[Frontiers in Bioscience 6, d1192-1206, October 1, 2001]
Structural Organization and Classification of the Human Mucin Genes
Nicolas Moniaux1, 2, Fabienne Escande2, Nicole Porchet2, Jean-Pierre Aubert2 and Surinder K. Batra1
1Department of Biochemistry and Molecular Biology, The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-4525, USA; 2Unité 377 INSERM, Place de Verdun, 59045 Lille Cedex and Laboratoire de Biochimie et de Biologie Moléculaire de l'Hôpital C. Huriez, 59037 Lille Cedex, France
TABLE OF CONTENTS
The cells of living organisms in contact with the external environment are constantly attacked by different kinds of substances such as micro-organisms, toxins, and pollutants. With evolution, defense mechanisms, such as the secretion of mucus has been developed. Mucins are the main components of mucus. They are synthesized and secreted by specialized cells of the epithelium and in some case, by non mucin-secreting cells. Little was known about the structure of mucins until a decade ago. This is principally due to heavy glycosylation of mucins, which complicated their analysis. With the application of molecular biological methods, structures of the mucin core peptides (apomucins) are beginning to be elucidated. A total of eleven human mucin (MUC) genes have been identified and numbered in chronological order of their description: MUC1-4, MUC5AC, MUC5B, MUC6-8, and MUC11-12. Of these, the complete cDNA sequence are published only for six mucins MUC1, MUC2, MUC4, MUC5B, MUC5AC, and MUC7. Human mucin genes, in general, show three common features: I) a nucleotide tandem repeat domain; II) a predicted peptide domain containing a high percentage of serines and threonines; III) complex RNA expression. The tandem repeats in mucins make up the majority of the backbone. Related to their structure, mucins can be classified in three distinct sub-families: gel-forming, soluble, and membrane-bound. Each member from one family possesses common characteristics and probably specific functions. For a long time, they were thought to have the unique function of protecting and lubricating the epithelial surfaces. The study of the mucins structure as well as the relationship between structure and function show that mucins also possess other important functions, such as growth, direct implication in the fetal development, the epithelial renewal and differentiation, the epithelial integrity, carcinogenesis, and metastasis. This review presents the actual knowledge on the mucins structure and the best-characterized function related to their structure.