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Q9UNG2

- TNF18_HUMAN

UniProt

Q9UNG2 - TNF18_HUMAN

Protein

Tumor necrosis factor ligand superfamily member 18

Gene

TNFSF18

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 2 (08 Mar 2011)
      Previous versions | rss
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    Functioni

    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.2 Publications

    GO - Molecular functioni

    1. receptor binding Source: ProtInc
    2. tumor necrosis factor receptor superfamily binding Source: UniProtKB

    GO - Biological processi

    1. cell-cell signaling Source: ProtInc
    2. negative regulation of apoptotic process Source: ProtInc
    3. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    4. regulation of T cell proliferation Source: UniProtKB
    5. signal transduction Source: ProtInc
    6. T cell proliferation involved in immune response Source: UniProtKB
    7. tumor necrosis factor-mediated signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Cytokine

    Keywords - Biological processi

    Adaptive immunity, Immunity

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:TNFSF18
    Synonyms:AITRL, GITRL, TL6
    ORF Names:UNQ149/PRO175
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:11932. TNFSF18.

    Subcellular locationi

    Cell membrane 1 Publication; Single-pass type II membrane protein 1 Publication

    GO - Cellular componenti

    1. cell surface Source: UniProtKB
    2. extracellular space Source: UniProtKB-KW
    3. integral component of membrane Source: UniProtKB-KW
    4. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA36624.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 199199Tumor necrosis factor ligand superfamily member 18PRO_0000185506Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi80 ↔ 1001 Publication
    Glycosylationi151 – 1511N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi183 – 1831N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ9UNG2.
    PRIDEiQ9UNG2.

    Expressioni

    Tissue specificityi

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

    Inductioni

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

    Gene expression databases

    BgeeiQ9UNG2.
    CleanExiHS_TNFSF18.
    GenevestigatoriQ9UNG2.

    Organism-specific databases

    HPAiHPA012699.

    Interactioni

    Subunit structurei

    Homodimer By similarity. Homotrimer.By similarity1 Publication

    Protein-protein interaction databases

    DIPiDIP-29882N.
    DIP-6243N.
    STRINGi9606.ENSP00000385470.

    Structurei

    Secondary structure

    1
    199
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi81 – 844
    Beta strandi91 – 944
    Beta strandi100 – 1056
    Beta strandi108 – 1114
    Beta strandi115 – 1239
    Beta strandi131 – 1333
    Beta strandi137 – 1415
    Beta strandi144 – 1496
    Beta strandi152 – 1543
    Beta strandi160 – 1645
    Beta strandi169 – 1768
    Helixi177 – 1793
    Beta strandi186 – 1938

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliQ9UNG2.
    SMRiQ9UNG2. Positions 77-199.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UNG2.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini23 – 5028CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini72 – 199128ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei51 – 7121Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the tumor necrosis factor family.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG39473.
    HOGENOMiHOG000026597.
    HOVERGENiHBG061857.
    InParanoidiQ9UNG2.
    KOiK05479.
    OMAiTYKEPAP.
    OrthoDBiEOG7S7SG4.
    PhylomeDBiQ9UNG2.
    TreeFamiTF338614.

    Family and domain databases

    Gene3Di2.60.120.40. 1 hit.
    InterProiIPR006052. TNF_dom.
    IPR008983. Tumour_necrosis_fac-like_dom.
    [Graphical view]
    PfamiPF00229. TNF. 1 hit.
    [Graphical view]
    SUPFAMiSSF49842. SSF49842. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q9UNG2-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTLHPSPITC EFLFSTALIS PKMCLSHLEN MPLSHSRTQG AQRSSWKLWL    50
    FCSIVMLLFL CSFSWLIFIF LQLETAKEPC MAKFGPLPSK WQMASSEPPC 100
    VNKVSDWKLE ILQNGLYLIY GQVAPNANYN DVAPFEVRLY KNKDMIQTLT 150
    NKSKIQNVGG TYELHVGDTI DLIFNSEHQV LKNNTYWGII LLANPQFIS 199
    Length:199
    Mass (Da):22,724
    Last modified:March 8, 2011 - v2
    Checksum:iC83A94645745DA58
    GO

    Sequence cautioni

    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.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS1305.2.
    RefSeqiNP_005083.2. NM_005092.3.
    UniGeneiHs.248197.

    Genome annotation databases

    EnsembliENST00000404377; ENSP00000385470; ENSG00000120337.
    GeneIDi8995.
    KEGGihsa:8995.
    UCSCiuc001giu.2. human.

    Polymorphism databases

    DMDMi325511353.

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS1305.2.
    RefSeqi NP_005083.2. NM_005092.3.
    UniGenei Hs.248197.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2Q1M X-ray 2.30 A 74-199 [» ]
    2R30 X-ray 3.20 A 74-199 [» ]
    2R32 X-ray 1.95 A 74-199 [» ]
    3B93 X-ray 2.20 A/B/C 72-199 [» ]
    3B94 X-ray 2.50 A/B/C/D 72-199 [» ]
    ProteinModelPortali Q9UNG2.
    SMRi Q9UNG2. Positions 77-199.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-29882N.
    DIP-6243N.
    STRINGi 9606.ENSP00000385470.

    Polymorphism databases

    DMDMi 325511353.

    Proteomic databases

    PaxDbi Q9UNG2.
    PRIDEi Q9UNG2.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000404377 ; ENSP00000385470 ; ENSG00000120337 .
    GeneIDi 8995.
    KEGGi hsa:8995.
    UCSCi uc001giu.2. human.

    Organism-specific databases

    CTDi 8995.
    GeneCardsi GC01M173009.
    H-InvDB HIX0028550.
    HGNCi HGNC:11932. TNFSF18.
    HPAi HPA012699.
    MIMi 603898. gene.
    neXtProti NX_Q9UNG2.
    PharmGKBi PA36624.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG39473.
    HOGENOMi HOG000026597.
    HOVERGENi HBG061857.
    InParanoidi Q9UNG2.
    KOi K05479.
    OMAi TYKEPAP.
    OrthoDBi EOG7S7SG4.
    PhylomeDBi Q9UNG2.
    TreeFami TF338614.

    Miscellaneous databases

    EvolutionaryTracei Q9UNG2.
    GeneWikii TNFSF18.
    GenomeRNAii 8995.
    NextBioi 33731.
    PROi Q9UNG2.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9UNG2.
    CleanExi HS_TNFSF18.
    Genevestigatori Q9UNG2.

    Family and domain databases

    Gene3Di 2.60.120.40. 1 hit.
    InterProi IPR006052. TNF_dom.
    IPR008983. Tumour_necrosis_fac-like_dom.
    [Graphical view ]
    Pfami PF00229. TNF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49842. SSF49842. 1 hit.
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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.
      , 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. 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.

    Entry informationi

    Entry nameiTNF18_HUMAN
    AccessioniPrimary (citable) accession number: Q9UNG2
    Secondary accession number(s): A9IQG8, O95852, Q6ISV1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 21, 2001
    Last sequence update: March 8, 2011
    Last modified: October 1, 2014
    This is version 109 of the entry and version 2 of the sequence. [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

    Caution

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3