TNF11_RAT
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 25-MAY-2022, entry version 132.
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}.
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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 GlyGen; Q9ESE2; 2 sites.
DR PaxDb; Q9ESE2; -.
DR GeneID; 117516; -.
DR KEGG; rno:117516; -.
DR UCSC; RGD:620784; rat.
DR CTD; 8600; -.
DR RGD; 620784; Tnfsf11.
DR eggNOG; ENOG502R8MX; Eukaryota.
DR InParanoid; Q9ESE2; -.
DR OrthoDB; 1404113at2759; -.
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: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:RGD.
DR GO; GO:0042802; F:identical protein binding; 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: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: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:0045780; P:positive regulation of bone resorption; IMP:RGD.
DR GO; GO:0051466; P:positive regulation of corticotropin-releasing hormone secretion; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; 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:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; 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:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; 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:0042327; P:positive regulation of phosphorylation; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; 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:1904616; P:regulation of actin binding; ISO:RGD.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; ISO:RGD.
DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR GO; GO:0009314; P:response to radiation; 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 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 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
