SEC53 was named based on its initial observed mutant phenotype that resulted in a defect early in the secretory pathway, in which cells do not properly process or transport proteins (5). SEC53 is also called ALG4, named for a defect in asparagine-linked glycosylation (2).

During N-linked glycosylation of proteins, oligosaccharide chains are assembled on the carrier molecule dolichyl pyrophosphate in the following order: 2 molecules of N-acetylglucosamine (GlcNAc), 9 molecules of mannose, and 3 molecules of glucose. These 14-residue oligosaccharide cores are then transferred to asparagine residues on nascent polypeptide chains in the endoplasmic reticulum (ER). As proteins progress through the Golgi apparatus, the oligosaccharide cores are modified by trimming and extension to generate a diverse array of glycosylated proteins (reviewed in 6, 7).

Sec53p is a phosphomannomutase that catalyzes the conversion of mannose-6-phosphate (Man-6-P) to mannose-1-phosphate (Man-1-P) (3) on the cytosolic surface of the endoplasmic reticulum (8). Man-1-P is subsequently converted to GDP-mannose, which is the source of some of the mannose moieties added to the growing oligosaccharide. At the restrictive temperature, sec53 mutants accumulate LLO's carrying GlcNAc and one to eight mannose moieties, but do not transfer these oligosaccharides to proteins (2). Note: Technically, the conversion of Man-6-P to Man-1-P is reversible, but the forward reaction is required for glycosylation to proceed.

Sec53p complements defective phosphomannomutase activity in Salmonella typhimurium and E. coli (3). Candida albicans PMM1 (phosphomannomutase 1) (9) and Kluyveromyces lactis SEC53 (10) complement sec53. There are two human homologs: PMM1 (11, 12) (OMIM) and PMM2 (OMIM). PMM2 deficiency causes congenital disorder of glycosylation type I-a, also known as Jaeken syndrome (OMIM).

Last updated: 2005-07-01