Nucleotide homologies in genes encoding members of the S100 protein family

Members of the S100 protein family exhibit a unique pattern of cell/tissue-specific expression and approx. 50% similarity at the amino-acid level. The cDNAs encoding many of these proteins from a variety of species are now available making a comparison of these family members at the nucleotide level possible. With few exceptions, family members exhibited less nucleotide identity than amino-acid similarity. Furthermore, the pattern of divergence calculated on the basis of nucleotide identity did not always agree with that calculated on the basis of amino-acid similarity. The majority of sequence diversity occurred in the nontranslated regions suggesting that these regions may be involved in directing the expression of particular members of the family to specific cell types. When comparisons of individual family members were made across species, the following order of species diversity was observed: rat/mouse < human/bovine < porcine < rabbit/avian < Xenopus laevis. The structure of the gene loci encoding these proteins was remarkably conserved both within family members of a given species as well as in individual family members from different species. Although there appears to be great diversity in the 5' flanking regions of these genes, members of the family share at least. one common potential regulatory element - the S100 protein element. Thus, membership in the S100 family could be ascertained on the basis of gene organization and the presence of an SPE. Although functional data are limited, the available data indicate that the regulation of the expression of S100 family members is complex and involves both positive and negative regulatory elements. Additional nucleic acid sequences and complimentary functional studies will be required to dissect the mechanisms which target the expression of the members of this family to specific cell types during development.