Tumor necrosis factor receptor-associated factor 3 (TRAF3)

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a multifunctional intracellular adaptor protein and E3 ubiquitin ligase that mediates signal transduction from the TNF receptor superfamily and other receptors (e.g., CD40, BAFF-R, lymphotoxin-beta receptor, IL-17 receptor), playing critical regulatory roles in both innate and adaptive immunity. TRAF3 is central in modulating signaling pathways such as NF-κB (both canonical and non-canonical) and type I interferon responses, thereby influencing cell survival, differentiation, and apoptosis. It is required for B and T lymphocyte homeostasis and for proper antiviral and inflammatory responses, with loss or mutation of TRAF3 contributing to susceptibility to cancer, immunodeficiency, autoimmunity, and some neuroinflammatory conditions.

Other names

CAP-1CRAF1CD40BPLAP1RNF118CD40 receptor-associated factor 1CD40-binding proteinLMP1-associated protein 1RING-type E3 ubiquitin transferase TRAF3IIAE5IMD132AIMD132B

Regulation of receptor-proximal signaling for TNF receptor family and certain cytokine pathways; Ubiquitin-mediated modulation of downstream kinases (e.g., NIK degradation); Inhibition or promotion of NF-κB pathway activation (canonical and non-canonical); Promotion of type I interferon production via TLR/RIG-I pathways through ubiquitination and kinase activation