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O43508

- TNF12_HUMAN

UniProt

O43508 - TNF12_HUMAN

Protein

Tumor necrosis factor ligand superfamily member 12

Gene

TNFSF12

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 1 (01 Jun 1998)
      Previous versions | rss
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    Functioni

    Binds to FN14 and possibly also to TNRFSF12/APO3. Weak inducer of apoptosis in some cell types. Mediates NF-kappa-B activation. Promotes angiogenesis and the proliferation of endothelial cells. Also involved in induction of inflammatory cytokines. Promotes IL8 secretion.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei93 – 942Cleavage

    GO - Molecular functioni

    1. cytokine activity Source: UniProtKB
    2. protein binding Source: UniProtKB
    3. receptor binding Source: ProtInc

    GO - Biological processi

    1. angiogenesis Source: UniProtKB-KW
    2. apoptotic process Source: ProtInc
    3. apoptotic signaling pathway Source: UniProtKB
    4. cell differentiation Source: UniProtKB-KW
    5. endothelial cell migration Source: UniProtKB
    6. immune response Source: InterPro
    7. positive regulation of angiogenesis Source: UniProtKB
    8. positive regulation of endothelial cell proliferation Source: UniProtKB
    9. positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
    10. signal transduction Source: ProtInc

    Keywords - Molecular functioni

    Cytokine, Developmental protein

    Keywords - Biological processi

    Angiogenesis, Apoptosis, Differentiation

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tumor necrosis factor ligand superfamily member 12
    Alternative name(s):
    APO3 ligand
    TNF-related weak inducer of apoptosis
    Short name:
    TWEAK
    Cleaved into the following 2 chains:
    Gene namesi
    Name:TNFSF12
    Synonyms:APO3L, DR3LG
    ORF Names:UNQ181/PRO207
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:11927. TNFSF12.

    Subcellular locationi

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

    GO - Cellular componenti

    1. extracellular space Source: UniProtKB-KW
    2. integral component of plasma membrane Source: ProtInc
    3. perinuclear region of cytoplasm Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Organism-specific databases

    Orphaneti1572. Common variable immunodeficiency.
    PharmGKBiPA162406662.
    PA36620.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 249249Tumor necrosis factor ligand superfamily member 12, membrane formPRO_0000034520Add
    BLAST
    Chaini94 – 249156Tumor necrosis factor ligand superfamily member 12, secreted formPRO_0000034521Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi139 – 1391N-linked (GlcNAc...)
    Disulfide bondi191 ↔ 2101 Publication

    Post-translational modificationi

    The soluble form derives from the membrane form by proteolytic processing.

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiO43508.
    PRIDEiO43508.

    PTM databases

    PhosphoSiteiO43508.

    Expressioni

    Tissue specificityi

    Highly expressed in adult heart, pancreas, skeletal muscle, brain, colon, small intestine, lung, ovary, prostate, spleen, lymph node, appendix and peripheral blood lymphocytes. Low expression in kidney, testis, liver, placenta, thymus and bone marrow. Also detected in fetal kidney, liver, lung and brain.

    Gene expression databases

    ArrayExpressiO43508.
    BgeeiO43508.
    GenevestigatoriO43508.

    Interactioni

    Subunit structurei

    Homotrimer Probable. Interacts with the angiogenic factor AGGF1/VG5Q.2 PublicationsCurated

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    TNFRSF12AQ9NP842EBI-6932080,EBI-2851995
    tnfrsf12aQ6SIX72EBI-6932080,EBI-8445678From a different organism.

    Protein-protein interaction databases

    BioGridi114279. 5 interactions.
    IntActiO43508. 5 interactions.
    MINTiMINT-8415042.
    STRINGi9606.ENSP00000293826.

    Structurei

    Secondary structure

    1
    249
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi108 – 1136
    Beta strandi133 – 1353
    Beta strandi143 – 1464
    Turni148 – 1503
    Beta strandi153 – 1553
    Beta strandi159 – 17315
    Beta strandi175 – 1839
    Beta strandi186 – 1938
    Beta strandi205 – 21814
    Beta strandi223 – 2275
    Turni238 – 2403
    Beta strandi241 – 2477

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4HT1X-ray2.50T97-249[»]
    ProteinModelPortaliO43508.
    SMRiO43508. Positions 105-249.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2121CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini43 – 249207ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei22 – 4221Helical; 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

    eggNOGiNOG45253.
    HOGENOMiHOG000134435.
    HOVERGENiHBG055510.
    KOiK05474.
    OMAiRIMSFIE.
    OrthoDBiEOG79KPGF.
    PhylomeDBiO43508.
    TreeFamiTF332331.

    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]
    SMARTiSM00207. TNF. 1 hit.
    [Graphical view]
    SUPFAMiSSF49842. SSF49842. 1 hit.
    PROSITEiPS50049. TNF_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O43508-1) [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

    MAARRSQRRR GRRGEPGTAL LVPLALGLGL ALACLGLLLA VVSLGSRASL    50
    SAQEPAQEEL VAEEDQDPSE LNPQTEESQD PAPFLNRLVR PRRSAPKGRK 100
    TRARRAIAAH YEVHPRPGQD GAQAGVDGTV SGWEEARINS SSPLRYNRQI 150
    GEFIVTRAGL YYLYCQVHFD EGKAVYLKLD LLVDGVLALR CLEEFSATAA 200
    SSLGPQLRLC QVSGLLALRP GSSLRIRTLP WAHLKAAPFL TYFGLFQVH 249
    Length:249
    Mass (Da):27,216
    Last modified:June 1, 1998 - v1
    Checksum:iE660843361C28EBA
    GO
    Isoform TWE-PRIL (identifier: O43508-2) [UniParc]FASTAAdd to Basket

    Also known as: TNFSF12-TNFSF13

    The sequence of this isoform differs from the canonical sequence as follows:
         167-249: VHFDEGKAVY...LTYFGLFQVH → SSDALEAWEN...HGTFLGFVKL

    Note: Based on a readthrough transcript which may produce a TWE-PRIL (TNFSF12-TNFSF13) fusion protein. Expressed at protein level in primary T-lymphocytes and monocytic cell lines.

    Show »
    Length:330
    Mass (Da):36,589
    Checksum:iFC6F3BCA29C029AE
    GO

    Sequence cautioni

    The sequence AAH19047.1 differs from that shown. Reason: Frameshift at position 125.

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei167 – 24983VHFDE…LFQVH → SSDALEAWENGERSRKRRAV LTQKQKKQHSVLHLVPINAT SKDDSDVTEVMWQPALRRGR GLQAQGYGVRIQDAGVYLLY SQVLFQDVTFTMGQVVSREG QGRQETLFRCIRSMPSHPDR AYNSCYSAGVFHLHQGDILS VIIPRARAKLNLSPHGTFLG FVKL in isoform TWE-PRIL. 1 PublicationVSP_045245Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF030099 mRNA. Translation: AAC51923.1.
    AF055872 mRNA. Translation: AAC39724.1.
    AY081051 mRNA. Translation: AAL90443.1.
    AY358870 mRNA. Translation: AAQ89229.1.
    AC016876 Genomic DNA. No translation available.
    BC019047 mRNA. Translation: AAH19047.1. Frameshift.
    CCDSiCCDS11109.1. [O43508-1]
    RefSeqiNP_003800.1. NM_003809.2. [O43508-1]
    NP_742086.1. NM_172089.3. [O43508-2]
    UniGeneiHs.54673.

    Genome annotation databases

    EnsembliENST00000293825; ENSP00000293825; ENSG00000239697. [O43508-1]
    GeneIDi407977.
    8742.
    KEGGihsa:407977.
    hsa:8742.
    UCSCiuc002ghg.3. human. [O43508-1]
    uc002ghi.1. human.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF030099 mRNA. Translation: AAC51923.1 .
    AF055872 mRNA. Translation: AAC39724.1 .
    AY081051 mRNA. Translation: AAL90443.1 .
    AY358870 mRNA. Translation: AAQ89229.1 .
    AC016876 Genomic DNA. No translation available.
    BC019047 mRNA. Translation: AAH19047.1 . Frameshift.
    CCDSi CCDS11109.1. [O43508-1 ]
    RefSeqi NP_003800.1. NM_003809.2. [O43508-1 ]
    NP_742086.1. NM_172089.3. [O43508-2 ]
    UniGenei Hs.54673.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4HT1 X-ray 2.50 T 97-249 [» ]
    ProteinModelPortali O43508.
    SMRi O43508. Positions 105-249.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114279. 5 interactions.
    IntActi O43508. 5 interactions.
    MINTi MINT-8415042.
    STRINGi 9606.ENSP00000293826.

    PTM databases

    PhosphoSitei O43508.

    Proteomic databases

    PaxDbi O43508.
    PRIDEi O43508.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000293825 ; ENSP00000293825 ; ENSG00000239697 . [O43508-1 ]
    GeneIDi 407977.
    8742.
    KEGGi hsa:407977.
    hsa:8742.
    UCSCi uc002ghg.3. human. [O43508-1 ]
    uc002ghi.1. human.

    Organism-specific databases

    CTDi 407977.
    8742.
    GeneCardsi GC17P007452.
    HGNCi HGNC:11927. TNFSF12.
    MIMi 602695. gene.
    neXtProti NX_O43508.
    Orphaneti 1572. Common variable immunodeficiency.
    PharmGKBi PA162406662.
    PA36620.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG45253.
    HOGENOMi HOG000134435.
    HOVERGENi HBG055510.
    KOi K05474.
    OMAi RIMSFIE.
    OrthoDBi EOG79KPGF.
    PhylomeDBi O43508.
    TreeFami TF332331.

    Miscellaneous databases

    ChiTaRSi TNFSF12-TNFSF13. human.
    GeneWikii TNFSF12.
    TNFSF12-TNFSF13.
    NextBioi 108346.
    PROi O43508.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O43508.
    Bgeei O43508.
    Genevestigatori O43508.

    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 ]
    SMARTi SM00207. TNF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49842. SSF49842. 1 hit.
    PROSITEi PS50049. TNF_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis."
      Chicheportiche Y., Bourdon P.R., Xu H., Hsu Y.-M., Scott H., Hession C., Garcia I., Browning J.L.
      J. Biol. Chem. 272:32401-32410(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), N-TERMINUS OF SOLUBLE FORM.
      Tissue: Fetal liver and Tonsil.
    2. "Identification of a ligand for the death-domain-containing receptor Apo3."
      Marsters S.A., Sheridan J.P., Pitti R.M., Brush J., Goddard A., Ashkenazi A.
      Curr. Biol. 8:525-528(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Fetal kidney.
    3. "An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein."
      Pradet-Balade B., Medema J.P., Lopez-Fraga M., Lozano J.C., Kolfschoten G.M., Picard A., Martinez-A C., Garcia-Sanz J.A., Hahne M.
      EMBO J. 21:5711-5720(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TWE-PRIL), SUBCELLULAR LOCATION.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    5. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
      Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
      , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
      Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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).
      Tissue: Tonsil.
    7. "TWEAK induces angiogenesis and proliferation of endothelial cells."
      Lynch C.N., Wang Y.C., Lund J.K., Chen Y.-W., Leal J.A., Wiley S.R.
      J. Biol. Chem. 274:8455-8459(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome."
      Tian X.-L., Kadaba R., You S.-A., Liu M., Timur A.A., Yang L., Chen Q., Szafranski P., Rao S., Wu L., Housman D.E., DiCorleto P.E., Driscoll D.J., Borrow J., Wang Q.
      Nature 427:640-645(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AGGF1/VG5Q.
    9. "TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor."
      Wiley S.R., Winkles J.A.
      Cytokine Growth Factor Rev. 14:241-249(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    10. "Crystal structure of human TWEAK in complex with the Fab fragment of a neutralizing antibody reveals insights into receptor binding."
      Lammens A., Baehner M., Kohnert U., Niewoehner J., von Proff L., Schraeml M., Lammens K., Hopfner K.P.
      PLoS ONE 8:E62697-E62697(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 97-249 IN COMPLEX WITH THE FAB FRAGMENT OF A NEUTRALIZING ANTIBODY, FUNCTION, SUBUNIT, DISULFIDE BOND.

    Entry informationi

    Entry nameiTNF12_HUMAN
    AccessioniPrimary (citable) accession number: O43508
    Secondary accession number(s): Q8IZK7, Q8WUZ7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 6, 2002
    Last sequence update: June 1, 1998
    Last modified: October 1, 2014
    This is version 130 of the entry and version 1 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

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: 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