ID TNF11_MOUSE Reviewed; 316 AA. AC O35235; O35306; Q3TWY5; Q9JJK8; Q9JJK9; Q9R1Y0; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 201. DE RecName: Full=Tumor necrosis factor ligand superfamily member 11; DE AltName: Full=Osteoclast differentiation factor; DE Short=ODF; DE AltName: Full=Osteoprotegerin ligand; DE Short=OPGL; DE AltName: Full=Receptor activator of nuclear factor kappa-B ligand; DE Short=RANKL; DE AltName: Full=TNF-related activation-induced cytokine; DE Short=TRANCE; DE AltName: CD_antigen=CD254; DE Contains: DE RecName: Full=Tumor necrosis factor ligand superfamily member 11, membrane form; DE Contains: DE RecName: Full=Tumor necrosis factor ligand superfamily member 11, soluble form; GN Name=Tnfsf11; Synonyms=Opgl, Rankl, Trance; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Hybridoma; RX PubMed=9312132; DOI=10.1074/jbc.272.40.25190; RA Wong B.R., Rho J., Arron J., Robinson E., Orlinick J., Chao M., RA Kalachikov S., Cayani E., Bartlett F.S. III, Frankel W.N., Lee S.Y., RA Choi Y.; RT "TRANCE is a novel ligand of the tumor necrosis factor receptor family that RT activates c-Jun N-terminal kinase in T cells."; RL J. Biol. Chem. 272:25190-25194(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Thymic lymphoma; RX PubMed=9367155; DOI=10.1038/36593; RA Anderson D.M., Maraskovsky E., Billingsley W.L., Dougall W.C., RA Tometsko M.E., Roux E.R., Teepe M.C., DuBose R.F., Cosman D., Galibert L.; RT "A homologue of the TNF receptor and its ligand enhance T-cell growth and RT dendritic-cell function."; RL Nature 390:175-179(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Bone marrow; RX PubMed=9568710; DOI=10.1016/s0092-8674(00)81569-x; RA Lacey D.L., Timms E., Tan H.-L., Kelley M.J., Dunstan C.R., Burgess T., RA Elliott R., Colombero A., Elliott G., Scully S., Hsu H., Sullivan J., RA Hawkins N., Davy E., Capparelli C., Eli A., Qian Y.-X., Kaufman S., RA Sarosi I., Shalhoub V., Senaldi G., Guo J., Delaney J., Boyle W.J.; RT "Osteoprotegerin ligand is a cytokine that regulates osteoclast RT differentiation and activation."; RL Cell 93:165-176(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Bone marrow stroma; RX PubMed=9520411; DOI=10.1073/pnas.95.7.3597; RA Yasuda H., Shima N., Nakagawa N., Yamaguchi K., Kinosaki M., Mochizuki S., RA Tomoyasu A., Yano K., Goto M., Murakami A., Tsuda E., Morinaga T., RA Higashio K., Udagawa N., Takahashi N., Suda T.; RT "Osteoclast differentiation factor is a ligand for RT osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to RT TRANCE/RANKL."; RL Proc. Natl. Acad. Sci. U.S.A. 95:3597-3602(1998). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RC STRAIN=129; RX PubMed=10196481; DOI=10.1016/s0378-1119(99)00025-6; RA Kodaira K., Kodaira K., Mizuno A., Yasuda H., Shima N., Murakami A., RA Ueda M., Higashio K.; RT "Cloning and characterization of the gene encoding mouse osteoclast RT differentiation factor."; RL Gene 230:121-127(1999). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). RX PubMed=11250921; DOI=10.1210/endo.142.4.8070; RA Ikeda T., Kasai M., Utsuyama M., Hirokawa K.; RT "Determination of three isoforms of the receptor activator of nuclear RT factor-kappaB ligand and their differential expression in bone and RT thymus."; RL Endocrinology 142:1419-1426(2001). