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Protein

Tumor necrosis factor receptor superfamily member 18

Gene

TNFRSF18

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

Functioni

Receptor for TNFSF18. Seems to be involved in interactions between activated T-lymphocytes and endothelial cells and in the regulation of T-cell receptor-mediated cell death. Mediated NF-kappa-B activation via the TRAF2/NIK pathway.

GO - Molecular functioni

GO - Biological processi

  • apoptotic signaling pathway Source: GO_Central
  • immune response Source: GO_Central
  • inflammatory response Source: GO_Central
  • multicellular organism development Source: GO_Central
  • negative regulation of apoptotic process Source: ProtInc
  • positive regulation of cell adhesion Source: UniProtKB
  • positive regulation of leukocyte migration Source: UniProtKB
  • positive regulation of tyrosine phosphorylation of STAT protein Source: UniProtKB
  • regulation of apoptotic process Source: GO_Central
  • regulation of cell proliferation Source: GO_Central
  • regulation of regulatory T cell differentiation Source: Reactome
  • response to lipopolysaccharide Source: GO_Central
  • signal transduction Source: ProtInc
  • tumor necrosis factor-mediated signaling pathway Source: Reactome

Keywordsi

Molecular functionReceptor
Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-HSA-5669034 TNFs bind their physiological receptors
R-HSA-8877330 RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 18
Alternative name(s):
Activation-inducible TNFR family receptor
Glucocorticoid-induced TNFR-related protein
CD_antigen: CD357
Gene namesi
Name:TNFRSF18
Synonyms:AITR, GITR
ORF Names:UNQ319/PRO364
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000186891.13
HGNCiHGNC:11914 TNFRSF18
MIMi603905 gene
neXtProtiNX_Q9Y5U5

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 domaini26 – 162ExtracellularSequence analysisAdd BLAST137
Transmembranei163 – 183HelicalSequence analysisAdd BLAST21
Topological domaini184 – 241CytoplasmicSequence analysisAdd BLAST58

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi8784
OpenTargetsiENSG00000186891
PharmGKBiPA36607

Chemistry databases

ChEMBLiCHEMBL3712995

Polymorphism and mutation databases

BioMutaiTNFRSF18
DMDMi13878830

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 251 PublicationAdd BLAST25
ChainiPRO_000003459526 – 241Tumor necrosis factor receptor superfamily member 18Add BLAST216

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi34 ↔ 49By similarity
Disulfide bondi74 ↔ 86By similarity
Disulfide bondi81 ↔ 94By similarity
Disulfide bondi115 ↔ 134By similarity
Disulfide bondi128 ↔ 153By similarity
Glycosylationi146N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9Y5U5
PeptideAtlasiQ9Y5U5
PRIDEiQ9Y5U5
ProteomicsDBi86508
86509 [Q9Y5U5-2]
86510 [Q9Y5U5-3]
TopDownProteomicsiQ9Y5U5-2 [Q9Y5U5-2]

Expressioni

Tissue specificityi

Expressed in lymph node, peripheral blood leukocytes and weakly in spleen.

Inductioni

Up-regulated in peripherical mononuclear cells after antigen stimulation/lymphocyte activation.

Gene expression databases

BgeeiENSG00000186891
CleanExiHS_TNFRSF18
ExpressionAtlasiQ9Y5U5 baseline and differential
GenevisibleiQ9Y5U5 HS

Organism-specific databases

HPAiHPA008025

Interactioni

Subunit structurei

Binds to TRAF1, TRAF2, and TRAF3, but not TRAF5 and TRAF6. Binds through its C-terminus to SIVA1/SIVA.

Binary interactionsi

WithEntry#Exp.IntActNotes
TNFSF18Q9UNG22EBI-3962532,EBI-15672281

Protein-protein interaction databases

BioGridi114312, 5 interactors
DIPiDIP-29883N
IntActiQ9Y5U5, 3 interactors
STRINGi9606.ENSP00000328207

Structurei

3D structure databases

ProteinModelPortaliQ9Y5U5
SMRiQ9Y5U5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati34 – 72TNFR-Cys 1Add BLAST39
Repeati74 – 112TNFR-Cys 2Add BLAST39
Repeati115 – 153TNFR-Cys 3Add BLAST39

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J0PX Eukaryota
ENOG410YX1D LUCA
GeneTreeiENSGT00730000111424
HOVERGENiHBG054195
InParanoidiQ9Y5U5
KOiK05154
OMAiTHNAVCV
OrthoDBiEOG091G03XW
PhylomeDBiQ9Y5U5
TreeFamiTF336151

