Mus musculus Gene: Traf3
Summary
InnateDB Gene IDBG-172558.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Traf3
Gene Name TNF receptor-associated factor 3
Synonyms AI528849; amn; CAP-1; CD40bp; CRAF1; LAP1; T-BAM;
Species Mus musculus
Ensembl Gene ENSMUSG00000021277
Encoded Proteins
TNF receptor-associated factor 3
TNF receptor-associated factor 3
TNF receptor-associated factor 3
TNF receptor-associated factor 3
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
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.
Traf3 is a highly versatile regulator that positively controls type I interferon production, and negatively regulates MAP kinase activation and alternative NFkB signalling.
Upon sensing dsRNA or dsDNA, Traf3 interacts with ER-to-Golgi transport proteins to induce Mavs-associated innate immune responses. (Demonstrated in human)
Traf3 expressed in myeloid cells regulates immune responses in myeloid cells and acts to inhibit inflammation and tumor development.
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.
InnateDB Annotation from Orthologs
Summary
[Homo sapiens] TRAF3 serves as a negative regulator of the non-canonical NF-kappaB pathway by specifically blocking the activation of NF-kappaB via TRAF2/5.
[Homo sapiens] 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.
[Homo sapiens] TRAF3 is a major regulator of type I interferon (IFN) production and the innate antiviral response.
[Homo sapiens] TRAF3 cooperates with ZMYND11 in the regulation of Epstein-Barr virus-derived LMP1/CTAR1-induced NF-kappaB activation.
[Homo sapiens] 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.
[Homo sapiens] TRAF3 is a highly versatile regulator that positively controls type I interferon production, and negatively regulates MAP kinase activation and alternative NFkB signalling.
[Homo sapiens] Upon sensing dsRNA or dsDNA, TRAF3 interacts with ER-to-Golgi transport proteins to induce MAVS-associated innate immune responses.
[Homo sapiens] Herpes simplex virus 1 protein, UL36 ubiquitin-specific protease (UL36USP), deubiquitinates TRAF3 and inhibits recruitment of TBK1 and counteracts the IFNB pathway
[Homo sapiens] HACE1 plays an inhibitory role in virus-induced signalling by disrupting the MAVS-TRAF3 complex.
Entrez Gene
Summary This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000131323:
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 12:111166370-111267153
Strand Forward strand
Band F1
Transcripts
ENSMUST00000021706 ENSMUSP00000021706
ENSMUST00000060274 ENSMUSP00000058361
ENSMUST00000117269 ENSMUSP00000112517
ENSMUST00000139162 ENSMUSP00000119010
ENSMUST00000143395
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 62 experimentally validated interaction(s) in this database.
They are also associated with 115 interaction(s) predicted by orthology.
Experimentally validated
Total 62 [view]
Protein-Protein 62 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 115 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004842 ubiquitin-protein transferase 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: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:0032648 regulation of interferon-beta production
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0042981 regulation of apoptotic process
GO:0045087 innate immune response (InnateDB)
GO:0050688 regulation of defense response to virus
Cellular Component
GO:0005768 endosome
GO:0009898 cytoplasmic side of plasma membrane
GO:0035631 CD40 receptor complex
Orthologs
Species
Homo sapiens
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
Non-SSD Ortholog
Possible paralog/unusual divergence/ gene prediction error
Not yet available
Non-SSD Ortholog
Possible paralog/unusual divergence/ gene prediction error
Pathways
NETPATH
REACTOME
Toll Like Receptor 3 (TLR3) Cascade pathway
Innate Immune System pathway
Negative regulators of RIG-I/MDA5 signaling pathway
Immune System pathway
Toll-Like Receptors Cascades pathway
Activated TLR4 signalling pathway
MyD88-independent cascade pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
TRIF-mediated TLR3/TLR4 signaling pathway
TRAF3-dependent IRF activation pathway pathway
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
KEGG
Toll-like receptor signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Hepatitis C pathway
Pathways in cancer pathway
Small cell lung cancer pathway
INOH
PID BIOCARTA
PID NCI
Pathway Predictions based on Human Orthology Data
NETPATH
TNFalpha pathway
RANKL pathway
TWEAK pathway
REACTOME
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
Innate Immune System pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Toll-Like Receptors Cascades pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Immune System pathway
MyD88-independent cascade pathway
TRAF3-dependent IRF activation pathway pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Negative regulators of RIG-I/MDA5 signaling pathway
KEGG
Toll-like receptor signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Hepatitis C pathway
Pathways in cancer pathway
Small cell lung cancer pathway
INOH
PID BIOCARTA
Tnfr2 signaling pathway [Biocarta view]
Cd40l signaling pathway [Biocarta view]
Yaci and bcma stimulation of b cell immune responses [Biocarta view]
PID NCI
CD40/CD40L signaling
Cross-References
SwissProt
TrEMBL D3Z343
UniProt Splice Variant
Entrez Gene 22031
UniGene Mm.27431 Mm.409384 Mm.468829
RefSeq NM_001048206 NM_001286122 NM_011632 XM_006515798 XM_006515799 XM_006515800 XM_006515801 XM_006515802
OMIM
CCDS CCDS26175 CCDS36563
HPRD
IMGT
MGI ID MGI:108041
MGI Symbol Traf3
EMBL AC122023 AC127580
GenPept
RNA Seq Atlas 22031