Alpha-1,2-mannosidase 1A (MAN1A1) (MAN1A1)

Alpha-1,2-mannosidase 1A (MAN1A1) is a key Golgi-localized enzyme responsible for the trimming of mannose residues during the maturation of N-linked glycoproteins (UniProt P33907). It specifically catalyzes the hydrolysis of alpha-1,2-linked mannose residues from Man9GlcNAc2 to produce Man8GlcNAc2, a vital step in the transition from high-mannose to complex-type glycans (PubMed: 25635007). This enzyme is also implicated in the quality control mechanism known as endoplasmic reticulum-associated degradation (ERAD), where it helps target misfolded proteins for proteasomal destruction (PubMed: 11433373). In oncology, MAN1A1 expression is often dysregulated; for instance, its downregulation is associated with increased metastasis and poor prognosis in certain cancers, such as breast and liver cancer, due to the resulting changes in cell surface glycan profiles (PubMed: 24607831). Conversely, its inhibition by small molecules like kifunensine is used in research to study glycan-dependent signaling and to enhance the immunogenicity of certain glycoproteins (PubMed: 19172136). While not yet a target for FDA-approved drugs, MAN1A1 remains a significant focus for therapeutic strategies aiming to modulate the glycome in cancer and viral infections. The enzyme's role in maintaining the balance of glycan structures makes it a sensitive point of intervention for diseases characterized by aberrant glycosylation. Therapeutic challenges include achieving selectivity over other mannosidase isoforms and managing the systemic effects of altered glycosylation.

Other names

Mannosyl-oligosaccharide 1,2-alpha-mannosidase IAMAN9-mannosidaseAlpha-1,2-mannosidase IAMan(9)-mannosidaseMAN1A

Inhibition of the enzymatic removal of alpha-1,2-linked mannose residues from precursor glycoproteins, thereby preventing the transition from high-mannose to complex-type N-glycans.