RIN1, 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 []. Previous studies showed that RIN1 interacts with EGF receptors via its SH2 domain and regulates trafficking and degradation of EGF receptors via its interaction with STAM, indicating a vital role for RIN1 in regulating endosomal trafficking of receptor tyrosine kinases (RTKs) []. RIN1 was first identified as a Ras-binding protein that suppresses the activated RAS2 allele in S. cerevisiae. RIN1 binds to the activated Ras through its carboxyl-terminal domain and this Ras-binding domain also binds to 14-3-3 proteins as Raf-1 does [].The SH2 domain of RIN1 are thought to interact with the phosphotyrosine-containing proteins, but the physiological partners for this domain are unknown. The proline-rich domain in RIN1 is similar to the consensus SH3 binding regions.
Vps9 is a cytosolic yeast protein required for localization of vacuolar proteins, such as the soluble vacuolar hydrolases CPY and PrA []. It may bind and act as an effector of a Rab GTPase and plays a role in vacuolar protein sorting (VPS) pathway. Vps9 contains a region called GBH domain that is related to mammalian Ras-binding proteins, Rin1 and JC265, and may negatively regulate Ras-mediated signaling in yeast Saccharomyces cerevisiae. This entry represents the N-terminal CUE domain that interacts specifically with monoubiquitin and regulates intramolecular monoubiquitylation [, ].
