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HK2 hexokinase 2 [ Homo sapiens (human) ]

Gene ID: 3099, updated on 3-Jan-2021

Summary

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Official Symbol
HK2provided by HGNC
Official Full Name
hexokinase 2provided by HGNC
Primary source
HGNC:HGNC:4923
See related
Ensembl:ENSG00000159399 MIM:601125
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
HKII; HXK2
Summary
Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes hexokinase 2, the predominant form found in skeletal muscle. It localizes to the outer membrane of mitochondria. Expression of this gene is insulin-responsive, and studies in rat suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells. [provided by RefSeq, Apr 2009]
Expression
Broad expression in fat (RPKM 34.4), colon (RPKM 24.2) and 19 other tissues See more
Orthologs
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Genomic context

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See HK2 in Genome Data Viewer
Location:
2p12
Exon count:
19
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (74834126..74893359)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (75059782..75120481)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105374808 Neighboring gene uncharacterized LOC102724497 Neighboring gene uncharacterized LOC102724482 Neighboring gene ribosomal protein S28 pseudogene 5 Neighboring gene long intergenic non-protein coding RNA 1291 Neighboring gene uncharacterized LOC105374809 Neighboring gene long intergenic non-protein coding RNA 1293

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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 Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Glycolytic enzyme hexokinase II is a putative therapeutic target in B-cell malignant lymphoma. Nakajima K, et al. Exp Hematol, 2019 Oct. PMID 31560931
  2. miR‑185 regulates the growth of osteosarcoma cells via targeting Hexokinase 2. Liu C, et al. Mol Med Rep, 2019 Sep. PMID 31524259, Free PMC Article
  3. Hexokinase II inhibition by 3-bromopyruvate sensitizes myeloid leukemic cells K-562 to anti-leukemic drug, daunorubicin. Rai Y, et al. Biosci Rep, 2019 Sep 30. PMID 31506393, Free PMC Article
  4. Hexokinase2 controls angiogenesis in melanoma by promoting aerobic glycolysis and activating the p38-MAPK signaling. Lu J, et al. J Cell Biochem, 2019 Dec. PMID 31270843
  5. Hexokinase-II Inhibition Synergistically Augments the Anti-tumor Efficacy of Sorafenib in Hepatocellular Carcinoma. Yoo JJ, et al. Int J Mol Sci, 2019 Mar 14. PMID 30875800, Free PMC Article

See all (212) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. miR-206 regulates non-small-cell lung cancer cell aerobic glycolysis by targeting hexokinase 2.
    Title: miR-206 regulates non-small-cell lung cancer cell aerobic glycolysis by targeting hexokinase 2.
  2. Quantitative Proteomics Analysis Revealed the Potential Role of lncRNA Ftx in Promoting Gastric Cancer Progression.
    Title: Quantitative Proteomics Analysis Revealed the Potential Role of lncRNA Ftx in Promoting Gastric Cancer Progression.
  3. CSN5 upregulates glycolysis to promote hepatocellular carcinoma metastasis via stabilizing the HK2 protein.
    Title: CSN5 upregulates glycolysis to promote hepatocellular carcinoma metastasis via stabilizing the HK2 protein.
  4. Hexokinase2 controls angiogenesis in melanoma by promoting aerobic glycolysis and activating the p38-MAPK signaling.
    Title: Hexokinase2 controls angiogenesis in melanoma by promoting aerobic glycolysis and activating the p38-MAPK signaling.
  5. Resibufogenin suppresses tumor growth and Warburg effect through regulating miR-143-3p/HK2 axis in breast cancer.
    Title: Resibufogenin suppresses tumor growth and Warburg effect through regulating miR-143-3p/HK2 axis in breast cancer.
  6. Hexokinase II inhibition by 3-bromopyruvate sensitizes myeloid leukemic cells K-562 to anti-leukemic drug, daunorubicin.
    Title: Hexokinase II inhibition by 3-bromopyruvate sensitizes myeloid leukemic cells K-562 to anti-leukemic drug, daunorubicin.
  7. The current study suggested that HK2 gene polymorphism may contribute to the genetic susceptibility to NTG.
    Title: Association of HK2 and NCK2 with normal-tension glaucoma in a population from the Republic of Korea.
  8. AKT2 and HK2 increase colon cancer cell migration and invasion. NF-kB, HIF1A, MMP2, and MMP9 were the downstream molecular targets of HK2.
    Title: AKT2 phosphorylation of hexokinase 2 at T473 promotes tumorigenesis and metastasis in colon cancer cells via NF-κB, HIF1α, MMP2, and MMP9 upregulation.
  9. Elevated Hexokinase II Expression Confers Acquired Resistance to 4-Hydroxytamoxifen in Breast Cancer.
    Title: Elevated Hexokinase II Expression Confers Acquired Resistance to 4-Hydroxytamoxifen in Breast Cancer Cells.
  10. zinc and p53 disrupt mitochondrial binding of HK2 in prostate cancer cells by phosphorylating VDAC1
    Title: Zinc and p53 disrupt mitochondrial binding of HK2 by phosphorylating VDAC1.
Submit: New GeneRIF Correction See all GeneRIFs (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

