Abstract
The maturation of N-glycans is initiated within the lumen of the endoplasmic reticulum (ER) immediately after transfer of the oligosaccharide precursor to nascent polypeptide chains (Kornfeld and Kornfeld 1985). These glycan processing steps include the sequential cleavage of three glucose (Glc) residues and four α1,2-mannose (α1,2-Man) residues prior to the addition of a GlcNAc residue and cleavage of the final α1,3-Man and α1,6-Man residues. The resulting GlcNAcMan3GlcNAc2-Asn core structure is then extended in the Golgi complex into complex type oligosaccharides (Fig. 115.1). The Glc residues are cleaved by a pair of endoplasmic reticulum (ER) resident glucosidases (MOGS and the heterodimeric GANAB/PRKCSH), and the α1,2-Man residues are removed by a family of α1,2-mannosidases that reside in the ER and Golgi complex. The α1,2-mannosidases are comprised of seven related gene products (Mast et al. 2005; Mast and Moremen 2006; Moremen and Molinari 2006). These enzymes are members of CAZy glycosylhydrolase family 47 (GH47) (Coutinho et al. 2003) and can be distinguished from the later acting α1,3-/α1,6-mannosidases in the Golgi complex, lysosomes, and cytosol (GH38 enzymes) by differences in sequence, protein structural domains, enzymatic characteristics, inhibitor profiles, and catalytic mechanisms (Moremen 2000; Moremen and Molinari 2006; Moremen and Touster 1988; Moremen et al. 1994). This chapter is focused on the N-glycan processing enzymes, ER α-mannosidase I (MAN1B1), and three Golgi α1,2-mannosidases (Golgi α-mannosidase IA (MAN1A1), Golgi α-mannosidase IB (MAN1A2), and Golgi α-mannosidase IC (MAN1C1)). Brief mention of the related EDEM proteins (EDEM1, EDEM2, and EDEM3) is made for comparison, as these ER-resident proteins are thought to play roles in targeting of misfolded proteins for ER-associated degradation (ERAD) rather than processing of glycoproteins for maturation to complex type structures within the secretory pathway.
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Moremen, K.W., Nairn, A.V. (2014). Mannosidase, Alpha, Class 1 (MAN1A1 (Golgi Alpha-Mannnosidase IA), Man1A2 (Golgi Alpha-Mannosidase IB), MAN1B1(ER Alpha-Mannosidase I), MAN1C1 (Golgi Alpha-Mannosidase IC)). In: Taniguchi, N., Honke, K., Fukuda, M., Narimatsu, H., Yamaguchi, Y., Angata, T. (eds) Handbook of Glycosyltransferases and Related Genes. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54240-7_84
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