Kinome Explained

In molecular biology, biochemistry and cell signaling the kinome of an organism is the complete set of protein kinases encoded in its genome. Kinases are usually enzymes that catalyze phosphorylation reactions (of amino acids) and fall into several groups and families, e.g., those that phosphorylate the amino acids serine and threonine, those that phosphorylate tyrosine and some that can phosphorylate both, such as the MAP2K and GSK families. The term was first used in 2002 by Gerard Manning and colleagues in twin papers analyzing the 518 human protein kinases, and refers to both protein kinases and protein pseudokinases^[1] and their evolution of protein kinases throughout the eukaryotes.^[2] Other kinomes have been determined for rice,^[3] several fungi, nematodes, and insects, sea urchins,^[4] Dictyostelium discoideum,^[5] and the process of infection by Mycobacterium tuberculosis.^[6] Although the primary sequence of protein kinases shows substantial divergence between unrelated eukaryotes, and amino acid differences in catalytic motifs have permitted their separation of kinomes into canonical and pseudokinase subtypes,^[7] the variation found in the amino acid motifs adjacent to the site of actual phosphorylation of substrates by eukaryotic kinases is much smaller.^[8]

As kinases are a major drug target and a major control point in cell behavior, the kinome has also been the target of large scale functional genomics with RNAi screens and of drug discovery efforts, especially in cancer therapeutics.^[9]

In animals, the kinome includes kinases that phosphorylate only tyrosine (tyrosine kinases), those that act on serine or threonine, and a few classes, such as GSK3 and MAP2K that can act on both. Research has shown that there are specialized protein domains that bind to phosphorylated serine and threonine residues, such as BRCA and FHA domains.

See also

• Kinase
• Pseudokinase
• Pseudoenzyme
• Phosphatome
• Protein phosphatase

External links

• KinBase
• Rice Kinome Database

Notes and References

1. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S . The protein kinase complement of the human genome. Science. 298. 5600. 1912–34. December 2002. 12471243. 10.1126/science.1075762. 2002Sci...298.1912M. 26554314.
2. Manning G, Plowman GD, Hunter T, Sudarsanam S . Evolution of protein kinase signaling from yeast to man. Trends Biochem. Sci.. 27. 10. 514–20. October 2002. 12368087. 10.1016/S0968-0004(02)02179-5.
3. Dardick C, Chen J, Richter T, Ouyang S, Ronald P . The Rice Kinase Database. A Phylogenomic Database for the Rice Kinome. Plant Physiol.. 143. 2. 579–86. February 2007. 17172291. 1803753. 10.1104/pp.106.087270.
4. Bradham CA, Foltz KR, Beane WS, etal . The sea urchin kinome: a first look. Dev. Biol.. 300. 1. 180–93. December 2006. 17027740. 10.1016/j.ydbio.2006.08.074. free.
5. Goldberg JM, Manning G, Liu A, etal . The Dictyostelium Kinome—Analysis of the Protein Kinases from a Simple Model Organism. PLOS Genet.. 2. 3. e38. March 2006. 16596165. 1420674. 10.1371/journal.pgen.0020038. free.
6. Hestvik AL, Hmama Z, Av-Gay Y . Kinome Analysis of Host Response to Mycobacterial Infection: a Novel Technique in Proteomics. Infect. Immun.. 71. 10. 5514–22. October 2003. 14500469. 201077. 10.1128/IAI.71.10.5514-5522.2003.
7. Reiterer V, Eyers PA, Farhan H . Day of the dead: pseudokinases and pseudophosphatases in physiology and disease.. Trends in Cell Biology . 24 . 9 . 489–505. 2014 . 24818526 . 10.1016/j.tcb.2014.03.008 .
8. Diks SH, Parikh K, van der Sijde M, Joore J, Ritsema T, Peppelenbosch MP . Evidence for a Minimal Eukaryotic Phosphoproteome?. PLOS ONE . 2 . 1 . 777. 2007 . 17712425 . 10.1371/journal.pone.0000777 . 1945084 . 2007PLoSO...2..777D. Insall . Robert. free.
9. Workman P. Drugging the cancer kinome: progress and challenges in developing personalized molecular cancer therapeutics. Cold Spring Harb. Symp. Quant. Biol.. 70. 499–515. 2005. 16869789. 10.1101/sqb.2005.70.020. free.