MUC4
Description
The MUC4 (mucin 4, cell surface associated) is a protein-coding gene located on chromosome 3.
Mucin-4 (MUC-4) is a mucin protein that in humans is encoded by the MUC4 gene. Like other mucins, MUC-4 is a high-molecular weight glycoprotein. 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. MUC-4 has been found to play various roles in the progression of cancer, particularly due to its signaling and anti-adhesive properties which contribute to tumor development and metastasis. It is also found to play roles in other diseases such as endometriosis and inflammatory bowel disease. MUC-4 belongs to the human mucin family that is membrane-anchored and can range in molecular weight from 550 to 930 kDa for the actual protein, and up to 4,650 kDa with glycosylation. MUC4 is an O-glycoprotein that can reach up to 2 micrometers outside the cell.
MUC4 is a membrane-bound mucin, a type of highly glycosylated protein that forms a major component of mucus, the viscous substance covering epithelial surfaces. MUC4 plays a crucial role in protecting the epithelium and is involved in its renewal and differentiation. It regulates cellular behavior by influencing cell-cell and cell-extracellular matrix interactions through its anti-adhesive properties. Additionally, MUC4 acts as an intramembrane ligand for ERBB2, a receptor tyrosine kinase. This interaction leads to specific phosphorylation of ERBB2, contributing to proliferation and differentiation of epithelial cells. In polarized epithelial cells, MUC4 segregates ERBB2 and other ERBB receptors, preventing ERBB2 from acting as a coreceptor. The MUC4-ERBB2 interaction enhances the expression of CDKN1B, a cell cycle regulator. However, the formation of a complex involving MUC4, ERBB2, ERBB3, and NRG1 leads to downregulation of CDKN1B, suppressing apoptosis and promoting proliferation. MUC4's contribution to tumor growth might be primarily through its ability to inhibit apoptosis rather than enhance proliferation.
MUC4 is also known as ASGP, HSA276359, MUC-4.
