ID   TNF11_RAT               Reviewed;         318 AA.
AC   Q9ESE2; Q91ZI9;
DT   06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   27-MAR-2024, entry version 139.
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Tibial bone;
RX   PubMed=11092398; DOI=10.1359/jbmr.2000.15.11.2178;
RA   Xu J.K., Tan J.K., Huang L., Gao X.H., Laird R., Liu D., Wysocki S.,
RA   Zheng M.H.;
RT   "Cloning, sequence and functional characterization of the rat homologue of
RT   receptor activator of NF-kB ligand.";
RL   J. Bone Miner. Res. 15:2178-2186(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 266-318.
RC   STRAIN=Fischer 344;
RX   PubMed=11804028;
RA   Odgren P.R., Kim N., van Wesenbeeck L., MacKay C., Mason-Savas A.,
RA   Safadi F.F., Popoff S.N., Lengner C., van-Hul W., Choi Y., Marks S.C. Jr.;
RT   "Evidence that the rat osteopetrotic mutation toothless (tl) is not in the
RT   TNFSF11 (TRANCE, RANKL, ODF, OPGL) gene.";
RL   Int. J. Dev. Biol. 45:853-859(2001).
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. Induces osteoclastogenesis by
CC       activating multiple signaling pathways in osteoclast precursor cells,
CC       chief among which is induction of long lasting oscillations in the
CC       intracellular concentration of Ca (2+) resulting in the activation of
CC       NFATC1, which translocates to the nucleus and induces osteoclast-
CC       specific gene transcription to allow differentiation of osteoclasts.
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.
CC       {ECO:0000250|UniProtKB:O14788, ECO:0000250|UniProtKB:O35235}.
CC   -!- SUBUNIT: Homotrimer. Interacts with TNFRSF11A and TNFRSF11B. Interacts
CC       with FBN1 (via N-terminal domain) in a Ca(+2)-dependent manner.
CC       Interacts with TNFAIP6 (via both Link and CUB domains).
CC       {ECO:0000250|UniProtKB:O35235}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type II
CC       membrane protein {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Tumor necrosis factor ligand superfamily member
CC       11, soluble form]: Secreted {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in thymus and bone tissues.
CC   -!- PTM: The soluble form derives from the membrane form by proteolytic
CC       processing. {ECO:0000250}.
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; AF187319; AAG17031.1; -; mRNA.
DR   EMBL; AF425669; AAL23963.1; -; mRNA.
DR   RefSeq; NP_476490.1; NM_057149.1.
DR   AlphaFoldDB; Q9ESE2; -.
DR   SMR; Q9ESE2; -.
DR   STRING; 10116.ENSRNOP00000013210; -.
DR   GlyCosmos; Q9ESE2; 2 sites, No reported glycans.
DR   GlyGen; Q9ESE2; 2 sites.
DR   PhosphoSitePlus; Q9ESE2; -.
DR   PaxDb; 10116-ENSRNOP00000013210; -.
DR   GeneID; 117516; -.
DR   KEGG; rno:117516; -.
DR   UCSC; RGD:620784; rat.
DR   AGR; RGD:620784; -.
DR   CTD; 8600; -.
DR   RGD; 620784; Tnfsf11.
DR   eggNOG; ENOG502R8MX; Eukaryota.
DR   InParanoid; Q9ESE2; -.
DR   OrthoDB; 5305009at2759; -.
DR   PhylomeDB; Q9ESE2; -.
DR   Reactome; R-RNO-5668541; TNFR2 non-canonical NF-kB pathway.
DR   Reactome; R-RNO-5669034; TNFs bind their physiological receptors.
DR   Reactome; R-RNO-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
DR   PRO; PR:Q9ESE2; -.
DR   Proteomes; UP000002494; Unplaced.
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:RGD.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0048018; F:receptor ligand activity; ISO:RGD.
DR   GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro.
DR   GO; GO:0032813; F:tumor necrosis factor receptor superfamily binding; ISO:RGD.
DR   GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR   GO; GO:0060348; P:bone development; ISO:RGD.
DR   GO; GO:0045453; P:bone resorption; ISO:RGD.
