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Protein

Tumor necrosis factor ligand superfamily member 18

Gene

Tnfsf18

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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 Expressed in 11 organ(s), highest expression level in zone of skin

Interactioni

Subunit structurei

Homotrimer. Homodimer.4 Publications

Binary interactionsi

GO - Molecular functioni

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

3D structure databases

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

Cross-referencesi

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

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...

Protein-protein interaction databases

DIPiDIP-29663N
IntActiQ7TS55, 1 interactor
STRINGi10090.ENSMUSP00000083251

Proteomic databases

MaxQBiQ7TS55
PaxDbiQ7TS55
PRIDEiQ7TS55

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8995
MGIiMGI:2673064 Tnfsf18

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-MMU-5669034 TNFs bind their physiological receptors

Miscellaneous databases

EvolutionaryTraceiQ7TS55
PROiPR:Q7TS55
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000066755 Expressed in 11 organ(s), highest expression level in zone of skin

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
ProtoNetiSearch...

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: November 7, 2018
This is version 101 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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