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2  structures 243  species 0  interactions 1791  sequences 97  architectures

Family: DENN (PF02141)

Summary: DENN (AEX-3) domain

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DENN (AEX-3) domain Provide feedback

DENN (after differentially expressed in neoplastic vs normal cells) is a domain which occurs in several proteins involved in Rab- mediated processes or regulation of MAPK signalling pathways [1].

Literature references

  1. Levivier E, Goud B, Souchet M, Calmels TP, Mornon JP, Callebaut I; , Biochem Biophys Res Commun 2001;287:688-695.: uDENN, DENN, and dDENN: indissociable domains in Rab and MAP kinases signaling pathways. PUBMED:11563850 EPMC:11563850


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001194

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 DENN domain.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan AVL9 (CL0330), which has the following description:

Members of this clan are involved in vesicle formation/trafficking.

The clan contains the following 5 members:

Afi1 Avl9 DENN DUF2347 SPA

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(40)
Full
(1791)
Representative proteomes NCBI
(1806)
Meta
(19)
RP15
(352)
RP35
(490)
RP55
(745)
RP75
(1055)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(40)
Full
(1791)
Representative proteomes NCBI
(1806)
Meta
(19)
RP15
(352)
RP35
(490)
RP55
(745)
RP75
(1055)
Alignment:
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Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(40)
Full
(1791)
Representative proteomes NCBI
(1806)
Meta
(19)
RP15
(352)
RP35
(490)
RP55
(745)
RP75
(1055)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: IPR001194
Previous IDs: none
Type: Family
Author: Mian N, Bateman A
Number in seed: 40
Number in full: 1791
Average length of the domain: 178.90 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 16.35 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.4 23.4
Trusted cut-off 23.4 23.4
Noise cut-off 23.3 23.1
Model length: 185
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the DENN domain has been found. There are 2 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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