MUC4

The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats. [provided by RefSeq]

Full Name

mucin 4, cell surface associated

Function

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 (PubMed:10880978).

These glycoproteins play important roles in the protection of the epithelium and are implicated in epithelial renewal and differentiation (PubMed:10880978).

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.

Biological Process

Cell-matrix adhesion Source: InterPro
Maintenance of gastrointestinal epithelium Source: UniProtKB
Regulation of signaling receptor activity Source: GO_Central

Cellular Location

Chain Mucin-4 beta chain:
Plasma membrane
Cell membrane
Note: Isoforms lacking the Cys-rich region, EGF-like domains and transmembrane region are secreted. Secretion occurs by splicing or proteolytic processing.
Chain Mucin-4 alpha chain:
Plasma membrane
Cell membrane
Secreted
Note: Forms a complex with Mucin-4 beta chain at the cell membrane.
Isoform 3:
Plasma membrane
Cell membrane
Isoform 11:
Secreted
Isoform 15:
Secreted
Isoform 17:
Plasma membrane
Cell membrane

Topology

Helical: 5369-5389

PTM

Proteolytically cleaved into 2 chains, mucin-4 alpha chain and mucin-4 beta chain.
Mucin-4 alpha chain:
Highly O-glycosylated.
Mucin-4 beta chain:
Is predominantly N-glycosylated.