TRAF6
GeneName
TRAF6
Summary
TRAF6, also known as TNF receptor associated factor 6, is a 60kDa protein that functions as an essential adaptor in various signalling pathways, particularly those related to the immune response and inflammation. It is predominantly expressed in the cytoplasm and is associated with multiple cellular components including the CD40 receptor complex, endosome membrane, and lipid droplets. TRAF6 plays a pivotal role in the activation of NF-kappaB and MAPK pathways, mediating responses to cytokines and stress signals. Its interactions with ubiquitin-conjugating enzymes and protein kinases facilitate the regulation of diverse biological processes, including antigen presentation, osteoclast differentiation, and the cellular response to lipopolysaccharide. TRAF6 is also involved in the assembly of autophagosomes and the regulation of apoptotic processes.
Importance
TRAF6 is relevant to: - The regulation of immune responses, particularly in the context of inflammation and infection through its role in NF-kappaB and MAPK signalling pathways. - Bone metabolism and diseases such as osteoporosis due to its involvement in osteoclast differentiation. - The development of therapeutic strategies targeting autoimmune diseases and cancer, given its central role in T cell activation and cytokine production. - The understanding of innate immune mechanisms, including responses to pathogen-associated molecular patterns via toll-like receptors.
Top Products
For researchers investigating TRAF6, we highly recommend the top-selling recombinant antibody, Anti-TRAF6 antibody [EP591Y] (ab33915). This antibody has been validated in knockout models, ensuring its reliability in various applications, including Western blotting (WB), immunohistochemistry (IHC), and flow cytometry (FC). With 175 citations, it is well-regarded in the research community, demonstrating its effectiveness and trustworthiness for TRAF6 detection. This product is an excellent choice for those seeking consistent and robust results in their studies.
Abcam Product Citation Summary
The data indicates that TRAF6 is a significant target in various studies related to immune response, autophagy, and inflammatory pathways. The use of Abcam antibodies in both mouse and human models highlights the relevance of TRAF6 in understanding mechanisms such as TLR signaling, NF-κB pathway activation, and the regulation of Tregs. The presence of studies involving osteoarthritis and rheumatoid arthritis suggests a potential role for TRAF6 in autoimmune conditions.
Abcam Product Citation Table
Domain
The coiled coil domain mediates homo- and hetero-oligomerization.
The MATH/TRAF domain binds to receptor cytoplasmic domains.
Function
E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2 (PubMed:11057907, PubMed:18347055, PubMed:19465916, PubMed:19713527, PubMed:27746020, PubMed:31620128). Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation (PubMed:19675569). Leads to the activation of NF-kappa-B and JUN (PubMed:16378096, PubMed:17135271, PubMed:17703191). Seems to also play a role in dendritic cells (DCs) maturation and/or activation (By similarity). Represses c-Myb-mediated transactivation, in B-lymphocytes (PubMed:18093978, PubMed:18758450). Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor (PubMed:12140561, PubMed:19825828, PubMed:8837778). Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation (By similarity). Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production (By similarity). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by initiating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: TRAF6 catalyzes initial 'Lys-63'-linked-polyubiquitin chains that are then branched via 'Lys-48'-linked polyubiquitin by HUWE1 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Participates also in the TCR signaling by ubiquitinating LAT (PubMed:23514740, PubMed:25907557).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Sumoylated on Lys-124, Lys-142 and Lys-453 with SUMO1.
Polyubiquitinated on Lys-124 by TRAF3IP2; after cell stimulation with IL17A (PubMed:19825828). Polyubiquitinated on Lys-124; after cell stimulation with IL1B or TGFB. This ligand-induced cell stimulation leads to dimerization/oligomerization of TRAF6 molecules, followed by auto-ubiquitination which involves UBE2N and UBE2V1 and leads to TRAF6 activation. This 'Lys-63' site-specific poly-ubiquitination appears to be associated with the activation of signaling molecules. Endogenous autoubiquitination occurs only for the cytoplasmic form. Deubiquitinated by USP10 in a TANK-dependent manner, leading to the negative regulation of NF-kappaB signaling upon DNA damage (PubMed:25861989). LRRC19 induces 'Lys-63' ubiquitination (PubMed:25026888). Ubiquitinated at Lys-319 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (By similarity).
(Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1 on both 'Lys-48' and 'Lys-63'-linked ubiquitin chains; leading to NF-kappa-B signaling inhibition.
Sequence Similarities
Belongs to the TNF receptor-associated factor family. A subfamily.
Tissue Specificity
Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Cellular localization
- Cytoplasm
- Cytoplasm
- Cell cortex
- Nucleus
- Lipid droplet
- Found in the nuclei of some aggressive B-cell lymphoma cell lines as well as in the nuclei of both resting and activated T- and B-lymphocytes. Found in punctate nuclear body protein complexes. Ubiquitination may occur in the cytoplasm and sumoylation in the nucleus. RSAD2/viperin recruits it to the lipid droplet (By similarity).
Alternative names
RNF85, TRAF6, TNF receptor-associated factor 6, E3 ubiquitin-protein ligase TRAF6, Interleukin-1 signal transducer, RING finger protein 85, RING-type E3 ubiquitin transferase TRAF6
Database links
swissprot:Q9Y4K3 omim:602355 entrezGene:7189
Other research areas
- Oncology