Fig. 1. Modular domains in the Abl family of tyrosine kinases. The extreme N-terminus of the c-Abl protein contains a variable region (V, light and dark gray), which in some family members contains a Cap region (dark gray) and/or a consensus motif for N-terminal myristoylation (Myr-). The Src homology-3 domain (SH3, yellow), Src homology-2 domain (SH2, green) and the catalytic domain (Kinase, dark blue) make up the remaining N-terminal half of c-Abl. In the C-terminal half there are four PXXPXK/R sequences (light blue), three nuclear localization sequences (NLS, black), one nuclear export sequence (NES, light green) and three high mobility group-like boxes (HLB, white). In addition, at the extreme C-terminus there is an actin-binding domain (Actin-BD), which contains a region that mediates binding to monomeric actin (G, pink) and a consensus motif that mediates binding to filamentous actin (F, orange). The regulatory Y245 and Y412 are indicated as red circles. The sequence conservation for these domains, regions and residues in other members of the Abl family is depicted here (in some cases not yet supported experimentally). The oncogenic forms of Abl contain modified N-termini: v-Abl contains a viral gag sequence and Bcr-Abl contains the N-terminal portion of the breakpoint cluster region protein, as labeled. Unique to Drosophila Abl is a consensus motif for binding to EVH1 domains (EFPPPPXD, purple) and unique to Arg is an additional C-terminal F-actin binding region (F-actin-BD 2).