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.
Background References
1. Tang J et al. The role of the AMOP domain in MUC4/Y-promoted tumour angiogenesis and metastasis in pancreatic cancer. J Exp Clin Cancer Res 35:91 (2016).
2. Lee H et al. DA-6034-induced mucin secretion via Ca2+-dependent pathways through P2Y receptor stimulation. Invest Ophthalmol Vis Sci 55:6565-74 (2014).
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.
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.