The Three Human Syntrophin Genes Are Expressed in Diverse Tissues, Have Distinct Chromosomal Locations, and Each Bind to Dystrophin and Its Relatives (*)

The syntrophins are a biochemically heterogeneous group of 58-kDa intracellular membrane-associated dystrophin-binding proteins. We have cloned and characterized human acidic (α1-) syntrophin and a second isoform of human basic (β2-) syntrophin. Comparison of the deduced amino acid structure of the three human isoforms of syntrophin (together with the previously reported human β1-syntrophin) demonstrates their overall similarity. The deduced amino acid sequences of human α1- and β2-syntrophin are nearly identical to their homologues in mouse, suggesting a strong functional conservation among the individual isoforms. Much like β1-syntrophin, human β2-syntrophin has multiple transcript classes and is expressed widely, although in a distinct pattern of relative abundance. In contrast, human α1-syntrophin is most abundant in heart and skeletal muscle, and less so in other tissues. Somatic cell hybrids and fluorescent in situ hybridization were both used to determine their chromosomal locations: β2-syntrophin to chromosome 16q22-23 and α1-syntrophin to chromosome 20q11.2. Finally, we used in vitro translated proteins in an immunoprecipitation assay to show that, like β1-syntrophin, both β2- and α1-syntrophin interact with peptides encoding the syntrophin-binding region of dystrophin, utrophin/dystrophin related protein, and the Torpedo 87K protein.

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