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...