Family and domain databases

CDDicd13417 TNFRSF18, 1 hit
InterProiView protein in InterPro
IPR001368 TNFR/NGFR_Cys_rich_reg
IPR022318 TNFR_18
IPR034018 TNFRSF18_N
PRINTSiPR01968 TNFACTORR18
SMARTiView protein in SMART
SM00208 TNFR, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y5U5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAQHGAMGAF RALCGLALLC ALSLGQRPTG GPGCGPGRLL LGTGTDARCC
60 70 80 90 100
RVHTTRCCRD YPGEECCSEW DCMCVQPEFH CGDPCCTTCR HHPCPPGQGV
110 120 130 140 150
QSQGKFSFGF QCIDCASGTF SGGHEGHCKP WTDCTQFGFL TVFPGNKTHN
160 170 180 190 200
AVCVPGSPPA EPLGWLTVVL LAVAACVLLL TSAQLGLHIW QLRSQCMWPR
210 220 230 240
ETQLLLEVPP STEDARSCQF PEEERGERSA EEKGRLGDLW V
Length:241
Mass (Da):26,000
Last modified:November 1, 1999 - v1
Checksum:i90DC3B4AA7E82CBE
GO
Isoform 2 (identifier: Q9Y5U5-2) [UniParc]FASTAAdd to basket
Also known as: GITR-D

The sequence of this isoform differs from the canonical sequence as follows:
     135-241: TQFGFLTVFP...EKGRLGDLWV → CWRCRRRPKT...SLAGPDGVGS

Show »
Length:255
Mass (Da):26,827
Checksum:iC986652AC97AF2CC
GO
Isoform 3 (identifier: Q9Y5U5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     194-201: SQCMWPRE → K

Show »
Length:234
Mass (Da):25,110
Checksum:i55DB593CD0B1DB45
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05235443T → R. Corresponds to variant dbSNP:rs11466676Ensembl.1
Natural variantiVAR_05235564E → K. Corresponds to variant dbSNP:rs11466687Ensembl.1
Natural variantiVAR_05235683D → N. Corresponds to variant dbSNP:rs11466688Ensembl.1
Natural variantiVAR_052357173V → M. Corresponds to variant dbSNP:rs11466693Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006508135 – 241TQFGF…GDLWV → CWRCRRRPKTPEAASSPRKS GASDRQRRRGGWETCGCEPG RPPGPPTAASPSPGAPQAAG ALRSALGRALLPWQQKWVQE GGSDQRPGPCSSAAAAGPCR RERETQSWPPSSLAGPDGVG S in isoform 2. 1 PublicationAdd BLAST107
Alternative sequenceiVSP_041021194 – 201SQCMWPRE → K in isoform 3. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF125304 mRNA Translation: AAD22635.1
AF117297 mRNA Translation: AAD19694.1
AF241229 mRNA Translation: AAF63506.1
AY358877 mRNA Translation: AAQ89236.1
BT019531 mRNA Translation: AAV38338.1
BT019532 mRNA Translation: AAV38339.1
AL162741 Genomic DNA No translation available.
CH471183 Genomic DNA Translation: EAW56282.1
CH471183 Genomic DNA Translation: EAW56283.1
BC152381 mRNA Translation: AAI52382.1
CCDSiCCDS10.1 [Q9Y5U5-1]
CCDS30552.1 [Q9Y5U5-3]
CCDS9.1 [Q9Y5U5-2]
RefSeqiNP_004186.1, NM_004195.2 [Q9Y5U5-1]
NP_683699.1, NM_148901.1 [Q9Y5U5-2]
NP_683700.1, NM_148902.1 [Q9Y5U5-3]
UniGeneiHs.212680

Genome annotation databases

EnsembliENST00000328596; ENSP00000328207; ENSG00000186891 [Q9Y5U5-2]
ENST00000379265; ENSP00000368567; ENSG00000186891 [Q9Y5U5-3]
ENST00000379268; ENSP00000368570; ENSG00000186891 [Q9Y5U5-1]
GeneIDi8784
KEGGihsa:8784
UCSCiuc001adb.4 human [Q9Y5U5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTNR18_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5U5
Secondary accession number(s): B1AME1
, O95851, Q5U0I4, Q9NYJ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 1, 1999
Last modified: July 18, 2018
This is version 157 of the entry and version 1 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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