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [8] RP PROTEIN SEQUENCE OF 139-147, PROTEOLYTIC PROCESSING, AND GLYCOSYLATION. RX PubMed=10224132; DOI=10.1074/jbc.274.19.13613; RA Lum L., Wong B.R., Josien R., Becherer J.D., Erdjument-Bromage H., RA Schloendorff J., Tempst P., Choi Y., Blobel C.P.; RT "Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)- RT converting enzyme-like protease in shedding of TRANCE, a TNF family member RT involved in osteoclastogenesis and dendritic cell survival."; RL J. Biol. Chem. 274:13613-13618(1999). RN [9] RP FUNCTION, AND INTERACTION WITH TNFAIP6. RX PubMed=18586671; DOI=10.1074/jbc.m802138200; RA Mahoney D.J., Mikecz K., Ali T., Mabilleau G., Benayahu D., Plaas A., RA Milner C.M., Day A.J., Sabokbar A.; RT "TSG-6 regulates bone remodeling through inhibition of osteoblastogenesis RT and osteoclast activation."; RL J. Biol. Chem. 283:25952-25962(2008). RN [10] RP INDUCTION BY CALCIUM. RX PubMed=21514407; DOI=10.1016/j.bone.2011.04.006; RA Lee H.L., Bae O.Y., Baek K.H., Kwon A., Hwang H.R., Qadir A.S., Park H.J., RA Woo K.M., Ryoo H.M., Baek J.H.; RT "High extracellular calcium-induced NFATc3 regulates the expression of RT receptor activator of NF-kappaB ligand in osteoblasts."; RL Bone 49:242-249(2011). RN [11] RP FUNCTION. RX PubMed=22437732; DOI=10.1002/jbmr.1600; RA Linares G.R., Brommage R., Powell D.R., Xing W., Chen S.T., Alshbool F.Z., RA Lau K.H., Wergedal J.E., Mohan S.; RT "Claudin 18 is a novel negative regulator of bone resorption and osteoclast RT differentiation."; RL J. Bone Miner. Res. 27:1553-1565(2012). RN [12] RP FUNCTION. RX PubMed=23395171; DOI=10.1016/j.cmet.2013.01.002; RA Kim H., Kim T., Jeong B.C., Cho I.T., Han D., Takegahara N., RA Negishi-Koga T., Takayanagi H., Lee J.H., Sul J.Y., Prasad V., Lee S.H., RA Choi Y.; RT "Tmem64 modulates calcium signaling during RANKL-mediated osteoclast RT differentiation."; RL Cell Metab. 17:249-260(2013). RN [13] RP FUNCTION, AND INTERACTION WITH FBN1. RX PubMed=24039232; DOI=10.1242/jcs.127571; RA Tiedemann K., Boraschi-Diaz I., Rajakumar I., Kaur J., Roughley P., RA Reinhardt D.P., Komarova S.V.; RT "Fibrillin-1 directly regulates osteoclast formation and function by a dual RT mechanism."; RL J. Cell Sci. 126:4187-4194(2013). RN [14] RP FUNCTION. RX PubMed=26644563; DOI=10.1073/pnas.1511285112; RA Decker C.E., Yang Z., Rimer R., Park-Min K.H., Macaubas C., Mellins E.D., RA Novack D.V., Faccio R.; RT "Tmem178 acts in a novel negative feedback loop targeting NFATc1 to RT regulate bone mass."; RL Proc. Natl. Acad. Sci. U.S.A. 112:15654-15659(2015). RN [15] RP FUNCTION. RX PubMed=27336669; DOI=10.1371/journal.pone.0157992; RA Omata Y., Nakamura S., Koyama T., Yasui T., Hirose J., Izawa N., RA Matsumoto T., Imai Y., Seo S., Kurokawa M., Tsutsumi S., Kadono Y., RA Morimoto C., Aburatani H., Miyamoto T., Tanaka S.; RT "Identification of Nedd9 as a TGF-beta-Smad2/3 Target Gene Involved in RT RANKL-Induced Osteoclastogenesis by Comprehensive Analysis."; RL PLoS ONE 11:e0157992-e0157992(2016). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 158-316, AND SUBUNIT. RX PubMed=11581298; DOI=10.1172/jci13890; RA Lam J., Nelson C.A., Ross F.P., Teitelbaum S.L., Fremont D.H.; RT "Crystal structure of the TRANCE/RANKL cytokine reveals determinants of RT receptor-ligand specificity."; RL J. Clin. Invest. 108:971-979(2001). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 137-316, AND SUBUNIT. RX PubMed=11733492; DOI=10.1074/jbc.m106525200; RA Ito S., Wakabayashi K., Ubukata O., Hayashi S., Okada F., Hata T.; RT "Crystal structure of the extracellular domain of mouse RANK ligand at 2.2- RT A resolution."; RL J. Biol. Chem. 277:6631-6636(2002). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 158-316 IN COMPLEX WITH TNFRSF11A, RP INTERACTION WITH TNFRSF11A, AND SUBUNIT. RX PubMed=20483727; DOI=10.4049/jimmunol.0904033; RA Liu C., Walter T.S., Huang P., Zhang S., Zhu X., Wu Y., Wedderburn L.R., RA Tang P., Owens R.J., Stuart D.I., Ren J., Gao B.; RT "Structural and functional insights of RANKL-RANK interaction and RT signaling."; RL J. Immunol. 184:6910-6919(2010). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 162-316 IN COMPLEX WITH TNFRSF11B. RX PubMed=23039992; DOI=10.1016/j.str.2012.08.030; RA Nelson C.A., Warren J.T., Wang M.W., Teitelbaum S.L., Fremont D.H.; RT "RANKL employs distinct binding modes to engage RANK and the RT osteoprotegerin decoy receptor."; RL Structure 20:1971-1982(2012). CC -!- FUNCTION: Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. CC Osteoclast differentiation and activation factor (PubMed:22437732). CC Augments the ability of dendritic cells to stimulate naive T-cell CC proliferation. May be an important regulator of interactions between T- CC cells and dendritic cells and may play a role in the regulation of the CC T-cell-dependent immune response. May also play an important role in CC enhanced bone-resorption in humoral hypercalcemia of malignancy (By CC similarity). Induces osteoclastogenesis by activating multiple CC signaling pathways in osteoclast precursor cells, chief among which is CC induction of long lasting oscillations in the intracellular CC concentration of Ca (2+) resulting in the activation of NFATC1, which CC translocates to the nucleus and induces osteoclast-specific gene CC transcription to allow differentiation of osteoclasts (PubMed:18586671, CC PubMed:24039232, PubMed:27336669). During osteoclast differentiation, CC in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and CC mitochondrial ROS generation necessary for proper osteoclast generation CC (PubMed:23395171, PubMed:26644563). {ECO:0000250|UniProtKB:O14788, CC ECO:0000269|PubMed:18586671, ECO:0000269|PubMed:22437732, CC ECO:0000269|PubMed:23395171, ECO:0000269|PubMed:24039232, CC ECO:0000269|PubMed:26644563, ECO:0000269|PubMed:27336669}. CC -!- SUBUNIT: Homotrimer (PubMed:11581298, PubMed:11733492, CC PubMed:20483727). Interacts with TNFRSF11A and TNFRSF11B CC (PubMed:20483727, PubMed:23039992). Interacts with FBN1 (via N-terminal CC domain) in a Ca(+2)-dependent manner (PubMed:24039232). Interacts with CC TNFAIP6 (via both Link and CUB domains). {ECO:0000269|PubMed:11581298, CC ECO:0000269|PubMed:11733492, ECO:0000269|PubMed:18586671, CC ECO:0000269|PubMed:20483727, ECO:0000269|PubMed:23039992, CC ECO:0000269|PubMed:24039232}. CC -!- INTERACTION: CC O35235-1; O35305: Tnfrsf11a; NbExp=6; IntAct=EBI-15890886, EBI-647362; CC O35235-1; O08712: Tnfrsf11b; NbExp=4; IntAct=EBI-15890886, EBI-16015871; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type II CC membrane protein. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type II CC membrane protein. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm. CC -!- SUBCELLULAR LOCATION: [Tumor necrosis factor ligand superfamily member CC 11, soluble form]: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O35235-1; Sequence=Displayed; CC Name=2; CC IsoId=O35235-2; Sequence=VSP_006449; CC Name=3; CC IsoId=O35235-3; Sequence=VSP_006448; CC -!- TISSUE SPECIFICITY: Highly expressed in thymus and lymph nodes, but not CC in non-lymphoid tissues and is abundantly expressed in T-cells but not CC in B-cells. A high level expression is also seen in the trabecular bone CC and lung. CC -!- INDUCTION: Induced by calcium in pre-osteoblasts and osteoblasts. CC {ECO:0000269|PubMed:21514407}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10224132}. CC -!- PTM: The soluble form of isoform 1 derives from the membrane form by CC proteolytic processing. The cleavage may be catalyzed by ADAM17. A CC further shorter soluble form was observed. CC {ECO:0000269|PubMed:10224132}. CC -!- DISEASE: Note=Deficiency in Tnfsf11 results in failure to form lobulo- CC alveolar mammary structures during pregnancy, resulting in death of CC newborns. Trance-deficient mice show severe osteopetrosis, with no CC osteoclasts, marrow spaces, or tooth eruption, and exhibit profound CC growth retardation at several skeletal sites, including the limbs, CC skull, and vertebrae and have marked chondrodysplasia, with thick, CC irregular growth plates and a relative increase in hypertrophic CC chondrocytes. CC -!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF013170; AAC71061.1; -; mRNA. DR EMBL; AF019048; AAB86812.1; -; mRNA. DR EMBL; AF053713; AAC40113.1; -; mRNA. DR EMBL; AB008426; BAA25425.1; -; mRNA. DR EMBL; AB022039; BAA36970.1; -; Genomic_DNA. DR EMBL; AB032771; BAA97257.1; -; mRNA. DR EMBL; AB032772; BAA97258.1; -; mRNA. DR EMBL; AB036798; BAA97259.1; -; mRNA. DR EMBL; AK159498; BAE35131.1; -; mRNA. DR CCDS; CCDS27294.1; -. [O35235-1] DR RefSeq; NP_035743.2; NM_011613.3. [O35235-1] DR PDB; 1IQA; X-ray; 2.20 A; A/B/C=157-316. DR PDB; 1JTZ; X-ray; 2.60 A; X/Y/Z=156-316. DR PDB; 1S55; X-ray; 1.90 A; A/B/C=161-316. DR PDB; 3ME2; X-ray; 2.80 A; A=158-316. DR PDB; 3QBQ; X-ray; 2.50 A; A/C=157-316. DR PDB; 4E4D; X-ray; 2.70 A; X=162-316. DR PDB; 4GIQ; X-ray; 2.70 A; A=158-316. DR PDBsum; 1IQA; -. DR PDBsum; 1JTZ; -. DR PDBsum; 1S55; -. DR PDBsum; 3ME2; -. DR PDBsum; 3QBQ; -. DR PDBsum; 4E4D; -. DR PDBsum; 4GIQ; -. DR AlphaFoldDB; O35235; -. DR SMR; O35235; -. DR BioGRID; 204255; 5. DR DIP; DIP-59480N; -. DR IntAct; O35235; 2. DR STRING; 10090.ENSMUSP00000022592; -. DR BindingDB; O35235; -. DR ChEMBL; CHEMBL3596084; -. DR GlyCosmos; O35235; 2 sites, No reported glycans. DR GlyGen; O35235; 2 sites. DR iPTMnet; O35235; -. DR PhosphoSitePlus; O35235; -. DR PaxDb; 10090-ENSMUSP00000022592; -. DR ProteomicsDB; 262840; -. [O35235-1] DR ProteomicsDB; 262841; -. [O35235-2] DR ABCD; O35235; 78 sequenced antibodies. DR Antibodypedia; 3366; 1504 antibodies from 50 providers. DR DNASU; 21943; -. DR Ensembl; ENSMUST00000022592.8; ENSMUSP00000022592.8; ENSMUSG00000022015.9. [O35235-1] DR GeneID; 21943; -. DR KEGG; mmu:21943; -. DR UCSC; uc007ush.1; mouse. [O35235-1] DR AGR; MGI:1100089; -. DR CTD; 8600; -. DR MGI; MGI:1100089; Tnfsf11. DR VEuPathDB; HostDB:ENSMUSG00000022015; -. DR eggNOG; ENOG502R8MX; Eukaryota. DR GeneTree; ENSGT01070000253816; -. DR