Tumor Necrosis Factor Receptor 2 Soluble (TNFRSF1B) Active Protein

The protein encoded by this gene is a member of the TNF-receptor superfamily. 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, 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. [provided by RefSeq, Jul 2008]

Function: Receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and BIRC3 to TNFRSF1B/TNFR2. This receptor mediates most of the metabolic effects of TNF-alpha. Isoform 2 blocks TNF-alpha-induced apoptosis, which suggests that it regulates TNF-alpha function by antagonizing its biological activity. Ref.4 Ref.19

Subunit structure: Binds to TRAF2. Interacts with BMX. Ref.18 Ref.19

Subcellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.4. Isoform 2: Secreted Ref.4. Tumor necrosis factor-binding protein 2: Secreted Ref.4.

Post-translational modification: Phosphorylated; mainly on serine residues and with a very low level on threonine residues.A soluble form (tumor necrosis factor binding protein 2) is produced from the membrane form by proteolytic processing.

Pharmaceutical use: Available under the name Enbrel (Immunex and Wyeth-Ayerst). Used to treat moderate to severe rheumatoid arthritis (RA). Enbrel consist of the extracellular ligand-binding portion of TNFRSF1B linked to an immunoglobulin Fc chain. It binds to TNF-alpha and blocks its interactions with receptors.

Sequence similarities: Contains 4 TNFR-Cys repeats.