Schematic of defined domains of NEDD9, including SH3, unstructured substrate domain (SD), serine rich (SR) four- helix bundle domain, and C-terminal focal adhesion targeting (FAT) domain containing a Src-binding region (SB). Diagram indicates some (not all) defined interactors with NEDD9, proximal to defined association motifs. These include the kinase FAK, which binds the SH3 domain. The SD contains multiple YxxP motifs, which are phosphorylated by Src-family kinases such as Fyn, Lck and Src to create binding sites for proteins with SH2 domains, such as Crk. Kinase Aurora-A binds NEDD9 and phosphorylates serine 296 in the SD, supporting mitotic activities. The FAT-like domain interacts with NSP and other proteins, and contributes to NEDD9 targeting to focal adhesions.