Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity). Forms oligomers. Interacts with 6 of the 7 known isoforms of 14-3-3 proteins. Transiently recruited to membranes to activate RAB12. Inactive DENND3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-858 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards RAB12.