Glucose-6-phosphate isomerase (GPI) (EC 5.3.1.9) or phosphoglucose isomerase (PGI) [1,2] is a dimeric enzyme that catalyzes the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. PGI is involved in different pathways: in most higher organisms it is involved in glycolysis; in mammals it is involved in gluconeogenesis; in plants in carbohydrate biosynthesis; in some bacteria it provides a gateway for fructose into the Entner-Doudouroff pathway. Besides it's role as a glycolytic enzyme, mammalian PGI can function as a tumor-secreted cytokine and an angiogenic factor (AMF) that stimulates endothelial cell motility. Mammalian PGI is also neuroleukin [3], a neurotrophic factor which supports the survival of various types of neurons.

The sequence of PGI is conserved among diverse species ranging from bacteria to mammals and structures form a similar fold (see <PDB:1IAT>) [4,5], comprised of two subdomains that each form an α-β-α sandwich, with the active site located in the cleft between the subdomains and on the dimer interface. A glutamate and a lysine residue as well as a histidine from the other protomer in the dimer are implicated in the catalytic mechanism. The structure resembles that of the SIS domain (see <PDOC51464>).

As signature patterns for this enzyme we selected two conserved regions, the first region is located in the central section of PGI, while the second one is located in its C-terminal section. We also developed a profile that covers the entire PGI.