Sialidase-2 (NEU2)

Sialidase-2 (NEU2) is a cytosolic exo-alpha-sialidase enzyme encoded by the NEU2 gene on human chromosome 2q37, belonging to the glycohydrolytic enzyme family that specifically catalyzes the hydrolytic cleavage of terminal N-acetylneuraminic acid (Neu5Ac) residues from glycans in glycoproteins, glycolipids, and oligosaccharides. It exhibits a pH optimum around 5.6-6.5, prefers alpha-(2->3)-sialylated gangliosides like GD1a and GT1b over alpha-(2->8)-linked GD1b, and hydrolyzes monomeric GM1 ganglioside but not its micellar form, with lower activity on mixed alpha-(2->3)/alpha-(2->6)-sialylated glycoproteins such as fetuin. The enzyme is a 380-amino-acid polypeptide with characteristic Asp blocks and a YRIP active site motif, showing cytosolic localization confirmed by cell fractionation and immunohistochemistry, though it can also associate with the plasma membrane. NEU2 plays a role in sialoglycan metabolism, modulating sialylation status which influences cell signaling, adhesion, and recognition processes. While not prominently linked to specific diseases, its involvement in sialic acid regulation suggests potential roles in conditions like skin aging or neural functions where sialidase activity impacts extracellular matrix or ganglioside signaling, and it serves as a model for developing selective inhibitors due to its stability and neutral pH activity. Research has identified DANA-based inhibitors with selectivity for NEU2 over other sialidases like NEU1, NEU3, and NEU4, highlighting its utility in probing sialidase functions, though no approved drugs target it clinically.

Other names

NEU2neuraminidase 2