Format

Send to:

Choose Destination

Links from PubMed

    • Showing Current items.

    GCK glucokinase [ Homo sapiens (human) ]

    Gene ID: 2645, updated on 10-Dec-2017
    Official Symbol
    GCKprovided by HGNC
    Official Full Name
    glucokinaseprovided by HGNC
    Primary source
    HGNC:HGNC:4195
    See related
    Ensembl:ENSG00000106633 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
    This gene encodes a member of the hexokinase family of proteins. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. 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. The use of multiple promoters and alternative splicing of this gene result in distinct protein isoforms that exhibit tissue-specific expression in the pancreas and liver. In the pancreas, this enzyme plays a role in glucose-stimulated insulin secretion, while in the liver, this enzyme is important in glucose uptake and conversion to glycogen. Mutations in this gene that alter enzyme activity have been associated with multiple types of diabetes and hyperinsulinemic hypoglycemia. [provided by RefSeq, Aug 2017]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    Location:
    7p13
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 7 NC_000007.14 (44143213..44189439, 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 uncharacterized LOC105375258 Neighboring gene myosin light chain 7 Neighboring gene uncharacterized LOC105375257 Neighboring gene YKT6 v-SNARE homolog Neighboring gene calcium/calmodulin dependent protein kinase II beta

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    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 association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians.
    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
    Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians.
    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 Interaction Database

    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    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 
    glucokinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    glucokinase activity TAS
    Traceable Author Statement
    more info
     
    glucose binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    NOT mannokinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    NADP metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    calcium ion import IEA
    Inferred from Electronic Annotation
    more info
     
    canonical glycolysis 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 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 
    glucose 6-phosphate metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    glucose homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    glycolytic process IBA
    Inferred from Biological aspect of Ancestor
    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 insulin secretion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of glycolytic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    regulation of glycolytic process TAS
    Traceable Author Statement
    more info
     
    regulation of insulin secretion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of potassium ion transport IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    cytosol IDA
    Inferred from Direct Assay
    more info
     
    cytosol TAS
    Traceable Author Statement
    more info
     
    mitochondrion IEA
    Inferred from Electronic Annotation
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    glucokinase
    Names
    ATP:D-hexose 6-phosphotransferase
    HK IV
    glucokinase (hexokinase 4)
    hexokinase D, pancreatic isozyme
    hexokinase type IV
    NP_000153.1
    NP_277042.1
    NP_277043.1
    XP_016867455.1

    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_008847.2 RefSeqGene

      Range
      13748..58900
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000162.4NP_000153.1  glucokinase isoform 1

      See identical proteins and their annotated locations for 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)
      AC006454, BC001890, M90299
      Consensus CDS
      CCDS5479.1
      UniProtKB/Swiss-Prot
      P35557
      UniProtKB/TrEMBL
      Q53Y25
      Related
      ENSP00000384247.3, OTTHUMP00000159306, ENST00000403799.7
      Conserved Domains (2) summary
      pfam00349
      Location:15215
      Hexokinase_1; Hexokinase
      cl27242
      Location:8458
      Hexokinase_2; Hexokinase
    2. NM_001354800.1NP_001341729.1  glucokinase isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC006454
      Conserved Domains (2) summary
      pfam00349
      Location:15215
      Hexokinase_1; Hexokinase
      cl27242
      Location:8456
      Hexokinase_2; Hexokinase
    3. NM_001354801.1NP_001341730.1  glucokinase isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC006454, M90299
      Conserved Domains (1) summary
      pfam03727
      Location:2118
      Hexokinase_2
    4. NM_001354802.1NP_001341731.1  glucokinase isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC006454
      Conserved Domains (1) summary
      pfam03727
      Location:175
      Hexokinase_2
    5. NM_001354803.1NP_001341732.1  glucokinase isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC006454, M90299
      Conserved Domains (1) summary
      pfam03727
      Location:19133
      Hexokinase_2
    6. NM_033507.2NP_277042.1  glucokinase isoform 2

      See identical proteins and their annotated locations for 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)
      AK122876, CD251038, M69051, M90299
      Consensus CDS
      CCDS5480.1
      UniProtKB/Swiss-Prot
      P35557
      Related
      ENSP00000223366.2, OTTHUMP00000159307, ENST00000345378.6
      Conserved Domains (3) summary
      COG5026
      Location:17459
      COG5026; Hexokinase [Carbohydrate transport and metabolism]
      pfam00349
      Location:17216
      Hexokinase_1; Hexokinase
      pfam03727
      Location:222456
      Hexokinase_2; Hexokinase
    7. NM_033508.2NP_277043.1  glucokinase isoform 3

      See identical proteins and their annotated locations for 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)
      AK122876, CD251038, DA640823, M69051, M90299
      Consensus CDS
      CCDS5481.1
      UniProtKB/Swiss-Prot
      P35557
      Related
      ENSP00000379142.3, OTTHUMP00000159308, ENST00000395796.7
      Conserved Domains (3) summary
      COG5026
      Location:13457
      COG5026; Hexokinase [Carbohydrate transport and metabolism]
      pfam00349
      Location:14214
      Hexokinase_1; Hexokinase
      pfam03727
      Location:220454
      Hexokinase_2; Hexokinase

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p7 Primary Assembly

      Range
      44143213..44189439 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017011966.1XP_016867455.1  glucokinase isoform X1

      Conserved Domains (2) summary
      pfam00349
      Location:15215
      Hexokinase_1; Hexokinase
      cl27242
      Location:8456
      Hexokinase_2; Hexokinase

    Alternate CHM1_1.1

    Genomic

    1. NC_018918.2 Alternate CHM1_1.1

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