Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of vertebrate Cdc42-Interacting Protein 4 and FormiN Binding Protein 1-Like
CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. FNBP1L, also called Toca-1 (Transducer of Cdc42-dependent actin assembly 1), forms a complex with neural WASP; the complex induces the formation of filopodia and endocytic vesicles. FNBP1L is required for Cdc42-induced actin assembly and is essential for autophagy of intracellular pathogens. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. CIP4 and FNBP1L contain an N-terminal F-BAR domain, a central HR1 domain, and a C-terminal SH3 domain. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; the HR1 domain of CIP4 binds Cdc42 and TC10. Translocation of CIP4 is facilitated by its binding to TC10 at the plasma membrane.