HOGENOM; CLU_070352_0_0_1; -. DR InParanoid; O35235; -. DR OMA; RAQMDPT; -. DR OrthoDB; 5305009at2759; -. DR PhylomeDB; O35235; -. DR TreeFam; TF332169; -. DR Reactome; R-MMU-5668541; TNFR2 non-canonical NF-kB pathway. DR Reactome; R-MMU-5669034; TNFs bind their physiological receptors. DR Reactome; R-MMU-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway. DR BioGRID-ORCS; 21943; 0 hits in 79 CRISPR screens. DR ChiTaRS; Tnfsf11; mouse. DR EvolutionaryTrace; O35235; -. DR PRO; PR:O35235; -. DR Proteomes; UP000000589; Chromosome 14. DR RNAct; O35235; Protein. DR Bgee; ENSMUSG00000022015; Expressed in kidney vasculature and 44 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005125; F:cytokine activity; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; IPI:MGI. DR GO; GO:0048018; F:receptor ligand activity; IDA:MGI. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro. DR GO; GO:0032813; F:tumor necrosis factor receptor superfamily binding; IPI:BHF-UCL. DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI. DR GO; GO:0060348; P:bone development; IMP:MGI. DR GO; GO:0045453; P:bone resorption; IDA:MGI. DR GO; GO:0055074; P:calcium ion homeostasis; IGI:MGI. DR GO; GO:0019722; P:calcium-mediated signaling; IDA:UniProtKB. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:MGI. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IDA:DFLAT. DR GO; GO:0006955; P:immune response; IEA:InterPro. DR GO; GO:0007254; P:JNK cascade; IGI:MGI. DR GO; GO:0048535; P:lymph node development; TAS:MGI. DR GO; GO:0060749; P:mammary gland alveolus development; IMP:MGI. DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IMP:MGI. DR GO; GO:0002548; P:monocyte chemotaxis; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0001503; P:ossification; IMP:MGI. DR GO; GO:0036035; P:osteoclast development; IDA:MGI. DR GO; GO:0030316; P:osteoclast differentiation; IDA:MGI. DR GO; GO:0002158; P:osteoclast proliferation; IDA:MGI. DR GO; GO:0038001; P:paracrine signaling; IDA:MGI. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:MGI. DR GO; GO:0045780; P:positive regulation of bone resorption; ISO:MGI. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:MGI. DR GO; GO:0051466; P:positive regulation of corticotropin-releasing hormone secretion; IDA:BHF-UCL. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0071848; P:positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling; ISO:MGI. DR GO; GO:0071812; P:positive regulation of fever generation by positive regulation of prostaglandin secretion; IDA:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI. DR GO; GO:0034112; P:positive regulation of homotypic cell-cell adhesion; ISO:MGI. DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; ISO:MGI. DR GO; GO:0046330; P:positive regulation of JNK cascade; IGI:MGI. DR GO; GO:2001206; P:positive regulation of osteoclast development; IDA:MGI. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IDA:MGI. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:MGI. DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:DFLAT. DR GO; GO:0050870; P:positive regulation of T cell activation; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0045670; P:regulation of osteoclast differentiation; IDA:MGI. DR GO; GO:0071847; P:TNFSF11-mediated signaling pathway; IDA:MGI. DR GO; GO:0044691; P:tooth eruption; IMP:MGI. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IGI:BHF-UCL. DR CDD; cd00184; TNF; 1. DR Gene3D; 2.60.120.40; -; 1. DR InterPro; IPR006052; TNF_dom. DR InterPro; IPR017355; TNF_ligand_10/11. DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom. DR PANTHER; PTHR11471; TUMOR NECROSIS FACTOR FAMILY MEMBER; 1. DR PANTHER; PTHR11471:SF3; TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 11; 1. DR Pfam; PF00229; TNF; 1. DR PIRSF; PIRSF038013; TNF10_TNF11; 1. DR SMART; SM00207; TNF; 1. DR SUPFAM; SSF49842; TNF-like; 1. DR PROSITE; PS50049; TNF_2; 1. DR Genevisible; O35235; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cytokine; Cytoplasm; KW Developmental protein; Differentiation; Direct protein sequencing; KW Glycoprotein; Membrane; Receptor; Reference proteome; Secreted; KW Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1..316 FT /note="Tumor necrosis factor ligand superfamily member 11, FT membrane form" FT /id="PRO_0000034516" FT CHAIN 139..316 FT /note="Tumor necrosis factor ligand superfamily member 11, FT soluble form" FT /id="PRO_0000034517" FT TOPO_DOM 1..48 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 49..69 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 70..316 FT /note="Extracellular" FT /evidence="ECO:0000255" FT REGION 1..42 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 27..42 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 138..139 FT /note="Cleavage" FT CARBOHYD 197 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 262 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..117 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11250921" FT /id="VSP_006448" FT VAR_SEQ 14..44 FT /note="SSEEMGSGPGVPHEGPLHPAPSAPAPAPPPA -> TP (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:11250921" FT /id="VSP_006449" FT CONFLICT 99 FT /note="D -> G (in Ref. 1; AAC71061, 3; AAC40113, 4; FT BAA25425, 5; BAA36970 and 6; BAA97257/BAA97259)" FT /evidence="ECO:0000305" FT CONFLICT 141..143 FT /note="Missing (in Ref. 5; BAA36970)" FT /evidence="ECO:0000305" FT STRAND 164..169 FT /evidence="ECO:0007829|PDB:1S55" FT HELIX 171..173 FT /evidence="ECO:0007829|PDB:3ME2" FT STRAND 177..179 FT /evidence="ECO:0007829|PDB:1S55" FT STRAND 181..183 FT /evidence="ECO:0007829|PDB:1JTZ" FT STRAND 186..190 FT /evidence="ECO:0007829|PDB:1S55" FT STRAND 194..201 FT /evidence="ECO:0007829|PDB:1S55" FT STRAND 204..207 FT /evidence="ECO:0007829|PDB:1S55" FT STRAND 211..224 FT /evidence="ECO:0007829|PDB:1S55" FT HELIX 225..227 FT /evidence="ECO:0007829|PDB:1S55" FT STRAND 233..248 FT /evidence="ECO:0007829|PDB:1S55" FT STRAND 251..262 FT /evidence="ECO:0007829|PDB:1S55" FT STRAND 265..282 FT /evidence="ECO:0007829|PDB:1S55" FT STRAND 286..293 FT /evidence="ECO:0007829|PDB:1S55" FT HELIX 295..297 FT /evidence="ECO:0007829|PDB:1S55" FT TURN 302..304 FT /evidence="ECO:0007829|PDB:1S55" FT STRAND 305..313 FT /evidence="ECO:0007829|PDB:1S55" SQ SEQUENCE 316 AA; 35003 MW; 8AF3825F92E0A786 CRC64; MRRASRDYGK YLRSSEEMGS GPGVPHEGPL HPAPSAPAPA PPPAASRSMF LALLGLGLGQ VVCSIALFLY FRAQMDPNRI SEDSTHCFYR ILRLHENADL QDSTLESEDT LPDSCRRMKQ AFQGAVQKEL QHIVGPQRFS GAPAMMEGSW LDVAQRGKPE AQPFAHLTIN AASIPSGSHK VTLSSWYHDR GWAKISNMTL SNGKLRVNQD GFYYLYANIC FRHHETSGSV PTDYLQLMVY VVKTSIKIPS SHNLMKGGST KNWSGNSEFH FYSINVGGFF KLRAGEEISI QVSNPSLLDP DQDATYFGAF KVQDID //