RANK Receptor

RANK (receptor activator of NFκB, also known as TRANCE receptor, osteoclast differentiation factor receptor [ODFR]) and TNFRSF11A is a member of the tumor necrosis factor receptor family. The full length human RANK cDNA encodes a type I transmembrane protein of 616 amino acids with a predicted 184 amino acid extracellular domain and a 383 amino acid cytoplasmic domain. The extracellular domain contains two potential N-linked glycosylation sites. RANK shares significant amino acid homology with other members of the TNF R family in its extracellular four cysteinerich repeats. Human and murine RANK share 81% amino acid identity in their extracellular domains. RANK is widely expressed with highest levels in skeletal muscle, thymus, liver, colon, small intestine and adrenal gland. RANK is expressed in dendritic cells. In activated human peripheral blood T lymphocytes, RANK expression is induced by IL4 and TGFβ. Multiple tumor necrosis factor receptor-associated factors (TRAFs) are involved in the signaling of RANK. TRANCE (TNF-related activation-induced cytokines, also known as RANK ligand [RANKL], osteoprotegerin ligand [OPGL], and osteoclast differentiation factor [ODF]) is the ligand for RANK. The biological functions mediated through RANK include activation of NFκB and c-jun N-terminal kinase, enhancement of T cell growth and dendritic cell function, induction of osteoclastogenesis, and lymph node organogenesis. Soluble RANK is able to block TRANCE induced biological activity.