DENN/MADD Domain Containing Protein 1C (DENND1C)

Clathrin-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1C, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 and bind to clathrin and clathrin adaptor protein-2 (AP2). Thus, connecdenns link RAB35 activation with the clathrin machinery.

The deduced 801-amino acid connecdenn-3 protein contains an N-terminal DENN domain with 3 DENN modules and C-terminal motifs for binding to the alpha ear of AP2 and to clathrin heavy chain (CLTC). Connecdenn-3 shares 32% amino acid identity with connecdenn-1. Western blot analysis showed that rat connecdenn-3 was ubiquitously expressed, with highest expression in brain.