Mucins are a group of high molecular weight glycoproteins consisting of a mucin core protein and O-linked carbohydrates. Mucin 4, a membrane-bound mucin, is the human homolog of the rat sialomucin complex (SMC). Mucin 4 protein consists of Mucin 4α, a large amino mucin type subunit, and Mucin 4β, a transmembrane subunit containing three EGF-like domains. The Mucin 4 gene is the predominant mucin gene expressed in the normal urothelium and is also expressed in several normal tissues such as trachea, lung and testis. Dysregulation of Mucin 4 results in high levels of expression in pancreatic tumors and tumor cell lines. Induction of Mucin 4 in pancreatic carcinoma by all-trans-retinoic acid is mediated through the retinoic acid receptor-α signaling pathway. TGFβ2 serves as an interim mediator of this regulated expression. Alternative splicing in the 3'-end of the Mucin 4 gene generates at least 12 splice variants, which are characterized as two distinct types, a secreted type and a membrane-associated type. Mucin 4 protein acts as a heterodimeric bifunctional cell-surface glycoprotein and forms thick mucous effusion in the diseased middle ear.
