Extensive sugar decoration

In the two previous chapters we dealt with problems of assigning function to proteins or protein domains. We concerned ourselves with methods relying on sequence similarity, i.e. methods based on local alignment or profiles. We will now see an example of a functional domain which is not easily identified on the basis of sequence similarity or with profiles. It has specific properties as it has a characteristic amino acid composition and functional properties based on that composition. However, the properties of the domain may not be captured on the basis of sequence alignment or by position-specific information. The domain in question is characteristic of a group of proteins referred to as mucins (Perez-Vilar and Hill, 1999; Hollingsworth and Swanson, 2004).

A characteristic property of all mucins is the ability to form gels. Mucins are a major component of the mucous layer that is present on the surface of epithelial cells of the lung and intestine. The proteins act as a diffusion barrier to prevent harmful microorganisms and substances having more intimate contact with the cell. Mucins also function as lubricants to protect epithelial cells from dehydration and physical and chemical injury. Because mucins protect against pathogens, they play an important role in immune defence. In addition, certain mucins are associated with colon cancer (Hollingsworth and Swanson, 2004) and there is a strong association between the mucin Muc2 and the inflammatory bowel disease ulcerative colitis. For example, inflammation of the large intestine similar to ulcerative colitis is observed in mice that are deficient in the mucin Muc2 (Heazlewood et al., 2008).