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    TNFSF10 TNF superfamily member 10 [ Homo sapiens (human) ]

    Gene ID: 8743, updated on 25-Jun-2017
    Official Symbol
    TNFSF10provided by HGNC
    Official Full Name
    TNF superfamily member 10provided by HGNC
    Primary source
    HGNC:HGNC:11925
    See related
    Ensembl:ENSG00000121858 MIM:603598; Vega:OTTHUMG00000156917
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TL2; APO2L; CD253; TRAIL; Apo-2L; TNLG6A
    Summary
    The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]
    Orthologs
    Location:
    3q26.31
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 3 NC_000003.12 (172505508..172523507, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (172223298..172241297, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene basic leucine zipper and W2 domains 1 pseudogene 1 Neighboring gene growth hormone secretagogue receptor Neighboring gene TBP-like 1 pseudogene Neighboring gene long intergenic non-protein coding RNA 2068 Neighboring gene solute carrier family 31 member 1 pseudogene 1

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Treatment of HIV-1 Env-pseudotyped virus-infected MDM cells with both soluble TRAIL and an agonistic anti-DR5 antibody AD5-10 induces activation of caspase-3, -8, and -9 PubMed
    env Treatment of CD4+ T cells with HIV-1 gp120 results in the upregulation of TRAIL death receptor expression and acquired sensitivity to TRAIL mediated cell death; this effect of gp120 requires the chemokine coreceptor CXCR4, but not CCR5 or the CD4 receptor PubMed
    env Treatment of human monocytes and primary neutrophils with N36 peptide from HIV-1 gp41 and F peptide from HIV-1 envelope protein gp120 increases endogenous tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression PubMed
    Envelope transmembrane glycoprotein gp41 env Treatment of human monocytes and primary neutrophils with N36 peptide from HIV-1 gp41 and F peptide from HIV-1 envelope protein gp120 increases endogenous tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression PubMed
    Tat tat Microarray analysis indicates HIV-1 Tat-induced upregulation of tumor necrosis factor (ligand) superfamily, member 10 (TNFSF10; TRAIL) in primary human brain microvascular endothelial cells PubMed
    tat HIV-1 and the viral protein Tat modulate the expression of tumor necrosis factor (ligand) superfamily, member 10 (TNFSF10; TRAIL) in immature dendritic cells and monocyte-derived macrophages PubMed
    tat Microarray analysis indicates HIV-1 Tat upregulates the interferon-responsive gene expression of many proteins, including TRAIL, in immature dendritic cells, an effect that likely facilitates the expansion of HIV-1 infection PubMed
    tat HIV-1 Tat inhibits apoptosis mediated by TRAIL in Jurkat T cells PubMed
    tat Upregulation of TRAIL by HIV-1 Tat induces bystander-mediated apoptosis in T cells PubMed
    Vif vif HIV-1 Vif downregulates the expression of tumor necrosis factor ligand superfamily, member 10 (TNFSF10) in Vif-expression T cells PubMed
    Vpr vpr HIV-1 Vpr upregulates the expression of TRAIL in human monocyte-derived dendritic cells PubMed

    Go to the HIV-1, Human Interaction Database

    • Apoptosis, organism-specific biosystem (from KEGG)
      Apoptosis, organism-specific biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
    • Apoptosis, organism-specific biosystem (from WikiPathways)
      Apoptosis, organism-specific biosystemApoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and ...
    • Apoptosis, conserved biosystem (from KEGG)
      Apoptosis, conserved biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
    • Apoptosis, organism-specific biosystem (from REACTOME)
      Apoptosis, organism-specific biosystemApoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and ...
    • Apoptosis Modulation and Signaling, organism-specific biosystem (from WikiPathways)
      Apoptosis Modulation and Signaling, organism-specific biosystemApoptosis, or cell death program, can be activated by various mechanisms within the extrinsic and the intrinsic pathway. While activation of cell death receptors leads to the engagement of the extrin...
    • CASP8 activity is inhibited, organism-specific biosystem (from REACTOME)
      CASP8 activity is inhibited, organism-specific biosystemCell death triggered by extrinsic stimuli via death receptors or toll-like receptors (e.g., TLR3, TLR4) may result in either apoptosis or regulated necrosis (necroptosis) (Holler N et al. 2000; Kalai...
    • Caspase activation via extrinsic apoptotic signalling pathway, organism-specific biosystem (from REACTOME)
      Caspase activation via extrinsic apoptotic signalling pathway, organism-specific biosystemKnown as the "death receptor pathway" the extrinsic or caspase 8/10 dependent pathway is activated by ligand binding. The "death receptors" are specialized cell-surface receptors including Fas/CD95, ...
    • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
      Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
    • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
      Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
    • Death Receptor Signalling, organism-specific biosystem (from REACTOME)
      Death Receptor Signalling, organism-specific biosystemThe death receptors, all cell-surface receptors, begin the process of caspase activation. The common feature of these type 1 transmembrane proteins is the "death-domain" a conserved cytoplasmic motif...
    • Dimerization of procaspase-8, organism-specific biosystem (from REACTOME)
      Dimerization of procaspase-8, organism-specific biosystemProcaspase-8 monomers undergo dimerization. The dimerization event occurs at death-inducing signaling complex (DISC) and results in a reposition of the procaspase-8 inter-subunit linker to become acc...
    • FoxO signaling pathway, organism-specific biosystem (from KEGG)
      FoxO signaling pathway, organism-specific biosystemThe forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative str...
    • Influenza A, organism-specific biosystem (from KEGG)
      Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
    • Influenza A, conserved biosystem (from KEGG)
      Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
    • Ligand-dependent caspase activation, organism-specific biosystem (from REACTOME)
      Ligand-dependent caspase activation, organism-specific biosystemCaspase-8 is synthesized as zymogen (procaspase-8) and is formed from procaspase-8 as a cleavage product. However, the cleavage itself appears not to be sufficient for the formation of an active casp...
    • Measles, organism-specific biosystem (from KEGG)
      Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
    • Measles, conserved biosystem (from KEGG)
      Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
    • Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Photodynamic therapy-induced AP-1 survival signaling., organism-specific biosystem (from WikiPathways)
      Photodynamic therapy-induced AP-1 survival signaling., organism-specific biosystemPhotodynamic therapy may induce an acute stress response mediated by mitogen-activated protein kinase kinase kinase 5 (MAP3K5), its downstream MAPKs that target c-Jun N-terminal kinase (JNK, MAPK8) a...
    • Programmed Cell Death, organism-specific biosystem (from REACTOME)
      Programmed Cell Death, organism-specific biosystemCell death is a fundamental cellular response that has a crucial role in shaping our bodies during development and in regulating tissue homeostasis by eliminating unwanted cells. There are a number o...
    • RIPK1-mediated regulated necrosis, organism-specific biosystem (from REACTOME)
      RIPK1-mediated regulated necrosis, organism-specific biosystemReceptor-interacting kinase protein 1 (RIPK1) and RIPK3-dependent necrosis is called necroptosis or programmed necrosis. The kinase activities of RIPK1 and RIPK3 are essential for the necroptotic cel...
    • Regulated Necrosis, organism-specific biosystem (from REACTOME)
      Regulated Necrosis, organism-specific biosystemNecrosis has traditionally been considered as a passive, unregulated cell death. However, accumulating evidence suggests that necrosis, like apoptosis, can be executed by genetically controlled and h...
    • Regulation by c-FLIP, organism-specific biosystem (from REACTOME)
      Regulation by c-FLIP, organism-specific biosystemc-FLIP proteins (CASP8 and FADD-like apoptosis regulators or c-FLICE inhibitory proteins) are death effector domain (DED)-containing proteins that are recruited to the death-inducing signaling comple...
    • Regulation of necroptotic cell death, organism-specific biosystem (from REACTOME)
      Regulation of necroptotic cell death, organism-specific biosystemA regulated balance between cell survival and cell death is essential for normal development and homeostasis of multicellular organisms. Defects in control of this balance may contribute to autoimmu...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • TP53 Network, organism-specific biosystem (from WikiPathways)
      TP53 Network, organism-specific biosystemP53 is not a lonely genome guardian, it operates with the assistance of p73 and p63 within a complex network including distinct but complementary pathways. This protein family presents a high le...
    • TRAIL signaling, organism-specific biosystem (from REACTOME)
      TRAIL signaling, organism-specific biosystemTumor necrosis factor-related apoptosis-inducing ligand or Apo 2 ligand (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) family. This group of apoptosis induction pathways all work throug...
    • TRAIL signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
      TRAIL signaling pathway, organism-specific biosystem
      TRAIL signaling pathway
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    cytokine activity IEA
    Inferred from Electronic Annotation
    more info
     
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    receptor binding TAS
    Traceable Author Statement
    more info
    PubMed 
    tumor necrosis factor receptor binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    activation of cysteine-type endopeptidase activity involved in apoptotic process TAS
    Traceable Author Statement
    more info
     
    activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
     
    apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    cell surface receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    cell-cell signaling TAS
    Traceable Author Statement
    more info
    PubMed 
    immune response IEA
    Inferred from Electronic Annotation
    more info
     
    male gonad development IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of extrinsic apoptotic signaling pathway via death domain receptors TAS
    Traceable Author Statement
    more info
     
    positive regulation of I-kappaB kinase/NF-kappaB signaling IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of cysteine-type endopeptidase activity involved in apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of extrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of release of cytochrome c from mitochondria IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of extrinsic apoptotic signaling pathway via death domain receptors TAS
    Traceable Author Statement
    more info
     
    response to insulin IEA
    Inferred from Electronic Annotation
    more info
     
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    extracellular exosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
     
    integral component of plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    Preferred Names
    tumor necrosis factor ligand superfamily member 10
    Names
    Apo-2 ligand
    TNF-related apoptosis inducing ligand TRAIL
    chemokine tumor necrosis factor ligand superfamily member 10
    tumor necrosis factor (ligand) family, member 10
    tumor necrosis factor (ligand) superfamily, member 10
    tumor necrosis factor apoptosis-inducing ligand splice variant delta
    tumor necrosis factor ligand 6A
    tumor necrosis factor superfamily member 10

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001190942.1NP_001177871.1  tumor necrosis factor ligand superfamily member 10 isoform 2

      See identical proteins and their annotated locations for NP_001177871.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two consecutive exons in the CDS, resulting in a frame-shift, as compared to variant 1. The resulting isoform (2) is shorter and has a different C-terminus, as compared to isoform 1.
      Source sequence(s)
      AC016938, AK296085, DA969653
      Consensus CDS
      CCDS54680.1
      UniProtKB/Swiss-Prot
      P50591
      Related
      ENSP00000389931.2, OTTHUMP00000211019, ENST00000420541.6, OTTHUMT00000346602
    2. NM_001190943.1NP_001177872.1  tumor necrosis factor ligand superfamily member 10 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks multiple 3' exons, but has an alternate 3' exon, as compared to variant 1. The resulting isoform (3) is very short and has a different C-terminus, as compared to isoform 1.
      Source sequence(s)
      AC007919, AC016938
    3. NM_003810.3NP_003801.1  tumor necrosis factor ligand superfamily member 10 isoform 1

      See identical proteins and their annotated locations for NP_003801.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC007919, AC016938, DA969653
      Consensus CDS
      CCDS3219.1
      UniProtKB/Swiss-Prot
      P50591
      UniProtKB/TrEMBL
      Q6IBA9
      Related
      ENSP00000241261.2, OTTHUMP00000211018, ENST00000241261.6, OTTHUMT00000346601
      Conserved Domains (1) summary
      pfam00229
      Location:153280
      TNF; TNF(Tumour Necrosis Factor) family

    RNA

    1. NR_033994.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an internal exon in the CDS, resulting in frame-shift and a premature translation termination, as compared to variant 1. The transcript is a nonsense-mediated mRNA decay candidate.
      Source sequence(s)
      AC016938, DA041872, DA969653

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p7 Primary Assembly

      Range
      172505508..172523507 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018914.2 Alternate CHM1_1.1

      Range
      172186184..172204170 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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