ID TNF18_MOUSE Reviewed; 173 AA. AC Q7TS55; Q7TNY2; Q80YG2; DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 1. DT 27-MAR-2024, entry version 127. DE RecName: Full=Tumor necrosis factor ligand superfamily member 18; DE AltName: Full=GITR ligand; DE Short=GITRL; DE AltName: Full=Glucocorticoid-induced TNF-related ligand; GN Name=Tnfsf18; Synonyms=Gitrl; 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], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC STRAIN=129/J; RX PubMed=14521928; DOI=10.1016/j.bbrc.2003.09.024; RA Yu K.Y., Kim H.S., Song S.Y., Min S.S., Jeong J.J., Youn B.S.; RT "Identification of a ligand for glucocorticoid-induced tumor necrosis RT factor receptor constitutively expressed in dendritic cells."; RL Biochem. Biophys. Res. Commun. 310:433-438(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RC STRAIN=BALB/cJ; RX PubMed=14647196; DOI=10.1038/sj.gene.6364026; RA Kim J.D., Choi B.K., Bae J.S., Lee U.H., Han I.S., Lee H.W., Youn B.S., RA Vinay D.S., Kwon B.S.; RT "Cloning and characterization of GITR ligand."; RL Genes Immun. 4:564-569(2003). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND RP TISSUE SPECIFICITY. RC STRAIN=CBA/CaJ; RX PubMed=14608036; DOI=10.1073/pnas.2334901100; RA Tone M., Tone Y., Adams E., Yates S.F., Frewin M.R., Cobbold S.P., RA Waldmann H.; RT "Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is RT costimulatory for T cells."; RL Proc. Natl. Acad. Sci. U.S.A. 100:15059-15064(2003). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBUNIT. RC STRAIN=C57BL/6J; TISSUE=Spleen; RX PubMed=15128759; DOI=10.4049/jimmunol.172.10.5823; RA Ji H.B., Liao G., Faubion W.A., Abadia-Molina A.C., Cozzo C., Laroux F.S., RA Caton A., Terhorst C.; RT "The natural ligand for glucocorticoid-induced TNF receptor-related protein RT abrogates regulatory T cell suppression."; RL J. Immunol. 172:5823-5827(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=DBA/2J; RA Bianchini R., Nocentini G., Ronchetti S., Ayroldi E., Riccardi C.; RT "Cloning and characterization of the mouse ortholog of human GITR ligand RT (TNFSF18)."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION. RX PubMed=23892569; DOI=10.1124/jpet.113.207605; RA Lacal P.M., Petrillo M.G., Ruffini F., Muzi A., Bianchini R., Ronchetti S., RA Migliorati G., Riccardi C., Graziani G., Nocentini G.; RT "Glucocorticoid-induced tumor necrosis factor receptor family-related RT ligand triggering upregulates vascular cell adhesion molecule-1 and RT intercellular adhesion molecule-1 and promotes leukocyte adhesion."; RL J. Pharmacol. Exp. Ther. 347:164-172(2013). RN [9] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=24107315; DOI=10.1096/fj.13-236505; RA Liao G., van Driel B., Magelky E., O'Keeffe M.S., de Waal Malefyt R., RA Engel P., Herzog R.W., Mizoguchi E., Bhan A.K., Terhorst C.; RT "Glucocorticoid-induced TNF receptor family-related protein ligand RT regulates the migration of monocytes to the inflamed intestine."; RL FASEB J. 28:474-484(2014). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 46-173, SUBUNIT, AND DISULFIDE RP BOND. RX PubMed=18182486; DOI=10.1073/pnas.0710529105; RA Chattopadhyay K., Ramagopal U.A., Brenowitz M., Nathenson S.G., Almo S.C.; RT "Evolution of GITRL immune function: murine GITRL exhibits unique RT structural and biochemical properties within the TNF superfamily."; RL Proc. Natl. Acad. Sci. U.S.A. 105:635-640(2008). RN [11] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 43-173, FUNCTION, SUBUNIT, AND RP DISULFIDE BOND. RX PubMed=18178614; DOI=10.1073/pnas.0711206105; RA Zhou Z., Tone Y., Song X., Furuuchi K., Lear J.D., Waldmann H., Tone M., RA Greene M.I., Murali R.; RT "Structural basis for ligand-mediated mouse GITR activation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:641-645(2008). RN [12] RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) OF 46-173, GLYCOSYLATION, SUBUNIT, RP AND DISULFIDE BOND. RX PubMed=19390148; DOI=10.1107/s0907444909005721; RA Chattopadhyay K., Ramagopal U.A., Nathenson S.G., Almo S.C.; RT "1.8 A structure of murine GITR ligand dimer expressed in Drosophila RT melanogaster S2 cells."; RL Acta Crystallogr. D 65:434-439(2009). CC -!