S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature)

The S100 protein family is the largest subgroup within the superfamily of proteins carrying the Ca 2+-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 extracellul...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2004-10, Vol.322 (4), p.1111-1122
Main Authors: Marenholz, Ingo, Heizmann, Claus W., Fritz, Günter
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Calcium
Chromosome 1q21
Comparative map
EF-hand
Evolution
Evolution, Molecular
Gene cluster
Heart Diseases - etiology
Humans
Inflammation - etiology
Mice
Models, Animal
Molecular Sequence Data
Mouse models
Multigene Family
Neoplasms - etiology
Neurodegenerative Diseases - etiology
Nomenclature
Phylogeny
Protein structure
Rats
S100 proteins
S100 Proteins - chemistry
S100 Proteins - classification
S100 Proteins - genetics
S100 Proteins - physiology
Terminology as Topic
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Summary:The S100 protein family is the largest subgroup within the superfamily of proteins carrying the Ca 2+-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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2004.07.096