosystemGlycolysis is the process of converting glucose into pyruvate and generating small amounts of ATP (energy) and NADH (reducing power). It is a central pathway that produces important precursor metabol...
Glycolysis / Gluconeogenesis, conserved biosystem (from KEGG)
Glycolysis / Gluconeogenesis, conserved biosystemGlycolysis is the process of converting glucose into pyruvate and generating small amounts of ATP (energy) and NADH (reducing power). It is a central pathway that produces important precursor metabol...
Glycolysis and Gluconeogenesis, organism-specific biosystem (from WikiPathways)
Glycolysis and Gluconeogenesis, organism-specific biosystem
Glycolysis and Gluconeogenesis
HIF-1-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
HIF-1-alpha transcription factor network, organism-specific biosystem
HIF-1-alpha transcription factor network
Hexose transport, organism-specific biosystem (from REACTOME)
Hexose transport, organism-specific biosystemHexoses, notably fructose, glucose, and galactose, generated in the lumen of the small intestine by breakdown of dietary carbohydrate are taken up by enterocytes lining the microvilli of the small in...
Insulin secretion, organism-specific biosystem (from KEGG)
Insulin secretion, organism-specific biosystemPancreatic beta cells are specialised endocrine cells that continuously sense the levels of blood sugar and other fuels and, in response, secrete insulin to maintain normal fuel homeostasis. Glucose-...
Insulin signaling pathway, organism-specific biosystem (from KEGG)
Insulin signaling pathway, organism-specific biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
Insulin signaling pathway, conserved biosystem (from KEGG)
Insulin signaling pathway, conserved biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
MAPK signaling pathway, organism-specific biosystem (from WikiPathways)
MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
Maturity onset diabetes of the young, organism-specific biosystem (from KEGG)
Maturity onset diabetes of the young, organism-specific biosystemAbout 2-5% of type II diabetic patients suffer from a monogenic disease with autosomal dominant inheritance. This monogenic form of type II diabetes is called maturity onset diabetes of the young (MO...
Maturity onset diabetes of the young, conserved biosystem (from KEGG)
Maturity onset diabetes of the young, conserved biosystemAbout 2-5% of type II diabetic patients suffer from a monogenic disease with autosomal dominant inheritance. This monogenic form of type II diabetes is called maturity onset diabetes of the young (MO...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of carbohydrates, organism-specific biosystem (from REACTOME)
Metabolism of carbohydrates, organism-specific biosystemThese pathways together are responsible for: 1) the extraction of energy and carbon skeletons for biosyntheses from dietary sugars and related molecules; 2) the short-term storage of glucose in the b...
Nucleotide sugar biosynthesis, glucose => UDP-glucose, organism-specific biosystem (from KEGG)
Nucleotide sugar biosynthesis, glucose => UDP-glucose, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Sugar metabolism
Nucleotide sugar biosynthesis, glucose => UDP-glucose, conserved biosystem (from KEGG)
Nucleotide sugar biosynthesis, glucose => UDP-glucose, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Sugar metabolism
Regulation of Glucokinase by Glucokinase Regulatory Protein, organism-specific biosystem (from REACTOME)
Regulation of Glucokinase by Glucokinase Regulatory Protein, organism-specific biosystemGlucokinase (GCK1) is negatively regulated by glucokinase regulatory protein (GKRP), which reversibly binds the enzyme to form an inactive complex. Binding is stimulated by fructose 6-phosphate and s...
Regulation of beta-cell development, organism-specific biosystem (from REACTOME)
Regulation of beta-cell development, organism-specific biosystemThe normal development of the pancreas during gestation has been intensively investigated over the past decade especially in the mouse (Servitja and Ferrer 2004; Chakrabarti and Mirmira 2003). Studie...
Regulation of gene expression in beta cells, organism-specific biosystem (from REACTOME)
Regulation of gene expression in beta cells, organism-specific biosystemTwo transcription factors, PDX1 and HNF1A, play key roles in maintaining the gene expression pattern characteristic of mature beta cells in the endocrine pancreas. Targets of these regulatory molecul...
SIDS Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
SIDS Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...
SLC-mediated transmembrane transport, organism-specific biosystem (from REACTOME)
SLC-mediated transmembrane transport, organism-specific biosystemProteins with transporting functions can be roughly classified into 3 categories: ATP-powered pumps, ion channels, and transporters. Pumps utilize the energy released by ATP hydrolysis to power the m...
Starch and sucrose metabolism, organism-specific biosystem (from KEGG)
Starch and sucrose metabolism, organism-specific biosystem
Starch and sucrose metabolism
Starch and sucrose metabolism, conserved biosystem (from KEGG)
Starch and sucrose metabolism, conserved biosystem
Starch and sucrose metabolism
Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
Transmembrane transport of small molecules, organism-specific biosystem
Transmembrane transport of small molecules
Type II diabetes mellitus, organism-specific biosystem (from KEGG)
Type II diabetes mellitus, organism-specific biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...
Type II diabetes mellitus, conserved biosystem (from KEGG)
Type II diabetes mellitus, conserved biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...
UDP-N-acetyl-D-galactosamine biosynthesis II, organism-specific biosystem (from BIOCYC)
UDP-N-acetyl-D-galactosamine biosynthesis II, organism-specific biosystem
UDP-N-acetyl-D-galactosamine biosynthesis II
glucose and glucose-1-phosphate degradation, organism-specific biosystem (from BIOCYC)
glucose and glucose-1-phosphate degradation, organism-specific biosystem
glucose and glucose-1-phosphate degradation
glycolysis, organism-specific biosystem (from BIOCYC)
glycolysis, organism-specific biosystem
glycolysis
homolactic fermentation, conserved biosystem (from BIOCYC)
homolactic fermentation, conserved biosystemGeneral Background Lactic acid fermentation is a process by which sugars such as glucose, fructose, and sucrose are converted into cellular energy and the metabolic byproduct lactate. It occurs in m...
trehalose degradation II (trehalase), organism-specific biosystem (from BIOCYC)
trehalose degradation II (trehalase), organism-specific biosystem
trehalose degradation II (trehalase)

