Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9Y5U5 (TNR18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:TNFRSF18
Synonyms:AITR, GITR
ORF Names:UNQ319/PRO364
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length241 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Binds to TRAF1, TRAF2, and TRAF3, but not TRAF5 and TRAF6. Binds through its C-terminus to SIVA1/SIVA. Ref.1

Subcellular location

Isoform 1: Cell membrane; Single-pass type I membrane protein.

Isoform 2: Secreted.

Tissue specificity

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

Induction

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

Sequence similarities

Contains 3 TNFR-Cys repeats.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y5U5-1)

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.
Isoform 2 (identifier: Q9Y5U5-2)

Also known as: GITR-D;

The sequence of this isoform differs from the canonical sequence as follows:
     135-241: TQFGFLTVFP...EKGRLGDLWV → CWRCRRRPKT...SLAGPDGVGS
Isoform 3 (identifier: Q9Y5U5-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Ref.9
Chain26 – 241216Tumor necrosis factor receptor superfamily member 18
PRO_0000034595

Regions

Topological domain26 – 162137Extracellular Potential
Transmembrane163 – 18321Helical; Potential
Topological domain184 – 24158Cytoplasmic Potential
Repeat34 – 7239TNFR-Cys 1
Repeat74 – 11239TNFR-Cys 2
Repeat115 – 15339TNFR-Cys 3

Amino acid modifications

Glycosylation1461N-linked (GlcNAc...) Potential
Disulfide bond34 ↔ 49 By similarity
Disulfide bond74 ↔ 86 By similarity
Disulfide bond81 ↔ 94 By similarity
Disulfide bond115 ↔ 134 By similarity
Disulfide bond128 ↔ 153 By similarity

Natural variations

Alternative sequence135 – 241107TQFGF…GDLWV → CWRCRRRPKTPEAASSPRKS GASDRQRRRGGWETCGCEPG RPPGPPTAASPSPGAPQAAG ALRSALGRALLPWQQKWVQE GGSDQRPGPCSSAAAAGPCR RERETQSWPPSSLAGPDGVG S in isoform 2.
VSP_006508
Alternative sequence194 – 2018SQCMWPRE → K in isoform 3.
VSP_041021
Natural variant431T → R.
Corresponds to variant rs11466676 [ dbSNP | Ensembl ].
VAR_052354
Natural variant641E → K.
Corresponds to variant rs11466687 [ dbSNP | Ensembl ].
VAR_052355
Natural variant831D → N.
Corresponds to variant rs11466688 [ dbSNP | Ensembl ].
VAR_052356
Natural variant1731V → M.
Corresponds to variant rs11466693 [ dbSNP | Ensembl ].
VAR_052357

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 90DC3B4AA7E82CBE

FASTA24126,000
        10         20         30         40         50         60 
MAQHGAMGAF RALCGLALLC ALSLGQRPTG GPGCGPGRLL LGTGTDARCC RVHTTRCCRD 

        70         80         90        100        110        120 
YPGEECCSEW DCMCVQPEFH CGDPCCTTCR HHPCPPGQGV QSQGKFSFGF QCIDCASGTF 

       130        140        150        160        170        180 
SGGHEGHCKP WTDCTQFGFL TVFPGNKTHN AVCVPGSPPA EPLGWLTVVL LAVAACVLLL 

       190        200        210        220        230        240 
TSAQLGLHIW QLRSQCMWPR ETQLLLEVPP STEDARSCQF PEEERGERSA EEKGRLGDLW 


V 

« Hide

Isoform 2 (GITR-D) [UniParc].

Checksum: C986652AC97AF2CC
Show »

FASTA25526,827
Isoform 3 [UniParc].

Checksum: 55DB593CD0B1DB45
Show »

FASTA23425,110

References

« Hide 'large scale' references
[1]"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] (ISOFORM 1), INTERACTION WITH TRAF1; TRAF2 AND TRAF3.
Tissue: Bone marrow.
[2]"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] (ISOFORM 3).
Tissue: T-cell.
[3]"Identification of three novel mRNA splice variants of GITR."
Nocentini G., Ronchetti S., Bartoli A., Spinicelli S., Delfino D., Brunetti L., Migliorati G., Riccardi C.
Cell Death Differ. 7:408-410(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Thymus.
[4]"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] (ISOFORM 1).
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"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].
[7]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].
[8]"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] (ISOFORM 1).
[9]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-40.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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. Translation: CAI23246.1.
AL162741 Genomic DNA. Translation: CAI23247.1.
CH471183 Genomic DNA. Translation: EAW56282.1.
CH471183 Genomic DNA. Translation: EAW56283.1.
BC152381 mRNA. Translation: AAI52382.1.
CCDSCCDS10.1. [Q9Y5U5-1]
CCDS30552.1. [Q9Y5U5-3]
CCDS9.1. [Q9Y5U5-2]
RefSeqNP_004186.1. NM_004195.2. [Q9Y5U5-1]
NP_683699.1. NM_148901.1. [Q9Y5U5-2]
NP_683700.1. NM_148902.1. [Q9Y5U5-3]
UniGeneHs.212680.

3D structure databases

ProteinModelPortalQ9Y5U5.
SMRQ9Y5U5. Positions 7-154.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114312. 5 interactions.
DIPDIP-29883N.
IntActQ9Y5U5. 1 interaction.
STRING9606.ENSP00000328207.

Chemistry

GuidetoPHARMACOLOGY1890.

Polymorphism databases

DMDM13878830.

Proteomic databases

PaxDbQ9Y5U5.
PRIDEQ9Y5U5.

Protocols and materials databases

DNASU8784.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328596; ENSP00000328207; ENSG00000186891. [Q9Y5U5-2]
ENST00000379265; ENSP00000368567; ENSG00000186891. [Q9Y5U5-3]
ENST00000379268; ENSP00000368570; ENSG00000186891. [Q9Y5U5-1]
GeneID8784.
KEGGhsa:8784.
UCSCuc001ada.3. human. [Q9Y5U5-1]
uc001add.3. human. [Q9Y5U5-2]

Organism-specific databases

CTD8784.
GeneCardsGC01M001128.
HGNCHGNC:11914. TNFRSF18.
HPAHPA008025.
MIM603905. gene.
neXtProtNX_Q9Y5U5.
PharmGKBPA36607.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46178.
HOVERGENHBG054195.
KOK05154.
OMAEGRCKPW.
OrthoDBEOG7XH6QM.
PhylomeDBQ9Y5U5.
TreeFamTF336151.

Gene expression databases

ArrayExpressQ9Y5U5.
BgeeQ9Y5U5.
CleanExHS_TNFRSF18.
GenevestigatorQ9Y5U5.

Family and domain databases

InterProIPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022318. TNFR_18.
[Graphical view]
PRINTSPR01968. TNFACTORR18.
SMARTSM00208. TNFR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTNFRSF18.
GenomeRNAi8784.
NextBio32932.
PROQ9Y5U5.
SOURCESearch...

Entry information

Entry nameTNR18_HUMAN
AccessionPrimary (citable) accession number: Q9Y5U5
Secondary accession number(s): B1AME1 expand/collapse secondary AC list , O95851, Q5U0I4, Q9NYJ9
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 126 of the entry and version 1 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

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

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

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries