uDENN, DENN, and dDENN: Indissociable domains in Rab and MAP kinases signaling pathways

DENN domains are found in a variety of signaling proteins but their exact f unction remains undefined. Some of the DENN-containing proteins, such as ra t Rab3GEP (Rab3 GDP/GTP exchange protein) or mouse Rab6IP1 (Rab6 interactin g protein 1) interact with GTPases of the Rab family. Others, such as human MADD (MAP (Mitogen-activated protein) kinase activating protein containing death domain) and human ST5 (Suppressor of turnoreginicity 5) gene product s are involved in regulation of MAPKs (Mitogen-activated protein kinases) s ignaling pathways. Using a combination of profile-based and bidimensional a nalyses, we show here that DENN domains are much larger than described to d ate in domain databases, always encircled on both sides by more divergent d omains, that we called uDENN and dDENN. These however share conserved amino acids which could play a key role in the DENN functions. (C) 2001 Academic Press.