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Protein Domain : IPR012227

Name  TNF receptor-associated factor TRAF Short Name  TNF_rcpt--assoc_TRAF
Type  Family Description  The tumour necrosis factor (TNF) receptor associated factors (TRAFs) are major signal transducers for the TNF receptor (TNFR) superfamily and the interleukin-1 receptor/Toll-like receptor superfamily in mammals []. TRAFs constitute a family of genetically conserved adapter proteins found in mammals (TRAF1-6) as well as in other multicellular organisms such as Drosophila [], Caenorhabditis elegans[]. TRAF2 is the prototypical member of the family. Mammalian TRAF1 and TRAF2 were the first members initially identified by their association with TNFR2. The TRAF1/TRAF2 and TRAF3/TRAF5 gene pairs may have arisen from recent independent gene duplications and to share a common ancestral gene. TRAF4 and TRAF6 precursor genes may have arisen earlier during evolution, with the divergence of the TRAF6 precursor occurring earliest of all. Except TRAF1, this PIRSF has a general domain architecture containing one N-terminal RING finger, a variable number of middle region of TRAF-type zinc finger and C2H2 type of zinc finger, and one C-terminal MATH domain. TRAF1 is unique in the family in that it lacks the N-terminal RING and zinc-finger domains []. This has rendered TRAF1 unable to promote TNF receptor signalling and act as a "dominant negative" TRAF []. Also TRAF1 is a substrate for caspases activated by TNF family death receptors []. The larger C-terminal cleaved fragment can bind to and sequester TRAF2 from TNFR1 complex, therefore modulating TNF induced NFkB activation []. A wide range of biological functions, such as adaptive and innate immunity, embryonic development, stress response and bone metabolism, are mediated by TRAFs through the induction of cell survival, proliferation, differentiation and death. TRAFs are functionally divergent from a perspective of both upstream and downstream TRAF signal transduction pathways and of signalling-dependent regulation of TRAF trafficking. Each TRAF protein interacts with and mediates the signal transduction of multiple receptors, and in turn each receptor utilises multiple TRAFs for specific functions []. About 40 interaction partners of TRAF have been described thus far, including receptors, kinases, regulators and adaptor proteins.TRAF proteins can be recruited to and activated by ligand-engaged receptors in least three distinct ways []. 1) Members of the TNFR superfamily that do not contain intracellular death domains, such as TNFR2 and CD40, recruit TRAFs directly via short sequences in their intracellular tails []. 2) Those that contain an intracellular death domain, such as TNFR1, first recruit an adapter protein, TRADD, via a death-domain-death-domain interaction, which then serves as a central platform of the TNFR1 signalling complex, which assembles TRAF2 and RIP for survival signalling, and FADD and caspase-8 for the induction of apoptosis. 3) Members of the IL-1R/TLR superfamily contain a protein interaction module known as the TIR domain, which recruits, sequentially, MyD88, a TIR domain and death domain containing protein, and IRAKs, adapter Ser/Thr kinases with death domains. IRAKs in turn associate with TRAF6 to elicit signalling by IL-1 and pathogenic components such as LPS. A common mechanism for the membrane-proximal event in TRAF signalling has been revealed by the conserved trimeric association in the crystal structure of the TRAF domain of TRAF2 [].For additional information please see [, ].

Publication Counts Displayer

6 Child Features

DB identifier Name Short Name Type
IPR027138 TNF receptor-associated factor 4 TRAF4 Family
IPR027139 TNF receptor-associated factor 6 TRAF6 Family
IPR027128 TNF receptor-associated factor 3 TRAF3 Family
IPR027136 TNF receptor-associated factor 1 TRAF1 Family
IPR027133 TNF receptor-associated factor 2 TRAF2 Family
IPR027130 TNF receptor-associated factor 5 TRAF5 Family

6 Contains

DB identifier Name Short Name Type
IPR002083 MATH MATH Domain
IPR001841 Zinc finger, RING-type Znf_RING Domain
IPR013083 Zinc finger, RING/FYVE/PHD-type Znf_RING/FYVE/PHD Domain
IPR017907 Zinc finger, RING-type, conserved site Znf_RING_CS Conserved_site
IPR018957 Zinc finger, C3HC4 RING-type Znf_C3HC4_RING-type Domain
IPR001293 Zinc finger, TRAF-type Znf_TRAF Domain

1 Cross References

Identifier
Source . Name

Subject . Primary Identifier
PIRSF015614 PIRSF IPR012227

3 Data Sets

Name URL
TrEMBL data set http://www.ebi.ac.uk/trembl/
InterPro data set  
InterPro GO Annotation data set  

0 Found In

3 GO Annotation


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
TNF receptor-associated factor TRAF   GO:0008270 zinc ion binding
TNF receptor-associated factor TRAF   GO:0007165 signal transduction
TNF receptor-associated factor TRAF   GO:0042981 regulation of apoptotic process

3 Ontology Annotations


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
TNF receptor-associated factor TRAF   GO:0008270 zinc ion binding
TNF receptor-associated factor TRAF   GO:0007165 signal transduction
TNF receptor-associated factor TRAF   GO:0042981 regulation of apoptotic process

0 Parent Features

11 Proteins

DB identifier Primary Accession
Organism . Name
FBpp0077119 Q9XYR0 Drosophila melanogaster
FBpp0306504 A8DYU9 Drosophila melanogaster
FBpp0279527 Q29LI9 Drosophila pseudoobscura
FBpp0171257 B4KES9 Drosophila mojavensis
FBpp0230538 B4MDS3 Drosophila virilis
FBpp0263293 B4NYJ2 Drosophila yakuba
A8XZK5_CAEBR A8XZK5 Caenorhabditis briggsae
G0MCG7_CAEBE G0MCG7 Caenorhabditis brenneri
G5EG80_CAEEL G5EG80 Caenorhabditis elegans
Q9UAC5_DROME Q9UAC5 Drosophila melanogaster
E3NF06_CAERE E3NF06 Caenorhabditis remanei