Cloning and characterization of human MUC19 gene.

The most recently discovered gel-forming mucin, MUC19, is expressed in both salivary glands and tracheal submucosal glands. We previously cloned the 3'-end partial sequence (AY236870), and here report the complete sequencing of the entire MUC19 cDNA. One highly variable region (HVR) was discovered in the 5' end of MUC19. A total of 20 different splicing variants were detected in HVR, and 18 variants are able to translate into proteins along with the rest of the MUC19 sequence. The longest variant of MUC19 consists of 182 exons, with a transcript of approximately 25 kb. A central exon of approximately 12 kb contains highly repetitive sequences and has no intron interruption. The deduced MUC19 protein has the bona fide gel-forming mucin structure, VWD-VWD-VWD-"threonine/serine-rich repeats"-VWC-CT. An unusual structural feature of MUC19, which is lacking in other gel-forming mucins, is its long amino terminus upstream of the first VWD domain. The long amino terminus is mostly translated from the sequences in HVR, and contains serine-rich repetitive sequences. To validate the integrity of the MUC19 sequence, primers from both the 3' and 5' end were used to demonstrate a similar tissue expression pattern of MUC19 in trachea and salivary glands. In addition, antibodies were developed against either the amino (N) or carboxy (C) terminus of MUC19, and similar antibody staining patterns were observed in both salivary and tracheal submucosal glands. In conclusion, we have cloned and elucidated the entire MUC19 gene, which will facilitate understanding of the function and regulation of this important, yet understudied, mucin gene in airway diseases.