Anti-TRAF3 from rabbit, purified by affinity chromatography

TNF receptor-associated factor 3 (UniProt Q13114; also known as CAP-1, CD40 receptor-associated factor 1, CD40-binding protein, CD40BP, CRAF1, LAP1, LMP1-associated protein 1) is encoded by the TRAF3 (also known as CAP1, CRAF1) gene (Gene ID 7187) in human. NF-kappaB-inducing kinase (NIK) is negatively regulated by a complex composed of the E3 ubiquitin ligases c-IAP1 and 2 (cellular inhibitor of apoptosis 1 and 2) and the adaptors TRAF2 and 3 (TNF receptor-associated factors 2 and 3). The TRAF2-TRAF3 complex bridges the c-IAPs and NIK into close proximity, where TRAF2 recruits c-IAP1/2 and TRAF3 binds to NIK. NF-kappaB signaling activation results in TRAF3 degradation, leading to upregulated NIK. TRAF3 deletion in B-cells results in uncontrolled growth and TRAF3 mutations have been identified in several human B-cell cancers, including Hodgkin lymphoma, splenic marginal zone lymphoma, and multiple myeloma. TRAF3 also plays an indirect role in promoting PI3K/AKT and JAK/STAT signalings, which are negatively regulated by NIK. TRAF3 prevents NIK from targeting PTEN to the plasma membrane and thereby promoting PI3K/AKT signaling. TRAF3 is required for normal T cells to function properly and anaplastic large cell lymphoma (ALCL) cells reply on PI3K/AKT and JAK/STAT signaling for proliferation. Opposite to B-cell cancers, TRAF3 knockdown triggers cell cycle arrest in ALCL cells. Human TRAF3 contains one RING-type (a.a. 68-77) and two TRAF-type (a.a. 135-190 and 191-249) zinc fingers, a , coiled coil (a.a. 267-338) regin, followed a C-terminal MATH (meprin and TRAF homology) domain (a.a. 415-560) that mediates interaction with receptor cytomplasmic domain.