TNFRSF1B
Description
The TNFRSF1B (TNF receptor superfamily member 1B) is a protein-coding gene located on chromosome 1.
TNFRSF1B, also known as Tumor necrosis factor receptor 2 (TNFR2) and CD120b, is one of two membrane receptors that binds tumor necrosis factor-alpha (TNFα). Like its counterpart, tumor necrosis factor receptor 1 (TNFR1), the extracellular region of TNFR2 consists of four cysteine-rich domains which allow for binding to TNFα. TNFR1 and TNFR2 possess different functions when bound to TNFα due to differences in their intracellular structures, such as TNFR2 lacking a death domain (DD). TNFRSF1B is a member of the tumor necrosis factor receptor superfamily, which also contains TNFRSF1A. This protein and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2 (TRAF2), which mediates anti-apoptotic signals. Knockout studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways. TNFR2 is neuroprotective, at least partly because it lacks an intracellular death domain. Patients with schizophrenia have increased levels of soluble tumor necrosis factor receptor 2 (sTNFR2). Targeting of TNRF2 in tumor cells is associated with increased tumor cell death and decreased progression of tumor cell growth. Increased expression of TNFR2 is found in breast cancer, cervical cancer, colon cancer, and renal cancer.
TNFRSF1B/TNFR2 exhibits high affinity for TNFSF2/TNF-alpha and a 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex, associated with TNFRSF1B/TNFR2, recruits the apoptotic suppressors BIRC2 and BIRC3. This receptor plays a major role in mediating the metabolic effects of TNF-alpha. Isoform 2 of TNFRSF1B/TNFR2 inhibits TNF-alpha-induced apoptosis, suggesting it regulates TNF-alpha's function by counteracting its biological activity.
TNFRSF1B is also known as CD120b, TBPII, TNF-R-II, TNF-R75, TNFBR, TNFR1B, TNFR2, TNFR80, p75, p75TNFR.
