Omannosyltransferases

O-mannosyltransferases are a family of glycosyltransferases that catalyze the transfer of mannose from dolichyl-phosphate mannose to serine or threonine residues on proteins, initiating O-linked mannosyl glycosylation. In eukaryotes they reside in the endoplasmic reticulum membrane and often function as multi-subunit complexes.

In budding yeast such as Saccharomyces cerevisiae, the PMT family (PMT1–PMT5) carries out O-mannosylation, which is important for cell wall integrity and protein folding; loss of PMT activity leads to reduced O-mannosylation and growth defects.

In vertebrates the best-characterized O-mannosyltransferases are POMT1 and POMT2, which form a heteromeric ER-associated complex that transfers the first mannose to serine or threonine residues on target proteins, including alpha-dystroglycan. This initial O-mannosylation is a prerequisite for further elaboration by additional glycosyltransferases (for example POMGNT1, POMGNT2, FKTN, FKRP, LARGE), generating a functional O-mannose–containing glycan that enables laminin binding.

Defects in protein O-mannosylation, including mutations in POMT1 or POMT2, underlie a group of muscular dystrophy-dystroglycanopathy disorders, collectively called dystroglycanopathies, which can affect muscle, brain, and eye development. The pathway is conserved in eukaryotes, with variation in the number of PMT family members across species.