DR   GO; GO:0055074; P:calcium ion homeostasis; ISO:RGD.
DR   GO; GO:0019722; P:calcium-mediated signaling; ISS:UniProtKB.
DR   GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
DR   GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:RGD.
DR   GO; GO:0006955; P:immune response; IEA:InterPro.
DR   GO; GO:0007254; P:JNK cascade; ISO:RGD.
DR   GO; GO:0060749; P:mammary gland alveolus development; ISO:RGD.
DR   GO; GO:0033598; P:mammary gland epithelial cell proliferation; ISO:RGD.
DR   GO; GO:0002548; P:monocyte chemotaxis; ISO:RGD.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0001503; P:ossification; ISO:RGD.
DR   GO; GO:0036035; P:osteoclast development; ISO:RGD.
DR   GO; GO:0030316; P:osteoclast differentiation; ISO:RGD.
DR   GO; GO:0002158; P:osteoclast proliferation; ISO:RGD.
DR   GO; GO:0038001; P:paracrine signaling; ISO:RGD.
DR   GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR   GO; GO:0045780; P:positive regulation of bone resorption; IMP:RGD.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISO:RGD.
DR   GO; GO:0051466; P:positive regulation of corticotropin-releasing hormone secretion; ISO:RGD.
DR   GO; GO:0071848; P:positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling; ISO:RGD.
DR   GO; GO:0071812; P:positive regulation of fever generation by positive regulation of prostaglandin secretion; ISO:RGD.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR   GO; GO:0034112; P:positive regulation of homotypic cell-cell adhesion; ISO:RGD.
DR   GO; GO:1902533; P:positive regulation of intracellular signal transduction; ISO:RGD.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; ISO:RGD.
DR   GO; GO:2001206; P:positive regulation of osteoclast development; ISO:RGD.
DR   GO; GO:0045672; P:positive regulation of osteoclast differentiation; IMP:RGD.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR   GO; GO:0042327; P:positive regulation of phosphorylation; ISO:RGD.
DR   GO; GO:0050870; P:positive regulation of T cell activation; ISO:RGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0045670; P:regulation of osteoclast differentiation; ISO:RGD.
DR   GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR   GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR   GO; GO:0071847; P:TNFSF11-mediated signaling pathway; ISO:RGD.
DR   GO; GO:0044691; P:tooth eruption; ISO:RGD.
DR   GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:RGD.
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.
PE   2: Evidence at transcript level;
KW   Cell membrane; Cytokine; Developmental protein; Differentiation;
KW   Glycoprotein; Membrane; Receptor; Reference proteome; Secreted;
KW   Signal-anchor; Transmembrane; Transmembrane helix.
FT   CHAIN           1..318
FT                   /note="Tumor necrosis factor ligand superfamily member 11,
FT                   membrane form"
FT                   /id="PRO_0000034518"
FT   CHAIN           141..318
FT                   /note="Tumor necrosis factor ligand superfamily member 11,
FT                   soluble form"
FT                   /id="PRO_0000034519"
FT   TOPO_DOM        1..47
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        48..68
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        69..318
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   REGION          13..41
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        27..41
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            140..141
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        199
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        264
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        317
FT                   /note="I -> M (in Ref. 2; AAL23963)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   318 AA;  35370 MW;  4B87A4D706AD098F CRC64;
     MRRANRDYGK YLRGSEEMGS CPGVPHEGPL HPAPSAPAPA PPPAASRFMF LALLGLGLGQ
     VVCSIALFLY FRAQMDPNRI SEDSTRCFYR ILRLRENTGL QDSTLESEDT EALPDSCRRM
     KQAFQGAVQR ELQHIVGPQR FSGVPAMMEG SWLDVARRGK PEAQPFAHLT INAADIPSGS
     HKVSLSSWYH DRGWAKISNM TLSNGKLRVN QDGFYYLYAN ICFRHHETSG SVPADYLQLM
     VYVVKTSIKI PSSHNLMKGG STKNWSGNSE FHFYSINVGG FFKLRAGEEI SVQVSNPSLL
     DPDQDATYFG AFKVQDID
//