Human TNF Receptor Associated Factor 3 (TRAF3) Protein

Background

TRAF3 is an adaptor protein that regulates signaling downstream of receptors like CD40, BAFF-R, and Toll-like receptors (TLRs), playing a crucial role in immune regulation, lymphocyte activation, and antiviral responses. Unlike TRAF1 and TRAF2, TRAF3 functions as a negative regulator of the non-canonical NF-κB pathway by targeting NIK (NF-κB-inducing kinase) for degradation, thereby preventing constitutive activation of NF-κB2 signaling. TRAF3 is widely expressed in immune cells, where it regulates B-cell survival, interferon production, and immune tolerance. Dysregulation of TRAF3 is associated with B-cell malignancies, autoimmune diseases, and viral infections due to uncontrolled NF-κB activation and impaired immune signaling. Functional studies in knockout models demonstrate defects in B-cell homeostasis, increased susceptibility to autoimmunity, and reduced antiviral immunity, underscoring its dual role in restraining excessive signaling and supporting immune regulation.