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. Regulates autophagy in response to starvation through Rab12 activation (PubMed:24719330, PubMed:25925668, PubMed:28249939). Starvation leads to ULK1/2-dependent phosphorylation of Ser-554 and Ser-572, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards Rab12 (PubMed:25925668). 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:21718402, PubMed:24719330). Starvation also induces phosphorylation at Tyr-940, which leads to up-regulated GEF activity and initiates autophagy (PubMed:28249939). Forms oligomers (PubMed:28249939). Interacts with 6 of the 7 known isoforms of 14-3-3 proteins (PubMed:25925668). 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-940 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards Rab12.