Human Gene TNFSF10 (uc003fid.3)
  Description: Homo sapiens tumor necrosis factor (ligand) superfamily, member 10 (TNFSF10), transcript variant 1, mRNA.
RefSeq Summary (NM_003810): 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].
Transcript (Including UTRs)
   Position: hg19 chr3:172,223,298-172,241,297 Size: 18,000 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg19 chr3:172,224,282-172,241,174 Size: 16,893 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:172,223,298-172,241,297)mRNA (may differ from genome)Protein (281 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TNF10_HUMAN
DESCRIPTION: RecName: Full=Tumor necrosis factor ligand superfamily member 10; AltName: Full=Apo-2 ligand; Short=Apo-2L; AltName: Full=TNF-related apoptosis-inducing ligand; Short=Protein TRAIL; AltName: CD_antigen=CD253;
FUNCTION: Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG. Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis.
COFACTOR: Binds 1 zinc ion per trimer.
SUBUNIT: Homotrimer.
INTERACTION: Q13618:CUL3; NbExp=2; IntAct=EBI-495373, EBI-456129; O00220:TNFRSF10A; NbExp=8; IntAct=EBI-495373, EBI-518861; O14763:TNFRSF10B; NbExp=23; IntAct=EBI-495373, EBI-518882;
SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein (Potential).
TISSUE SPECIFICITY: Widespread; most predominant in spleen, lung and prostate.
SIMILARITY: Belongs to the tumor necrosis factor family.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TNFSF10ID42632ch3q26.html";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TNFSF10
CDC HuGE Published Literature: TNFSF10
Positive Disease Associations: chronic lymphocytic leukaemia; Waldenstrom macroglobulinaemia
Related Studies:
  1. chronic lymphocytic leukaemia; Waldenstrom macroglobulinaemia
    Xueying Sharon Liang , et al. British journal of haematology 2009 146(4):418-23, Common genetic variants in candidate genes and risk of familial lymphoid malignancies., British journal of haematology 2009 146(4):418-23. [PubMed 19573080]

-  MalaCards Disease Associations
  MalaCards Gene Search: TNFSF10
Diseases sorted by gene-association score: malignant glioma (11), ulceroglandular tularemia (8), primary effusion lymphoma (8), dystrophinopathies (8), pharyngoconjunctival fever (7), ameloblastoma (6), mesothelioma, somatic (5), post-transplant lymphoproliferative disease (5), pancreatic cancer (5), colorectal cancer (4), lung cancer (4), prostate cancer (3), chronic lymphocytic leukemia (3), hepatocellular carcinoma (2), ovarian cancer, somatic (2), breast cancer (2), medulloblastoma (2), ewing sarcoma (2), renal cell carcinoma (2), adamantinoma of long bones (2), leukemia, acute promyelocytic, somatic (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 70.56 RPKM in Minor Salivary Gland
Total median expression: 866.62 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -25.80123-0.210 Picture PostScript Text
3' UTR -249.96984-0.254 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006052 - TNF
IPR021184 - TNF_CS
IPR017355 - TNF_ligand_10/11
IPR008983 - Tumour_necrosis_fac-like

Pfam Domains:
PF00229 - TNF(Tumour Necrosis Factor) family

SCOP Domains:
49842 - TNF-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1D0G - X-ray MuPIT 1D2Q - X-ray MuPIT 1D4V - X-ray MuPIT 1DG6 - X-ray MuPIT 1DU3 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P50591
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005102 receptor binding
GO:0005125 cytokine activity
GO:0005164 tumor necrosis factor receptor binding
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0032813 tumor necrosis factor receptor superfamily binding
GO:0042802 identical protein binding
GO:0046872 metal ion binding

