RIN3, 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. RIN3 stimulates the formation of GTP-bound Rab31, a Rab5-subfamily GTPase, and forms enlarged vesicles and tubular structures, where it colocalizes with Rab31. Transferrin appears to be transported partly through the RIN3-positive vesicles to early endosomes. RIN3 interacts via its Pro-rich domain with amphiphysin II, which contains an SH3 domain and participates in receptor-mediated endocytosis. RIN3, a Rab5 and Rab31 GEF, plays an important role in the transport pathway from plasma membrane to early endosomes. Mutations in the region between the SH2 and RH domain of RIN3 specifically abolished its GEF action on Rab31, but not Rab5. RIN3 was also found to partially translocate the cation-dependent mannose 6-phosphate receptor from the trans-Golgi network to peripheral vesicles and that this is dependent on its Rab31-GEF activity. These data indicate that RIN3 specifically acts as a GEF for Rab31 []. This entry represents the SH2 domain of RIN3.
