TNR18_HUMAN
ID TNR18_HUMAN Reviewed; 241 AA.
AC Q9Y5U5; B1AME1; O95851; Q5U0I4; Q9NYJ9;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 18;
DE AltName: Full=Activation-inducible TNFR family receptor;
DE AltName: Full=Glucocorticoid-induced TNFR-related protein;
DE AltName: CD_antigen=CD357;
DE Flags: Precursor;
GN Name=TNFRSF18; Synonyms=AITR, GITR; ORFNames=UNQ319/PRO364;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH TRAF1; TRAF2
RP AND TRAF3.
RC TISSUE=Bone marrow;
RX PubMed=10074428; DOI=10.1016/s0960-9822(99)80093-1;
RA Gurney A.L., Marsters S.A., Huang R.M., Pitti R.M., Mark D.T.,
RA Baldwin D.T., Gray A.M., Dowd A.D., Brush A.D., Heldens A.D., Schow A.D.,
RA Goddard A.D., Wood W.I., Baker K.P., Godowski P.J., Ashkenazi A.;
RT "Identification of a new member of the tumor necrosis factor family and its
RT receptor, a human ortholog of mouse GITR.";
RL Curr. Biol. 9:215-218(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=T-cell;
RX PubMed=10037686; DOI=10.1074/jbc.274.10.6056;
RA Kwon B., Yu K.-Y., Ni J., Yu G.-L., Jang I.-K., Kim Y.-J., Xing L., Liu D.,
RA Wang S.-X., Kwon B.S.;
RT "Identification of a novel activation-inducible protein of the tumor
RT necrosis factor receptor superfamily and its ligand.";
RL J. Biol. Chem. 274:6056-6061(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
RX PubMed=10836847; DOI=10.1038/sj.cdd.4400670;
RA Nocentini G., Ronchetti S., Bartoli A., Spinicelli S., Delfino D.,
RA Brunetti L., Migliorati G., Riccardi C.;
RT "Identification of three novel mRNA splice variants of GITR.";
RL Cell Death Differ. 7:408-410(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 26-40.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
CC -!- FUNCTION: Receptor for TNFSF18. Seems to be involved in interactions
CC between activated T-lymphocytes and endothelial cells and in the
CC regulation of T-cell receptor-mediated cell death. Mediated NF-kappa-B
CC activation via the TRAF2/NIK pathway.
CC -!- SUBUNIT: Binds to TRAF1, TRAF2, and TRAF3, but not TRAF5 and TRAF6.
CC Binds through its C-terminus to SIVA1/SIVA.
CC -!- INTERACTION:
CC Q9Y5U5; Q9UNG2: TNFSF18; NbExp=2; IntAct=EBI-3962532, EBI-15672281;
CC Q9Y5U5-2; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-12197205, EBI-947187;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y5U5-1; Sequence=Displayed;
CC Name=2; Synonyms=GITR-D;
CC IsoId=Q9Y5U5-2; Sequence=VSP_006508;
CC Name=3;
CC IsoId=Q9Y5U5-3; Sequence=VSP_041021;
CC -!- TISSUE SPECIFICITY: Expressed in lymph node, peripheral blood
CC leukocytes and weakly in spleen.
CC -!- INDUCTION: Up-regulated in peripherical mononuclear cells after antigen
CC stimulation/lymphocyte activation.
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DR EMBL; AF125304; AAD22635.1; -; mRNA.
DR EMBL; AF117297; AAD19694.1; -; mRNA.
DR EMBL; AF241229; AAF63506.1; -; mRNA.
DR EMBL; AY358877; AAQ89236.1; -; mRNA.
DR EMBL; BT019531; AAV38338.1; -; mRNA.
DR EMBL; BT019532; AAV38339.1; -; mRNA.
DR EMBL; AL162741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471183; EAW56282.1; -; Genomic_DNA.
DR EMBL; CH471183; EAW56283.1; -; Genomic_DNA.
DR EMBL; BC152381; AAI52382.1; -; mRNA.
