Target intelligence / Profile preview

Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1)

Target
MAN1A1
Molecular classification
Enzyme, Glycoside hydrolase (family 47), Mannosidase
01

Overview

Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1) is a Golgi-resident enzyme involved in the maturation of Asn-linked (N-linked) oligosaccharides during protein glycosylation. Specifically, MAN1A1 is one of three human Golgi alpha-1,2-mannosidases (along with MAN1A2 and MAN1C1), which trim mannose residues from Man9GlcNAc2 to produce Man5GlcNAc2, a critical step for the formation of complex N-glycans[1][4]. This process is required for proper protein folding, quality control, and trafficking of glycoproteins. The regulation and activity of MAN1A1 affect cell growth, cell–cell adhesion, motility, and protein degradation pathways[1]. Inhibition of this enzyme disrupts these processes, which has implications for cancer cell proliferation and is being investigated as a potential therapeutic strategy[6]. MAN1A1 belongs to glycoside hydrolase family 47 and, like other members of this family, adopts a (α/α)7 barrel fold, using a coordinated Ca2+ ion in its active site for catalysis[3].

Other names
Golgi mannosidase IAGolgi alpha-mannosidase IAAlpha-1,2-mannosidase IAMAN1A1
02

Mechanism of action

Competitive inhibition of the enzymatic active site, blocking mannose residue trimming from glycoproteins

03

Biological functions

N-glycan maturationProtein quality control (ER-associated degradation, ERAD)Protein folding regulation
04

Disease associations

CancerPotential involvement in other diseases related to defective glycosylation
05

Safety considerations

Disruption may lead to improper protein folding and ER stressSystemic glycosylation defects if completely blockedPotential off-target toxicity with broad-acting inhibitors
06

Interacting drugs

1-deoxymannojirimycin (inhibitor)

1 more in the full profile.

07

Biomarkers

Null (no widely established biomarkers for patient selection or efficacy monitoring for this specific target; altered N-glycan profiles may be detected in pathway studies)

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