HK3
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Hexokinase 3 also known as HK3 is an
allosteric enzyme is inhibited by its product glucose-6-phosphate. [provided by RefSeq, Apr 2009][7]
Structure
HK3 is one of four highly homologous hexokinase isoforms in mammalian cells.
Function
As a cytoplasmic isoform of hexokinase and a member of the sugar kinase family, HK3
attenuated by intracellular ATP.[9] Uniquely, HK3 can be inhibited by glucose at high concentrations.[14][17] HK3 is also less sensitive to G6P inhibition.[9][14]
Despite its lack of mitochondrial association, HK3 also functions to protect the cell against
hypoxia is known to induce HK3 expression through a HIF-dependent pathway. The inducible expression of HK3 indicates its adaptive role in metabolic responses to changes in the cellular environment.[10]
In particular, HK3 is ubiquitously expressed in tissues, albeit at relatively low abundance.myeloid cells, particularly granulocytes.[18]
Clinical significance
HK3 is found to be overexpressed in
RARA and CEBPA.[15][18] Regarding acute lymphoblastic leukemia (ALL), functional enrichment analysis revealed HK3 as a key gene and suggests that HK3 shares antiapoptotic function with HK1 and HK2.[16]
Interactions
The HK3 promoter is known to interact with
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
Glycolysis and Gluconeogenesis edit
- ^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000160883 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025877 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8812439.
- PMID 8941369.
- ^ "Entrez Gene: HK3 hexokinase 3 (white cell)".
- S2CID 23521290.
- ^ PMID 23068103.
- ^ PMID 21072205.
- ^ S2CID 40877603.
- ^ PMID 9493266.
- ^ S2CID 1851264.
- ^ PMID 9468341.
- ^ PMID 22498738.
- ^ PMID 25172542.
- ^ PMID 9540816.
- ^ PMID 24584857.
- S2CID 25298962.
Further reading
- Reid S, Masters C (1985). "On the developmental properties and tissue interactions of hexokinase". Mechanisms of Ageing and Development. 31 (2): 197–212. S2CID 40877603.
- Rijksen G, Staal GE, Beks PJ, Streefkerk M, Akkerman JW (December 1982). "Compartmentation of hexokinase in human blood cells. Characterization of soluble and particulate enzymes". Biochimica et Biophysica Acta (BBA) - General Subjects. 719 (3): 431–7. S2CID 24438788.
- Adkins JN, Varnum SM, Auberry KJ, Moore RJ, Angell NH, Smith RD, Springer DL, Pounds JG (December 2002). "Toward a human blood serum proteome: analysis by multidimensional separation coupled with mass spectrometry". Molecular & Cellular Proteomics. 1 (12): 947–55. PMID 12543931.
- Palma F, Agostini D, Mason P, Dachà M, Piccoli G, Biagiarelli B, Fiorani M, Stocchi V (February 1996). "Purification and characterization of the carboxyl-domain of human hexokinase type III expressed as fusion protein". Molecular and Cellular Biochemistry. 155 (1): 23–9. S2CID 6748596.
- Povey S, Corney G, Harris H (May 1975). "Genetically determined polymorphism of a form of hexokinase, HK III, found in human leucocytes". Annals of Human Genetics. 38 (4): 407–15. S2CID 26343683.
- Anderson NL, Anderson NG (November 2002). "The human plasma proteome: history, character, and diagnostic prospects". Molecular & Cellular Proteomics. 1 (11): 845–67. PMID 12488461.
- He C, Kraft P, Chen C, Buring JE, Paré G, Hankinson SE, Chanock SJ, Ridker PM, Hunter DJ, Chasman DI (June 2009). "Genome-wide association studies identify loci associated with age at menarche and age at natural menopause". Nature Genetics. 41 (6): 724–8. PMID 19448621.
- Fonteyne P, Casneuf V, Pauwels P, Van Damme N, Peeters M, Dierckx R, Van de Wiele C (August 2009). "Expression of hexokinases and glucose transporters in treated and untreated oesophageal adenocarcinoma". Histology and Histopathology. 24 (8): 971–7. PMID 19554504.
- Sui D, Wilson JE (October 2000). "Interaction of insulin-like growth factor binding protein-4, Miz-1, leptin, lipocalin-type prostaglandin D synthase, and granulin precursor with the N-terminal half of type III hexokinase". Archives of Biochemistry and Biophysics. 382 (2): 262–74. PMID 11068878.
- Lowes W, Walker M, Alberti KG, Agius L (Jan 1998). "Hexokinase isoenzymes in normal and cirrhotic human liver: suppression of glucokinase in cirrhosis". Biochimica et Biophysica Acta (BBA) - General Subjects. 1379 (1): 134–42. PMID 9468341.
- Furuta H, Nishi S, Le Beau MM, Fernald AA, Yano H, Bell GI (August 1996). "Sequence of human hexokinase III cDNA and assignment of the human hexokinase III gene (HK3) to chromosome band 5q35.2 by fluorescence in situ hybridization". Genomics. 36 (1): 206–9. PMID 8812439.
External links
- Overview of all the structural information available in the PDB for UniProt: P52790 (Hexokinase-3) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.