Membrane-bound mucin, a family of highly glycosylated proteins that constitute the major component of the mucus, the slimy and viscous secretion covering epithelial surfaces . These glycoproteins play important roles in the protection of the epithelium and are implicated in epithelial renewal and differentiation . Regulates cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and its ability to act as an intramembrane ligand for ERBB2. Plays an important role in proliferation and differentiation of epithelial cells by inducing specific phosphorylation of ERBB2. In polarized epithelial cells, segregates ERBB2 and other ERBB receptors and prevents ERBB2 from acting as a coreceptor. The interaction with ERBB2 leads to enhanced expression of CDKN1B. The formation of a MUC4-ERBB2-ERBB3-NRG1 complex leads to down-regulation of CDKN1B, resulting in repression of apoptosis and stimulation of proliferation. Its ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation.
Subcellular locations: Cell membrane
Isoforms lacking the Cys-rich region, EGF-like domains and transmembrane region are secreted. Secretion occurs by splicing or proteolytic processing.
Subcellular locations: Cell membrane, Secreted
Forms a complex with Mucin-4 beta chain at the cell membrane.
Subcellular locations: Cell membrane
Subcellular locations: Secreted
Subcellular locations: Secreted
Subcellular locations: Cell membrane
Expressed in the thymus, thyroid, lung, trachea, esophagus, stomach, small intestine, colon, testis, prostate, ovary, uterus, placenta, and mammary and salivary glands. Expressed in carcinomas arising from some of these epithelia, such as lung cancers, squamous cell carcinomas of the upper aerodigestive tract, mammary carcinomas, biliary tract, colon, and cervix cancers. Minimally or not expressed in the normal pancreas or chronic pancreatitis, but is highly expressed in pancreatic tumors and pancreatic tumor cell lines.