DR CCDS; CCDS10.1; -. [Q9Y5U5-1]
DR CCDS; CCDS30552.1; -. [Q9Y5U5-3]
DR CCDS; CCDS9.1; -. [Q9Y5U5-2]
DR RefSeq; NP_004186.1; NM_004195.2. [Q9Y5U5-1]
DR RefSeq; NP_683699.1; NM_148901.1. [Q9Y5U5-2]
DR RefSeq; NP_683700.1; NM_148902.1. [Q9Y5U5-3]
DR PDB; 7KHD; X-ray; 2.96 A; C/D=26-162.
DR PDB; 7LAW; X-ray; 2.75 A; R/S=26-161.
DR PDBsum; 7KHD; -.
DR PDBsum; 7LAW; -.
DR AlphaFoldDB; Q9Y5U5; -.
DR SMR; Q9Y5U5; -.
DR BioGRID; 114312; 14.
DR DIP; DIP-29883N; -.
DR IntAct; Q9Y5U5; 3.
DR STRING; 9606.ENSP00000328207; -.
DR ChEMBL; CHEMBL3712995; -.
DR GlyGen; Q9Y5U5; 1 site.
DR iPTMnet; Q9Y5U5; -.
DR PhosphoSitePlus; Q9Y5U5; -.
DR BioMuta; TNFRSF18; -.
DR DMDM; 13878830; -.
DR jPOST; Q9Y5U5; -.
DR MassIVE; Q9Y5U5; -.
DR PaxDb; Q9Y5U5; -.
DR PeptideAtlas; Q9Y5U5; -.
DR PRIDE; Q9Y5U5; -.
DR ProteomicsDB; 86508; -. [Q9Y5U5-1]
DR ProteomicsDB; 86509; -. [Q9Y5U5-2]
DR ProteomicsDB; 86510; -. [Q9Y5U5-3]
DR TopDownProteomics; Q9Y5U5-2; -. [Q9Y5U5-2]
DR ABCD; Q9Y5U5; 41 sequenced antibodies.
DR Antibodypedia; 2154; 992 antibodies from 41 providers.
DR DNASU; 8784; -.
DR Ensembl; ENST00000328596.10; ENSP00000328207.6; ENSG00000186891.14. [Q9Y5U5-2]
DR Ensembl; ENST00000379265.5; ENSP00000368567.5; ENSG00000186891.14. [Q9Y5U5-3]
DR Ensembl; ENST00000379268.7; ENSP00000368570.2; ENSG00000186891.14. [Q9Y5U5-1]
DR GeneID; 8784; -.
DR KEGG; hsa:8784; -.
DR MANE-Select; ENST00000379268.7; ENSP00000368570.2; NM_004195.3; NP_004186.1.
DR UCSC; uc001adb.4; human. [Q9Y5U5-1]
DR CTD; 8784; -.
DR DisGeNET; 8784; -.
DR GeneCards; TNFRSF18; -.
DR HGNC; HGNC:11914; TNFRSF18.
DR HPA; ENSG00000186891; Tissue enhanced (skin).
DR MIM; 603905; gene.
DR neXtProt; NX_Q9Y5U5; -.
DR OpenTargets; ENSG00000186891; -.
DR PharmGKB; PA36607; -.
DR VEuPathDB; HostDB:ENSG00000186891; -.
DR eggNOG; ENOG502SAN0; Eukaryota.
DR GeneTree; ENSGT00730000111424; -.
DR HOGENOM; CLU_1017554_0_0_1; -.
DR InParanoid; Q9Y5U5; -.
DR OMA; HFCIWSL; -.
DR PhylomeDB; Q9Y5U5; -.
DR TreeFam; TF336151; -.
DR PathwayCommons; Q9Y5U5; -.
DR Reactome; R-HSA-5669034; TNFs bind their physiological receptors.
DR Reactome; R-HSA-8877330; RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs).
DR SignaLink; Q9Y5U5; -.
DR BioGRID-ORCS; 8784; 13 hits in 1070 CRISPR screens.
