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

Summary

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; AllianceGenome:HGNC:11925
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; TANCR; 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]
Expression: Ubiquitous expression in lung (RPKM 64.9), placenta (RPKM 44.9) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q26.31

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (172505508..172523430, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (175290584..175308501, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (172223298..172241220, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL.
Title: The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL.
Acquired Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Resistance of Human Colorectal Cancer Cells Is Linked to Histone Acetylation and Is Synergistically Ameliorated by Combination with HDAC Inhibitors.
Title: Acquired Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Resistance of Human Colorectal Cancer Cells Is Linked to Histone Acetylation and Is Synergistically Ameliorated by Combination with HDAC Inhibitors.
ELF3 plays an important role in defining TRAIL sensitivity in breast cancer by modulating the expression of decoy receptor 2 (DCR2).
Title: ELF3 plays an important role in defining TRAIL sensitivity in breast cancer by modulating the expression of decoy receptor 2 (DCR2).
Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.
Title: Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.
Significance of TRAIL/Apo-2 ligand and its death receptors in apoptosis and necroptosis signalling: Implications for cancer-targeted therapeutics.
Title: Significance of TRAIL/Apo-2 ligand and its death receptors in apoptosis and necroptosis signalling: Implications for cancer-targeted therapeutics.
Heparan sulfate promotes TRAIL-induced tumor cell apoptosis.
Title: Heparan sulfate promotes TRAIL-induced tumor cell apoptosis.
KCNK5 Regulating Potassium Efflux and Inducing Pyroptosis in Corneal Epithelial Cells Through TNFSF10-Mediated Autophagy in Dry Eye.
Title: KCNK5 Regulating Potassium Efflux and Inducing Pyroptosis in Corneal Epithelial Cells Through TNFSF10-Mediated Autophagy in Dry Eye.
The E3 ubiquitin ligase Itch regulates death receptor and cholesterol trafficking to affect TRAIL-mediated apoptosis.
Title: The E3 ubiquitin ligase Itch regulates death receptor and cholesterol trafficking to affect TRAIL-mediated apoptosis.
Hyperthermia maintains death receptor expression and promotes TRAIL-induced apoptosis.
Title: Hyperthermia maintains death receptor expression and promotes TRAIL-induced apoptosis.
Selective CDK9 knockdown sensitizes TRAIL response by suppression of antiapoptotic factors and NF-kappaB pathway.
Title: Selective CDK9 knockdown sensitizes TRAIL response by suppression of antiapoptotic factors and NF-kappaB pathway.

Submit: New GeneRIF Correction See all GeneRIFs (842)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

TNFSF10_266 (e-PCR)
- UniSTS:277832

SHGC-77549 (e-PCR)
- UniSTS:16727

RH66570 (e-PCR)
- UniSTS:45442

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables TRAIL binding	IEA Inferred from Electronic Annotation more info
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	TAS Traceable Author Statement more info	PubMed
enables tumor necrosis factor receptor binding	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in TRAIL-activated apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in cell surface receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in immune response	IEA Inferred from Electronic Annotation more info
involved_in male gonad development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IEP Inferred from Expression Pattern more info	PubMed
involved_in positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of extrinsic apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of extrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of release of cytochrome c from mitochondria	IDA Inferred from Direct Assay more info	PubMed
involved_in response to insulin	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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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 ligand 6A; tumor necrosis factor superfamily member 10

NCBI Reference Sequences (RefSeq)

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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)

NM_001190942.2 → NP_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

Consensus CDS

CCDS54680.1

UniProtKB/Swiss-Prot

P50591

Related

ENSP00000389931.2, ENST00000420541.6
NM_001190943.2 → NP_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

Related

ENST00000466777.1
NM_003810.4 → NP_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

Consensus CDS

CCDS3219.1

UniProtKB/Swiss-Prot

A1Y9B3, P50591

UniProtKB/TrEMBL

A0A0U5EM55, Q6IBA9

Related

ENSP00000241261.2, ENST00000241261.7

Conserved Domains (1) summary

pfam00229
Location:153 → 280

TNF; TNF(tumor Necrosis Factor) family

RNA

NR_033994.2 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