MUC3 HUMAN INTESTINAL MUCIN - ANALYSIS OF GENE STRUCTURE, THE CARBOXYL-TERMINUS, AND A NOVEL UPSTREAM REPETITIVE REGION

MUC3 is a large mucin glycoprotein expressed by the human intestine an d gall bladder. in this manuscript, we present details of the deduced protein structure of MUC3. The MUC3 carboxyl-terminal domain is 617 re sidues in length, including 511 residues of a non-repetitive mucin-lik e domain (27% Thr, 22% Ser and 11% Pro) and a 106-residue Cys-rich dom ain with homology to the epidermal growth factor (EGF) - like structur al motifs found in many proteins. The region of MUGS located upstream of the previously described. 51-base pair (bp) tandem repeats, which e ncode a major Ser and Thr-rich domain, consists of a second type of re petitive structure with an imperfect periodicity of approximately 1125 bp. This domain is also mucin-like and appears to be considerably lar ger than 2000 residues (6000 bp), The MUC3 gene itself is large and co mplex, using pulse field gel electrophoresis and blot analysis, the sm allest fragment found that contained all human genomic DNA hybridizing 60 the 51-bp tandem repeat probe was 200 kilobases with restriction e nzyme SwaI. Both PvuII and PstI produced two sets of hybridizing fragm ents that were hypervariable within the human population with a patter n suggestive of both a variation in the number of tandem repeats (VNTR ) and sequence polymorphism These fragments varied independently of ea ch other, bat no genetic recombination was detected in a study of 40 h uman families. Thus, the MUC3 gene encodes a very large glycoprotein w ith a structure very different from that of any mucin currently descri bed.