Class I alpha-1,2-mannosidase (MAN1)

Class I alpha-1,2-mannosidase (MAN1) refers to a group of calcium-dependent enzymes, including ER mannosidase I (MAN1B1) and Golgi mannosidases (MAN1A1, MAN1A2, MAN1C1), that belong to the glycosyl hydrolase family 47 (UniProt P33908, Q9UKM7) [1.1.1, 1.1.2]. These enzymes are essential for the early stages of N-glycan processing, specifically the trimming of alpha-1,2-linked mannose residues from precursor glycoproteins in the endoplasmic reticulum and Golgi apparatus [1.1.3, 1.3.2]. This process is a critical checkpoint for protein quality control, as it determines whether a glycoprotein proceeds to mature complex-type glycan formation or is targeted for endoplasmic reticulum-associated degradation (ERAD) [1.1.4, 1.5.2]. In oncology, altered expression of these mannosidases is associated with tumor progression, metastasis, and poor prognosis in cancers such as hepatocellular and breast carcinoma [1.3.1, 1.3.5]. Pharmacological inhibitors like kifunensine are utilized in research to block ERAD, potentially allowing for the rescue of misfolded but functional proteins in lysosomal storage disorders and sarcoglycanopathies, or to modulate immune recognition of tumor cells [1.2.3, 1.2.4]. These inhibitors act by mimicking the mannose substrate and binding to the enzyme's active site, thereby preventing glycan maturation [1.3.4].

Other names

ER mannosidase IGolgi mannosidase IMAN1A1MAN1A2MAN1B1MAN1C1Glycosyl hydrolase family 47GH47Mannosyl-oligosaccharide 1,2-alpha-mannosidase

Competitive inhibition of the enzyme's active site, preventing the removal of alpha-1,2-linked mannose residues from N-glycan precursors, which inhibits glycoprotein maturation and endoplasmic reticulum-associated degradation (ERAD) [1.3.4, 1.5.2].