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Protein

Tumor necrosis factor ligand superfamily member 18

Gene

TNFSF18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Cytokine that binds to TNFRSF18/AITR/GITR. Regulates T-cell responses. Can function as costimulator and lower the threshold for T-cell activation and T-cell proliferation. Important for interactions between activated T-lymphocytes and endothelial cells. Mediates activation of NF-kappa-B. Triggers increased phosphorylation of STAT1 and up-regulates expression of VCAM1 and ICAM1 (PubMed:23892569). Promotes leukocyte adhesion to endothelial cells (PubMed:23892569). Regulates migration of monocytes from the splenic reservoir to sites of inflammation (By similarity).By similarity3 Publications

Caution

It is uncertain whether Met-1 or Met-23 is the initiator.Curated

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionCytokine
Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-5669034 TNFs bind their physiological receptors

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor ligand superfamily member 18
Alternative name(s):
Activation-inducible TNF-related ligand
Short name:
AITRL
Glucocorticoid-induced TNF-related ligand
Short name:
hGITRL
Gene namesi
Name:TNFSF18
Synonyms:AITRL, GITRL, TL6
ORF Names:UNQ149/PRO175
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000120337.8
HGNCiHGNC:11932 TNFSF18
MIMi603898 gene
neXtProtiNX_Q9UNG2

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 domaini23 – 50CytoplasmicSequence analysisAdd BLAST28
Transmembranei51 – 71Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini72 – 199ExtracellularSequence analysisAdd BLAST128

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8995
OpenTargetsiENSG00000120337
PharmGKBiPA36624

Polymorphism and mutation databases

BioMutaiTNFSF18
DMDMi325511353

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001855061 – 199Tumor necrosis factor ligand superfamily member 18Add BLAST199

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi80 ↔ 1001 Publication
Glycosylationi151N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi183N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9UNG2
PeptideAtlasiQ9UNG2
PRIDEiQ9UNG2
ProteomicsDBi85288

Expressioni

Tissue specificityi

Expressed at high levels in the small intestine, ovary, testis, kidney and endothelial cells.

Inductioni

Up-regulated after stimulation by bacterial lipopolysaccharides (LPS).

Gene expression databases

BgeeiENSG00000120337 Expressed in 46 organ(s), highest expression level in anterior cingulate cortex
CleanExiHS_TNFSF18
ExpressionAtlasiQ9UNG2 baseline and differential
GenevisibleiQ9UNG2 HS

Interactioni

Subunit structurei

Homodimer (By similarity). Homotrimer.By similarity1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114476, 53 interactors
DIPiDIP-29882N
IntActiQ9UNG2, 1 interactor
STRINGi9606.ENSP00000385470

Structurei

Secondary structure

1199
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UNG2
SMRiQ9UNG2
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UNG2

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
InParanoidiQ9UNG2
KOiK05479
OMAiCVAKFGP
OrthoDBiEOG091G0U1B
PhylomeDBiQ9UNG2
TreeFamiTF338614

Family and domain databases

Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR008983 Tumour_necrosis_fac-like_dom
SUPFAMiSSF49842 SSF49842, 1 hit

Sequencei

Sequence statusi: Complete.

Q9UNG2-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTLHPSPITC EFLFSTALIS PKMCLSHLEN MPLSHSRTQG AQRSSWKLWL
60 70 80 90 100
FCSIVMLLFL CSFSWLIFIF LQLETAKEPC MAKFGPLPSK WQMASSEPPC
110 120 130 140 150
VNKVSDWKLE ILQNGLYLIY GQVAPNANYN DVAPFEVRLY KNKDMIQTLT
160 170 180 190
NKSKIQNVGG TYELHVGDTI DLIFNSEHQV LKNNTYWGII LLANPQFIS
Length:199
Mass (Da):22,724
Last modified:March 8, 2011 - v2
Checksum:iC83A94645745DA58
GO

