Dual-Domain Kinases

<p>The <i>Dictyostelium</i> dual-domain kinases are drawn to scale. The kinase domains are shown in blue, broken by a dashed line in instances where there is a large insert in the kinase domains. The classification (group/family/subfamily) of each kinase domain is indicated above each domain. An X through the kinase domain indicates that it is predicted to be catalytically inactive.</p

Protein Kinase Pseudogenes

<p>The genomic loci for putative pseudogenes, together with their most likely parental genes, are shown. Pseudogene exons are shaded yellow, and parental gene exons are shaded orange. Stop codons are indicated with an asterisk, and frameshifts by “fs.” The percentage identity in amino acid sequence between pairs of sequences is shown to the right of the drawings. The number of ESTs, as reported at <a href="http://www.dictybase.org," target="_blank">http://www.dictybase.org,</a> is shown. The results of RT-PCR experiments are shown. +, a product was obtained; −, no product was obtained; ND, not determined. All are drawn to the scale shown in the bottom right of the figure, except Gdt3_ps, which has a condensed scale. For DDB0187382_ps and DDB0204419_ps, no putative parental gene could be identified.</p

Group-Level Comparison of the <i>Dictyostelium</i> and Other Kinomes

<p>Pie charts depict the proportion of the kinome that is devoted to the major groups in <i>Dictyostelium,</i> yeast, worm, flies, and humans. The size of the pie is proportional to the number of kinase domains in each organism, and the total number of kinases in each group is shown in the slice. Data for other organisms are from KinBase (<a href="http://kinase.com" target="_blank">http://kinase.com</a>). The portion of each group that is in families or subfamilies not found in the other four kinomes is indicated with a black arc drawn outside the slice for that group.</p

Receptor Kinases

<p>The 17 <i>Dictyostelium</i> kinases that are strongly predicted to have TMDs are depicted. The drawings are approximately to scale.</p

Summary of Kinase Subfamily Invention and Loss

<p>Comparison of <i>Dictyostelium</i> with four other kinomes suggests that 75 distinct subfamilies existed in their common ancestor, and that new subfamilies were born (positive numbers) and lost (negative numbers) in most lineages. Numbers in parenthesis indicate “unique” kinases within each lineage that may be classified as novel subfamilies when more kinomes are analyzed. Most notably, S. cerevisiae has lost 24 subfamilies present in the common ancestor, while metazoans invented an additional 80 conserved subfamilies.</p

Tree of the <i>Dictyostelium</i> Kinome

<p>A tree of 248 <i>Dictyostelium</i> ePK domains is presented. Pseudogenes, Chromosome 2 duplications, and sequences with very divergent ePK domains were omitted. The N- and C-terminus domains of dual-domain kinases, respectively designated by an “-a” or “-b” extension, were analyzed independently. Group and family names are shown in bold type, subfamily names in plain type, and <i>Dictyostelium</i>-specific families and subfamilies in italic. Selected protein names are shown in red. Branch lengths reflect relative distances between ePK domains. A branching order could not be assigned in the region indicated by the small gray circle because of the diversity of the sequences.</p

Putative nuclear export signals.

<p>The signals according to Wada et al. (1998) have been identified manually. Sequences in brackets had too weak characteristics to define them as explicit nuclear export signals.</p

Structural homology among the <i>D. discoideum</i> Arps.

<p>The sequences were modeled in comparison to the Act8-type actin (upper left). Whereas Arps 1, 2 and 3 show high similarity to the three-dimensional structure of actin, Arp 5, 6 and 11 are clearly different. Attempts to model Arps 4 and 8 failed due to low structural homology and the absence of available templates. Filactin (Fia, lower right) shows high structural homology in the actin domain. Modeling was done using the Swiss Model Server <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002654#pone.0002654-Schwede1" target="_blank">[58]</a>, graphics were generated with the YASARA molecular visualization software <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002654#pone.0002654-Kalay1" target="_blank">[59]</a>.</p

Occurrence of Arps in model organisms. (* assembly).

<p>Occurrence of Arps in model organisms. (* assembly).</p

Actin pseudogenes in the <i>D. discoideum</i> genome (aa: amino acids).

<p>Actin pseudogenes in the <i>D. discoideum</i> genome (aa: amino acids).</p