TNF11_MOUSE
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 03-AUG-2022, entry version 192.
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 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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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. Augments the ability
CC of dendritic cells to stimulate naive T-cell proliferation. May be an
CC important regulator of interactions between T-cells and dendritic cells
CC and may play a role in the regulation of the T-cell-dependent immune
CC response. May also play an important role in enhanced bone-resorption
CC in humoral hypercalcemia of malignancy (By similarity). Induces
CC osteoclastogenesis by activating multiple signaling pathways in
CC osteoclast precursor cells, chief among which is induction of long
CC lasting oscillations in the intracellular concentration of Ca (2+)
CC resulting in the activation of NFATC1, which translocates to the
CC nucleus and induces osteoclast-specific gene transcription to allow
CC differentiation of osteoclasts (PubMed:24039232, PubMed:18586671).
CC During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent
CC manner induces activation of CREB1 and mitochondrial ROS generation
CC necessary for proper osteoclast generation (PubMed:23395171,
CC PubMed:26644563). {ECO:0000250|UniProtKB:O14788,
CC ECO:0000269|PubMed:23395171, ECO:0000269|PubMed:24039232,
CC ECO:0000269|PubMed:26644563}.
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 -!- 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}.
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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 DIP; DIP-59480N; -.
DR IntAct; O35235; 2.
DR STRING; 10090.ENSMUSP00000022592; -.
DR BindingDB; O35235; -.
DR ChEMBL; CHEMBL3596084; -.
DR GlyGen; O35235; 2 sites.
DR PhosphoSitePlus; O35235; -.
DR PaxDb; O35235; -.
DR PRIDE; O35235; -.
DR ProteomicsDB; 262840; -. [O35235-1]
DR ProteomicsDB; 262841; -. [O35235-2]
DR ABCD; O35235; 78 sequenced antibodies.
DR Antibodypedia; 3366; 1186 antibodies from 49 providers.
DR DNASU; 21943; -.
DR Ensembl; ENSMUST00000022592; ENSMUSP00000022592; ENSMUSG00000022015. [O35235-1]
DR GeneID; 21943; -.
DR KEGG; mmu:21943; -.
DR UCSC; uc007ush.1; mouse. [O35235-1]
DR CTD; 8600; -.
DR MGI; MGI:1100089; Tnfsf11.
DR VEuPathDB; HostDB:ENSMUSG00000022015; -.
DR eggNOG; ENOG502R8MX; Eukaryota.
DR GeneTree; ENSGT01050000244878; -.
DR HOGENOM; CLU_070352_0_0_1; -.
DR InParanoid; O35235; -.
DR OMA; HIVRSQH; -.
DR OrthoDB; 1404113at2759; -.
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 74 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 42 other tissues.
DR Genevisible; O35235; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; 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: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:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
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:0045780; P:positive regulation of bone resorption; ISO: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:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA: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:0043406; P:positive regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO: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:0042327; P:positive regulation of phosphorylation; IDA:DFLAT.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:MGI.
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:0043491; P:protein kinase B signaling; IMP:MGI.
DR GO; GO:1904616; P:regulation of actin binding; IDA: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 Pfam; PF00229; TNF; 1.
DR PIRSF; PIRSF038013; TNF10_TNF11; 1.
DR SMART; SM00207; TNF; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50049; TNF_2; 1.
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
