Mucin Precursors Identification and Analysis of Their Intracellular Processing

MUC-type mucins are generally very large glycoproteins. They are encoded by very large mRNAs, and possess polypeptides between 200 and more than 900 kDa(l). The only notable exception is MUC7, which is considerably smaller, i.e. thepolypeptide is only 39 kDa (). Without exception however, mucins are very heavily Oglycosylated: Up to 50-80% of their molecular mass is due to O-glycosylation (,). Moreover, potential N-glycosylation sites are found in virtually all mucin sequences, and in several MUCs N-glycosylation is actually demonstrated (,). Human MUC2 for instance contains 30 potential N-glycosylation sites, and if these are all used, the N-glycans together would constitute a molecular mass of about 60 kDa. It is only the very large size of the mature mucins, that makes the amount of N-glycosylation seem insignificant (). Generally, the sizes of the mature mucins are difficult to estimate; The approximations run from 1 to 20 MDa for single mucin molecules, which hampers many forms of biochemical analysis (). Also, the extensive glycosylation of mucins results in an intrinsically very heterogeneous population of mature mucins.