Associated conditions

Description Tests
Bivariate genome-wide association analyses of femoral neck bone geometry and appendicular lean mass.
GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Rev rev HIV-1 Rev interacting protein, hexokinase 2 (HK2), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells PubMed
Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of hexokinase 2 (HK2) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • DKFZp686M1669

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
  
fructokinase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
fructokinase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
glucokinase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
glucokinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
glucose binding IEA
Inferred from Electronic Annotation
more info
  
hexokinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
mannokinase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
apoptotic mitochondrial changes IDA
Inferred from Direct Assay
more info
 PubMed 
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
 PubMed 
cellular response to leukemia inhibitory factor IEA
Inferred from Electronic Annotation
more info
  
establishment of protein localization to mitochondrion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
fructose 6-phosphate metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
glucose 6-phosphate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
glucose 6-phosphate metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
glycolytic process IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
glycolytic process TAS
Traceable Author Statement
more info
 PubMed 
lactation IEA
Inferred from Electronic Annotation
more info
  
maintenance of protein location in mitochondrion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
negative regulation of mitochondrial membrane permeability IEA
Inferred from Electronic Annotation
more info
  
negative regulation of reactive oxygen species metabolic process IEA
Inferred from Electronic Annotation
more info
  
positive regulation of angiogenesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
regulation of glucose import IEA
Inferred from Electronic Annotation
more info
  
response to hypoxia IEA
Inferred from Electronic Annotation
more info
  
response to ischemia IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
centrosome IDA
Inferred from Direct Assay
more info
  
cytosol IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
cytosol IDA
Inferred from Direct Assay
more info
  
cytosol TAS
Traceable Author Statement
more info
  
intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
membrane HDA PubMed 
mitochondrial outer membrane IDA
Inferred from Direct Assay
more info
 PubMed 
mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
mitochondrion IDA
Inferred from Direct Assay
more info
  
plasma membrane IEA
Inferred from Electronic Annotation
more info
  
sarcoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
hexokinase-2
Names
hexokinase type II
hexokinase-2, muscle
hexokinase-B
muscle form hexokinase
NP_000180.2
NP_001358454.1
XP_005264337.1
XP_011531109.1
XP_016859434.1

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.

mRNA and Protein(s)

  1. NM_000189.5 → NP_000180.2  hexokinase-2 isoform 1

    See identical proteins and their annotated locations for NP_000180.2

    Status: REVIEWED

    Source sequence(s)
    AC019069, AC104135
    Consensus CDS
    CCDS1956.1
    UniProtKB/Swiss-Prot
    P52789
    Related
    ENSP00000290573.2, ENST00000290573.7
    Conserved Domains (3) summary
    PTZ00107
    Location:12 → 460
    PTZ00107; hexokinase; Provisional
    pfam00349
    Location:471 → 667
    Hexokinase_1
    pfam03727
    Location:673 → 907
    Hexokinase_2

  2. NM_001371525.1 → NP_001358454.1  hexokinase-2 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC019069, AC104135
    Related
    ENSP00000387140.1, ENST00000409174.1
    Conserved Domains (3) summary
    PTZ00107
    Location:1 → 432
    PTZ00107; hexokinase; Provisional
    pfam00349
    Location:443 → 639
    Hexokinase_1
    pfam03727
    Location:645 → 879
    Hexokinase_2

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

    Range
    74834126..74893359
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005264280.2 → XP_005264337.1  hexokinase-2 isoform X1

    Conserved Domains (3) summary
    PTZ00107
    Location:12 → 460
    PTZ00107; hexokinase; Provisional
    pfam00349
    Location:21 → 219
    Hexokinase_1; Hexokinase
    pfam03727
    Location:694 → 928
    Hexokinase_2; Hexokinase

  2. XM_011532807.2 → XP_011531109.1  hexokinase-2 isoform X2

    Conserved Domains (3) summary
    PTZ00107
    Location:430 → 897
    PTZ00107; hexokinase; Provisional
    pfam00349
    Location:439 → 656
    Hexokinase_1; Hexokinase
    pfam03727
    Location:662 → 896
    Hexokinase_2; Hexokinase

  3. XM_017003945.2 → XP_016859434.1  hexokinase-2 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P52789.2 GenPept UniProtKB/Swiss-Prot:P52789

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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