Hexokinase (IPR001312)

Short name: Hexokinase

Overlapping homologous superfamilies


Family relationships


Hexokinase (EC: [PMID: 2199258, PMID: 1783373] is an important glycolytic enzyme that catalyzes the phosphorylation of keto- and aldohexoses (e.g. glucose, mannose and fructose) using MgATP as the phosphoryl donor.

In vertebrates there are four major isoenzymes, commonly referred as types I, II, III and IV. Type IV hexokinase, which is often incorrectly designated glucokinase [PMID: 1957348], is only expressed in liver and pancreatic beta-cells and plays an important role in modulating insulin secretion; it is a protein of a molecular mass of about 50 Kd. Hexokinases of types I to III, which have low Km values for glucose, have a molecular mass of about 100 Kd. Structurally they consist of a very small N-terminal hydrophobic membrane-binding domain followed by two highly similar domains of 450 residues. The first domain has lost its catalytic activity and has evolved into a regulatory domain.

In yeast there are three different isoenzymes: hexokinase PI (gene HXK1), PII (gene HXKB), and glucokinase (gene GLK1). All three proteins have a molecular mass of about 50 Kd.

The hexokinase domain has an alpha/beta fold and is distinctly folded in two subdomains of unequal size: the large and small subdomains. The large subdomain comprises a six-stranded mixed beta-sheet and a number of additional alpha-helices. On one side, the sheet packs against the small subdomain, and on the other side it is shielded by several alpha-helices. The dominant feature of the small subdomain is a five stranded mixed beta-sheet. The sheet is flanked by two helices on one side and by one helix on the other. The subdomain also has an additional beta-sheet formed by two antiparallel strands [PMID: 10749890, PMID: 9493266].

All these enzymes contain one (or two in the case of types I to III isozymes) strongly conserved region which has been shown [PMID: 3579310] to be involved in substrate binding.

GO terms

Biological Process

GO:0005975 carbohydrate metabolic process
GO:0001678 cellular glucose homeostasis

Molecular Function

GO:0005524 ATP binding
GO:0005536 glucose binding
GO:0004396 hexokinase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles