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. A heterodimeric complex, composed of a mucin-4 alpha chain and a cysteine-rich transmembrane mucin-4 beta chain (PubMed:7440586). Mucin-4 beta chain interacts with ERBB2 via the EGF-like domain 1. In nonpolarized cells, associates with ERBB2 and ERBB3 (PubMed:12386815, PubMed:16624867). Secreted by proteolytic processing. Expression is developmentally regulated in the mammary gland, dramatically increases in the lactating gland compared with the virgin mammary gland, while decreasing again during mammary gland involution. Expressed in 13762 ascites cells. Overexpressed in some aggressive mammary tumors. Overexpression seems to block cell-cell and cell-matrix interactions to protect tumor cells from immune surveillance, and to promote metastasis. Essentially composed of an array of serine- and threonine-rich tandem repeats which is highly polymorphic, the variable number of tandem repeats (VNTR) region. Proteolytically cleaved into 2 subunits, mucin-4 alpha chain and mucin-4 beta chain. Mucin-4 alpha subunit is highly O-glycosylated. Mucin-4 beta subunit is predominantly N-glycosylated. The variable number of tandem repeats (VNTR) region, an array of serine- and threonine-rich tandem repeats, is encoded by a single exon (exon 2) which is highly polymorphic.