DR GeneWiki; TNFRSF18; -.
DR GenomeRNAi; 8784; -.
DR Pharos; Q9Y5U5; Tbio.
DR PRO; PR:Q9Y5U5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9Y5U5; protein.
DR Bgee; ENSG00000186891; Expressed in skin of abdomen and 116 other tissues.
DR ExpressionAtlas; Q9Y5U5; baseline and differential.
DR Genevisible; Q9Y5U5; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005031; F:tumor necrosis factor receptor activity; TAS:ProtInc.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; IMP:UniProtKB.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd13417; TNFRSF18; 1.
DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR InterPro; IPR022318; TNFR_18.
DR InterPro; IPR034018; TNFRSF18_N.
DR PRINTS; PR01968; TNFACTORR18.
DR SMART; SM00208; TNFR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell membrane;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Membrane;
KW Receptor; Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 26..241
FT /note="Tumor necrosis factor receptor superfamily member
FT 18"
FT /id="PRO_0000034595"
FT TOPO_DOM 26..162
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..241
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 34..72
FT /note="TNFR-Cys 1"
FT REPEAT 74..112
FT /note="TNFR-Cys 2"
FT REPEAT 115..153
FT /note="TNFR-Cys 3"
FT REGION 214..241
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 217..241
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..49
FT /evidence="ECO:0000250"
FT DISULFID 74..86
FT /evidence="ECO:0000250"
FT DISULFID 81..94
FT /evidence="ECO:0000250"
FT DISULFID 115..134
FT /evidence="ECO:0000250"
FT DISULFID 128..153
FT /evidence="ECO:0000250"
FT VAR_SEQ 135..241
FT /note="TQFGFLTVFPGNKTHNAVCVPGSPPAEPLGWLTVVLLAVAACVLLLTSAQLG
FT LHIWQLRSQCMWPRETQLLLEVPPSTEDARSCQFPEEERGERSAEEKGRLGDLWV ->
FT CWRCRRRPKTPEAASSPRKSGASDRQRRRGGWETCGCEPGRPPGPPTAASPSPGAPQAA
FT GALRSALGRALLPWQQKWVQEGGSDQRPGPCSSAAAAGPCRRERETQSWPPSSLAGPDG
FT VGS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10836847"
FT /id="VSP_006508"
FT VAR_SEQ 194..201
FT /note="SQCMWPRE -> K (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10037686"
FT /id="VSP_041021"
FT VARIANT 43
FT /note="T -> R (in dbSNP:rs11466676)"
FT /id="VAR_052354"
FT VARIANT 64
FT /note="E -> K (in dbSNP:rs11466687)"
FT /id="VAR_052355"
FT VARIANT 83
FT /note="D -> N (in dbSNP:rs11466688)"
FT /id="VAR_052356"
FT VARIANT 173
FT /note="V -> M (in dbSNP:rs11466693)"
FT /id="VAR_052357"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:7KHD"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:7KHD"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:7KHD"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:7KHD"
FT STRAND 98..107
FT /evidence="ECO:0007829|PDB:7KHD"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:7KHD"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:7KHD"
FT TURN 134..138
FT /evidence="ECO:0007829|PDB:7KHD"
FT STRAND 140..143
FT /evidence="ECO:0007829|PDB:7KHD"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:7KHD"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:7KHD"
SQ SEQUENCE 241 AA; 26000 MW; 90DC3B4AA7E82CBE CRC64;
MAQHGAMGAF RALCGLALLC ALSLGQRPTG GPGCGPGRLL LGTGTDARCC RVHTTRCCRD
YPGEECCSEW DCMCVQPEFH CGDPCCTTCR HHPCPPGQGV QSQGKFSFGF QCIDCASGTF
SGGHEGHCKP WTDCTQFGFL TVFPGNKTHN AVCVPGSPPA EPLGWLTVVL LAVAACVLLL
TSAQLGLHIW QLRSQCMWPR ETQLLLEVPP STEDARSCQF PEEERGERSA EEKGRLGDLW
V
