Figure 4. Statistical Coupling Analysis (SCA) of the Eukaryotic Protein Kinases.

The analysis was performed for two different multiple sequence alignments of the kinase catalytic domain: one specific to the CMGC kinases (635 sequences), and one containing 7128 kinases sampled across the kinome.

A. Histogram showing the distribution of pairwise sequence identities computed across all pairs of sequences in the CMGC alignment.

B. As in (A) but for the kinome wide alignment. Both alignments show a unimodal distribution with a mean pairwise sequence identity near ~25%.

C. Sector positions derived from the CMGC alignment (blue) or kinome-wide alignment (yellow) are distributed along the primary and secondary structure of the CMGC/MAPK ERK2. Subfamily-specific regions, such as the MAPK-insert, are only part of the sector derived from the CMGC alignment.

D. The relationship between the sector and positional conservation (computed as the Kullback-Leibler relative entropy, D_i) for both the CMGC and kinome-wide alignments. Sector positions are highlighted in blue or yellow for the CMGC and kinome-wide alignments respectively. Red stars indicate highly conserved positions (defined as D_i > 2.0 in the kinome-wide alignment).

E. The kinome-wide and CMGC-specific sectors (yellow and blue transparent surfaces, respectively) mapped on human ERK2 (gray ribbon) (PDB: 2ERK). Conserved positions are shown as red spheres.