Tumor necrosis factor ligand superfamily member 11

Details

Name
Tumor necrosis factor ligand superfamily member 11
Kind
protein
Synonyms
  • ODF
  • OPGL
  • Osteoclast differentiation factor
  • Osteoprotegerin ligand
  • RANKL
  • Receptor activator of nuclear factor kappa-B ligand
  • TNF-related activation-induced cytokine
  • TRANCE
Gene Name
TNFSF11
UniProtKB Entry
O14788Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0006789|Tumor necrosis factor ligand superfamily member 11
MRRASRDYTKYLRGSEEMGGGPGAPHEGPLHAPPPPAPHQPPAASRSMFVALLGLGLGQV
VCSVALFFYFRAQMDPNRISEDGTHCIYRILRLHENADFQDTTLESQDTKLIPDSCRRIK
QAFQGAVQKELQHIVGSQHIRAEKAMVDGSWLDLAKRSKLEAQPFAHLTINATDIPSGSH
KVSLSSWYHDRGWAKISNMTFSNGKLIVNQDGFYYLYANICFRHHETSGDLATEYLQLMV
YVTKTSIKIPSSHTLMKGGSTKYWSGNSEFHFYSINVGGFFKLRSGEEISIEVSNPSLLD
PDQDATYFGAFKVRDID
Number of residues
317
Molecular Weight
35477.81
Theoretical pI
7.74
GO Classification
Functions
identical protein binding
Processes
calcium-mediated signaling / cellular response to leukemia inhibitory factor / JNK cascade / negative regulation of transcription by RNA polymerase II / osteoclast development / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of canonical NF-kappaB signal transduction / positive regulation of DNA-binding transcription factor activity / positive regulation of ERK1 and ERK2 cascade / positive regulation of gene expression / positive regulation of JNK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of transcription by RNA polymerase II / tooth eruption
General Function
Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy (PubMed:22664871). Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation (By similarity)
Specific Function
Cytokine activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
48-68
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0012451|Tumor necrosis factor ligand superfamily member 11 (TNFSF11)
ATGCGCCGCGCCAGCAGAGACTACACCAAGTACCTGCGTGGCTCGGAGGAGATGGGCGGC
GGCCCCGGAGCCCCGCACGAGGGCCCCCTGCACGCCCCGCCGCCGCCTGCGCCGCACCAG
CCCCCTGCCGCCTCCCGCTCCATGTTCGTGGCCCTCCTGGGGCTGGGGCTGGGCCAGGTT
GTCTGCAGCGTCGCCCTGTTCTTCTATTTCAGAGCGCAGATGGATCCTAATAGAATATCA
GAAGATGGCACTCACTGCATTTATAGAATTTTGAGACTCCATGAAAATGCAGATTTTCAA
GACACAACTCTGGAGAGTCAAGATACAAAATTAATACCTGATTCATGTAGGAGAATTAAA
CAGGCCTTTCAAGGAGCTGTGCAAAAGGAATTACAACATATCGTTGGATCACAGCACATC
AGAGCAGAGAAAGCGATGGTGGATGGCTCATGGTTAGATCTGGCCAAGAGGAGCAAGCTT
GAAGCTCAGCCTTTTGCTCATCTCACTATTAATGCCACCGACATCCCATCTGGTTCCCAT
AAAGTGAGTCTGTCCTCTTGGTACCATGATCGGGGTTGGGCCAAGATCTCCAACATGACT
TTTAGCAATGGAAAACTAATAGTTAATCAGGATGGCTTTTATTACCTGTATGCCAACATT
TGCTTTCGACATCATGAAACTTCAGGAGACCTAGCTACAGAGTATCTTCAACTAATGGTG
TACGTCACTAAAACCAGCATCAAAATCCCAAGTTCTCATACCCTGATGAAAGGAGGAAGC
ACCAAGTATTGGTCAGGGAATTCTGAATTCCATTTTTATTCCATAAACGTTGGTGGATTT
TTTAAGTTACGGTCTGGAGAGGAAATCAGCATCGAGGTCTCCAACCCCTCCTTACTGGAT
CCGGATCAGGATGCAACATACTTTGGGGCTTTTAAAGTTCGAGATATAGATTGA
Chromosome Location
13
Locus
13q14.11
External Identifiers
ResourceLink
UniProtKB IDO14788
UniProtKB Entry NameTNF11_HUMAN
GenBank Gene IDAF013171
GeneCard IDTNFSF11
GenAtlas IDTNFSF11
HGNC IDHGNC:11926
PDB ID(s)3URF, 5BNQ
KEGG IDhsa:8600
NCBI Gene ID8600
General References
  1. Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L: A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 1997 Nov 13;390(6656):175-9. [Article]
  2. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998 Apr 17;93(2):165-76. [Article]
  3. Nagai M, Kyakumoto S, Sato N: Cancer cells responsible for humoral hypercalcemia express mRNA encoding a secreted form of ODF/TRANCE that induces osteoclast formation. Biochem Biophys Res Commun. 2000 Mar 16;269(2):532-6. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett FS 3rd, Frankel WN, Lee SY, Choi Y: TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J Biol Chem. 1997 Oct 3;272(40):25190-4. [Article]
  6. Luan X, Lu Q, Jiang Y, Zhang S, Wang Q, Yuan H, Zhao W, Wang J, Wang X: Crystal structure of human RANKL complexed with its decoy receptor osteoprotegerin. J Immunol. 2012 Jul 1;189(1):245-52. doi: 10.4049/jimmunol.1103387. Epub 2012 Jun 4. [Article]
  7. Sobacchi C, Frattini A, Guerrini MM, Abinun M, Pangrazio A, Susani L, Bredius R, Mancini G, Cant A, Bishop N, Grabowski P, Del Fattore A, Messina C, Errigo G, Coxon FP, Scott DI, Teti A, Rogers MJ, Vezzoni P, Villa A, Helfrich MH: Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. Nat Genet. 2007 Aug;39(8):960-2. Epub 2007 Jul 15. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
AMGN-0007investigationalunknowntargetDetails
DenosumabapprovedyestargetantibodyDetails
LenalidomideapprovedyestargetinhibitorDetails
ThiocolchicosideexperimentalunknowntargetantagonistDetails