The MUC3 gene encodes a transmembrane mucin and is alternatively spliced

Epithelial mucins are a family of secreted and cell surface glycoproteins e xpressed by epithelial tissues and implicated in epithelial cell protection , adhesion modulation and signaling. The gene encoding human MUC3 (hMUC3), localised to chromosome 7q22, is most highly expressed in the small intesti ne. It has previously been reported to be a non-transmembrane mucin with mi nimal homology to its suggested orthologues from rat (rMuc3) and mouse (mMu c3). RT-PCR was performed to investigate the carboxyl terminus of the publi shed sequence of hMUC3 from normal colon and small intestine tissues and al so from a series of 10 colorectal cancer cell lines. Two distinct PCR produ cts were identified. In contrast to the previously published hRMUC3 sequenc e, which terminates shortly after a single cysteine-rich EGF-like domain, c onceptual protein translation of the dominant and largest PCR product ident ified two extracellular cysteine-rich EGF-like domains separated by an N-gl ycosylation-rich domain and a potential coiled-coil region, followed by a p utative transmembrane region and a 75 amino acid cytoplasmic tail. The smal ler of the two PCR products was found to be an alternative splice variant o f MUC3 including the first EG;F-like domain but lacking part of the second EGF-like domain and the transmembrane region. Nine out of 10 colorectal can cer cell lines were found to express MUC3. Interestingly, one of the cell l ines, LoVo, expressed predominantly the alternative splice form lacking a t ransmembrane domain. Structural homology of the new protein sequence of hMU C3 with rMuc3 and mMuc3 indicates it is closely related to the rodent prote ins and is likely to be involved in ligand-binding and intracellular signal ing. The new finding that MUC3 encodes a transmembrane molecule presents a new paradigm for the structure of this mucin and the manner in which it may function, (C) 1999 Academic Press.