Protein Kinase Evolution

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Ancient Kinase Evolution

Most protein kinases belong to the protein kinase-like (PKL) fold. PKLs are found in eukaryotes, bacteria, archaea, and many viruses, and mediate phosphorylation of both proteins and various small molecules. Within eukaryotes, most PKL protein kinases belong to the ePK (eukaryotic protein kinase) superfamily, which is eukaryote-specific.

Eukaryotic Protein Kinases (ePK)

These typically constitute ~2% of all genes in most eukaryotic genomes, making them probably the most successful expanded family in all the eukaryotes. While there is considerable turnover and invention of new kinases in different species, a core of 50-60 kinases are found in most organisms, and likely present in the common ancestor of all extant eukaryotes (see


Archaeae have a very simple set of PKL protein kinases: every archaeal genome has just 3 kinases: Bud32, Rio1, and Rio2. Each is also present in all eukaryotes, almost always in single copies (metazoans also have a Rio3). The functions of all three are relatively mysterious and varied, though the Rio's have been associated with translation, jibing with the commonality between eukaryotes and archaeae in the translational apparatus. Bud32 is associated with p53 and gene regulation in metazoans, and with telomere biology, which may also correlate with the archaeal-eukaryotic link in DNA biology. As far as we know (in 2011), archaeae have no other PKLs.


Bacteria have a wide array of PKL families, with a spotty phylogenetic distribution. Like histidine kinases, they vary a lot even between closely-related species, providing specificity for individual species.

The PKN family of protein kinases is very similar to ePKs.

The CAK group of small molecule kinases is the largest and most diverse. Named after Choline and Aminoglycoside Kinases, it also includes a wide variety of uncharacterized genes. It also contains three related families that are better defined: Homoserine Kinases, Fructosamine Kinases and MTRKs. Other families of PKL kinases are found in bacteria include UbiB (homologs of the eukaryotic ABC1 kinases), KdoK (lipopolysaccharide kinase) and PI3K (phosphatidyl inositol kinases, also found in eukaryotes)

Evolution of Tyrosine Phosphorylation

See Evolution of tyrosine kinases