RIN2 and RIN3 are two closely related RPM1-interacting proteins conserved in higher eukaryotes. They are orthologs of the mammalian autocrine motility factor receptor (AMFR), a cytokine receptor localized in both plasma membrane caveolae and the endoplasmic reticulum (ER). RIN2 and RIN3 have been identified as membrane-bound RING-finger type ubiquitin ligases with six apparent transmembrane domains, a RING-finger domain and a CUE domain. They act as positive regulators of RPM1- and RPS2-dependent hypersensitive response (HR) [].This entry represents the CUE domain found in plant RIN2 and RIN3.
RIN2, a member of the RIN (AKA Ras interaction/interference) family, have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs. Ras induces activation of Rab5 through RIN2, which is a direct downstream target of Ras and a direct upstream regulator of Rab5. In other words, it is the binding of the GTP-bound form of Ras to the RA domain of RIN2 that enhances the GEF activity toward Rab5. It is thought that the RA domain negatively regulates the Rab5 GEF activity. In steady state, RIN2 is likely to form a closed conformation by an intramolecular interaction between the RA domain and the Vps9p-like (Rab5 GEF) domain, negatively regulating the Rab5 GEF activity. In the active state, the binding of Ras to the RA domain may reduce the intramolecular interaction and stabilize an open conformation of RIN2 [, ]. This entry represents the SH3 domain of RIN2.
