HK2 hexokinase 2 [Homo sapiens (human)] - Gene

Summary

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: mouse all

Genomic context

Location:: 2p12

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
109.20190905	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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Results found that hepatocellular carcinoma (HCC) patients with increased HK-II expression in the TCGA database showed poor overall survival. These results suggest that HK-II expression might be a prognostic factor in HCC.
Title: Hexokinase-II Inhibition Synergistically Augments the Anti-tumor Efficacy of Sorafenib in Hepatocellular Carcinoma.
Study in cancer cell lines identify that K63-linked ubiquitination by HECTH9 regulates the mitochondrial localization and function of hexokinase 2 (HK2). Histological analyses show that HECTH9 expression is upregulated and correlated with disease progression in prostate cancer. Results suggest that HECTH9 is a novel regulator of HK2 and cancer metabolism.
Title: Non-proteolytic ubiquitination of Hexokinase 2 by HectH9 controls tumor metabolism and cancer stem cell expansion.
our results indicate that TLR4-dependent upregulation of glycolysis in human MoDCs involves a p38-MAPK-dependent HIF-1alpha accumulation, leading to an increased HK activity supported by enhanced HK2 expression.
Title: Toll-like Receptor 4-Induced Glycolytic Burst in Human Monocyte-Derived Dendritic Cells Results from p38-Dependent Stabilization of HIF-1α and Increased Hexokinase II Expression.
TTP acts as a negative regulator of HK2 expression and glucose metabolism in cancer cells.
Title: Tristetraprolin-mediated hexokinase 2 expression regulation contributes to glycolysis in cancer cells.
Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer.
Title: Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer.
High expression of HK2 is associated with chemoresistance of pediatric acute myeloid leukemia.
Title: Knockdown of LncRNA-UCA1 suppresses chemoresistance of pediatric AML by inhibiting glycolysis through the microRNA-125a/hexokinase 2 pathway.
results highlight a non-metabolic role of HK2 as transcriptional coactivator of Nrf2 to regulate XOR expression under conditions of proinflammatory and metabolic stresses.
Title: Hexokinase 2 and nuclear factor erythroid 2-related factor 2 transcriptionally coactivate xanthine oxidoreductase expression in stressed glioma cells.
we provided the clinical relevance that miR-202 was down-regulated in Chronic myeloid leukemia (CML) patients and patients with lower miR-202 expression displayed higher HK2 expression.
Title: Overexpression of <i>miR-202</i> resensitizes imatinib resistant chronic myeloid leukemia cells through targetting Hexokinase 2.
Regulation of glycolytic metabolism by autophagy in liver cancer involves selective autophagic degradation of hexokinase 2
Title: Regulation of glycolytic metabolism by autophagy in liver cancer involves selective autophagic degradation of HK2 (hexokinase 2).
our findings indicated that PIM2 was a novel regulator of HK2, and suggested a new strategy to treat breast cancer.
Title: PIM2-mediated phosphorylation of hexokinase 2 is critical for tumor growth and paclitaxel resistance in breast cancer.

Submit: New GeneRIF Correction See all GeneRIFs (125)

