The TNF Superfamily consists of ligands, receptors and regulators. Ligand members share a variety of common features including a homologous extracellular motif, the TNF homology domain (THD). TNF Superfamily ligands are generally type II transmembrane proteins that become soluble upon cleavage of the extracellular region, although most soluble forms show reduced signaling activity. Ligands bind to TNF Superfamily receptors (TNFR) which are mostly type I transmembrane glycoproteins, containing one to six ligand-binding cysteine-rich domains (CRDs). Some TNFR contain death domains that initiate caspase activation upon binding.
The TNF Superfamily currently consists of 19 ligands and 29 receptors in humans. In mice, an additional 3 receptors have been identified. TNF Superfamily members are known to function in various processes including apoptosis, proliferation, and immune cell regulation.