TWEAK belongs to the TNF family of ligands, and signals through TWEAKR, also known as TNFRSF12A. TWEAK is expressed in a variety of tissues, including the adult heart, pancreas, skeletal muscle, small intestine, spleen and peripheral blood lymphocytes. TWEAK has the ability to induce NF-kappaB activation and chemokine secretion, and to exert an apoptotic activity in certain cells, such as HT-29 human adenocarcinoma cells when cultured in the presence of IFN-gamma. TWEAK also promotes proliferation and migration of endothelial cells. The human TWEAK gene encodes for a 249 amino acid type II transmembrane protein, which contains a 21 amino acid cytoplasmic domain, a 21 amino acid transmembrane domain, and a 207 amino acid extracellular domain. Recombinant Human TWEAK is a soluble 17.0 kDa polypeptide (154 amino acid residues) comprising the TNF-homologous region of TWEAK, and is generated by proteolytic processing of the full length membrane-anchored TWEAK protein.