The domain within your query sequence starts at position 512 and ends at position 588; the E-value for the dDENN domain shown below is 4.06e-21.

LNIQIREVFANRFTQMFADYEVFVIQPSQDKESWFTNREQMQNFDKASFLSDQPEPYLPF
LSRFLETQMFASFIDNK

dDENN

Domain always found downstream of DENN domain, found in a variety of signalling proteins

• SMART accession number: SM00801
• Description: The dDENN domain is part of the tripartite DENN domain. It is always found downstream of the DENN domain itself, which is found in a variety of signalling proteins involved in Rab-mediated processes or regulation of MAPKs signalling pathways. The DENN domain is always encircled on both sides by more divergent domains, called uDENN (for upstream DENN) and dDENN (for downstream DENN). The function of the DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity.
• Interpro abstract (IPR005112):

  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 [ (PUBMED:11563850) (PUBMED: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 [ (PUBMED: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 dDENN domain.

There are 10946 dDENN domains in 10941 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: signalling

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Levivier E, Goud B, Souchet M, Calmels TP, Mornon JP, Callebaut I
• uDENN, DENN, and dDENN: indissociable domains in Rab and MAP kinases signaling pathways.
• Biochem Biophys Res Commun. 2001; 287: 688-95

DENN domains are found in a variety of signaling proteins but their exact function remains undefined. Some of the DENN-containing proteins, such as rat Rab3GEP (Rab3 GDP/GTP exchange protein) or mouse Rab6IP1 (Rab6 interacting 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 tumoreginicity 5) gene products are involved in regulation of MAPKs (Mitogen-activated protein kinases) signaling pathways. Using a combination of profile-based and bidimensional analyses, we show here that DENN domains are much larger than described to date in domain databases, always encircled on both sides by more divergent domains, that we called uDENN and dDENN. These however share conserved amino acids which could play a key role in the DENN functions.

Structure (3D structures containing this domain)

3D Structures of dDENN domains in PDB

PDB code	Title
3tw8	GEF domain of DENND 1B in complex with Rab GTPase Rab35

Links (links to other resources describing this domain)

• PFAM: dDENN
• INTERPRO: IPR005112
• PROSITE: DDENN