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TNFSF10 tumor necrosis factor (ligand) superfamily, member 10 [ Homo sapiens (human) ]

Gene ID: 8743, updated on 22-Dec-2014
Official Symbol
TNFSF10provided by HGNC
Official Full Name
tumor necrosis factor (ligand) superfamily, member 10provided by HGNC
Primary source
HGNC:HGNC:11925
See related
Ensembl:ENSG00000121858; HPRD:04670; 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
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]
See TNFSF10 in Epigenomics, MapViewer
Location:
3q26
Exon count:
6
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 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 solute carrier family 31 (copper transporter), member 1 pseudogene 1 Neighboring gene neutral cholesterol ester hydrolase 1 Neighboring gene nucleosome assembly protein 1-like 5 pseudogene

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

Go to the HIV-1, Human Interaction Database

  • 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, organism-specific biosystem (from KEGG)
    Apoptosis, organism-specific biosystemApoptosis is a genetically controlled mechanisms of cell death involved in the regulation of tissue homeostasis. The 2 major pathways of apoptosis are the extrinsic (Fas and other TNFR superfamily me...
  • Apoptosis, conserved biosystem (from KEGG)
    Apoptosis, conserved biosystemApoptosis is a genetically controlled mechanisms of cell death involved in the regulation of tissue homeostasis. The 2 major pathways of apoptosis are the extrinsic (Fas and other TNFR superfamily me...
  • 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...
  • Caspase-8 activation by cleavage, organism-specific biosystem (from REACTOME)
    Caspase-8 activation by cleavage, 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...
  • 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...
  • Extrinsic Pathway for Apoptosis, organism-specific biosystem (from REACTOME)
    Extrinsic Pathway for Apoptosis, 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, ...
  • 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 ...
  • 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...
  • 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...
  • 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
 
Component Evidence Code Pubs
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IEA
Inferred from Electronic Annotation
more info
 
extracellular vesicular exosome IDA
Inferred from Direct Assay
more info
PubMed 
integral component of plasma membrane TAS
Traceable Author Statement
more info
PubMed 
Preferred Names
tumor necrosis factor ligand superfamily member 10
Names
tumor necrosis factor ligand superfamily member 10
Apo-2 ligand
TNF-related apoptosis inducing ligand TRAIL
tumor necrosis factor (ligand) family, member 10
chemokine tumor necrosis factor ligand superfamily member 10
tumor necrosis factor apoptosis-inducing ligand splice variant delta

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 proteins identical to 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, OTTHUMP00000211019, ENST00000420541, 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 proteins identical to 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, OTTHUMP00000211018, ENST00000241261, OTTHUMT00000346601
    Conserved Domains (1) summary
    cd00184
    Location:122278
    TNF; Tumor Necrosis Factor; TNF superfamily members include the cytokines: TNF (TNF-alpha), LT (lymphotoxin-alpha, TNF-beta), CD40 ligand, Apo2L (TRAIL), Fas ligand, and osteoprotegerin (OPG) ligand. These proteins generally have an intracellular N-terminal ...

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 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000003.12 

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

Alternate CHM1_1.1

Genomic

  1. NC_018914.2 

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

Alternate HuRef

Genomic

  1. AC_000135.1 

    Range
    169593908..169611904
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)