ID TNF18_HUMAN Reviewed; 199 AA. AC Q9UNG2; A9IQG8; O95852; Q6ISV1; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 08-MAR-2011, sequence version 2. DT 25-JAN-2012, entry version 88. DE RecName: Full=Tumor necrosis factor ligand superfamily member 18; DE AltName: Full=Activation-inducible TNF-related ligand; DE Short=AITRL; DE AltName: Full=Glucocorticoid-induced TNF-related ligand; DE Short=hGITRL; GN Name=TNFSF18; Synonyms=AITRL, GITRL, TL6; ORFNames=UNQ149/PRO175; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-199. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 17-199. RX MEDLINE=22887296; 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., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 23-199. RC TISSUE=Umbilical vein; RX MEDLINE=99175482; 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., RA Schow A.D., Goddard A.D., Wood W.I., Baker K.P., Godowski P.J., RA Ashkenazi A.; RT "Identification of a new member of the tumor necrosis factor family RT and its receptor, a human ortholog of mouse GITR."; RL Curr. Biol. 9:215-218(1999). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 31-199. RC TISSUE=Brain; RX MEDLINE=99156876; 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., RA Liu D., 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 [8] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17449724; DOI=10.1189/jlb.0906568; RA Tuyaerts S., Van Meirvenne S., Bonehill A., Heirman C., Corthals J., RA Waldmann H., Breckpot K., Thielemans K., Aerts J.L.; RT "Expression of human GITRL on myeloid dendritic cells enhances their RT immunostimulatory function but does not abrogate the suppressive RT effect of CD4+CD25+ regulatory T cells."; RL J. Leukoc. Biol. 82:93-105(2007). RN [9] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 74-199, FUNCTION, SUBUNIT, RP AND DISULFIDE BOND. RX PubMed=18040044; DOI=10.1073/pnas.0709264104; RA Chattopadhyay K., Ramagopal U.A., Mukhopadhaya A., Malashkevich V.N., RA Dilorenzo T.P., Brenowitz M., Nathenson S.G., Almo S.C.; RT "Assembly and structural properties of glucocorticoid-induced TNF RT receptor ligand: implications for function."; RL Proc. Natl. Acad. Sci. U.S.A. 104:19452-19457(2007). CC -!- FUNCTION: Cytokine that binds to TNFRSF18/AITR/GITR. Regulates T- CC cell responses. Can function as costimulator and lower the CC threshold for T-cell activation and T-cell proliferation. CC Important for interactions between activated T-lymphocytes and CC endothelial cells. Mediates activation of NF-kappa-B. CC -!- SUBUNIT: Homodimer (By similarity). Homotrimer. CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane CC protein. CC -!- TISSUE SPECIFICITY: Expressed at high levels in the small CC intestine, ovary, testis, kidney and endothelial cells. CC -!- INDUCTION: Up-regulated after stimulation by bacterial CC lipopolysaccharides (LPS). CC -!- SIMILARITY: Belongs to the tumor necrosis factor family. CC -!- CAUTION: It is uncertain whether Met-1 or Met-23 is the initiator. CC -!