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S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature)
Authors:Marenholz Ingo  Heizmann Claus W  Fritz Günter
Institution:Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zürich Steinwiesstrasse 75, #8032 Zürich, Switzerland. i.marenholz@mdc-berlin.de
Abstract:The S100 protein family is the largest subgroup within the superfamily of proteins carrying the Ca2+-binding EF-hand motif. Despite their small molecular size and their conserved functional domain of two distinct EF-hands, S100 proteins developed a plethora of tissue-specific intra- and extracellular functions. Accordingly, various diseases such as cardiomyopathies, neurodegenerative and inflammatory disorders, and cancer are associated with altered S100 protein levels. Here, we review the different S100 protein functions and related diseases from an evolutionary point of view. We analyzed the structural variations, which are the basis of functional diversification, as well as the genomic organization of the S100 family in human and compared it with the S100 repertoires in mouse and rat. S100 genes and proteins are highly conserved between the different mammalian species. Moreover, we identified evolutionary related subgroups of S100 proteins within the three species, which share functional similarity and form subclusters on the genomic level. The available S100-specific mouse models are summarized and the consequences of our results are discussed with regard to the use of genetically engineered mice as human disease models. An update of the S100 nomenclature is included, because some of the recently identified S100 genes and pseudogenes had to be renamed.
Keywords:S100 proteins  Nomenclature  EF-hand  Calcium  Protein structure  Evolution  Gene cluster  Chromosome 1q21  Comparative map  Mouse models
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