- FUNCTION: Cytokine that binds to TNFRSF18/AITR/GITR (PubMed:14521928, CC PubMed:14647196). Regulates T-cell responses (PubMed:14647196). Can CC function as costimulator and lower the threshold for T-cell activation CC and T-cell proliferation (PubMed:14608036, PubMed:15128759). Important CC for interactions between activated T-lymphocytes and endothelial cells. CC Mediates activation of NF-kappa-B (PubMed:14521928, PubMed:14647196, CC PubMed:18178614). Triggers increased phosphorylation of STAT1 and up- CC regulates expression of VCAM1 and ICAM1 (By similarity). Promotes CC leukocyte adhesion to endothelial cells (PubMed:23892569). Regulates CC migration of monocytes from the splenic reservoir to sites of CC inflammation (PubMed:24107315). {ECO:0000250|UniProtKB:Q9UNG2, CC ECO:0000269|PubMed:14521928, ECO:0000269|PubMed:14608036, CC ECO:0000269|PubMed:14647196, ECO:0000269|PubMed:15128759, CC ECO:0000269|PubMed:18178614, ECO:0000269|PubMed:23892569, CC ECO:0000269|PubMed:24107315}. CC -!- SUBUNIT: Homotrimer. Homodimer. {ECO:0000269|PubMed:15128759, CC ECO:0000269|PubMed:18178614, ECO:0000269|PubMed:18182486, CC ECO:0000269|PubMed:19390148}. CC -!- INTERACTION: CC Q7TS55; O35714: Tnfrsf18; NbExp=4; IntAct=EBI-523345, EBI-523358; CC Q7TS55; Q7TS55: Tnfsf18; NbExp=4; IntAct=EBI-523345, EBI-523345; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14521928, CC ECO:0000269|PubMed:14608036}; Single-pass type II membrane protein CC {ECO:0000269|PubMed:14521928, ECO:0000269|PubMed:14608036}. CC -!- TISSUE SPECIFICITY: Detected in immature and mature dendritic cells and CC in macrophages (at protein level). Detected in spleen, lung, heart, CC thymus, monocytes, macrophages, B-cells and dendritic cells. CC {ECO:0000269|PubMed:14521928, ECO:0000269|PubMed:14608036, CC ECO:0000269|PubMed:14647196}. CC -!- INDUCTION: Up-regulated by exposure to bacterial lipopolysaccharide CC (LPS). {ECO:0000269|PubMed:14608036}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19390148}. CC -!- DISRUPTION PHENOTYPE: Reduced levels of pro-inflammatory macrophages in CC the peritoneal cavity following injection with thioglycollate broth to CC induce peritonitis and reduced AGTR1 levels in spleen macrophages. CC {ECO:0000269|PubMed:24107315}. 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; AY359852; AAQ55265.1; -; mRNA. DR EMBL; AY267900; AAP96745.1; -; mRNA. DR EMBL; AJ577579; CAE12166.1; -; mRNA. DR EMBL; AJ577580; CAE12167.1; -; mRNA. DR EMBL; AY320040; AAP70494.1; -; mRNA. DR EMBL; AY234223; AAO89011.1; -; mRNA. DR EMBL; AC163268; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC137814; AAI37815.1; -; mRNA. DR EMBL; BC137815; AAI37816.1; -; mRNA. DR CCDS; CCDS15417.1; -. DR RefSeq; NP_899247.3; NM_183391.3. DR PDB; 2Q8O; X-ray; 1.75 A; A/B=43-173. DR PDB; 2QDN; X-ray; 2.09 A; A/B=46-173. DR PDB; 3B9I; X-ray; 2.49 A; A/B=46-173. DR PDB; 3FC0; X-ray; 1.76 A; A/B=46-173. DR PDB; 7E57; X-ray; 3.30 A; A/B=1-173. DR PDB; 7KHX; X-ray; 3.21 A; A/B=42-173. DR PDBsum; 2Q8O; -. DR PDBsum; 2QDN; -. DR PDBsum; 3B9I; -. DR PDBsum; 3FC0; -. DR PDBsum; 7E57; -. DR PDBsum; 7KHX; -. DR AlphaFoldDB; Q7TS55; -. DR SMR; Q7TS55; -. DR DIP; DIP-29663N; -. DR IntAct; Q7TS55; 1. DR STRING; 10090.ENSMUSP00000083251; -. DR GlyCosmos; Q7TS55; 1 site, No reported glycans. DR GlyGen; Q7TS55; 1 site. DR MaxQB; Q7TS55; -. DR PaxDb; 10090-ENSMUSP00000083251; -. DR Antibodypedia; 2126; 650 antibodies from 38 providers. DR DNASU; 240873; -. DR Ensembl; ENSMUST00000086084.2; ENSMUSP00000083251.2; ENSMUSG00000066755.3. DR GeneID; 240873; -. DR KEGG; mmu:240873; -. DR UCSC; uc007dfo.2; mouse. DR AGR; MGI:2673064; -. DR CTD; 8995; -. DR MGI; MGI:2673064; Tnfsf18. DR VEuPathDB; HostDB:ENSMUSG00000066755; -. DR eggNOG; ENOG502SWIC; Eukaryota. DR GeneTree; ENSGT00390000002560; -. DR HOGENOM; CLU_134507_0_0_1; -. DR InParanoid; Q7TS55; -. DR OMA; YKEPAPF; -. DR OrthoDB; 5263857at2759; -. DR PhylomeDB; Q7TS55; -. DR TreeFam; TF338614; -. DR Reactome; R-MMU-5669034; TNFs bind their physiological receptors. DR BioGRID-ORCS; 240873; 1 hit in 76 CRISPR screens. DR EvolutionaryTrace; Q7TS55; -. DR PRO; PR:Q7TS55; -. DR Proteomes; UP000000589; Chromosome 1. DR RNAct; Q7TS55; Protein. DR Bgee; ENSMUSG00000066755; Expressed in mesodermal cell in embryo and 5 other cell types or tissues. