Tumor necrosis factor (ligand) superfamily, member 11
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PDB rendering based on 1s55.
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Available structures: 1s55
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Identifiers
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Symbol(s)
| TNFSF11; ODF; CD254; OPGL; RANKL; TRANCE; hRANKL2; sOdf
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External IDs
| OMIM: 602642 MGI: 1100089 Homologene: 2744
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Gene Ontology
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Molecular Function:
| • receptor activity • cytokine activity • tumor necrosis factor receptor binding • protein binding
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Cellular Component:
| • extracellular region • extracellular space • integral to plasma membrane • membrane
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Biological Process:
| • ossification • immune response • multicellular organismal development • organ morphogenesis • cell differentiation • bone resorption • positive regulation of osteoclast differentiation • protein homooligomerization
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RNA expression pattern
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Additional recommended knowledge
More reference expression data
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Orthologs
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| Human
| Mouse
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Entrez
| 8600
| 21943
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Ensembl
| ENSG00000120659
| ENSMUSG00000022015
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Uniprot
| O14788
| Q059M3
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Refseq
| NM_003701 (mRNA) NP_003692 (protein)
| NM_011613 (mRNA) NP_035743 (protein)
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Location
| Chr 13: 42.03 - 42.08 Mb
| Chr 14: 77.01 - 77.04 Mb
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Pubmed search
| [1]
| [2]
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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.[1]
See also
References
- ^ Entrez Gene: TNFSF11 tumor necrosis factor (ligand) superfamily, member 11.
Further reading
- 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:10.1586/14737140.7.2.221. 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.
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