ID:TRAF3_HUMAN DESCRIPTION: RecName: Full=TNF receptor-associated factor 3; AltName: Full=CAP-1; AltName: Full=CD40 receptor-associated factor 1; Short=CRAF1; AltName: Full=CD40-binding protein; Short=CD40BP; AltName: Full=LMP1-associated protein 1; Short=LAP1; FUNCTION: Regulates pathways leading to the activation of NF- kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa- B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14. SUBUNIT: Homotrimer. Heterotrimer with TRAF2 and TRAF5. Interacts with LTBR/TNFRSF3, TNFRSF4, TNFRSF5/CD40, TNFRSF8/CD30, TNFRSF13C TNFRSF17/BCMA, TLR4 and EDAR. Interacts with MAP3K5, MAP3K14, TRAIP/TRIP, TDP2/TTRAP, TANK/ITRAF and TRAF3IP1. Interaction with TNFRSF5/CD40 is modulated by TANK/ITRAF, which competes for the same binding site. Interacts with TICAM1. Interacts with TRAFD1. Interacts with OTUB1, OTUB2 and OTUD5. Interacts with RNF216, MAVS, OPTN and TBK1. Identified in a complex with TRAF2, MAP3K14 and BIRC3. Interacts with BIRC2 and BIRC3. Upon exposure to bacterial lipopolysaccharide (LPS), recruited to a transient complex containing TLR4, TRAF3, TRAF6, IKBKG, MAP3K7, MYD88, TICAM1, BIRC2, BIRC3 and UBE2N (By similarity). Interacts with Epstein-Barr virus protein LMP1. Interacts (via RING-type zinc finger domain) with SRC. INTERACTION: Q9QYP6:Azi2 (xeno); NbExp=2; IntAct=EBI-357631, EBI-6115874; P25942:CD40; NbExp=3; IntAct=EBI-357631, EBI-525714; P15314:Irf1 (xeno); NbExp=2; IntAct=EBI-357631, EBI-6115486; Q92844:TANK; NbExp=3; IntAct=EBI-357631, EBI-356349; Q8TDR0:TRAF3IP1; NbExp=8; IntAct=EBI-357631, EBI-928811; A2APF7:Zbp1 (xeno); NbExp=2; IntAct=EBI-357631, EBI-6115394; SUBCELLULAR LOCATION: Cytoplasm (Probable). Endosome (By similarity). Mitochondrion. Note=Undergoes endocytosis together with TLR4 upon LPS signaling (By similarity). Associated with mitochondria in response to virus. DOMAIN: The MATH/TRAF domain binds to receptor cytoplasmic domains. DOMAIN: The Ring-type zinc finger domain is required for its function in down-regulation of NFKB2 proteolytic processing (By similarity). PTM: Undergoes 'Lys-48'-linked polyubiquitination, leading to its proteasomal degradation in response to signaling by TNFSF13B, TLR4 or through CD40. Undergoes 'Lys-63'-linked ubiquitination during early stages of virus infection, and 'Lys-48'-linked ubiquitination during later stages. Undergoes both 'Lys-48'-linked and 'Lys-63'-linked ubiquitination in response to TLR3 and TLR4 signaling (By similarity). Deubiquitinated by OTUB1, OTUB2 and OTUD5. SIMILARITY: Belongs to the TNF receptor-associated factor family. A subfamily. SIMILARITY: Contains 1 MATH domain. SIMILARITY: Contains 1 RING-type zinc finger. SIMILARITY: Contains 2 TRAF-type zinc fingers. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TRAF3ID271.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13114
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001817 regulation of cytokine production GO:0002224 toll-like receptor signaling pathway GO:0002376 immune system process GO:0006915 apoptotic process GO:0007165 signal transduction GO:0008063 Toll signaling pathway GO:0016567 protein ubiquitination GO:0016579 protein deubiquitination 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:0035666 TRIF-dependent toll-like receptor signaling pathway GO:0042981 regulation of apoptotic process GO:0045087 innate immune response GO:0050688 regulation of defense response to virus
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
