HUMAN MUCIN GENE MUC5B, THE 10.7-KB LARGE CENTRAL EXON ENCODES VARIOUS ALTERNATE SUBDOMAINS RESULTING IN A SUPER-REPEAT - STRUCTURAL EVIDENCE FOR A 11P15.5 GENE FAMILY

Human mucin gene MUC5B is mapped clustered with MUC6, MUC2, and MUC5AC on chromosome 11p15.5. We report here the isolation of three overlapp ing genomic clones of human MUC5B spanning approximately 40 kilobases. We have determined their partial restriction maps and the intron-exon boundaries of the central region encoding a single open reading frame . This coding region has been completely sequenced. Its length is 10,7 13 base pairs, and it encodes a 3570-amino acid peptide. Nineteen subd omains have been individualized. Some subdomains show similarity to ea ch other, creating larger composite repeat units that we have called s uper-repeats. Four super-repeats of 528 amino acid residues are thus o bserved within the central exon. Each comprises (i) a subdomain compos ed of 11 repeats of the irregular repeat of 29 amino acid residues, (i i) a unique conserved subdomain with no typical repeat, and (iii) a cy steine-rich subdomain. This latter subdomain has high sequence similar ity to the cysteine-rich domains described in MUC2 and MUC5AC. Sequenc e data of these three genes, together with their clustered organizatio n, lead us to suggest that they may be a part of a multigene family. T he super-repeat present in MUC5B is the largest ever determined in muc in genes and the central exon of this gene is, by far, the largest rep orted for a vertebrate gene.