Kinome

{{Short description|Set of all protein kinases encoded in a genome}} {{About|the term in molecular biology|the plant and food|Zanthoxylum piperitum}} 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<ref name="Human_Kinome">{{cite journal |vauthors=Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S |title=The protein kinase complement of the human genome |journal=Science |volume=298 |issue=5600 |pages=1912–34 |date=December 2002 |pmid=12471243 |doi=10.1126/science.1075762 |bibcode=2002Sci...298.1912M |s2cid=26554314 |url= }}</ref> and their evolution of protein kinases throughout the eukaryotes.<ref name="Kinome_Evolution">{{cite journal |vauthors=Manning G, Plowman GD, Hunter T, Sudarsanam S |title=Evolution of protein kinase signaling from yeast to man |journal=Trends Biochem. Sci. |volume=27 |issue=10 |pages=514–20 |date=October 2002 |pmid=12368087 |doi=10.1016/S0968-0004(02)02179-5 |url= }}</ref> Other kinomes have been determined for rice,<ref name="Dardick">{{cite journal |vauthors=Dardick C, Chen J, Richter T, Ouyang S, Ronald P |title=The Rice Kinase Database. A Phylogenomic Database for the Rice Kinome |journal=Plant Physiol. |volume=143 |issue=2 |pages=579–86 |date=February 2007 |pmid=17172291 |pmc=1803753 |doi=10.1104/pp.106.087270 |url= }}</ref> several fungi, nematodes, and insects, sea urchins,<ref name="Bradham">{{cite journal |vauthors=Bradham CA, Foltz KR, Beane WS, etal |title=The sea urchin kinome: a first look |journal=Dev. Biol. |volume=300 |issue=1 |pages=180–93 |date=December 2006 |pmid=17027740 |doi=10.1016/j.ydbio.2006.08.074 |url= |doi-access=free }}</ref> ''Dictyostelium discoideum'',<ref name="Goldberg">{{cite journal |vauthors=Goldberg JM, Manning G, Liu A, etal |title=The Dictyostelium Kinome—Analysis of the Protein Kinases from a Simple Model Organism |journal=PLOS Genet. |volume=2 |issue=3 |pages=e38 |date=March 2006 |pmid=16596165 |pmc=1420674 |doi=10.1371/journal.pgen.0020038 |url= |doi-access=free }}</ref> and the process of infection by ''Mycobacterium tuberculosis''.<ref name="TB-Human_Kinome">{{cite journal |vauthors=Hestvik AL, Hmama Z, Av-Gay Y |title=Kinome Analysis of Host Response to Mycobacterial Infection: a Novel Technique in Proteomics |journal=Infect. Immun. |volume=71 |issue=10 |pages=5514–22 |date=October 2003 |pmid=14500469 |pmc=201077 |doi=10.1128/IAI.71.10.5514-5522.2003 |url= }}</ref> 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,<ref>{{cite journal |vauthors=Reiterer V, Eyers PA, Farhan H |title=Day of the dead: pseudokinases and pseudophosphatases in physiology and disease.|journal=Trends in Cell Biology |volume=24 |issue=9 |pages=489–505|year=2014 |pmid=24818526 |doi=10.1016/j.tcb.2014.03.008 }}</ref> the variation found in the amino acid motifs adjacent to the site of actual phosphorylation of substrates by eukaryotic kinases is much smaller.<ref>{{cite journal |vauthors=Diks SH, Parikh K, van der Sijde M, Joore J, Ritsema T, Peppelenbosch MP |title=Evidence for a Minimal Eukaryotic Phosphoproteome?|journal=PLOS ONE |volume=2 |issue=1 |pages=777|year=2007 |pmid=17712425 |doi=10.1371/journal.pone.0000777 |pmc=1945084 |bibcode=2007PLoSO...2..777D|editor1-last=Insall |editor1-first=Robert|doi-access=free}}</ref>

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.<ref name="Workman">{{cite journal |author=Workman P |title=Drugging the cancer kinome: progress and challenges in developing personalized molecular cancer therapeutics |journal=Cold Spring Harb. Symp. Quant. Biol. |volume=70 |issue= |pages=499–515 |year=2005 |pmid=16869789 |doi=10.1101/sqb.2005.70.020 |url= |doi-access=free }}</ref>

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.{{Citation needed|date=June 2009}} Research has shown that there are specialized protein domains that bind to phosphorylated serine and threonine residues, such as BRCA and FHA domains.{{citation needed|date=December 2018}}

==References== {{reflist|2}}

==External links== * [http://kinase.com/kinbase/index.html KinBase] * [https://web.archive.org/web/20080723230101/http://rkd.ucdavis.edu/ Rice Kinome Database]

Category:Proteomics Category:Protein kinases