The Human Kinome

Following analysis of the human genome, a recent paper has identified 518 human protein kinases comprising 478 eukaryotic protein kinases (ePKs) and 40 atypical protein kinases (aPKs).44,45 Of these 518 human kinases, 510 have orthologs in the mouse kinome, which has recently been described,46 whereas the homology with worm, fly, and yeast kinomes shows clear evolutionary development, underlying the importance of kinases in regulating cellular function.47

The 518 human kinases have been classified into seven groups (TK, tyrosine kinase;TKL, tyrosine kinase-like; STE, homolog to yeast sterile 7, 11, and 20 kinases; CK1, containing casein kinase; AGC, containing protein kinase A (PKA), G (PKG), and C (PKC); CAMK, calcium/calmodulin-dependent-like kinase; CMGC, containing cyclin-dependent kinase (CDK), mitogen-activated protein kinase (MAPK), glycogen synthase kinase 3 (GSK-3), and Cdc2-like kinase (CLK) kinases), which are further divided into 134 families and 201 subfamilies (Figure 1).44,48 Hierarchical clustering based on the sequence of the catalytic domain is useful in defining kinase families, but does not cluster kinases by biochemical role or by inhibition profile. The latter can be achieved using selectivity data, and a recent paper describes this approach, using published data on 43 kinases.24

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