Mannosidase alpha class 1C member 1 (MAN1C1)

Mannosidase alpha class 1C member 1 (MAN1C1) is a glycoside hydrolase enzyme localized primarily in the Golgi apparatus and extracellular vesicles, catalyzing the trimming of mannose resides from N-glycans on glycoproteins as part of their maturation process. This activity is essential for protein quality control, specifically targeting terminally misfolded glycoproteins for ER-associated degradation. MAN1C1 influences cell surface glycoprotein organization, migration, and adhesion, notably through modulation of CD147 compartmentalization—an inducer of matrix metalloproteinases—and thus plays a role in epithelial wound healing. Reduced expression is found in early stages of renal and liver cancers, acting as a tumor suppressor by promoting apoptosis and inhibiting proliferation and migration. Increased expression in glioma stem cells correlates with poor survival and enhanced immunological activity, making MAN1C1 a candidate biomarker and potential immunotherapeutic target. No approved drugs specifically target MAN1C1, but its glycosylation pathway is of pharmacological interest. Therapeutic targeting requires careful safety evaluation due to the enzyme’s central role in proteostasis and broad tissue distribution.

Other names

Mannosyl-oligosaccharide 1,2-alpha-mannosidase ICMAN1C1MAN1A3MAN1CAlpha-1,2-mannosidase ICHMICpp6318Processing alpha-1,2-mannosidase IC

Chemical or genetic inhibition of MAN1C1 reduces cell migration and invasion capabilities, impairs proper glycoprotein lateral compartmentalization, and can suppress tumor phenotypes Potential mechanism: Inhibition of N-glycan processing leads to accumulation of uncleaved glycoproteins, inducing ER stress and apoptosis in tumor cells