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

NHGRI GWAS Catalog

Description
Bivariate genome-wide association analyses of femoral neck bone geometry and appendicular lean mass. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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 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
Carbohydrate digestion and absorption, organism-specific biosystem (from KEGG)
Carbohydrate digestion and absorption, organism-specific biosystemDietary carbohydrate in humans and omnivorous animals is a major nutrient. The carbohydrates that we ingest vary from the lactose in milk to complex carbohydrates. These carbohydrates are digested t...
Carbohydrate digestion and absorption, conserved biosystem (from KEGG)
Carbohydrate digestion and absorption, conserved biosystemDietary carbohydrate in humans and omnivorous animals is a major nutrient. The carbohydrates that we ingest vary from the lactose in milk to complex carbohydrates. These carbohydrates are digested t...
Carbon metabolism, organism-specific biosystem (from KEGG)
Carbon metabolism, organism-specific biosystemCarbon metabolism is the most basic aspect of life. This map presents an overall view of central carbon metabolism, where the number of carbons is shown for each compound denoted by a circle, excludi...
Carbon metabolism, conserved biosystem (from KEGG)
Carbon metabolism, conserved biosystemCarbon metabolism is the most basic aspect of life. This map presents an overall view of central carbon metabolism, where the number of carbons is shown for each compound denoted by a circle, excludi...
Central carbon metabolism in cancer, organism-specific biosystem (from KEGG)
Central carbon metabolism in cancer, organism-specific biosystemMalignant transformation of cells requires specific adaptations of cellular metabolism to support growth and survival. In the early twentieth century, Otto Warburg established that there are fundamen...
Central carbon metabolism in cancer, conserved biosystem (from KEGG)
Central carbon metabolism in cancer, conserved biosystemMalignant transformation of cells requires specific adaptations of cellular metabolism to support growth and survival. In the early twentieth century, Otto Warburg established that there are fundamen...
Fructose and mannose metabolism, organism-specific biosystem (from KEGG)
Fructose and mannose metabolism, organism-specific biosystem
Fructose and mannose metabolism
Fructose and mannose metabolism, conserved biosystem (from KEGG)
Fructose and mannose metabolism, conserved biosystem
Fructose and mannose metabolism
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 metabolism, organism-specific biosystem (from REACTOME)
Glucose metabolism, organism-specific biosystemGlucose is the major form in which dietary sugars are made available to cells of the human body. Its breakdown is a major source of energy for all cells, and is essential for the brain and red blood ...
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, organism-specific biosystem (from REACTOME)
Glycolysis, organism-specific biosystemThe reactions of glycolysis (e.g., van Wijk and van Solinge 2005) convert glucose 6-phosphate to pyruvate. The entire process is cytosolic. Glucose 6-phosphate is reversibly isomerized to form fructo...
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 biosystemGlycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO? + H+. The free energy released in this process is used to form the ATP and NADH. Gluconeogenesis is a metab...
HIF-1 signaling pathway, organism-specific biosystem (from KEGG)
HIF-1 signaling pathway, organism-specific biosystemHypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a c...
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 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...
Metabolic pathways, organism-specific biosystem (from KEGG)
Metabolic pathways, organism-specific biosystem
Metabolic pathways
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...
Neomycin, kanamycin and gentamicin biosynthesis, organism-specific biosystem (from KEGG)
Neomycin, kanamycin and gentamicin biosynthesis, organism-specific biosystem
Neomycin, kanamycin and gentamicin biosynthesis
Neomycin, kanamycin and gentamicin biosynthesis, conserved biosystem (from KEGG)
Neomycin, kanamycin and gentamicin biosynthesis, conserved biosystem
Neomycin, kanamycin and gentamicin biosynthesis
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; Other carbohydrate metabolism
Nucleotide sugar biosynthesis, glucose => UDP-glucose, conserved biosystem (from KEGG)
Nucleotide sugar biosynthesis, glucose => UDP-glucose, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Other carbohydrate metabolism
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...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D2S2601 (e-PCR)
- UniSTS:10815

SHGC-57291 (e-PCR)
- UniSTS:43104

GDB:451610 (e-PCR)
- UniSTS:157326

RH65294 (e-PCR)
- UniSTS:85667

GDB:271353 (e-PCR)
- UniSTS:156359

GDB:631172 (e-PCR)
- UniSTS:158419

RH120627 (e-PCR)
- UniSTS:132568

Homology

Homologs of the HK2 gene: The HK2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, C.elegans, rice, and frog.
Orthologs from Annotation Pipeline: 160 organisms have orthologs with human gene HK2
Orthologs

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	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
cell	IEA Inferred from Electronic Annotation more info
cytosol	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	TAS Traceable Author Statement more info
membrane	HDA more info	PubMed
mitochondrial outer membrane	IDA Inferred from Direct Assay more info	PubMed
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

EC 2.7.1.1

NP_001358454.1

EC 2.7.1.1

XP_005264337.1

EC 2.7.1.1

XP_011531109.1

EC 2.7.1.1

XP_016859434.1

EC 2.7.1.1

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)

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, ENST00000290573.6

Conserved Domains (3) summary

PTZ00107
Location:12 → 460

PTZ00107; hexokinase; Provisional

pfam00349
Location:21 → 219

Hexokinase_1; Hexokinase

pfam03727
Location:673 → 907

Hexokinase_2; Hexokinase
NM_001371525.1 → NP_001358454.1 hexokinase-2 isoform 2

Status: REVIEWED

Source sequence(s)

AC019069, AC104135

Related

ENSP00000387140.1, ENST00000409174.1

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20190905

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p13 Primary Assembly

Range

74834126..74893359

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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