Sequence cautioni

The sequence AAH93986 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAI12033 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAQ89227 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG36082 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence EAW90937 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL031599 Genomic DNA No translation available.
CH471067 Genomic DNA Translation: EAW90937.1 Different initiation.
BC069111 mRNA Translation: AAH69111.1
BC069319 mRNA Translation: AAH69319.1
BC093986 mRNA Translation: AAH93986.1 Different initiation.
BC112032 mRNA Translation: AAI12033.1 Different initiation.
AK313273 mRNA Translation: BAG36082.1 Different initiation.
AY358868 mRNA Translation: AAQ89227.1 Different initiation.
AF125303 mRNA Translation: AAD22634.1
AF117713 mRNA Translation: AAD19695.1
CCDSiCCDS1305.2
RefSeqiNP_005083.2, NM_005092.3
UniGeneiHs.248197

Genome annotation databases

EnsembliENST00000404377; ENSP00000385470; ENSG00000120337
GeneIDi8995
KEGGihsa:8995
UCSCiuc001giu.3 human

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL031599 Genomic DNA No translation available.
CH471067 Genomic DNA Translation: EAW90937.1 Different initiation.
BC069111 mRNA Translation: AAH69111.1
BC069319 mRNA Translation: AAH69319.1
BC093986 mRNA Translation: AAH93986.1 Different initiation.
BC112032 mRNA Translation: AAI12033.1 Different initiation.
AK313273 mRNA Translation: BAG36082.1 Different initiation.
AY358868 mRNA Translation: AAQ89227.1 Different initiation.
AF125303 mRNA Translation: AAD22634.1
AF117713 mRNA Translation: AAD19695.1
CCDSiCCDS1305.2
RefSeqiNP_005083.2, NM_005092.3
UniGeneiHs.248197

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Q1MX-ray2.30A74-199[»]
2R30X-ray3.20A74-199[»]
2R32X-ray1.95A74-199[»]
3B93X-ray2.20A/B/C72-199[»]
3B94X-ray2.50A/B/C/D72-199[»]
ProteinModelPortaliQ9UNG2
SMRiQ9UNG2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114476, 53 interactors
DIPiDIP-29882N
IntActiQ9UNG2, 1 interactor
STRINGi9606.ENSP00000385470

Polymorphism and mutation databases

BioMutaiTNFSF18
DMDMi325511353

Proteomic databases

PaxDbiQ9UNG2
PeptideAtlasiQ9UNG2
PRIDEiQ9UNG2
ProteomicsDBi85288

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000404377; ENSP00000385470; ENSG00000120337
GeneIDi8995
KEGGihsa:8995
UCSCiuc001giu.3 human

Organism-specific databases

CTDi8995
DisGeNETi8995
EuPathDBiHostDB:ENSG00000120337.8
GeneCardsiTNFSF18
H-InvDBiHIX0028550
HGNCiHGNC:11932 TNFSF18
MIMi603898 gene
neXtProtiNX_Q9UNG2
OpenTargetsiENSG00000120337
PharmGKBiPA36624
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J65W Eukaryota
ENOG41117Z4 LUCA
GeneTreeiENSGT00390000002560
HOGENOMiHOG000026597
HOVERGENiHBG061857
InParanoidiQ9UNG2
KOiK05479
OMAiCVAKFGP
OrthoDBiEOG091G0U1B
PhylomeDBiQ9UNG2
TreeFamiTF338614

Enzyme and pathway databases

ReactomeiR-HSA-5669034 TNFs bind their physiological receptors

Miscellaneous databases

EvolutionaryTraceiQ9UNG2
GeneWikiiTNFSF18
GenomeRNAii8995
PROiPR:Q9UNG2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000120337 Expressed in 46 organ(s), highest expression level in anterior cingulate cortex
CleanExiHS_TNFSF18
ExpressionAtlasiQ9UNG2 baseline and differential
GenevisibleiQ9UNG2 HS

Family and domain databases

Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR008983 Tumour_necrosis_fac-like_dom
SUPFAMiSSF49842 SSF49842, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTNF18_HUMAN
AccessioniPrimary (citable) accession number: Q9UNG2
Secondary accession number(s): A9IQG8, O95852, Q6ISV1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: March 8, 2011
Last modified: September 12, 2018
This is version 133 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. 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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