PMC:441373 / 21932-25481 JSONTXT

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The main conserved feature of the TACC family, the TACC domain, is located at the carboxy terminus of the protein. In the case of the C. elegans TAC protein, this structure comprises the majority of the protein and is encoded by two of the three exons of the gene. In the higher organisms, D. melanogaster, and the deuterostomes C. intestinalis to human, this feature is also encoded by the final exons of the gene (five in D. melanogaster, seven in the deuterostome genes). Outside of the TACC domain, however, TACC family members show relatively little homology. It is interesting that each TACC gene contains one large exon, which shows considerable variability between TACC orthologues, and constitutes the main difference between the TACC3 genes in the vertebrates (see below). In deuterostomes, this exon contains the SDP repeat (or in the case of the murine TACC3's, a rodent-specific 24 amino acid repeat), which is responsible for the binding of the SWI/SNF chromatin remodeling complex component GAS41 [15,16].\nOf the vertebrate TACC proteins, the TACC3 orthologues show the greatest variability in size and sequence, ranging in size from 599 amino acids for the rat TACC3 protein, to 942 amino acids in the Danio rerio protein. The reasons for these differences are apparent from the genomic structure of the TACC3 orthologues. TACC3 can be divided into three sections: a conserved N-terminal region (CNTR) of 108 amino acids, encoded by exons 2 and 3 in each vertebrate TACC3 gene, the conserved TACC domain distributed over the final seven exons, and a highly variable central region. The lack of conservation in both size and sequence of the central portion of the TACC3 proteins of human and mouse has been previously noted, and accounts for the major difference between these two orthologues [2]. The majority of this central portion, which contains the SDP repeat motifs, is encoded by one exon in human and the pufferfish (emb|CAAB01001184). In rodents, however, this region is almost entirely composed of seven 24 amino acid repeats, which are located in a single exon of the mouse and rat TACC3 genes. It has been previously reported that there are four mouse TACC3 splice variants that differ in the number of these repeats [2,7,17]. As these repeats are present in a single exon, it appears likely that these different sequences may be the result of the DNA polymerases used in the cDNA synthesis and/or PCR reaction stuttering through the repeat motif. The correct sequence, reported by Sadek et al [7], is the one used throughout the entirety of this manuscript. These repeats are not evident in the rabbit protein, or any other TACC protein, and may indicate that the rodent TACC3 has evolved distinct functions, as has already been noted for the amphibian Xenopus TACC3, maskin 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