TNF18_MOUSE
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 03-AUG-2022, entry version 119.
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}.
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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 GlyGen; Q7TS55; 1 site.
DR MaxQB; Q7TS55; -.
DR PaxDb; Q7TS55; -.
DR PRIDE; Q7TS55; -.
DR Antibodypedia; 2126; 598 antibodies from 37 providers.
DR DNASU; 240873; -.
DR Ensembl; ENSMUST00000086084; ENSMUSP00000083251; ENSMUSG00000066755.
DR GeneID; 240873; -.
DR KEGG; mmu:240873; -.
DR UCSC; uc007dfo.2; mouse.
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; 1513112at2759; -.
DR PhylomeDB; Q7TS55; -.
DR TreeFam; TF338614; -.
DR Reactome; R-MMU-5669034; TNFs bind their physiological receptors.
DR BioGRID-ORCS; 240873; 0 hits in 71 CRISPR screens.
DR EvolutionaryTrace; Q7TS55; -.
DR PRO; PR:Q7TS55; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q7TS55; protein.
DR Bgee; ENSMUSG00000066755; Expressed in uterus and 5 other tissues.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
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; 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; PTHR15267; 1.
DR Pfam; PF00229; TNF; 1.
DR SUPFAM; SSF49842; SSF49842; 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