General gene information

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Markers

GDB:191176 (e-PCR)
- UniSTS:155648

RH11460 (e-PCR)
- UniSTS:29022

SHGC-12738 (e-PCR)
- UniSTS:49837

GDB:3754299 (e-PCR)
- UniSTS:30160

GDB:1317412 (e-PCR)
- UniSTS:25306

Genotypes

See GCK SNP Geneview Report
See GCK SNP Genotype Report
See GCK SNP Variation Viewer Report

Homology

Homologs of the GCK gene: The GCK gene is conserved in chimpanzee, Rhesus monkey, cow, mouse, rat, chicken, zebrafish, fruit fly, A.thaliana, and rice.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ADP binding	IEA Inferred from Electronic Annotation more info
ATP binding	IDA Inferred from Direct Assay more info	PubMed
NOT fructokinase activity	IBA Inferred from Biological aspect of Ancestor more info
glucokinase activity	IDA Inferred from Direct Assay more info	PubMed
glucose binding	IDA Inferred from Direct Assay more info	PubMed
magnesium ion binding	IEA Inferred from Electronic Annotation more info
NOT mannokinase activity	IBA Inferred from Biological aspect of Ancestor more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein phosphatase binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
NADP metabolic process	IEA Inferred from Electronic Annotation more info
calcium ion import	IEA Inferred from Electronic Annotation more info
carbohydrate metabolic process	TAS Traceable Author Statement more info
cellular glucose homeostasis	IBA Inferred from Biological aspect of Ancestor more info
cellular response to glucose starvation	IEA Inferred from Electronic Annotation more info
cellular response to insulin stimulus	ISS Inferred from Sequence or Structural Similarity more info
cellular response to leptin stimulus	ISS Inferred from Sequence or Structural Similarity more info
detection of glucose	IMP Inferred from Mutant Phenotype more info	PubMed
elevation of cytosolic calcium ion concentration	IEA Inferred from Electronic Annotation more info
endocrine pancreas development	TAS Traceable Author Statement more info
fructose 2,6-bisphosphate metabolic process	IEA Inferred from Electronic Annotation more info
glucose homeostasis	IMP Inferred from Mutant Phenotype more info
glucose transport	TAS Traceable Author Statement more info
glycogen biosynthetic process	IEA Inferred from Electronic Annotation more info
glycolysis	IEA Inferred from Electronic Annotation more info
hexose transport	TAS Traceable Author Statement more info
negative regulation of epinephrine secretion	IEA Inferred from Electronic Annotation more info
negative regulation of gluconeogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of glycogen biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of glycolysis	IEA Inferred from Electronic Annotation more info
positive regulation of insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of phosphorylation	IEA Inferred from Electronic Annotation more info
regulation of glucose transport	TAS Traceable Author Statement more info
regulation of glycolysis	NAS Non-traceable Author Statement more info	PubMed
regulation of insulin secretion	IMP Inferred from Mutant Phenotype more info
regulation of potassium ion transport	IEA Inferred from Electronic Annotation more info
second-messenger-mediated signaling	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info
transmembrane transport	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cell cortex part	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
mitochondrion	IEA Inferred from Electronic Annotation more info
nucleoplasm	TAS Traceable Author Statement more info
secretory granule	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: glucokinase

Names: glucokinase; HK IV; hexokinase-4; hexokinase-D; hexokinase type IV; hexokinase D, pancreatic isozyme; ATP:D-hexose 6-phosphotransferase

NP_000153.1

EC 2.7.1.2

NP_277042.1

EC 2.7.1.2

NP_277043.1

EC 2.7.1.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008847.1 RefSeqGene

Range

5001..50153

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000162.3 → NP_000153.1 glucokinase isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the isoform expressed specifically in pancreatic islet beta cells. Its first exon is specific to this variant, which has a unique 5' UTR. Isoform 1 has a distinct N-terminus; the remainder of the protein is identical to isoforms 2 and 3.

