DENN/MADD Domain Containing Protein 1A (DENND1A)

DENND1A, 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 1,016-amino acid protein contains an N-terminal DENN domain composed of 3 DENN modules, followed by a PxxP-rich domain. Connecdenn also contains 3 motifs, FSDVF, DPF, and WETFE, for binding to the alpha ear of AP2. Immunofluorescence microscopy of cultured rat brain hippocampal neurons showed connecdenn in neuronal cell bodies and along dendrites in a punctate distribution, where it partly colocalized with the presynaptic marker synaptophysin (SYP).