Group-specific component is not only a vitamin-D-binding protein.

The vitamin-D-binding protein (DBP), also called group-specific component, is well known for two main reasons: its genetic polymorphism, and its binding affinities for actin and vitamin D compounds. In recent years, additional binding affinities have been described for this puzzling molecule, without any significant biological explanations being given for these observations. The molecular genetic data for DBP are analyzed in order to show that the affinities for vitamin D are supported by the genetic variability. The molecular evolution of the protein shows that the ancestral gene was present long before the development of related genes, such as those for albumin and alpha-fetoprotein. Other affinities for actin, C5a-desArg and for a B lymphocyte mitogen are also discussed. DBP is mainly present in the circulating blood as an apoprotein. The cytoplasmic presence of DBP has not been confirmed, and the major question today is to understand the biological role of this protein. In the last part of the review, the discussion focuses on relating the different binding affinities of DBP to its biological activities. Avenues for future research are also outlined: these include DBP metabolism, the differentiation of macrophages, and the activity of DBP during embryonic development.