Biological Process:
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006955 immune response
GO:0007165 signal transduction
GO:0007166 cell surface receptor signaling pathway
GO:0007267 cell-cell signaling
GO:0008584 male gonad development
GO:0010469 regulation of receptor activity
GO:0032868 response to insulin
GO:0043065 positive regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0090200 positive regulation of release of cytochrome c from mitochondria
GO:1902041 regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AK296085 - Homo sapiens cDNA FLJ51976 complete cds, moderately similar to Tumor necrosis factor ligand superfamily member 10.
U37518 - Human TNF-related apoptosis inducing ligand TRAIL mRNA, complete cds.
BC032722 - Homo sapiens tumor necrosis factor (ligand) superfamily, member 10, mRNA (cDNA clone MGC:45300 IMAGE:5504670), complete cds.
BC020220 - Homo sapiens tumor necrosis factor (ligand) superfamily, member 10, mRNA (cDNA clone IMAGE:4585594), containing frame-shift errors.
U57059 - Homo sapiens Apo-2 ligand mRNA, complete cds.
CR456895 - Homo sapiens full open reading frame cDNA clone RZPDo834F0111D for gene TNFSF10, tumor necrosis factor (ligand) superfamily, member 10; complete cds, incl. stopcodon.
EU183231 - Homo sapiens tumor necrosis factor apoptosis-inducing ligand splice variant delta mRNA, complete cds, alternatively spliced.
AK312742 - Homo sapiens cDNA, FLJ93150, Homo sapiens tumor necrosis factor (ligand) superfamily, member 10(TNFSF10), mRNA.
BT019564 - Homo sapiens tumor necrosis factor (ligand) superfamily, member 10 mRNA, complete cds.
DQ890873 - Synthetic construct clone IMAGE:100003503; FLH166686.01X; RZPDo839C0288D tumor necrosis factor (ligand) superfamily, member 10 (TNFSF10) gene, encodes complete protein.
KJ897900 - Synthetic construct Homo sapiens clone ccsbBroadEn_07294 TNFSF10 gene, encodes complete protein.
DQ894029 - Synthetic construct Homo sapiens clone IMAGE:100008489; FLH166682.01L; RZPDo839C0287D tumor necrosis factor (ligand) superfamily, member 10 (TNFSF10) gene, encodes complete protein.
AB590324 - Synthetic construct DNA, clone: pFN21AE2179, Homo sapiens TNFSF10 gene for tumor necrosis factor (ligand) superfamily, member 10, without stop codon, in Flexi system.
CU689506 - Synthetic construct Homo sapiens gateway clone IMAGE:100020757 5' read TNFSF10 mRNA.
BC009795 - Homo sapiens, tumor necrosis factor (ligand) superfamily, member 10, clone IMAGE:4249793, mRNA.
AY312579 - Homo sapiens chemokine tumor necrosis factor ligand superfamily member 10 (TNFSF10) mRNA, partial cds, alternatively spliced.
DQ848564 - Homo sapiens tumor necrosis factor ligand superfamily member 10 splice variant (TNFSF10) mRNA, complete cds, alternatively spliced.
JD149300 - Sequence 130324 from Patent EP1572962.
JD366282 - Sequence 347306 from Patent EP1572962.
JD051525 - Sequence 32549 from Patent EP1572962.
JD411174 - Sequence 392198 from Patent EP1572962.
JD074590 - Sequence 55614 from Patent EP1572962.
JD155805 - Sequence 136829 from Patent EP1572962.
JD185297 - Sequence 166321 from Patent EP1572962.
JD185298 - Sequence 166322 from Patent EP1572962.
JD185299 - Sequence 166323 from Patent EP1572962.
JD185300 - Sequence 166324 from Patent EP1572962.
JD292537 - Sequence 273561 from Patent EP1572962.
JD366278 - Sequence 347302 from Patent EP1572962.
JD366279 - Sequence 347303 from Patent EP1572962.
JD366280 - Sequence 347304 from Patent EP1572962.
JD366281 - Sequence 347305 from Patent EP1572962.
JD105770 - Sequence 86794 from Patent EP1572962.
JD116840 - Sequence 97864 from Patent EP1572962.
JD517382 - Sequence 498406 from Patent EP1572962.
JD105769 - Sequence 86793 from Patent EP1572962.
JD149295 - Sequence 130319 from Patent EP1572962.
JD353991 - Sequence 335015 from Patent EP1572962.
JD149289 - Sequence 130313 from Patent EP1572962.
JD377956 - Sequence 358980 from Patent EP1572962.
JD185292 - Sequence 166316 from Patent EP1572962.
JD366272 - Sequence 347296 from Patent EP1572962.
JD249515 - Sequence 230539 from Patent EP1572962.
JD085069 - Sequence 66093 from Patent EP1572962.
JD447641 - Sequence 428665 from Patent EP1572962.
JD331989 - Sequence 313013 from Patent EP1572962.
JD175707 - Sequence 156731 from Patent EP1572962.
JD531471 - Sequence 512495 from Patent EP1572962.
JD231800 - Sequence 212824 from Patent EP1572962.
JD536254 - Sequence 517278 from Patent EP1572962.
JD440973 - Sequence 421997 from Patent EP1572962.
JD314702 - Sequence 295726 from Patent EP1572962.
JD224088 - Sequence 205112 from Patent EP1572962.
JD145233 - Sequence 126257 from Patent EP1572962.
JD376844 - Sequence 357868 from Patent EP1572962.
JD438819 - Sequence 419843 from Patent EP1572962.
JD264131 - Sequence 245155 from Patent EP1572962.
JD110540 - Sequence 91564 from Patent EP1572962.
JD329284 - Sequence 310308 from Patent EP1572962.
JD350752 - Sequence 331776 from Patent EP1572962.
JD043578 - Sequence 24602 from Patent EP1572962.
JD344233 - Sequence 325257 from Patent EP1572962.
JD381239 - Sequence 362263 from Patent EP1572962.
JD512675 - Sequence 493699 from Patent EP1572962.
JD412723 - Sequence 393747 from Patent EP1572962.
JD197773 - Sequence 178797 from Patent EP1572962.
JD212381 - Sequence 193405 from Patent EP1572962.
JD522873 - Sequence 503897 from Patent EP1572962.
JD149727 - Sequence 130751 from Patent EP1572962.
JD352238 - Sequence 333262 from Patent EP1572962.
JD298098 - Sequence 279122 from Patent EP1572962.
AK309200 - Homo sapiens cDNA, FLJ99241.
DL491773 - Novel nucleic acids.
JD419082 - Sequence 400106 from Patent EP1572962.
JD422896 - Sequence 403920 from Patent EP1572962.
JD348902 - Sequence 329926 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04060 - Cytokine-cytokine receptor interaction
hsa04210 - Apoptosis
hsa04650 - Natural killer cell mediated cytotoxicity

