Mucin

Mucins are a family of large, heavily glycosylated proteins. Although some mucins are membrane-bound due to the presence of a hydrophobic membrane-spanning domain that favors retention in the plasma membrane, the concentration here is on those mucins that are secreted on mucosal surfaces and saliva.

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Glycosylation and aggregation

Mucin genes encode mucin monomers that are synthesized as rod-shape apomucin cores that are post-translationally modified by exceptionally abundant glycosylation.

The dense "sugar coating" of mucins gives them considerable water-holding capacity and also makes them resistant to proteolysis, which may be important in maintaining mucosal barriers.

Mucins are secreted as massive aggregates of proteins with molecular masses of roughly 1 to 10 million Da. Within these aggregates, monomers are linked to one another mostly by non-covalent interactions, although intermolecular disulfide bonds may also play a role in this process.

Regions

Two distinctly different regions are found in mature mucins:

• The amino- and carboxy-terminal regions are very lightly glycosylated, but rich in cysteines, which are likely involved in establishing disulfide linkages within and among mucin monomers.

• A large central region formed of multiple tandem repeats of 10 to 80 residue sequences in which up to half of the amino acids are serine or threonine. This area becomes saturated with hundreds of O-linked oligosaccharides. N-linked oligosaccharides are also found on mucins, but much less abundantly.

Genes

At least 19 human mucin genes have been distinguished by cDNA cloning — MUC1, 2, 3A, 3B, 4, 5AC, 5B, 6-9, 11-13, and 15-19.

The major secreted airway mucins are MUC5AC and MUC5B, while MUC2 is secreted mostly in the intestine but also in the airway.

Clinical significance

Increased mucin production occurs in many adenocarcinomas, including cancer of the pancreas, lung, breast, ovary, colon, etc. Mucins are also overexpressed in lung diseases such as asthma, bronchitis, COPD or cystic fibrosis. Two membrane mucins, MUC1 and MUC4 have been extensively studied in relation to their pathological implication in the disease process. Moreover, mucins are also being investigated for their potential as diagnostic markers.

References

• Singh, A.P. et al. "Inhibition of MUC4 expression suppresses pancreatic tumor cell growth and metastasis." Cancer Research 2004 Jan 15;64(2):622-30. PMID 14744777

• Ali, M.S., et al. "Major secretory mucin expression in chronic sinusitis." Otolaryngol Head Neck Surg. 2005 Sep; 133(3); 423-8. PMID 16143194

• Perez-Vilar, J. and Hill, R. L. Mucin Family of Glycoproteins. Encyclopedia of Biological Chemistry (Lennarz & Lane, EDs.) Academic Press/Elsevier, Oxford, 2004, vol. 2, pp 758-764

• Singh, A.P. et al. "Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas". Prostate. 2006 Mar 1;66(4):421-9. PMID 16302265

• Singh, A.P. et al. "Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy." Cancer Research 2007 Jan 15, 67(2):433-6. PMID 17234748