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Protein

Tumor necrosis factor ligand superfamily member 18

Gene

Tnfsf18

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cytokine that binds to TNFRSF18/AITR/GITR (PubMed:14521928, PubMed:14647196). Regulates T-cell responses (PubMed:14647196). Can function as costimulator and lower the threshold for T-cell activation and T-cell proliferation (PubMed:14608036, PubMed:15128759). Important for interactions between activated T-lymphocytes and endothelial cells. Mediates activation of NF-kappa-B (PubMed:14521928, PubMed:14647196, PubMed:18178614). Triggers increased phosphorylation of STAT1 and up-regulates expression of VCAM1 and ICAM1 (By similarity). Promotes leukocyte adhesion to endothelial cells (PubMed:23892569). Regulates migration of monocytes from the splenic reservoir to sites of inflammation (PubMed:24107315).By similarity7 Publications

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • tumor necrosis factor receptor binding Source: InterPro
  • tumor necrosis factor receptor superfamily binding Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • cell-cell signaling Source: GO_Central
  • negative regulation of T-helper 17 cell lineage commitment Source: UniProtKB
  • positive regulation of cell adhesion Source: UniProtKB
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of leukocyte migration Source: MGI
  • positive regulation of macrophage chemotaxis Source: UniProtKB
  • positive regulation of monocyte chemotaxis Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of protein homodimerization activity Source: UniProtKB
  • positive regulation of tyrosine phosphorylation of STAT protein Source: MGI
  • regulation of dendritic cell chemotaxis Source: UniProtKB
  • regulation of T cell proliferation Source: UniProtKB
  • T cell proliferation involved in immune response Source: UniProtKB
  • tumor necrosis factor-mediated signaling pathway Source: UniProtKB

Keywordsi

Molecular functionCytokine
Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-MMU-5669034. TNFs bind their physiological receptors.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor ligand superfamily member 18
Alternative name(s):
GITR ligand
Short name:
GITRL
Glucocorticoid-induced TNF-related ligand
Gene namesi
Name:Tnfsf18
Synonyms:Gitrl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2673064. Tnfsf18.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 20CytoplasmicSequence analysisAdd BLAST20
Transmembranei21 – 41Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini42 – 173ExtracellularSequence analysisAdd BLAST132

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Reduced levels of proinflammatory macrophages in the peritoneal cavity following injection with thioglycollate broth to induce peritonitis and reduced AGTR1 levels in spleen macrophages.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004153331 – 173Tumor necrosis factor ligand superfamily member 18Add BLAST173

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi52 ↔ 723 Publications
Glycosylationi74N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ7TS55.
PaxDbiQ7TS55.
PRIDEiQ7TS55.

Expressioni

Tissue specificityi

Detected in immature and mature dendritic cells and in macrophages (at protein level). Detected in spleen, lung, heart, thymus, monocytes, macrophages, B-cells and dendritic cells.3 Publications

Inductioni

Up-regulated by exposure to bacterial lipopolysaccharide (LPS).1 Publication

Gene expression databases

BgeeiENSMUSG00000066755.

Interactioni

Subunit structurei

Homotrimer. Homodimer.4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • tumor necrosis factor receptor binding Source: InterPro
  • tumor necrosis factor receptor superfamily binding Source: UniProtKB

Protein-protein interaction databases

DIPiDIP-29663N.
IntActiQ7TS55. 1 interactor.
STRINGi10090.ENSMUSP00000083251.

Structurei

Secondary structure

1173
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi53 – 57Combined sources5
Turni58 – 61Combined sources4
Beta strandi62 – 69Combined sources8
Beta strandi71 – 75Combined sources5
Beta strandi81 – 83Combined sources3
Beta strandi87 – 95Combined sources9
Helixi100 – 102Combined sources3
Beta strandi109 – 115Combined sources7
Beta strandi118 – 127Combined sources10
Beta strandi130 – 138Combined sources9
Beta strandi143 – 149Combined sources7
Helixi151 – 153Combined sources3
Beta strandi160 – 165Combined sources6
Beta strandi169 – 171Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Q8OX-ray1.75A/B43-173[»]
2QDNX-ray2.09A/B46-173[»]
3B9IX-ray2.49A/B46-173[»]
3FC0X-ray1.76A/B46-173[»]
ProteinModelPortaliQ7TS55.
SMRiQ7TS55.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ7TS55.

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J65W. Eukaryota.
ENOG41117Z4. LUCA.
GeneTreeiENSGT00390000002560.
HOGENOMiHOG000026597.
HOVERGENiHBG061857.
InParanoidiQ7TS55.
KOiK05479.
OMAiCVAKFGP.
OrthoDBiEOG091G0U1B.
PhylomeDBiQ7TS55.
TreeFamiTF338614.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiView protein in InterPro
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
PfamiView protein in Pfam
PF00229. TNF. 1 hit.
SUPFAMiSSF49842. SSF49842. 1 hit.

Sequencei

Sequence statusi: Complete.

Q7TS55-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEEMPLRESS PQRAERCKKS WLLCIVALLL MLLCSLGTLI YTSLKPTAIE
60 70 80 90 100
SCMVKFELSS SKWHMTSPKP HCVNTTSDGK LKILQSGTYL IYGQVIPVDK
110 120 130 140 150
KYIKDNAPFV VQIYKKNDVL QTLMNDFQIL PIGGVYELHA GDNIYLKFNS
160 170
KDHIQKTNTY WGIILMPDLP FIS
Length:173
Mass (Da):19,732
Last modified:October 1, 2003 - v1
Checksum:i0F08494CACF424D2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48A → V in AAP96745 (PubMed:14647196).Curated1
Sequence conflicti157T → N in AAP96745 (PubMed:14647196).Curated1
Sequence conflicti157T → N in CAE12166 (PubMed:14608036).Curated1
Sequence conflicti157T → N in CAE12167 (PubMed:14608036).Curated1
Sequence conflicti157T → N in AAO89011 (Ref. 5) Curated1
Sequence conflicti157T → N in AAI37815 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY359852 mRNA. Translation: AAQ55265.1.
AY267900 mRNA. Translation: AAP96745.1.
AJ577579 mRNA. Translation: CAE12166.1.
AJ577580 mRNA. Translation: CAE12167.1.
AY320040 mRNA. Translation: AAP70494.1.
AY234223 mRNA. Translation: AAO89011.1.
AC163268 Genomic DNA. No translation available.
BC137814 mRNA. Translation: AAI37815.1.
BC137815 mRNA. Translation: AAI37816.1.
CCDSiCCDS15417.1.
RefSeqiNP_899247.3. NM_183391.3.
UniGeneiMm.276823.

Genome annotation databases

EnsembliENSMUST00000086084; ENSMUSP00000083251; ENSMUSG00000066755.
GeneIDi240873.
KEGGimmu:240873.
UCSCiuc007dfo.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiTNF18_MOUSE
AccessioniPrimary (citable) accession number: Q7TS55
Secondary accession number(s): Q7TNY2, Q80YG2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 25, 2012
Last sequence update: October 1, 2003
Last modified: October 25, 2017
This is version 98 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families