Recombinant Human Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), partial

Function

Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of NFATC1 and activation of PLCG2 (By similarity). Involved in the regulation of interactions between T-cells and dendritic cells (By similarity)

Subcellular Location

Cell membrane (Single-pass type I membrane protein)

Disease Association

Familial expansile osteolysis (FEO) : Rare autosomal dominant bone disorder characterized by focal areas of increased bone remodeling. The osteolytic lesions develop usually in the long bones during early adulthood. FEO is often associated with early-onset deafness and loss of dentition. [The disease is caused by variants affecting the gene represented in this entry] | Paget disease of bone 2, early-onset (PDB2) : A form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. [The disease is caused by variants affecting the gene represented in this entry] | Osteopetrosis, autosomal recessive 7 (OPTB7) : A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB7 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development. OPTB7 is associated with hypogammaglobulinemia. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Ubiquitous expression with high levels in skeletal muscle, thymus, liver, colon, small intestine and adrenal gland

Subunit

Binds to the clefts between the subunits of the TNFSF11 ligand trimer to form a heterohexamer (By similarity). Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL (PubMed:23478294). Interacts with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6 (PubMed:9774460). Interacts (via cytoplasmic domain) with GAB2 (PubMed:15750601). Interacts (via cytoplasmic domain); with EEIG1 (via N-terminus); when in the presence of TNFSF11/RANKL (By similarity). After TNFSF11 stimulation, interacts (via IVVY motif) with STAC2; this interaction affects TNFRSF11A interaction with PLCG2 and GAB2 (By similarity)

• Anderson D.M. et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. — Nature (1997)
• Sirinian C. et al. Alternative splicing generates a truncated isoform of human TNFRSF11A (RANK) with an altered capacity to activate NF-kappaB. — Gene (2013)
• Papanastasiou A.D. et al. Alternative splicing generates multiple human TNFRSF11A (RANK) isoforms. (JUN-)
• Totoki Y. et al. Homo sapiens protein coding cDNA. (MAR-)
• Nakagawa N. et al. RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. — Biochem. Biophys. Res. Commun. (1998)
• Wong B.R. et al. The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor. — J. Biol. Chem. (1998)
• Wada T. et al. The molecular scaffold Gab2 is a crucial component of RANK signaling and osteoclastogenesis. — Nat. Med. (2005)
• Dephoure N. et al. A quantitative atlas of mitotic phosphorylation. — Proc. Natl. Acad. Sci. U.S.A. (2008)