Figure 5.

Splicing to generate a premature termination codon is evolutionarily conserved in CLKs. The CDC-like kinases (CLKs) are splicing regulators that affect splicing decisions through the phosphorylation of SR proteins. (a) Our screen of SWISS-PROT revealed that human CLK1, CLK2 and CLK3 paralogs all generate PTC⁺ alternative isoforms. The splicing pattern that generates these isoforms, skipping exon 4, is conserved in each. This splicing pattern causes a frameshift and a PTC. The percent identities from global alignments between corresponding exons and introns are shown in purple. (b) CLKs were identified in mouse through existing annotation and in the predicted genes of the sea squirt C. intestinalis using an HMM constructed with annotated CLKs from a variety of organisms. An EST analysis revealed that the alternative splicing pattern that generates PTC⁺ alternative isoforms was conserved in all three sets of orthologs in human and mouse. The same splicing pattern was also found in the only C. intestinalis homolog. A relatively high degree of sequence similarity was found to be present in the introns flanking the alternative exon.