Figure 2

Gene structure and isoforms generated by alternative splicing of dynactin1. The gene structure was reconstructed with WebScipio and represents the dynactin1 (p150) homolog of Homo sapiens encoded by 32 exons including four alternatively spliced exons (A). Dark gray bars represent exons, light gray bars indicate introns, and coloured bars symbolize the alternatively spliced exons. For better visualisation, exons and introns are scaled differently. ATG in orange rectangles represent translation start positions. Translation start codons exist in exons 1, 2, and 6, respectively. The zero in green rectangles represents the first reading frame. A zoomed view on the exons 21–25 shows intron retention of intron 22 (dark-green bar) that results in the translation of exon 23 in a different reading frame leading to a premature stop codon (light-green bar). The protein sequences for the alternative exons are given (B) as well as a short summary of the combinations of the alternatively spliced exons that have been found in full-length cDNA data (C). Due to missing full-length cDNA sequences the inclusion or exclusion of alternative exon 27 could not be determined for all combinations of exons 5 to 7 (ND = not determined). The sequence logos (D) illustrate the sequence conservation within the multiple sequence alignment of the CAP-Gly domain. For better orientation, the sequences of three representative CAP-Gly domains are shown: the human CAP-Gly domain as the main target of disease associated mutations, the Saccharomyces cerevisiae and the Dictyostelium CAP-Gly domains as representatives of widely used model organisms. β-strands as determined from the crystal structure are drawn as yellow arrows. Green dots point to amino acids of the human CAP-Gly domain that have been proposed to constitute the second EB1-binding site [59] and red dots highlight residues that are part of the conserved EEY/F motif binding site [25, 59, 60]. Some mutations as found in human diseases are given below the reference sequences with numbering referring to human dynactin1.