BioCarta from NCI Cancer Genome Anatomy Project
h_deathPathway - Induction of apoptosis through DR3 and DR4/5 Death Receptors

Reactome (by CSHL, EBI, and GO)

Protein P50591 (Reactome details) participates in the following event(s):

R-HSA-75238 TRAIL binds TRAIL receptors
R-HSA-141139 Trimerization of TRAIL:TRAIL receptor complex
R-HSA-75187 TRAIL:TRAIL receptor trimers bind FADD
R-HSA-75146 TRAIL:TRAIL Receptor Trimer:FADD complex binds procaspase-8
R-HSA-141316 TRAIL:TRAIL-Receptor2 Trimer:FADD complex binds procaspase-10
R-HSA-141156 TRAIL-mediated dimerization of procaspase-8
R-HSA-3371359 FLIP(L) and procaspase-8 form heterodimer in TRAIL signaling
R-HSA-3465429 FLIP(S) and procaspase-8 form heterodimer
R-HSA-5675456 FLIP(L) and procaspase-8 form heterodimer
R-HSA-75158 TRAIL signaling
R-HSA-73887 Death Receptor Signalling
R-HSA-162582 Signal Transduction
R-HSA-69416 Dimerization of procaspase-8
R-HSA-3371378 Regulation by c-FLIP
R-HSA-140534 Ligand-dependent caspase activation
R-HSA-5218900 CASP8 activity is inhibited
R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-5675482 Regulation of necroptotic cell death
R-HSA-109581 Apoptosis
R-HSA-5213460 RIPK1-mediated regulated necrosis
R-HSA-5357801 Programmed Cell Death
R-HSA-5218859 Regulated Necrosis

-  Other Names for This Gene
  Alternate Gene Symbols: A1Y9B3, APO2L, NM_003810, NP_003801, P50591, TNF10_HUMAN, TRAIL
UCSC ID: uc003fid.3
RefSeq Accession: NM_003810
Protein: P50591 (aka TNF10_HUMAN or TN10_HUMAN)
CCDS: CCDS3219.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_003810.3
exon count: 5CDS single in 3' UTR: no RNA size: 1953
ORF size: 846CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1892.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.