Tracing the evolutionary origin of the TFF-domain, an ancient motif at mucous surfaces

Mammalian trefoil factor family (TFF)-domain peptides promote gastrointestinal protection, healing and cell migration and may act as tumour suppressors. TFF-like domains also constitute modules of composite proteins like mucin glycoproteins and zona pellucida proteins. Database searches with a modified, less stringent consensus sequence - C-x(5,6)-[ST]-x(3)-C-x(4,5)-C-C-[FYWH]-x(2, 24)-C-[FY] - revealed that ancestors of the TFF-domain arose before amphibian evolution. Eggshell proteins and a zona pellucida-like protein in teleost species, an epidermis-specific protein in a tunicate as well as an open reading frame in a nematode exhibited TFF-like motifs suggesting that they most likely originated in some multicellular organism.