InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: TRAF3

Summary

InnateDB Gene

IDBG-21240.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TRAF3

Gene Name

TNF receptor-associated factor 3

Synonyms

CAP-1; CAP1; CD40bp; CRAF1; IIAE5; LAP1

Species

Homo sapiens

Ensembl Gene

ENSG00000131323

Encoded Proteins

IDBP-21242

TNF receptor-associated factor 3

IDBP-21244

TNF receptor-associated factor 3

IDBP-245022

TNF receptor-associated factor 3

IDBP-585812

TNF receptor-associated factor 3

IDBP-589921

TNF receptor-associated factor 3

IDBP-597497

TNF receptor-associated factor 3

IDBP-597289

TNF receptor-associated factor 3

IDBP-594624

TNF receptor-associated factor 3

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 15708970

TRAF3 serves as a negative regulator of the non-canonical NF-kappaB pathway by specifically blocking the activation of NF-kappaB via TRAF2/5.

PMID 16858409

TRAF3 is required for type I interferon production in response to intracellular double-stranded RNA. Similarly, a direct and specific interaction of the TRAF domain of TRAF3 with the TRAF-interaction motif (TIM) of MAVS is required for optimal MAVS-mediated antiviral responses.

PMID 16306936

TRAF3 is a major regulator of type I interferon (IFN) production and the innate antiviral response.

PMID 20138174

TRAF3 cooperates with ZMYND11 in the regulation of Epstein-Barr virus-derived LMP1/CTAR1-induced NF-kappaB activation.

PMID 20832341

TRAF3 functions downstream of multiple TNF receptors and receptors that induce interferon (IFN)-alpha, IFN-beta, and IFN-lambda production, including Toll-like receptor 3 (TLR3). TLR3-mediated immunity against primary infection by herpes simplex virus-1 (HSV-1) in the central nervous system is critically dependent on TRAF3.

PMID 21660053

TRAF3 is a highly versatile regulator that positively controls type I interferon production, and negatively regulates MAP kinase activation and alternative NFkB signalling.

PMID 22792062

Upon sensing dsRNA or dsDNA, TRAF3 interacts with ER-to-Golgi transport proteins to induce MAVS-associated innate immune responses.

PMID 23986588

Herpes simplex virus 1 protein, UL36 ubiquitin-specific protease (UL36USP), deubiquitinates TRAF3 and inhibits recruitment of TBK1 and counteracts the IFNB pathway

PMID 27213432

HACE1 plays an inhibitory role in virus-induced signalling by disrupting the MAVS-TRAF3 complex.

InnateDB Annotation from Orthologs

Summary

PMID 16306937

[Mus musculus] Traf3 is a component of Toll/interleukin-1 receptor (TIR) signalling complexes that is recruited along with Traf6. Traf3 is essential for the induction of type I interferons (IFN) and the anti-inflammatory cytokine interleukin 10, but is dispensable for expression of pro-inflammatory cytokines.

PMID 21660053

[Mus musculus] Traf3 is a highly versatile regulator that positively controls type I interferon production, and negatively regulates MAP kinase activation and alternative NFkB signalling.

PMID 22792062

[Mus musculus] Upon sensing dsRNA or dsDNA, Traf3 interacts with ER-to-Golgi transport proteins to induce Mavs-associated innate immune responses. (Demonstrated in human)

PMID 25422508

[Mus musculus] Traf3 expressed in myeloid cells regulates immune responses in myeloid cells and acts to inhibit inflammation and tumor development.

PMID 26305951

[Mus musculus] Usp25 physically associates with Traf3 and Traf6 after infection by RNA or DNA viruses and promotes innate antiviral responses by protecting virus-induced proteasome-dependent or independent degradation of Traf3 and Traf6.

Entrez Gene

Summary

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from, members of the TNF receptor (TNFR) superfamily. This protein participates in the signal transduction of CD40, a TNFR family member important for the activation of the immune response. This protein is found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation. Epstein-Barr virus encoded latent infection membrane protein-1 (LMP1) can interact with this and several other members of the TRAF family, which may be essential for the oncogenic effects of LMP1. Several alternatively spliced transcript variants encoding three distinct isoforms have been reported. [provided by RefSeq, Dec 2010]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 14:102777476-102911500

Strand

Forward strand

Band

q32.32

Transcripts

ENST00000351691	ENSP00000332468
ENST00000347662	ENSP00000328003
ENST00000392745	ENSP00000376500
ENST00000560371	ENSP00000454207
ENST00000539721	ENSP00000445998
ENST00000560463	ENSP00000453623
ENST00000558700	ENSP00000453031
ENST00000558880
ENST00000559734	ENSP00000453032

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 195 experimentally validated interaction(s) in this database.
They are also associated with 27 interaction(s) predicted by orthology.

Experimentally validated
Total	195 [view]
Protein-Protein	192 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	27 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0004871	signal transducer activity
GO:0005164	tumor necrosis factor receptor binding
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity
GO:0019901	protein kinase binding
GO:0031625	ubiquitin protein ligase binding
GO:0031996	thioesterase binding

Biological Process

GO:0001817	regulation of cytokine production
GO:0002224	toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006915	apoptotic process
GO:0007165	signal transduction
GO:0008063	Toll signaling pathway
GO:0016567	protein ubiquitination
GO:0030162	regulation of proteolysis
GO:0032088	negative regulation of NF-kappaB transcription factor activity
GO:0032480	negative regulation of type I interferon production
GO:0032648	regulation of interferon-beta production
GO:0033209	tumor necrosis factor-mediated signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0042981	regulation of apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0050688	regulation of defense response to virus