Protein kinase family classification

FIGURE 8.6 Parallel pathways to transcription and the MAP kinase family. The MAP kinases can be classified into three groups, based on the identity of the intermediate residue in their dual phosphorylation motifs (TEY, TGY, or TPY). This classification also defines three distinct signal-transduction pathways indicated as the ERK, the JNK/SAPK, and the p38/HOG pathway, each having unique protein kinases acting upstream. 

Selected entries from Methods in Enzymology [vol, page(s)] General Protein kinase classification, 200, 3 protein kinase catalytic domain sequence database identification of conserved features of primary structure and classification of family members,... 

Naumann, T. and Matter, H. (2002) Structural classification of protein kinases using 3d molecular interaction field analysis of their ligand binding sites Target family landscapes../. Med. Chem. 45, 2366-2378. 

The nonreceptor PTKs are a large group of signaling proteins that have diverse roles in the control of cell proliferation, differentiation, and death. Some are widely expressed others are restricted to particular tissues. Their early classification was dominated by the discovery of pp60src, to the extent that the major group of kinases were simply known as the Src family. There are at least ten known subfamilies of nonreceptor PTKs. 

Additional information <1, 2> (this group of enzymes is under review by NC-IUBMB, recommendation for a nomenclature system based on acceptor amino acid specificity rather than on protein substrate. In accordance with this system protein-tyrosine kinases would belong to EC 2.7.1 l.X, <1,2> [1] The present data set is restricted to a literature review and does not contain a complete description of kinases. Classification system based on kinase domain phylogeny revealing families of enzymes with related substrate specificities, <1,2> [3]) [1, 3]... 

Protein families are proteins related by structure or function. A protein family may be structurally diverse but have a particular cluster of amino acids at the active site that defines the class according to some catalytic function (e.g., dehydrogenases and kinases). Alternatively, proteins may have a structural motif that defines the class (e.g., helix-loop-helix motif of the EF-hand calcium-binding proteins). Proteins with identical function in different organisms often have slightly different primary structures (see below). The presence of certain amino acids relative to others in primary sequences allows putative protein sequences from the Human Genome Project, for example, to be classified into general protein families. Whether this initial classification is valid remains to be seen. 

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