However, the presence of the VNTR, as well as the cDNA sequence within the PTS domain, is not highly conserved evolutionarily, highlighting the distinct possibility that broad functional differences exist between species. Our data indicate that the PTS domain of the LOUREIRIN-B chicken MUC2 protein contains a vastly different repeat structure than the human protein. Although the chicken PTS region is shorter, the central repeat motif is 69 amino acids in length and shows very little identity with the human motif. Recent in vitro studies using human intestinal cells demonstrated that the intestinal mucins isolated from chicken were detrimental to the proliferation of Campylobacter jejuni, an infectious bacteria causing acute gastroenteritis in humans but not in chicken. In addition these studies demonstrated that the chicken mucins attenuated the invasiveness of Campylobacter jejuni, suggesting that differences in mucin protein sequence or structure between humans and chicken could account for the differences in susceptibility to infection. Alternatively, the functional differences between human and chicken may imply species-specific divergence in intestinal mucus composition and/or structures. This could also occur through differences in posttranslational modifications of the human and chicken proteins. Outside of the PTS domain, the human and chicken MUC2 proteins share large blocks of highly conserved sequences, strongly suggesting that this variable PTS region could account for the phenotypic differences. Plausibly, MUC2 is of 
utmost importance, as the functionality of intestinal mucus was proposed to rely primarily on MUC2 encoded mucins. Therefore, the full understanding of the functional divergence and prognostic implications of chicken mucins compared to their mammalian orthologues necessitates identification and comparisons of the gene sequences across species. Although identification of new MUC family members is ongoing, sequencing of most MUCIN genes is hampered due to the highly complex PTS cassettes clustered throughout the gene, and several gaps still remain in mouse and human family members. In the case of the secretory mucins, this can largely be accounted for by the large, frequently repetitive PTS region. The presence of several different polymorphic elements in many of the MUCIN genes hinders annotation efforts at the gene and protein levels, and could even hamper the understanding of the biological Orbifloxacin significance and disease associations of the diverse family members. In the endoplasmic reticulum, MUC2 forms disulfide-linked dimers via the VWD domains of the amino-terminus, while the CT knot in the carboxy-terminus supports disulfide-linked trimerization in the trans-Golgi network. CysD domains exert non-covalent cross-linkages in the MUC2 gel formation process, likely contributing to tertiary structure and determination of the pore size of the mucus network. Chicken may plausibly carry more CysD domains than that of human, which may suggest that the polymeric net-like structure contains smaller pores in chickens than humans. This could account for differences in innate defense response to pathogens. The conservation of a cationic domain at the C-terminus observed in rodents was not found in chickens. In human MUC2, two different PTS domains have been identified, both of which are located on the same large exon separated by,600 bp. One region consists of repeats that are interrupted in places by 21 to 24 bp segments. The other is composed of an uninterrupted array of a tandem 23-amino acid repeat cassette.