InterPro domain: IPR040032

This entry includes proteins containing an N-terminal tripartite DENN domain, including DENND1A (also known as connecdenn 1), DENND1B (connecdenn 2) and DENND1C (connecdenn 3). These proteins act as guanine-nucleotide exchange factors for Rab35 through the DENN domain. Inactive GDP-bound RAB35 is converted into its active GTP-bound form by the exchange of GDP to GTP. The DENN domains of DENND1A and DENND1B, but not DENND1C, bind Rab35, indicating that binding and activation are separate. The C-termini of DENND1A, DENND1B and DENND1C differ significantly, but each binds to clathrin and to the clathrin adaptor AP-2. This is a means to regulate clathrin-mediated endocytosis of synaptic vesicles and exit from early endosomes [ 1 ].

1. The connecdenn family, Rab35 guanine nucleotide exchange factors interfacing with the clathrin machinery. J. Biol. Chem. 285, 10627-37