Tripartite DENN domain (IPR037516)

Short name: Tripartite_DENN

Overlapping homologous superfamilies


Domain relationships



The tripartite DENN (after differentially expressed in neoplastic versus normal cells) domain is found in several proteins that share common structural features and have been shown to be guanine nucleotide exchange factors (GEFs) for Rab GTPases, which are regulators of practically all membrane trafficking events in eukaryotes. The tripartite DENN domain is composed of three distinct modules which are always associated due to functional and/or structural constraints: upstream DENN or uDENN, the better conserved central or core or cDENN, and downstream or dDENN regions. 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, PMID: 22065758, PMID: 23248642, PMID: 22977732].

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.

The DENN domain forms a heart-shaped structure, with the N- terminal residues forming one and the C-terminal residues forming the second one. The N-terminal half forms the uDENN domain and consists of a central antiparallel beta-sheet layered between one helix and two helices. A long random-coil region links the two lobes. The C-terminal lobe is composed of the cDENN and dDENN domains. The cDENN domain is an alpha/beta three layered sandwich domain with a central sheet of 5-strands. The dDENN domain is an all- alpha helical domain, whose core contains two alpha-hairpins which diverge rapidly in sequence [PMID: 22065758, PMID: 22977732].

This domain represents the entire tripartite DENN domain.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles