Recombinant Human TRAF3 protein

Specifications

Form

Liquid

General info

Function

Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types (PubMed : 33148796, PubMed : 33608556). In TLR and RLR signaling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome (PubMed : 25847972, PubMed : 27980081). Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via 'Lys-48'-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines. Alternatively, when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-linked polyubiquitination and subsequently binds to RALGDS, mobilizing the exocyst complex to rapidly expel intracellular bacteria back for clearance (PubMed : 27438768). Acts also as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.

Sequence similarities

Belongs to the TNF receptor-associated factor family. A subfamily.

Post-translational modifications

Undergoes 'Lys-48'-linked polyubiquitination, leading to its proteasomal degradation in response to signaling by TNFSF13B, TLR4 or through CD40. 'Lys-48'-linked polyubiquitinated form is deubiquitinated by OTUD7B, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. 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. 'Lys-63'-linked ubiquitination can be mediated by TRIM35. Deubiquitinated by OTUB1, OTUB2 and OTUD5. Undergoes 'Lys-63'-linked deubiquitination by MYSM1 to terminate the pattern-recognition receptors/PRRs pathways (By similarity). Undergoes also 'Lys-29'-linked ubiquitination on Cys-56 and Cys-124 by NEDD4L; leading to increased 'Lys-48'- and 'Lys-63'-linked ubiquitination as well as increased binding to TBK1 (PubMed:33608556). TLR4 signals emanating from bacteria containing vesicles trigger 'Lys-33'-linked polyubiquitination that promotes the assembly of the exocyst complex thereby connecting innate immune signaling to the cellular trafficking apparatus (PubMed:27438768). Deubiquitinated by USP25 during viral infection, leading to TRAF3 stabilization and type I interferon production (By similarity). Ubiquitinated at Lys-329 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (By similarity). 'Lys-63'-linked ubiquitination by FBXO11 in a NEDD8-dependent manner promotes the amplification of IFN-I signaling (PubMed:36897010).. (Microbial infection) Cleaved by enterovirus D68 protease 2A; leading to inhibition of NF-kappa-B or IFN-beta triggered by TRAF3.

Subcellular localisation

Endosome