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Evolution of protein kinase substrate recognition at the active site

Fig 1

Family and subfamily divergent residues.

(A) Kinase domain phylogeny for 2,094 different kinase domains, spanning 9 species. Each sequence has been coloured according to its group membership. (B) Explanation of the score used to identify divergent residues. RC: conservation of the residue within the family of interest. AC: extent to which the ancestral residues are conserved between sister clades in the phylogeny. p(AC): a measure of confidence in the ancestral sequence prediction. A full explanation is given in the Materials and methods section. (C–F) Examples of residues predicted to be functionally divergent in the SRPK (PDB: 1WBP), CDC7 (PDB: 4F9A), CAMK2 (PDB: 5H9B), and PLK (PDB: 4B6L with peptide binding modelled) families. In these 4 examples, kinase residues have been numbered according to their position in the protein kinase domain (Pfam: PF00069). The peptides and/or proteins that physically interact with the kinase have been coloured in yellow. AC, ancestral conservation; AGC, (PKA, PKG, PKC); AUR, Aurora Kinase; CAMK, Calcium- and Calmodulin-regulated kinases; CAMK2, Calcium/calmodulin-dependent protein kinase type 2; CDC7, Cell Division Cycle 7-related protein kinase; CK1, Casein Kinase 1; CK 2, Casein Kinase 2; CLK, CDK-Like Kinase; CMGC, (cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAP kinases), glycogen synthase kinases (GSK) and CDK-like kinases (CLKs)); PDB, Protein Data Bank; PHK, Phosphorylase Kinase; Pfam, Protein families; PLK,; Polo-like kinase RC, recent conservation; SRPK, SR-rich protein kinase; STE, sterile mutant; TK, tyrosine kinase; TKL, Tyrosine Kinase-Like.

Fig 1