Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

2.7.1.1

Official Name

hexokinase

Name from literature

hexokinase

Pathway from literature

glycolysis

Pathway from KEGG

Carbohydrate Metabolism; Starch and sucrose metabolism; map00500

Carbohydrate Metabolism; Aminosugars metabolism; map00530

Carbohydrate Metabolism; Fructose and mannose metabolism; map00051

Carbohydrate Metabolism; Glycolysis / Gluconeogenesis; map00010

Carbohydrate Metabolism; Galactose metabolism; map00052

Biosynthesis of Secondary Metabolites; Streptomycin biosynthesis; map00521

Organisms

Human (9606)

Genome localization

5q35.2[3101 ], 2p13[3099 ], 10q22[3098 ],

Comments

D-Glucose, D-mannose, D-fructose, sorbitol and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase.

Rate-limiting Description

"Of glycolytic enzymes, the activity of hexokinase, known as a rate limiting enzyme in glycolysis, is amazingly high in malignant tumor cells." (10946615)

"Since hexokinase is the first rate limiting enzyme in the glycolytic pathway, elevated levels of Type II like hexokinase in tumors are of great significance in this context." (9199203)

"Gene array analysis revealed that both hexokinase 1 as the rate-limiting enzyme for 18F-FDG trapping and pancreas-specific glucose transporter 2 were significantly downregulated whereas thymidine kinase 1, responsible for 18F-FLT trapping, was significantly upregulated in the tumor cell lines, compared with normal pancreatic duct cells and pancreatic tumor tissue." (18632830)

Regulatory Information

Upstream transcription factor

7709;4609;6720;3091

Regulatory type

Detail

key enzyme;

"We analyzed the expressions of hexokinase II (HK II), a key enzyme in glycolysis, and VEGF in hepatocellular carcinoma (HCC) and metastatic liver cancer in relation to tumor vascularity, and the participation of hypoxia-inducible factor-1 (HIF-1) was studied. " (14672622)

regulatory enzyme;

"Recent studies have shown that mutations in human beta-cell glucokinase that impair the activity of this key regulatory enzyme of glycolysis can cause early-onset non-insulin-dependent diabetes mellitus (NIDDM). " (8194664)

transcriptional factor;SREBP-1c(6720)

"SRE binding protein-1c is involved in the effect of insulin on HKII gene transcription." (14747281)

transcriptional factor;"HIF-1(3091),c-myc(4609)"

"HIF-1 cooperates with dysregulated c-Myc to promote glycolysis by induction of hexokinase 2 and pyruvate dehydrogenase kinase 1." (17785433)

phosphorylation;

P52789

phosphorylation;

P52790

phosphorylation;

P19367:from_uniprot:27_Phosphotyrosine

phosphorylation;

P52789:from_uniprot:461_Phosphotyrosine

transcriptional factor;ZBTB17(7709)

"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." (11068878)

transcriptional factor;ZBTB17(7709)

"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." (11068878)

Gene ontology

Gene ontology

GO:0016020 (C) membrane [P52790 ];
GO:0004396 (F) hexokinase activity [P52789, Q2TB90, P52790, Q16779, P19367, P78542 ];
GO:0006096 (P) glycolysis [P52789, Q2TB90, P52790, P19367 ];
GO:0005829 (C) cytosol [P52789, P52790, P19367 ];
GO:0005741 (C) mitochondrial outer membrane [P52789, P19367 ];
GO:0005524 (F) ATP binding [P52789, Q2TB90, P52790, P19367 ];

Tissue expression

Tissue From HPRD

Kidney [00809 ];
Spermatozoa [00809 ];
Granulocyte [00806 ];
Lung [00806 ];
Testis [00809 ];
Skeletal muscle [03080 ];
Liver [00809, 00806 ];
Placenta [00809 ];
Red blood cell [00809, 00806 ];
Lymphocyte [00806 ];
Reticulocyte [00809 ];
Spleen [00806 ];

Tissue specificity

Isoform 2 is erythrocyte specific;
isoform 3 and isoform 4 are testis-specific [P19367 ];

Predominant hexokinase isozyme expressed in insulin-responsive tissues such as skeletal muscle [P52789 ];

Subcellular localization

Localization

mitochondrion [P52789, P19367 ];

Disease relevance

Disease

Defects in HK1 are the cause of hexokinase deficiency [MIM:235700]. Hexokinase deficiency is a rare autosomal recessive disease with nonspherocytic hemolytic anemia as the predominant clinical feature [P19367 ];

Links

SwissProt

P19367; P52789; P52790; P78542; Q16779; Q2TB90

Entrez Gene

3098; 3099; 3101

HPRD

03080; 00806; 00809



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min