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; AllianceGenome:HGNC:4923
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
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Genomic context

Location:: 2p12

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (74834127..74893359)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (74842983..74902233)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (75061254..75120486)

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?

A gain of function mutation in AKT1 increases hexokinase 2 and diminishes oxidative stress in meningioma.
Title: A gain of function mutation in AKT1 increases hexokinase 2 and diminishes oxidative stress in meningioma.
The knockdown of lncRNA DLGAP1-AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR-451a/HK2 axis.
Title: The knockdown of lncRNA DLGAP1-AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR-451a/HK2 axis.
PDLIM1 interacts with HK2 to promote gastric cancer progression through enhancing the Warburg effect via Wnt/beta-catenin signaling.
Title: PDLIM1 interacts with HK2 to promote gastric cancer progression through enhancing the Warburg effect via Wnt/β-catenin signaling.
[Expression and Prognostic Impact of HK2 in Bone Marrow of Patients with Newly Diagnosed Acute Myeloid Leukemia].
Title: [Expression and Prognostic Impact of HK2 in Bone Marrow of Patients with Newly Diagnosed Acute Myeloid Leukemia].
LncRNA-SNHG1 promotes paclitaxel resistance of gastric cancer cells through modulating the miR-216b-5p-hexokianse 2 axis.
Title: LncRNA-SNHG1 promotes paclitaxel resistance of gastric cancer cells through modulating the miR-216b-5p-hexokianse 2 axis.
microRNA-143 interferes the EGFR-stimulated glucose metabolism to re-sensitize 5-FU resistant colon cancer cells via targeting hexokinase 2.
Title: microRNA-143 interferes the EGFR-stimulated glucose metabolism to re-sensitize 5-FU resistant colon cancer cells via targeting hexokinase 2.
MCL1 regulates AML cells metabolism via direct interaction with HK2. Metabolic signature at onset predicts overall survival in AMLs' patients.
Title: MCL1 regulates AML cells metabolism via direct interaction with HK2. Metabolic signature at onset predicts overall survival in AMLs' patients.
Hexokinase 2 confers radio-resistance in hepatocellular carcinoma by promoting autophagy-dependent degradation of AIMP2.
Title: Hexokinase 2 confers radio-resistance in hepatocellular carcinoma by promoting autophagy-dependent degradation of AIMP2.
Glycolytic enzyme HK2 promotes PD-L1 expression and breast cancer cell immune evasion.
Title: Glycolytic enzyme HK2 promotes PD-L1 expression and breast cancer cell immune evasion.
Hsa_circ_0000591 drives osteosarcoma glycolysis and progression by sequestering miR-194-5p and elevating HK2 expression.
Title: Hsa_circ_0000591 drives osteosarcoma glycolysis and progression by sequestering miR-194-5p and elevating HK2 expression.

Submit: New GeneRIF Correction See all GeneRIFs (210)

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

EBI GWAS Catalog

Description
Bivariate genome-wide association analyses of femoral neck bone geometry and appendicular lean mass. EBI GWAS Catalog EBI GWAS 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

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables fructokinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables fructokinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables glucokinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glucokinase activity	IDA Inferred from Direct Assay more info	PubMed
enables glucokinase activity	TAS Traceable Author Statement more info
enables glucose binding	IEA Inferred from Electronic Annotation more info
enables hexokinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within apoptotic mitochondrial changes	IDA Inferred from Direct Assay more info	PubMed
involved_in canonical glycolysis	TAS Traceable Author Statement more info
involved_in carbohydrate phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to leukemia inhibitory factor	IEA Inferred from Electronic Annotation more info
involved_in establishment of protein localization to mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in fructose 6-phosphate metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucose 6-phosphate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glucose 6-phosphate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glucose metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glycolytic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glycolytic process	TAS Traceable Author Statement more info	PubMed
involved_in intracellular glucose homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in lactation	IEA Inferred from Electronic Annotation more info
involved_in maintenance of protein location in mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of mitochondrial membrane permeability	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of reactive oxygen species metabolic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of glucose import	IEA Inferred from Electronic Annotation more info
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to ischemia	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in centrosome	IDA Inferred from Direct Assay more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in membrane	HDA more info	PubMed
located_in mitochondrial outer membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in 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

XP_047300040.1

EC 2.7.1.1

XP_047300041.1

EC 2.7.1.1

XP_054197615.1

EC 2.7.1.1

XP_054197616.1

EC 2.7.1.1

XP_054197617.1

EC 2.7.1.1

XP_054197618.1

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

D6W5J2, P52789, Q8WU87, Q9UN82

UniProtKB/TrEMBL

A8K2U2

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

Status: REVIEWED

Source sequence(s)

AC019069, AC104135

Consensus CDS

CCDS92787.1

UniProtKB/TrEMBL

E9PB90, Q68E10

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: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

74834127..74893359

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005264280.3 → XP_005264337.1 hexokinase-2 isoform X1

UniProtKB/TrEMBL

A8K2U2

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_011532807.3 → XP_011531109.1 hexokinase-2 isoform X3

UniProtKB/TrEMBL

A8K2U2

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_017003945.3 → XP_016859434.1 hexokinase-2 isoform X4

UniProtKB/TrEMBL

A8K2U2
XM_047444084.1 → XP_047300040.1 hexokinase-2 isoform X2
XM_047444085.1 → XP_047300041.1 hexokinase-2 isoform X2