HK2

From Wikipedia, the free encyclopedia

Hexokinase 2

PDB rendering based on 2nzt.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2NZT

Identifiers

Symbols

HK2; HKII; HXK2

External IDs

OMIM: 601125 MGI: 1315197 HomoloGene: 37273 ChEMBL: 2640 GeneCards: HK2 Gene

EC number

2.7.1.1

Gene Ontology
Molecular function	• glucokinase activity • hexokinase activity • ATP binding • glucose binding • fructokinase activity • mannokinase activity
Cellular component	• mitochondrial outer membrane • cytosol
Biological process	• cellular glucose homeostasis • carbohydrate metabolic process • glycolysis • lactation • apoptotic mitochondrial changes • hexose transport • glucose transport • small molecule metabolic process • regulation of glucose import • glucose 6-phosphate metabolic process • transmembrane transport
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 2:
75.06 – 75.12 Mb

Chr 6:
82.73 – 82.77 Mb

PubMed search

Hexokinase 2 also known as HK2 is an enzyme which in humans is encoded by the HK2 gene.^[1]

Function

Hexokinases phosphorylate glucose to produce glucose 6-phosphate, thus committing glucose to the glycolytic pathway. 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.^[2]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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Glycolysis and Gluconeogenesis edit

↑ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

References

↑ Lehto M, Xiang K, Stoffel M, Espinosa R, Groop LC, Le Beau MM, Bell GI (December 1993). "Human hexokinase II: localization of the polymorphic gene to chromosome 2". Diabetologia 36 (12): 1299–302. doi:10.1007/BF00400809. PMID 8307259.
↑ "Entrez Gene: HK2 hexokinase 2".

Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
Mamede M, Higashi T, Kitaichi M, et al. (2005). "18FFDG Uptake and PCNA, Glut-1, and Hexokinase-II Expressions in Cancers and Inflammatory Lesions of the Lung". Neoplasia 7 (4): 369–79. doi:10.1593/neo.04577. PMC 1501150. PMID 15967114.
Machida K, Ohta Y, Osada H (2006). "Suppression of apoptosis by cyclophilin D via stabilization of hexokinase II mitochondrial binding in cancer cells". J. Biol. Chem. 281 (20): 14314–20. doi:10.1074/jbc.M513297200. PMID 16551620.
Ahn KJ, Kim J, Yun M, et al. (2009). "Enzymatic properties of the N- and C-terminal halves of human hexokinase II". BMB Rep 42 (6): 350–5. doi:10.5483/BMBRep.2009.42.6.350. PMID 19558793.
Printz RL, Osawa H, Ardehali H, et al. (1997). "Hexokinase II gene: structure, regulation and promoter organization". Biochem. Soc. Trans. 25 (1): 107–12. PMID 9056853.
Peng Q, Zhou J, Zhou Q, et al. (2009). "Silencing hexokinase II gene sensitizes human colon cancer cells to 5-fluorouracil". Hepatogastroenterology 56 (90): 355–60. PMID 19579598.
Shulga N, Wilson-Smith R, Pastorino JG (2009). "Hexokinase II Detachment from the Mitochondria Potentiates Cisplatin Induced Cytotoxicity through a Caspase-2 dependent Mechanism". Cell Cycle 8 (20): 3355–64. doi:10.4161/cc.8.20.9853. PMC 2829766. PMID 19770592.
He HC, Bi XC, Zheng ZW, et al. (2009). "Real-time quantitative RT-PCR assessment of PIM-1 and hK2 mRNA expression in benign prostate hyperplasia and prostate cancer". Med. Oncol. 26 (3): 303–8. doi:10.1007/s12032-008-9120-9. PMID 19003546.
Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
Sakai N, Terami H, Suzuki S, et al. (2008). "Identification of NR5A1 (SF-1/AD4BP) gene expression modulators by large-scale gain and loss of function studies". J. Endocrinol. 198 (3): 489–97. doi:10.1677/JOE-08-0027. PMID 18579725.
Foster LJ, Rudich A, Talior I, et al. (2006). "Insulin-dependent interactions of proteins with GLUT4 revealed through stable isotope labeling by amino acids in cell culture (SILAC)". J. Proteome Res. 5 (1): 64–75. doi:10.1021/pr0502626. PMID 16396496.
Arzoine L, Zilberberg N, Ben-Romano R, Shoshan-Barmatz V (2009). "Voltage-dependent anion channel 1-based peptides interact with hexokinase to prevent its anti-apoptotic activity". J. Biol. Chem. 284 (6): 3946–55. doi:10.1074/jbc.M803614200. PMID 19049977.
Gimenez-Cassina A, Lim F, Cerrato T, et al. (2009). "Mitochondrial hexokinase II promotes neuronal survival and acts downstream of glycogen synthase kinase-3". J. Biol. Chem. 284 (5): 3001–11. doi:10.1074/jbc.M808698200. PMID 19033437.
Peng Q, Zhou Q, Zhou J, et al. (2008). "Stable RNA interference of hexokinase II gene inhibits human colon cancer LoVo cell growth in vitro and in vivo". Cancer Biol. Ther. 7 (7): 1128–35. doi:10.4161/cbt.7.7.6199. PMID 18535403.
Rodríguez-Enríquez S, Marín-Hernández A, Gallardo-Pérez JC, Moreno-Sánchez R (2009). "Kinetics of transport and phosphorylation of glucose in cancer cells". J. Cell. Physiol. 221 (3): 552–9. doi:10.1002/jcp.21885. PMID 19681047.
Kim JW, Gao P, Liu YC, et al. (2007). "Hypoxia-Inducible Factor 1 and Dysregulated c-Myc Cooperatively Induce Vascular Endothelial Growth Factor and Metabolic Switches Hexokinase 2 and Pyruvate Dehydrogenase Kinase 1". Mol. Cell. Biol. 27 (21): 7381–93. doi:10.1128/MCB.00440-07. PMC 2169056. PMID 17785433.
Fonteyne P, Casneuf V, Pauwels P, et al. (2009). "Expression of hexokinases and glucose transporters in treated and untreated oesophageal adenocarcinoma". Histol. Histopathol. 24 (8): 971–7. PMID 19554504.
Palmieri D, Fitzgerald D, Shreeve SM, et al. (2009). "Analyses of Resected Human Brain Metastases of Breast Cancer Reveal the Association between Up-regulation of Hexokinase 2 and Poor Prognosis". Mol. Cancer Res. 7 (9): 1438–45. doi:10.1158/1541-7786.MCR-09-0234. PMC 2746883. PMID 19723875.
Peng QP, Zhou JM, Zhou Q, et al. (2008). "Downregulation of the hexokinase II gene sensitizes human colon cancer cells to 5-fluorouracil". Chemotherapy 54 (5): 357–63. doi:10.1159/000153655. PMID 18772588.
Paudyal B, Oriuchi N, Paudyal P, et al. (2008). "Expression of glucose transporters and hexokinase II in cholangiocellular carcinoma compared using [18F]-2-fluro-2-deoxy-D-glucose positron emission tomography". Cancer Sci. 99 (2): 260–6. doi:10.1111/j.1349-7006.2007.00683.x. PMID 18271924.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Metabolism: carbohydrate metabolism: glycolysis/gluconeogenesis enzymes