- SEQUENCE CAUTION: CC Sequence=AAH93986.1; Type=Erroneous initiation; Note=Translation N-terminally extended; CC Sequence=AAI12033.1; Type=Erroneous initiation; Note=Translation N-terminally extended; CC Sequence=AAQ89227.1; Type=Erroneous initiation; Note=Translation N-terminally extended; CC Sequence=BAG36082.1; Type=Erroneous initiation; Note=Translation N-terminally extended; CC Sequence=EAW90937.1; Type=Erroneous initiation; Note=Translation N-terminally extended; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AL031599; CAP58846.1; -; Genomic_DNA. DR EMBL; CH471067; EAW90937.1; ALT_INIT; Genomic_DNA. DR EMBL; BC069111; AAH69111.1; -; mRNA. DR EMBL; BC069319; AAH69319.1; -; mRNA. DR EMBL; BC093986; AAH93986.1; ALT_INIT; mRNA. DR EMBL; BC112032; AAI12033.1; ALT_INIT; mRNA. DR EMBL; AK313273; BAG36082.1; ALT_INIT; mRNA. DR EMBL; AY358868; AAQ89227.1; ALT_INIT; mRNA. DR EMBL; AF125303; AAD22634.1; -; mRNA. DR EMBL; AF117713; AAD19695.1; -; mRNA. DR IPI; IPI00935899; -. DR RefSeq; NP_005083.2; NM_005092.3. DR UniGene; Hs.248197; -. DR PDB; 2Q1M; X-ray; 2.30 A; A=74-199. DR PDB; 2R30; X-ray; 3.20 A; A=74-199. DR PDB; 2R32; X-ray; 1.95 A; A=74-199. DR PDB; 3B93; X-ray; 2.20 A; A/B/C=72-199. DR PDB; 3B94; X-ray; 2.50 A; A/B/C/D=72-199. DR PDBsum; 2Q1M; -. DR PDBsum; 2R30; -. DR PDBsum; 2R32; -. DR PDBsum; 3B93; -. DR PDBsum; 3B94; -. DR ProteinModelPortal; Q9UNG2; -. DR SMR; Q9UNG2; 77-199. DR DIP; DIP-29882N; -. DR DIP; DIP-6243N; -. DR STRING; Q9UNG2; -. DR DMDM; 13124621; -. DR PRIDE; Q9UNG2; -. DR Ensembl; ENST00000239468; ENSP00000239468; ENSG00000120337. DR Ensembl; ENST00000404377; ENSP00000385470; ENSG00000120337. DR GeneID; 8995; -. DR KEGG; hsa:8995; -. DR CTD; 8995; -. DR GeneCards; GC01M173009; -. DR H-InvDB; HIX0028550; -. DR HGNC; HGNC:11932; TNFSF18. DR HPA; HPA012699; -. DR MIM; 603898; gene. DR neXtProt; NX_Q9UNG2; -. DR PharmGKB; PA36624; -. DR eggNOG; prNOG13005; -. DR GeneTree; ENSGT00390000002560; -. DR HOVERGEN; HBG061857; -. DR InParanoid; Q9UNG2; -. DR OMA; FEVRLYK; -. DR OrthoDB; EOG40GCRS; -. DR ArrayExpress; Q9UNG2; -. DR Bgee; Q9UNG2; -. DR CleanEx; HS_TNFSF18; -. DR Genevestigator; Q9UNG2; -. DR GermOnline; ENSG00000120337; Homo sapiens. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW. DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW. DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro. DR GO; GO:0006916; P:anti-apoptosis; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0006955; P:immune response; IEA:InterPro. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR InterPro; IPR006052; TNF. DR InterPro; IPR008983; Tumour_necrosis_fac-like. DR Gene3D; G3DSA:2.60.120.40; Tumour_necrosis_fac-like; 1. DR KO; K05479; -. DR Pfam; PF00229; TNF; 1. DR SUPFAM; SSF49842; TNF_like; 1. DR PROSITE; PS00251; TNF_1; FALSE_NEG. DR PROSITE; PS50049; TNF_2; FALSE_NEG. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Cell membrane; Complete proteome; KW Cytokine; Disulfide bond; Glycoprotein; Immunity; Membrane; KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1 199 Tumor necrosis factor ligand superfamily FT member 18. FT /FTId=PRO_0000185506. FT TOPO_DOM 23 50 Cytoplasmic (Potential). FT TRANSMEM 51 71 Helical; Signal-anchor for type II FT membrane protein; (Potential). FT TOPO_DOM 72 199 Extracellular (Potential). FT CARBOHYD 151 151 N-linked (GlcNAc...) (Potential). FT CARBOHYD 183 183 N-linked (GlcNAc...) (Potential). FT DISULFID 80 100 FT HELIX 42 68 FT STRAND 81 84 FT STRAND 91 94 FT STRAND 100 105 FT STRAND 108 111 FT STRAND 115 123 FT STRAND 137 141 FT STRAND 144 149 FT STRAND 152 154 FT STRAND 160 164 FT STRAND 169 176 FT HELIX 177 179 FT STRAND 186 193 SQ SEQUENCE 199 AA; 22724 MW; C83A94645745DA58 CRC64; MTLHPSPITC EFLFSTALIS PKMCLSHLEN MPLSHSRTQG AQRSSWKLWL FCSIVMLLFL CSFSWLIFIF LQLETAKEPC MAKFGPLPSK WQMASSEPPC VNKVSDWKLE ILQNGLYLIY GQVAPNANYN DVAPFEVRLY KNKDMIQTLT NKSKIQNVGG TYELHVGDTI DLIFNSEHQV LKNNTYWGII LLANPQFIS //