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

Gene ID: 2645, updated on 28-Jul-2014
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]
Location:
7p15.3-p15.1
Exon count:
12
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 7 NC_000007.14 (44144271..44189423, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (44183870..44229022, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene RNA, 5S ribosomal pseudogene 230 Neighboring gene myosin, light chain 7, regulatory Neighboring gene YKT6 v-SNARE homolog (S. cerevisiae) Neighboring gene calcium/calmodulin-dependent protein kinase II beta

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
NHGRI GWA Catalog
A study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.
NHGRI GWA Catalog
Common variants at 10 genomic loci influence hemoglobin A₁(C) levels via glycemic and nonglycemic pathways.
NHGRI GWA Catalog
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.
NHGRI GWA Catalog
Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits.
NHGRI GWA Catalog
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
NHGRI GWA Catalog
New susceptibility loci in MYL2, C12orf51 and OAS1 associated with 1-h plasma glucose as predisposing risk factors for type 2 diabetes in the Korean population.
NHGRI GWA Catalog
Novel association of HK1 with glycated hemoglobin in a non-diabetic population: a genome-wide evaluation of 14,618 participants in the Women's Genome Health Study.
NHGRI GWA Catalog
Variants in MTNR1B influence fasting glucose levels.
NHGRI GWA Catalog

Replication interactions

Interaction Pubs
Knockdown of glucokinase (hexokinase 4) (GCK) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Pr55(Gag) gag The amplified luminescent proximity homogeneous assay (AlphaScreen) identifies the interaction of HIV-1 Gag with GCK PubMed

Go to the HIV-1, Human Protein Interaction Database

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

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
 
carbohydrate phosphorylation IEA
Inferred from Electronic Annotation
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 
endocrine pancreas development TAS
Traceable Author Statement
more info
 
fructose 2,6-bisphosphate metabolic process IEA
Inferred from Electronic Annotation
more info
 
glucose 6-phosphate metabolic process IEA
Inferred from Electronic Annotation
more info
 
glucose homeostasis IMP
Inferred from Mutant Phenotype
more info
 
glucose metabolic process IEA
Inferred from Electronic Annotation
more info
 
glucose transport TAS
Traceable Author Statement
more info
 
glycogen biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
glycolytic process 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 cytosolic calcium ion concentration IEA
Inferred from Electronic Annotation
more info
 
positive regulation of glycogen biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of glycolytic process 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 glycolytic process 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 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
 
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
NP_277042.1
NP_277043.1

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

  1. NG_008847.1 

    Range
    5001..50153
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000162.3NP_000153.1  glucokinase isoform 1

    See proteins identical to NP_000153.1

    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
    cd00012
    Location:75278
    Blast Score: 204
    NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily
    COG5026
    Location:8458
    Blast Score: 752
    COG5026; Hexokinase [Carbohydrate transport and metabolism]
    pfam03727
    Location:219456
    Blast Score: 904
    Hexokinase_2; Hexokinase
  2. NM_033507.1NP_277042.1  glucokinase isoform 2

    See proteins identical to NP_277042.1

    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
    cd00012
    Location:76279
    Blast Score: 203
    NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily
    COG5026
    Location:17459
    Blast Score: 746
    COG5026; Hexokinase [Carbohydrate transport and metabolism]
    pfam03727
    Location:220457
    Blast Score: 906
    Hexokinase_2; Hexokinase
  3. NM_033508.1NP_277043.1  glucokinase isoform 3

    See proteins identical to NP_277043.1

    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
    cd00012
    Location:74277
    Blast Score: 208
    NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily
    COG5026
    Location:13457
    Blast Score: 749
    COG5026; Hexokinase [Carbohydrate transport and metabolism]
    pfam03727
    Location:218455
    Blast Score: 910
    Hexokinase_2; Hexokinase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000007.14 

    Range
    44144271..44189423
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000139.1 

    Range
    44069141..44114301
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018918.2 

    Range
    44187724..44232886
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)