NEU3

This gene product belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipids. It is localized in the plasma membrane, and its activity is specific for gangliosides. It may play a role in modulating the ganglioside content of the lipid bilayer.

Full Name

neuraminidase 3

Function

Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosacharides. Displays high catalytic efficiency for gangliosides including alpha-(2->3)-sialylated GD1a and GM3 and alpha-(2->8)-sialylated GD3 (PubMed:11298736, PubMed:15847605, PubMed:10861246, PubMed:20511247, PubMed:28646141, PubMed:10405317, PubMed:12011038).

Plays a role in the regulation of transmembrane signaling through the modulation of ganglioside content of the lipid bilayer and by direct interaction with signaling receptors, such as EGFR (PubMed:17334392, PubMed:25922362).

Desialylates EGFR and activates downstream signaling in proliferating cells (PubMed:25922362).

Contributes to clathrin-mediated endocytosis by regulating sorting of endocytosed receptors to early and recycling endosomes (PubMed:26251452).

Biological Process

Carbohydrate metabolic process Source: MGI
Ganglioside catabolic process Source: UniProtKB
Glycosphingolipid metabolic process Source: Reactome
Negative regulation of clathrin-dependent endocytosis Source: UniProtKB
Oligosaccharide catabolic process Source: UniProtKB
Positive regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB

Cellular Location

Endosome
Early endosome membrane
Recycling endosome membrane
Lysosome
Lysosome membrane
Plasma membrane
Cell membrane
Other locations
caveola
Note: Associates with the external leaflet of the plasma membrane (By similarity). S-acylated NEU3 likely spans the lipid bilayer with a portion of C-terminus exposed to the cytosol and the catalytic region facing the extracellular space (PubMed:28646141).

PTM

Palmitoylated; may regulate intracellular trafficking and anchorage to plasma membrane and endomembranes.