Mannosyl-oligosaccharide 1,2-α-mannosidase IB (MAN1A2)

Mannosyl-oligosaccharide 1,2-α-mannosidase IB (MAN1A2) is a type II transmembrane glycoside hydrolase located in the Golgi apparatus. It belongs to glycosyl hydrolase family 47 and catalyzes the progressive trimming of α-1,2-linked mannose residues from Man9GlcNAc2-containing N-glycans to produce Man5GlcNAc2. This step is essential in the maturation of N-linked glycoproteins destined for various cellular compartments. MAN1A2 thereby participates in protein quality control, including the ER-associated degradation (ERAD) of misfolded glycoproteins. Altered activity or expression of MAN1A2 can affect cellular homeostasis and glycoprotein composition, and has been implicated in cancer, congenital disorders of glycosylation, and potentially neurodegenerative conditions[1][2][7]. The enzyme is of interest as a potential therapeutic target, although most clinical research to date has focused on related mannosidases.

Other names

Golgi α-1,2-mannosidase IBα-1,2-mannosidase IBMAN1A2Mannosidase IA (sometimes confused; IA, IB, and IC are distinct isozymes)Glycosyl hydrolase family 47 member (GH47)Mannosyl-oligosaccharide alpha-1,2-mannosidase B

Inhibition of MAN1A2 leads to the accumulation of high-mannose oligosaccharides on glycoproteins. This can disrupt protein maturation and trafficking, affect immune recognition, and alter cell signaling—mechanisms relevant for anti-cancer strategies. For candidate inhibitors like 1-deoxymannojirimycin, the mechanism is competitive inhibition at the active site.