Schematic representation of ubiquitination-mediated action of Ras isoforms. H/N-Ras mono- and di-ubiquitination controlled by Rabex-5 promotes their endosomal association, leading to the attenuation of Ras-ERK signalling. On the other hand, K-Ras mono-ubiquitination catalysed by a yet unknown E3 ligase inhibits its GAP-mediated hydrolysis, leading to an increase in its GTP-bound active form and strengthening Ras-ERK signalling. Both Rin1 and Rabex-5 are GEFs for the GTPase Rab5, however the GEF activity of Rabex-5 is not required for ubiquitinating H/N-Ras, while Rin1 GEF activity is necessary for enhancing Rabex5-mediated ubiquitination of the H/N-Ras isoforms. Gray arrows indicate catalysis, black arrows indicate transformation and red blunt arrows indicate inhibition.