Gel-forming mucins appeared early in metazoan evolution

Abstract

Mucins are proteins that cover and protect epithelial cells and are characterized by domains rich in proline, threonine, and serine that are heavily glycosylated (PTS or mucin domains). Because of their sequence polymorphism, these domains cannot be used for evolutionary analysis. Instead, we have made use of the von Willebrand D (VWD) and SEA domains, typical for mucins. A number of animal genomes were examined for these domains to identify mucin homologues, and domains of the resulting proteins were used in phylogenetic studies. The frog Xenopus tropicalis stands out because the number of gel-forming mucins has markedly increased to at least 25 as compared with 5 for higher animals. Furthermore, the frog Muc2 homologues contain unique PTS domains where cysteines are abundant. This animal also has a unique family of secreted mucin-like proteins with alternating PTS and SEA domains, a type of protein also identified in the fishes. The evolution of the Muc4 mucin seems to have occurred by recruitment of a PTS domain to AMOP, NIDO, and VWD domains from a sushi domain-containing family of proteins present in lower animals, and Xenopus is the most deeply branching animal where a protein similar to the mammalian Muc4 was identified. All transmembrane mucins seem to have appeared in the vertebrate lineage, and the MUC1 mucin is restricted to mammals. In contrast, proteins with properties of the gel-forming mucins were identified also in the starlet sea anemone Nematostella vectensis, demonstrating an early origin of this group of mucins. bioinformatics ͉ von Willebrand domain ͉ SEA domain ͉ protein evolution ͉ mucus

The Lectin Domain of the Polypeptide GalNAc Transferase Family of Glycosyltransferases (ppGalNAc Ts) Acts as a Switch Directing Glycopeptide Substrate Glycosylation in an N- or C-terminal Direction, Further Controlling Mucin Type O-Glycosylation

“…Because the role of the mucin domain in these glycoproteins has been thought to produce a stable extended hydrophilic motif, the actual glycosylation pattern has usually been thought to be of relatively low importance. This is supported by the very low sequence conservation across mammalian and insect species of the glycosylated domains of the secreted mucins (7,8). Nevertheless, it cannot be ruled out that in some cases, O-glycosylated domains may present a molecular code for the specific recognition of additional binding partners, thus playing potential roles in protein sorting, targeting, and turnover (9 -15).…”

“…7E), were subtracted from the distributions obtained for the glycosylated peptides GPIV and GPV, respectively. 7 These difference plots for all eight transferase isoforms, grouped by glycopeptide utilization, are shown in Fig. 8.…”

A sticky end for gastrointestinal helminths; the role of the mucus barrier

“…There have been 18 family members identified in humans, which have orthologues in mice and a subset of these mucins are selectively expressed at different anatomical sites along the GI tract 18, 19, 20, 21. Mucins can further be classified into 2 major subtypes: transmembrane and secreted mucins.…”

The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host–microbial interactions

“…The small PTS domain has, on the other hand, more degenerate repeats, and the PTS sequences known for mouse and rat Muc2 also suggest less perfect repeats. Studies on the evolution of mucins show that there is no amino acid sequence conservation of the PTS domains between species, and it was not possible to use these domains for mucin ortholog mining (24). There is, thus, a low selection pressure for a specific amino acid sequence when comparing the PTS domain of the same mucin between species.…”

“…3 (22, 23). Typical for mucins is the PTS domain with a high frequency of the amino acids proline, threonine, and serine (24). These domains are often made up by repetitive sequences ordered in tandem and thus referred to as tandem repeats.…”