Tumor necrosis factor (ligand) superfamily, member 11
| PDB rendering based on 1s55.
| Available structures: 1s55
|| TNFSF11; ODF; CD254; OPGL; RANKL; TRANCE; hRANKL2; sOdf
| External IDs
|| OMIM: 602642 MGI: 1100089 Homologene: 2744
| Molecular Function:
|| • receptor activity|
• cytokine activity
• tumor necrosis factor receptor binding
• protein binding
| Cellular Component:
|| • extracellular region|
• extracellular space
• integral to plasma membrane
| Biological Process:
|| • ossification|
• immune response
• multicellular organismal development
• organ morphogenesis
• cell differentiation
• bone resorption
• positive regulation of osteoclast differentiation
• protein homooligomerization
| RNA expression pattern
Additional recommended knowledge
More reference expression data
|| NM_003701 (mRNA)|
|| Chr 13: 42.03 - 42.08 Mb
|| Chr 14: 77.01 - 77.04 Mb
| Pubmed search
RANKL (Receptor Activator for Nuclear Factor κ B Ligand), also known as TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and ODF (osteoclast differentiation factor) is a molecule important in bone metabolism. This natural and necessary surface-bound molecule activates osteoclasts, cells involved in bone resorption. Overproduction of RANKL is implicated in a variety of degenerative bone diseases, such as rheumatoid arthritis and osteomyelitis.
RANKL also has a function in the immune system, where it is expressed by T helper cells and is thought to be involved in dendritic cell maturation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of the RANKL gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found.
- ^ Entrez Gene: TNFSF11 tumor necrosis factor (ligand) superfamily, member 11.
- Whyte M (2006). "The long and the short of bone therapy". N Engl J Med 354 (8): 860-3. PMID 16495400. link
- Buckley KA, Fraser WD (2003). "Receptor activator for nuclear factor kappaB ligand and osteoprotegerin: regulators of bone physiology and immune responses/potential therapeutic agents and biochemical markers.". Ann. Clin. Biochem. 39 (Pt 6): 551-6. PMID 12564836.
- Jeffcoate W (2005). "Vascular calcification and osteolysis in diabetic neuropathy-is RANK-L the missing link?". Diabetologia 47 (9): 1488-92. doi:10.1007/s00125-004-1477-5. PMID 15322748.
- Collin-Osdoby P (2005). "Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin.". Circ. Res. 95 (11): 1046-57. doi:10.1161/01.RES.0000149165.99974.12. PMID 15564564.
- Whyte MP, Mumm S (2005). "Heritable disorders of the RANKL/OPG/RANK signaling pathway.". Journal of musculoskeletal & neuronal interactions 4 (3): 254-67. PMID 15615493.
- Clohisy DR, Mantyh PW (2005). "Bone cancer pain and the role of RANKL/OPG.". Journal of musculoskeletal & neuronal interactions 4 (3): 293-300. PMID 15615497.
- Anandarajah AP, Schwarz EM (2006). "Anti-RANKL therapy for inflammatory bone disorders: Mechanisms and potential clinical applications.". J. Cell. Biochem. 97 (2): 226-32. doi:10.1002/jcb.20674. PMID 16240334.
- Baud'huin M, Duplomb L, Ruiz Velasco C, et al. (2007). "Key roles of the OPG-RANK-RANKL system in bone oncology.". Expert Rev Anticancer Ther 7 (2): 221-32. doi:10.1586/14737126.96.36.199. PMID 17288531.
- Yogo K, Ishida-Kitagawa N, Takeya T (2007). "Negative autoregulation of RANKL and c-Src signaling in osteoclasts.". J. Bone Miner. Metab. 25 (4): 205-10. doi:10.1007/s00774-007-0751-2. PMID 17593489.
- Boyce BF, Xing L (2007). "Biology of RANK, RANKL, and osteoprotegerin.". Arthritis Res. Ther. 9 Suppl 1: S1. doi:10.1186/ar2165. PMID 17634140.
- McClung M (2007). "Role of RANKL inhibition in osteoporosis.". Arthritis Res. Ther. 9 Suppl 1: S3. doi:10.1186/ar2167. PMID 17634142.