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Protein

Tumor necrosis factor ligand superfamily member 18

Gene

TNFSF18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

  1. receptor binding Source: ProtInc
  2. tumor necrosis factor receptor superfamily binding Source: UniProtKB

GO - Biological processi

  1. cell-cell signaling Source: ProtInc
  2. negative regulation of apoptotic process Source: ProtInc
  3. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  4. regulation of T cell proliferation Source: UniProtKB
  5. signal transduction Source: ProtInc
  6. T cell proliferation involved in immune response Source: UniProtKB
  7. tumor necrosis factor-mediated signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Adaptive immunity, Immunity

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
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:11932. TNFSF18.

Subcellular locationi

Cell membrane 1 Publication; Single-pass type II membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 5028CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei51 – 7121Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini72 – 199128ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: UniProtKB
  2. extracellular space Source: UniProtKB-KW
  3. integral component of membrane Source: UniProtKB-KW
  4. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA36624.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 199199Tumor necrosis factor ligand superfamily member 18PRO_0000185506Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi80 ↔ 1001 Publication
Glycosylationi151 – 1511N-linked (GlcNAc...)Sequence Analysis
Glycosylationi183 – 1831N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9UNG2.
PRIDEiQ9UNG2.

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

BgeeiQ9UNG2.
CleanExiHS_TNFSF18.
GenevestigatoriQ9UNG2.

Organism-specific databases

HPAiHPA012699.

Interactioni

Subunit structurei

Homodimer (By similarity). Homotrimer.By similarity1 Publication

Protein-protein interaction databases

DIPiDIP-29882N.
DIP-6243N.
STRINGi9606.ENSP00000385470.

Structurei

Secondary structure

1
199
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi81 – 844Combined sources
Beta strandi91 – 944Combined sources
Beta strandi100 – 1056Combined sources
Beta strandi108 – 1114Combined sources
Beta strandi115 – 1239Combined sources
Beta strandi131 – 1333Combined sources
Beta strandi137 – 1415Combined sources
Beta strandi144 – 1496Combined sources
Beta strandi152 – 1543Combined sources
Beta strandi160 – 1645Combined sources
Beta strandi169 – 1768Combined sources
Helixi177 – 1793Combined sources
Beta strandi186 – 1938Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 77-199.
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

eggNOGiNOG39473.
GeneTreeiENSGT00390000002560.
HOGENOMiHOG000026597.
HOVERGENiHBG061857.
InParanoidiQ9UNG2.
KOiK05479.
OMAiTYKEPAP.
OrthoDBiEOG7S7SG4.
PhylomeDBiQ9UNG2.
TreeFamiTF338614.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
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 AAH93986.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAI12033.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAQ89227.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG36082.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence EAW90937.1 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. Translation: CAP58846.1.
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.2. human.

Polymorphism databases

DMDMi325511353.

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. Translation: CAP58846.1.
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
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. Positions 77-199.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-29882N.
DIP-6243N.
STRINGi9606.ENSP00000385470.

Polymorphism databases

DMDMi325511353.

Proteomic databases

PaxDbiQ9UNG2.
PRIDEiQ9UNG2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000404377; ENSP00000385470; ENSG00000120337.
GeneIDi8995.
KEGGihsa:8995.
UCSCiuc001giu.2. human.

Organism-specific databases

CTDi8995.
GeneCardsiGC01M173009.
H-InvDBHIX0028550.
HGNCiHGNC:11932. TNFSF18.
HPAiHPA012699.
MIMi603898. gene.
neXtProtiNX_Q9UNG2.
PharmGKBiPA36624.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG39473.
GeneTreeiENSGT00390000002560.
HOGENOMiHOG000026597.
HOVERGENiHBG061857.
InParanoidiQ9UNG2.
KOiK05479.
OMAiTYKEPAP.
OrthoDBiEOG7S7SG4.
PhylomeDBiQ9UNG2.
TreeFamiTF338614.

Miscellaneous databases

EvolutionaryTraceiQ9UNG2.
GeneWikiiTNFSF18.
GenomeRNAii8995.
NextBioi33731.
PROiQ9UNG2.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UNG2.
CleanExiHS_TNFSF18.
GenevestigatoriQ9UNG2.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-199.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 17-199.
  6. "Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR."
    Gurney A.L., Marsters S.A., Huang R.M., Pitti R.M., Mark D.T., Baldwin D.T., Gray A.M., Dowd A.D., Brush A.D., Heldens A.D., Schow A.D., Goddard A.D., Wood W.I., Baker K.P., Godowski P.J., Ashkenazi A.
    Curr. Biol. 9:215-218(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-199.
    Tissue: Umbilical vein.
  7. "Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand."
    Kwon B., Yu K.-Y., Ni J., Yu G.-L., Jang I.-K., Kim Y.-J., Xing L., Liu D., Wang S.-X., Kwon B.S.
    J. Biol. Chem. 274:6056-6061(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-199.
    Tissue: Brain.
  8. "Expression of human GITRL on myeloid dendritic cells enhances their immunostimulatory function but does not abrogate the suppressive effect of CD4+CD25+ regulatory T cells."
    Tuyaerts S., Van Meirvenne S., Bonehill A., Heirman C., Corthals J., Waldmann H., Breckpot K., Thielemans K., Aerts J.L.
    J. Leukoc. Biol. 82:93-105(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  9. "Glucocorticoid-induced tumor necrosis factor receptor family-related ligand triggering upregulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and promotes leukocyte adhesion."
    Lacal P.M., Petrillo M.G., Ruffini F., Muzi A., Bianchini R., Ronchetti S., Migliorati G., Riccardi C., Graziani G., Nocentini G.
    J. Pharmacol. Exp. Ther. 347:164-172(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Assembly and structural properties of glucocorticoid-induced TNF receptor ligand: implications for function."
    Chattopadhyay K., Ramagopal U.A., Mukhopadhaya A., Malashkevich V.N., Dilorenzo T.P., Brenowitz M., Nathenson S.G., Almo S.C.
    Proc. Natl. Acad. Sci. U.S.A. 104:19452-19457(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 74-199, FUNCTION, SUBUNIT, DISULFIDE BOND.

Entry informationi

Entry nameiTNF18_HUMAN
AccessioniPrimary (citable) accession number: Q9UNG2
Secondary accession number(s): A9IQG8, O95852, Q6ISV1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: March 8, 2011
Last modified: January 7, 2015
This is version 111 of the entry and version 2 of the sequence. [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

Caution

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.