RIN Family Proteins (RIN1, RIN2, and RIN3)
The RIN1 and RIN2 genes were first identified in a selection for expressed human cDNAs that suppress phenotypes associated with oncogenic RAS mutations in a yeast model system (Colicelli et al. 1991). Subsequent analysis demonstrated that RIN1 binds specifically to activated (GTP-bound) human HRAS (Han and Colicelli 1995; Han et al. 1997), suggesting that RIN1 is a downstream effector of RAS family proteins. RIN2 and RIN3 also bind to activated HRAS (Rodriguez-Viciana et al. 2004). All three RIN proteins contain a carboxy terminal RAS association (RA) domain that mediates this interaction (Colicelli (2004)).
It was subsequently reported that RIN1 encodes a VPS9-related guanine nucleotide exchange factor (GEF) function specific for the RAB5 family of early endocytosis GTPase (Tall et al. 2001). RIN2 and RIN3 also encode VPS9-type GEF domains upstream of the RA domain. This suggests that RIN family proteins are RAS effectors...
- Dhaka A, Costa RM, Hu H, Irvin DK, Patel A, Kornblum HI, et al. The Ras effector Rin1 modulates the formation of aversive memories. J Neuroscience. 2003;23:748–57.Google Scholar
- Woller B, Luiskandl S, Popovic M, Prieler BE, Ikoge G, Mutzl M, et al. Rin-like, a novel regulator of endocytosis, acts as guanine nucleotide exchange factor for Rab5a and Rab22. Biochim Biophys Acta. 2011;1813(6):1198–210.Google Scholar