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. 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; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro. DR GO; GO:0032813; F:tumor necrosis factor receptor superfamily binding; IDA:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:2000329; P:negative regulation of T-helper 17 cell lineage commitment; IMP:UniProtKB. DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB. DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:UniProtKB. DR GO; GO:0002687; P:positive regulation of leukocyte migration; ISO:MGI. DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IMP:UniProtKB. DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IMP:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI. DR GO; GO:2000508; P:regulation of dendritic cell chemotaxis; IMP:UniProtKB. DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IMP:UniProtKB. DR GO; GO:0042129; P:regulation of T cell proliferation; IDA:UniProtKB. DR GO; GO:0002309; P:T cell proliferation involved in immune response; IDA:UniProtKB. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB. DR Gene3D; 2.60.120.40; -; 1. DR InterPro; IPR006052; TNF_dom. DR InterPro; IPR042380; TNFSF18. DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom. DR PANTHER; PTHR15267; TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 18; 1. DR PANTHER; PTHR15267:SF1; TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 18; 1. DR Pfam; PF00229; TNF; 1. DR SUPFAM; SSF49842; TNF-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Cell membrane; Cytokine; Disulfide bond; KW Glycoprotein; Immunity; Membrane; Reference proteome; Signal-anchor; KW Transmembrane; Transmembrane helix. FT CHAIN 1..173 FT /note="Tumor necrosis factor ligand superfamily member 18" FT /id="PRO_0000415333" FT TOPO_DOM 1..20 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 21..41 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 42..173 FT /note="Extracellular" FT /evidence="ECO:0000255" FT CARBOHYD 74 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 52..72 FT /evidence="ECO:0000269|PubMed:18178614, FT ECO:0000269|PubMed:18182486, ECO:0000269|PubMed:19390148" FT CONFLICT 48 FT /note="A -> V (in Ref. 2; AAP96745)" FT /evidence="ECO:0000305" FT CONFLICT 157 FT /note="T -> N (in Ref. 2; AAP96745, 3; CAE12166/CAE12167, FT 5; AAO89011 and 7; AAI37815)" FT /evidence="ECO:0000305" FT STRAND 53..57 FT /evidence="ECO:0007829|PDB:2Q8O" FT TURN 58..61 FT /evidence="ECO:0007829|PDB:2Q8O" FT STRAND 62..69 FT /evidence="ECO:0007829|PDB:2Q8O" FT STRAND 71..75 FT /evidence="ECO:0007829|PDB:2Q8O" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:2Q8O" FT STRAND 87..95 FT /evidence="ECO:0007829|PDB:2Q8O" FT HELIX 100..102 FT /evidence="ECO:0007829|PDB:2Q8O" FT STRAND 109..115 FT /evidence="ECO:0007829|PDB:2Q8O" FT STRAND 118..127 FT /evidence="ECO:0007829|PDB:2Q8O" FT STRAND 130..138 FT /evidence="ECO:0007829|PDB:2Q8O" FT STRAND 143..149 FT /evidence="ECO:0007829|PDB:2Q8O" FT HELIX 151..153 FT /evidence="ECO:0007829|PDB:2Q8O" FT STRAND 160..165 FT /evidence="ECO:0007829|PDB:2Q8O" FT STRAND 171..173 FT /evidence="ECO:0007829|PDB:3FC0" SQ SEQUENCE 173 AA; 19732 MW; 0F08494CACF424D2 CRC64; MEEMPLRESS PQRAERCKKS WLLCIVALLL MLLCSLGTLI YTSLKPTAIE SCMVKFELSS SKWHMTSPKP HCVNTTSDGK LKILQSGTYL IYGQVIPVDK KYIKDNAPFV VQIYKKNDVL QTLMNDFQIL PIGGVYELHA GDNIYLKFNS KDHIQKTNTY WGIILMPDLP FIS //