UNIPROT #

Q99102

PROTEIN NAME

Mucin-4

GENE NAME

MUC4

SYNONYMS

MUC-4, ASGP, ASGP-1, ASGP-2, MUC4

TISSUE SPECIFICITY

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.

DEVELOPMENTAL STAGE

Expressed early in the primitive gut before respiratory and digestive epithelial cells have acquired their tissue and cell specificity. Expressed at the basal surface of the epithelium from week 14 to 26 weeks and then predominantly localized in only parietal cells. Immediately before birth, found in the cytoplasm of the mucous columnar epithelial cells. In the embryo expressed in skin, then disappears late in gestation.

POST-TRANSLATIONAL MODIFICATION

Proteolytically cleaved into 2 chains, mucin-4 alpha chain and mucin-4 beta chain.; mucrnin-4 alpha chain is highly O-glycosylated.; mucin-4 beta chain is predominantly N-glycosylated.

SUBCELLULAR LOCATION

Membrane. Note=Isoforms lacking the Cys-rich region, EGF-like domains and transmembrane region are secreted. Secretion occurs by splicing or proteolytic processing.; [Mucin-4 beta chain]: Cell membrane; Single-pass membrane protein.; [Mucin-4 alpha chain]: Secreted.; [Isoform 3]: Cell membrane; Single-pass membrane protein.; [Isoform 11]: Secreted.; [Isoform 15]: Secreted.; [Isoform 17]: Cell membrane; Single-pass membrane protein.

FUNCTION

May play a role in tumor progression. Ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation. Has anti-adhesive properties. Seems to alter cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and in its ability to act as an intramembrane ligand for ERBB2. Plays an important role in cell proliferation and differentiation of epithelial cells by inducing specific phosphorylation of ERBB2. The MUC4-ERBB2 complex causes site-specific phosphorylation of the ERBB2 'Tyr-1248'. 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.