Target intelligence / Profile preview

Golgi alpha-1,2-mannosidase IA, IB, and IC (MAN1A1, MAN1A2, MAN1C1)

Target
MAN1A1, MAN1A2, MAN1C1
Molecular classification
Enzyme, Glycosidase, Glycoside hydrolase family 47 (GH47)
01

Overview

Golgi alpha-1,2-mannosidases IA, IB, and IC are members of the glycoside hydrolase family 47 (GH47) and localize predominantly to the Golgi apparatus in mammalian cells. They catalyze the hydrolysis of terminal alpha-1,2-linked mannose residues from Man8-9GlcNAc2 intermediates, yielding Man5GlcNAc2, a key step in the maturation of N-linked glycoproteins. This action is crucial for proper glycoprotein folding, trafficking, and quality control, and these enzymes contribute to both normal glycoprotein processing and endoplasmic reticulum-associated degradation (ERAD) by generating glycan signals that mark misfolded proteins for degradation. Dysregulation or inhibition of these enzymes can influence disease processes such as cancer and congenital disorders of glycosylation.

Other names
Golgi alpha-mannosidase IGolgi mannosidase I subfamilyGlycoside hydrolase family 47 (GH47) mannosidasesMAN1A1 (Mannosidase alpha class 1A member 1, "mannosidase IA")MAN1A2 (Mannosidase alpha class 1A member 2, "mannosidase IB")MAN1C1 (Mannosidase alpha class 1C member 1, "mannosidase IC")
02

Mechanism of action

Competitive inhibition of the alpha-1,2-mannosidase active site by structural analogs of mannose or transition-state mimics, preventing processing of N-linked glycans and altering glycoprotein maturation

03

Biological functions

N-glycan processing in the Golgi apparatusTrimming high-mannose N-glycans during glycoprotein maturationContributing to endoplasmic reticulum-associated degradation (ERAD) by marking misfolded glycoproteins for degradationQuality control of glycoprotein folding and trafficking
04

Disease associations

Cancer (abnormal glycosylation is linked to tumor biology, and related mannosidases are anti-cancer drug targets)Protein misfolding disorders (due to defective glycoprotein quality control)Other: General involvement in diseases of glycoprotein metabolism
05

Safety considerations

Broad inhibition of glycan processing may disrupt normal cellular function, potentially leading to toxicity or adverse immunological effectsDisruption of ER/Golgi quality control can impair protein maturation and trafficking, causing adverse cellular outcomes
06

Interacting drugs

1-deoxymannojirimycin (inhibitor)

1 more in the full profile.

07

Biomarkers

Abnormal N-glycan processing patterns (e.g., accumulation of specific high-mannose structures) may serve as biomarkers for altered Golgi mannosidase activity in diseases

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