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    TNFRSF10A TNF receptor superfamily member 10a [ Homo sapiens (human) ]

    Gene ID: 8797, updated on 25-May-2017
    Official Symbol
    TNFRSF10Aprovided by HGNC
    Official Full Name
    TNF receptor superfamily member 10aprovided by HGNC
    Primary source
    HGNC:HGNC:11904
    See related
    Ensembl:ENSG00000104689 MIM:603611; Vega:OTTHUMG00000097843
    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
    DR4; APO2; CD261; TRAILR1; TRAILR-1
    Summary
    The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. [provided by RefSeq, Jul 2008]
    Orthologs
    Location:
    8p21.3
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 8 NC_000008.11 (23191457..23225167, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (23048970..23082680, complement)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC254896 Neighboring gene TNF receptor superfamily member 10c Neighboring gene TNF receptor superfamily member 10d Neighboring gene ribosomal protein L23a pseudogene 55 Neighboring gene uncharacterized LOC389641 Neighboring gene charged multivesicular body protein 7

    • 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?

    NHGRI GWAS Catalog

    Description
    Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population.
    NHGRI GWA Catalog
    Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder.
    NHGRI GWA Catalog
    Seven new loci associated with age-related macular degeneration.
    NHGRI GWA Catalog

    Replication interactions

    Interaction Pubs
    Infectious wild type HIV-1 production is restricted by 293T cells over-expressing TNFRSF10A PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 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 Gp120-induced M-CSF downregulates the TRAIL receptor TRAIL-R1/DR4 and upregulates the anti-apoptotic genes Bfl-1 and Mcl-1 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, 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, ...
    • Cell surface interactions at the vascular wall, organism-specific biosystem (from REACTOME)
      Cell surface interactions at the vascular wall, organism-specific biosystemLeukocyte extravasation is a rigorously controlled process that guides white cell movement from the vascular lumen to sites of tissue inflammation. The powerful adhesive interactions that are require...
    • 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...
    • Direct p53 effectors, organism-specific biosystem (from Pathway Interaction Database)
      Direct p53 effectors, organism-specific biosystem
      Direct p53 effectors
    • Gene Expression, organism-specific biosystem (from REACTOME)
      Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
    • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
      Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • 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...
    • 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 Regulates Transcription of Cell Death Genes, organism-specific biosystem (from REACTOME)
      TP53 Regulates Transcription of Cell Death Genes, organism-specific biosystemThe tumor suppressor TP53 (p53) exerts its tumor suppressive role in part by regulating transcription of a number of genes involved in cell death, mainly apoptotic cell death. The majority of apoptot...
    • TP53 Regulates Transcription of Death Receptors and Ligands, organism-specific biosystem (from REACTOME)
      TP53 Regulates Transcription of Death Receptors and Ligands, organism-specific biosystemPro-apoptotic transcriptional targets of TP53 are TRAIL death receptors TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2), as well as the FASL/CD95L death receptor FAS (CD95). T...
    • 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
    • Transcriptional Regulation by TP53, organism-specific biosystem (from REACTOME)
      Transcriptional Regulation by TP53, organism-specific biosystemThe tumor suppressor TP53 (encoded by the gene p53) is a transcription factor. Under stress conditions, it recognizes specific responsive DNA elements and thus regulates the transcription of many gen...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • MGC9365

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    TRAIL binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    death receptor activity TAS
    Traceable Author Statement
    more info
    PubMed 
    protease binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    receptor activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    tumor necrosis factor-activated receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Process Evidence Code Pubs
    TRAIL-activated apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    activation of NF-kappaB-inducing kinase activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    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 NAS
    Non-traceable Author Statement
    more info
    PubMed 
    cell surface receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    cellular response to mechanical stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    extrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    extrinsic apoptotic signaling pathway via death domain receptors NAS
    Non-traceable Author Statement
    more info
    PubMed 
    immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    leukocyte migration TAS
    Traceable Author Statement
    more info
     
    multicellular organism development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    negative regulation of extrinsic apoptotic signaling pathway via death domain receptors TAS
    Traceable Author Statement
    more info
     
    regulation of apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    regulation of apoptotic process TAS
    Traceable Author Statement
    more info
     
    regulation of cell proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    regulation of extrinsic apoptotic signaling pathway via death domain receptors TAS
    Traceable Author Statement
    more info
     
    response to lipopolysaccharide IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    tumor necrosis factor-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    integral component of membrane IC
    Inferred by Curator
    more info
    PubMed 
    integral component of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    intracellular IEA
    Inferred from Electronic Annotation
    more info
     
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    tumor necrosis factor receptor superfamily member 10A
    Names
    TNF-related apoptosis-inducing ligand receptor 1
    TRAIL receptor 1
    TRAIL-R1
    cytotoxic TRAIL receptor
    death receptor 4
    tumor necrosis factor receptor superfamily member 10a variant 2
    tumor necrosis factor receptor superfamily, member 10a

    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.

    Genomic

    1. NG_032107.1 RefSeqGene

      Range
      5001..38711
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_003844.3NP_003835.3  tumor necrosis factor receptor superfamily member 10A

      See identical proteins and their annotated locations for NP_003835.3

      Status: REVIEWED

      Source sequence(s)
      BC012866, CN423254, DB101031
      Consensus CDS
      CCDS6039.1
      UniProtKB/Swiss-Prot
      O00220
      Related
      ENSP00000221132.3, OTTHUMP00000123526, ENST00000221132.7, OTTHUMT00000215133
      Conserved Domains (2) summary
      cd08315
      Location:367454
      Death_TRAILR_DR4_DR5; Death domain of Tumor necrosis factor-Related Apoptosis-Inducing Ligand Receptors
      cd10580
      Location:129230
      TNFRSF10; Tumor necrosis factor receptor superfamily member 10 (TNFRSF10), includes TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2)

    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_000008.11 Reference GRCh38.p7 Primary Assembly

      Range
      23191457..23225167 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018919.2 Alternate CHM1_1.1

      Range
      23251086..23284807 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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