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Q9UNG2 (TNF18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:TNFSF18
Synonyms:AITRL, GITRL, TL6
ORF Names:UNQ149/PRO175
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length199 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9

Subunit structure

Homodimer By similarity. Homotrimer. Ref.9

Subcellular location

Cell membrane; Single-pass type II membrane protein Ref.8.

Tissue specificity

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

Induction

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

Sequence similarities

Belongs to the tumor necrosis factor family.

Caution

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

Sequence caution

The sequence AAH93986.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAI12033.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAQ89227.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAG36082.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence EAW90937.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
   Cellular componentCell membrane
Membrane
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionCytokine
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell proliferation involved in immune response

Inferred from sequence or structural similarity. Source: UniProtKB

cell-cell signaling

Traceable author statement Ref.6. Source: ProtInc

negative regulation of apoptotic process

Traceable author statement Ref.6. Source: ProtInc

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of T cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

signal transduction

Traceable author statement Ref.6. Source: ProtInc

tumor necrosis factor-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell surface

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionreceptor binding

Traceable author statement Ref.6. Source: ProtInc

tumor necrosis factor receptor superfamily binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 199199Tumor necrosis factor ligand superfamily member 18
PRO_0000185506

Regions

Topological domain23 – 5028Cytoplasmic Potential
Transmembrane51 – 7121Helical; Signal-anchor for type II membrane protein; Potential
Topological domain72 – 199128Extracellular Potential

Amino acid modifications

Glycosylation1511N-linked (GlcNAc...) Potential
Glycosylation1831N-linked (GlcNAc...) Potential
Disulfide bond80 ↔ 100 Ref.9

Secondary structure

.......................... 199
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UNG2 [UniParc].

Last modified March 8, 2011. Version 2.
Checksum: C83A94645745DA58

FASTA19922,724
        10         20         30         40         50         60 
MTLHPSPITC EFLFSTALIS PKMCLSHLEN MPLSHSRTQG AQRSSWKLWL FCSIVMLLFL 

        70         80         90        100        110        120 
CSFSWLIFIF LQLETAKEPC MAKFGPLPSK WQMASSEPPC VNKVSDWKLE ILQNGLYLIY 

       130        140        150        160        170        180 
GQVAPNANYN DVAPFEVRLY KNKDMIQTLT NKSKIQNVGG TYELHVGDTI DLIFNSEHQV 

       190 
LKNNTYWGII LLANPQFIS 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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. expand/collapse author list , 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]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
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]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_005083.2. NM_005092.3.
UniGeneHs.248197.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalQ9UNG2.
SMRQ9UNG2. Positions 77-199.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-29882N.
DIP-6243N.
STRING9606.ENSP00000385470.

Polymorphism databases

DMDM325511353.

Proteomic databases

PaxDbQ9UNG2.
PRIDEQ9UNG2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000239468; ENSP00000239468; ENSG00000120337.
ENST00000404377; ENSP00000385470; ENSG00000120337.
GeneID8995.
KEGGhsa:8995.
UCSCuc001giu.2. human.

Organism-specific databases

CTD8995.
GeneCardsGC01M173009.
H-InvDBHIX0028550.
HGNCHGNC:11932. TNFSF18.
HPAHPA012699.
MIM603898. gene.
neXtProtNX_Q9UNG2.
PharmGKBPA36624.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39473.
HOGENOMHOG000026597.
HOVERGENHBG061857.
InParanoidQ9UNG2.
KOK05479.
OMATYKEPAP.
OrthoDBEOG7S7SG4.
PhylomeDBQ9UNG2.
TreeFamTF338614.

Gene expression databases

BgeeQ9UNG2.
CleanExHS_TNFSF18.
GenevestigatorQ9UNG2.

Family and domain databases

Gene3D2.60.120.40. 1 hit.
InterProIPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamPF00229. TNF. 1 hit.
[Graphical view]
SUPFAMSSF49842. SSF49842. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ9UNG2.
GeneWikiTNFSF18.
GenomeRNAi8995.
NextBio33731.
PROQ9UNG2.
SOURCESearch...

Entry information

Entry nameTNF18_HUMAN
AccessionPrimary (citable) accession number: Q9UNG2
Secondary accession number(s): A9IQG8, O95852, Q6ISV1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: March 8, 2011
Last modified: April 16, 2014
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM