whole genome duplications after the cephalochordate/vertebrate split, there are several paralogs in every group. Thus ERK1 and ERK2 both correspond to the Drosophila kinase rolled, JNK1, JNK2 and JNK3 are all orthologous to the gene basket in Drosophila. Although among the p38 group, p38 alpha and beta are clearly paralogous pairs, and so are p38 gamma and delta in vertebrates, the timing of the base split is less clear, given that many metazoans already possess multiple p38 homologs (there are three p38-type kinases in Drosophila, Mpk2(p38a), p38b and p38c). The single ERK5 protein appears to fill a very specialized role (essential for vascular development in vertebrates) wherever it is present. This lineage has been deleted in protostomes, together with its upstream pathway components (MEKK2/3, MKK5), although they are clearly present in cnidarians, sponges and even in certain unicellular organisms (e.g. the choanoflagellate Monosiga brevicollis) closely related to the origins of multicellular animals. The split between classical and some atypical MAP kinases happened quite early. This is suggested not just by the high divergence between extant genes, but also recent discoveries of atypical MAPKs in primitive, basal eukaryotes. The genome sequencing of Giardia lamblia revealed the presence of two MAPK genes, one of them similar to the already-well-known mammalian MAPKs (ERKs, p38s, etc.), the other one showing similarities to the mammalian ERK7 protein. The situation is similar in the multicellular amoeba Dictyostelium discoideum, where the ddERK1 protein appears to be a classical MAPK, while ddERK2 more closely resembles our ERK7 and ERK3/4 proteins. Atypical MAPKs can also be found in higher plants, although they are poorly known. Similar to the situation in mammals, most aspects of atypical MAPKs are uncharacterized due to the lack of research focus on this area. Substrate and partner recognition As typical for the CMGC kinase group, the catalytic site of MAP kinases has a very loose consensus sequence for substrates. Like all their relatives, they only require the target serine / threonine amino acids to be followed by a small amino acid, preferably proline ("proline-directed kinases"). But as SP/TP sites are extremely common in all proteins, additional substrate-recognition mechanisms have evolved to ensure signaling fidelity. Unlike their closest relatives, the cyclin-dependent kinases (CDKs), where substrates are recognized by the cyclin subunit, MAPKs associate with their substrates via auxiliary binding regions on their kinase domains. The most important such region consists of the hydrophobic docking groove and