This domain of unknown function is found in O-mannosyl-transferases TMTC1-4, and constitutes a loop between TM7 and TM8 located in the ER lumen that contains a small hydrophobic, but not membrane-embedded helix. This loop is critical for catalysis and binding of ligands, especially the lipid-linked sugar moiety [].TMTCs transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases acting primarily on the cadherin superfamily; each member has distinct roles in decorating the cadherin domains with O-linked mannose glycans at specific regions. These proteins also act as O-mannosyl-transferase on other proteins such as PDIA3 [].