Source sequence(s)

BC001890, M90299

Consensus CDS

CCDS5479.1

UniProtKB/Swiss-Prot

P35557

UniProtKB/TrEMBL

Q53Y25

Related

ENSP00000384247, OTTHUMP00000159306, ENST00000403799, OTTHUMT00000251069

Conserved Domains (3) summary

COG5026
Location:8 – 458
Blast Score: 722

COG5026; Hexokinase [Carbohydrate transport and metabolism]

pfam03727
Location:219 – 456
Blast Score: 908

Hexokinase_2; Hexokinase

cd00012
Location:75 – 278
Blast Score: 202

NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily
NM_033507.1 → NP_277042.1 glucokinase isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes the major isoform expressed in liver. Its first exon is specific to the liver transcripts, variants 2 and 3, but it lacks a second liver-specific exon found in variant 3. Isoform 2 has a distinct N-terminus; the remainder of the protein is identical to isoforms 1 and 3.

Source sequence(s)

AC006454, AK122876, CD251038, M69051, M90299

Consensus CDS

CCDS5480.1

UniProtKB/Swiss-Prot

P35557

Related

ENSP00000223366, OTTHUMP00000159307, ENST00000345378, OTTHUMT00000251070

Conserved Domains (3) summary

PLN02914
Location:5 – 459
Blast Score: 724

PLN02914; hexokinase

pfam03727
Location:220 – 457
Blast Score: 910

Hexokinase_2; Hexokinase

cd00012
Location:76 – 279
Blast Score: 201

NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily
NM_033508.1 → NP_277043.1 glucokinase isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) is the minor form expressed in liver. Its first exon is specific to the liver transcripts, variants 2 and 3; its second exon is unique to this transcript. Isoform 3 has a distinct N-terminus; the remainder of the protein is identical to isoforms 1 and 2.

Source sequence(s)

AC006454, CD251038, DA640823, M69051, M90299

Consensus CDS

CCDS5481.1

UniProtKB/Swiss-Prot

P35557

Related

ENSP00000379142, OTTHUMP00000159308, ENST00000395796, OTTHUMT00000251071

Conserved Domains (3) summary

PLN02914
Location:2 – 457
Blast Score: 738

PLN02914; hexokinase

pfam03727
Location:218 – 455
Blast Score: 914

Hexokinase_2; Hexokinase

cd00012
Location:74 – 277
Blast Score: 205

NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000007.13 Reference GRCh37.p10 Primary Assembly

Range

44183870..44229022, complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000139.1 Alternate HuRef

Range

44069141..44114301, complement

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Alternate CRA_TCAGchr7v2

Genomic

AC_000068.1 Alternate CRA_TCAGchr7v2

Range

44223370..44268527, complement

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Alternate CHM1_1.0

Genomic

NC_018918.1 Alternate CHM1_1.0

Range

44159372..44204538, complement

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Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AACC02000110.1 (1446277..1491434)	None
genomic	ABBA01058215.1 (39937..85097)	None
genomic	AC006454.4 (63162..108330)	None
genomic	AF041013.1	AAB97681.1
genomic	AF041014.1	AAB97682.1
genomic	AF041022.1	AAB97680.1
		AAB97681.1
		AAB97682.1
genomic	AMYH01017209.1 (40199..85365)	None
genomic	CH236960.1	EAL23764.1
		EAL23765.1
		EAL23766.1
genomic	CH471128.2	EAW61114.1
		EAW61115.1
		EAW61116.1
genomic	HB877574.1	CBF63115.1
genomic	HC934983.1	CBU87991.1
genomic	M90298.1	AAA67541.1
		AAA67542.1
mRNA	AK122876.1	BAG53774.1
mRNA	BC001890.1	AAH01890.1
mRNA	BT007062.1	AAP35711.1
mRNA	CD251038.1	None
mRNA	DA640823.1	None
mRNA	EU008605.1	ABS31137.1
mRNA	M69051.1	AAB59563.1
mRNA	M88011.1	AAA51824.1
mRNA	M90299.1	AAA52562.1
other-genetic	DQ893835.2	ABM84761.1