cDENN domain (IPR001194)
Short name: cDENN_dom
Overlapping homologous superfamilies
The tripartite DENN (after differentially expressed in neoplastic versus normal cells) domain is found in several proteins involved in Rab-mediated processes or regulation of MAPKs (Mitogen-activated preotein kinases) signaling pathways. It actually consists of three parts as the original DENN domain is always encircled on both sides by more divergent domains, called uDENN (after upstream DENN) and dDENN (for downstream DENN). The tripartite DENN domain is found associated with other domains, such as RUN, PLAT, PH, PPR, WD-40, GRAM or C1. The function of DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity [PMID: 11563850, PMID: 12906859].
The general characteristics of DENN domains - three regions dDENN, DENN itself, and uDENN having different patterns of sequence conservation and separated by sequences of variable length - suggest that they are composed of at least three sub-domains which may feature distinct folds but which are always associated due to functional and/or structural constraints [PMID: 11563850].
Some proteins known to contain a tripartite DENN domain are listed below:
- Rat Rab3 GDP/GTP exchange protein (Rab3GEP)
- Human mitogen-activated protein kinase activating protein containing death domain (MADD). It is orthologous to Rab3GEP
- Caenorhabditis elegans regulator of presynaptic activity aex-3, the ortholog of Rab3GEP
- Mouse Rab6 interacting protein 1 (Rab6IP1)
- Human SET domain-binding factor 1(SBF1)
- Human suppressor of tumoreginicity 5 (ST5)
- Human C-MYC promoter-binding protein IRLB
This entry represents the core or cDENN domain.