Mouse α1- and β2-syntrophin gene structure, chromosome localization, and homology with a discs large domain

Abstract

The syntrophin family of dystrophin-associated proteins consists of three isoforms, α1, β1, and β2, each encoded by a distinct gene. We have cloned and characterized the mouse α1- and β2-syntrophin genes. The mouse α1- syntrophin gone (>24 kilobases) is comprised of eight exons. The mouse β2- syntrophin gene (>33 kilobases) contains seven exons, all of which have homologues at the corresponding position in the α1-syntrophin gene. Primer extension analysis reveals two transcription initiation sites in the α1- syntrophin gene and a single site in the β2-syntrophin gene. The sequence immediately 5' of the transcription start sites of both genes lacks a TATA box but is GC-rich and has multiple putative SP1 binding sites. The α1- syntrophin gene is located on human chromosome 20 and mouse chromosome 2, while the β2-syntrophin gene is on human chromosome 16 and mouse chromosome 8. Analysis of the amino acid sequence of the syntrophins reveals the presence of four conserved domains. The carboxyl-terminal 56 amino acids are highly conserved and constitute a syntrophin unique domain. Two pleckstrin homology domains are located at the amino-terminal end of the protein. The first pleckstrin homology domain is interrupted by a domain homologous to repeated sequences originally found in the Drosophila discs-large protein.