Mannosidase alpha class 1A member 1 (MAN1A1)

Mannosidase alpha class 1A member 1 (MAN1A1) is a Golgi-localized enzyme belonging to the glycosyl hydrolase 47 family, primarily responsible for the early stages of N-glycan processing [UniProt: P33907]. It specifically catalyzes the removal of alpha-1,2-linked mannose residues from Man9GlcNAc2 to produce Man6GlcNAc2, a critical step for the subsequent synthesis of complex and hybrid N-glycans [NCBI Gene: 4121]. In oncology, MAN1A1 is recognized for its role in regulating the glyco-checkpoint; its downregulation is frequently observed in aggressive cancers like breast and hepatocellular carcinoma, leading to an accumulation of high-mannose glycans that promote tumor cell migration and immune evasion [PMID: 29453315, PMID: 24607494]. While small molecule inhibitors such as kifunensine are widely used in research to block this pathway, therapeutic strategies targeting MAN1A1 mRNA via RNA interference (RNAi) or antisense oligonucleotides are being explored to modulate glycan-dependent signaling in the tumor microenvironment [PMID: 31515460]. Understanding the balance of MAN1A1 activity is crucial, as its dysregulation significantly impacts the stability and function of various cell surface receptors, including integrins and growth factor receptors [PMID: 25666607]. Furthermore, MAN1A1 expression levels serve as potential prognostic biomarkers in several malignancies, reflecting the metabolic state of the cell's glycosylation machinery.

Other names

Alpha-1,2-mannosidase IAMannosyl-oligosaccharide 1,2-alpha-mannosidase IAHUMM3HUMM9

Inhibition of alpha-1,2-mannosidase activity or reduction of MAN1A1 expression to modulate N-glycan maturation and cell surface glycan profiles.