Glycolysis

Gluconeogenesis only

to oxaloacetate:	Pyruvate carboxylase Phosphoenolpyruvate carboxykinase

from lactate (Cori cycle):	Lactate dehydrogenase

from alanine (Alanine cycle):	Alanine transaminase

from glycerol:	Glycerol kinase Glycerol dehydrogenase

Regulatory

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

Mitochondrial proteins

Outer membrane

fatty acid degradation	Carnitine palmitoyltransferase I Long-chain-fatty-acid—CoA ligase

tryptophan metabolism	Kynureninase

monoamine neurotransmitter metabolism	Monoamine oxidase

Intermembrane space

Inner membrane

oxidative phosphorylation	Coenzyme Q – cytochrome c reductase Cytochrome c NADH dehydrogenase Succinate dehydrogenase

pyrimidine metabolism	Dihydroorotate dehydrogenase

mitochondrial shuttle	Malate-aspartate shuttle Glycerol phosphate shuttle

other	Glutamate aspartate transporter Glycerol-3-phosphate dehydrogenase ATP synthase Carnitine palmitoyltransferase II Uncoupling protein

Matrix

citric acid cycle	Citrate synthase Aconitase Isocitrate dehydrogenase Oxoglutarate dehydrogenase complex Succinyl coenzyme A synthetase Fumarase Malate dehydrogenase

anaplerotic reactions	Aspartate transaminase Glutamate dehydrogenase Pyruvate dehydrogenase complex

urea cycle	Carbamoyl phosphate synthetase I Ornithine transcarbamylase N-Acetylglutamate synthase

alcohol metabolism	ALDH2

PMPCB

Other/to be sorted

steroidogenesis	Cholesterol side-chain cleavage enzyme Steroid 11-beta-hydroxylase Aldosterone synthase Frataxin

Mitochondrial membrane transport protein Mitochondrial permeability transition pore Mitochondrial carrier

Mitochondrial DNA

Complex I	MT-ND1 MT-ND2 MT-ND3 MT-ND4 MT-ND4L MT-ND5 MT-ND6

Complex III	MT-CYB

Complex IV	MT-CO1 MT-CO2 MT-CO3

ATP synthase	MT-ATP6 MT-ATP8

tRNA	MT-TA MT-TC MT-TD MT-TE MT-TF MT-TG MT-TH MT-TI MT-TK MT-TL1 MT-TL2 MT-TM MT-TN MT-TP MT-TQ MT-TR MT-TS1 MT-TS2 MT-TT MT-TV MT-TW MT-TY

see also mitochondrial diseases
B strc: edmb (perx), skel (ctrs), epit, cili, mito, nucl (chro)

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HK2

Function

Interactive pathway map

References

Further reading