TRAF3
Description
The TRAF3 (TNF receptor associated factor 3) is a protein-coding gene located on chromosome 14.
TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene. 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. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported. TRAF3 has been shown to interact with: Haploinsufficiency of TRAF3 in humans is associated with various immunodeficiency and autoimmunity diseases.
TRAF3 is a cytoplasmic E3 ubiquitin ligase that plays a crucial role in regulating various signaling pathways, including NF-kappa-B, MAPK, and IRF pathways. These pathways control numerous biological processes in both immune and non-immune cells. In TLR and RLR signaling pathways, TRAF3 acts as an E3 ubiquitin ligase, promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on substrates like ASC. This leads to the activation of the type I interferon response or the inflammasome. Following the activation of specific TLRs, such as TLR4, TRAF3 functions as a negative NF-kappa-B regulator, potentially to prevent excessive inflammatory responses. Degradation of TRAF3 via 'Lys-48'-linked polyubiquitination is essential for MAPK activation and the production of inflammatory cytokines. Alternatively, when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-linked polyubiquitination and binds to RALGDS, mobilizing the exocyst complex for rapid expulsion of intracellular bacteria. TRAF3 also acts as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development. It is necessary for normal antibody isotype switching from IgM to IgG and plays a role in T-cell-dependent immune responses. Furthermore, TRAF3 down-regulates proteolytic processing of NFKB2, thereby inhibiting non-canonical activation of NF-kappa-B. It promotes ubiquitination and proteasomal degradation of MAP3K14.
TRAF3 is also known as CAP-1, CAP1, CD40bp, CRAF1, IIAE5, LAP1, RNF118.
Associated Diseases
- Herpes simplex virus encephalitis
- Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5
