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

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Summary

Official Symbol: TNFSF10provided by HGNC
Official Full Name: tumor necrosis factor (ligand) superfamily, member 10provided by HGNC
Primary source: 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]

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Genomic context

Location :: 3q26

Sequence :: Chromosome: 3; NC_000003.11 (172223298..172241297, complement)

See TNFSF10 in Epigenomics, MapViewer

Chromosome 3 - NC_000003.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Study provides proof of principle that TRAIL combined with simultaneously targeting the Bcl-2 and Akt signaling pathways may have potential as a novel future treatment strategy for nasopharyngeal carcinoma (NPC).
Title: Simultaneously targeting Bcl-2 and Akt pathways reverses resistance of nasopharyngeal carcinoma to TRAIL synergistically.
is associated with impaired regulation of CD4+CD25- T cells by regulatory T cells in patients with rheumatoid arthritis
Title: TRAIL is associated with impaired regulation of CD4+CD25- T cells by regulatory T cells in patients with rheumatoid arthritis.
TRAIL dependent fratricidal killing of gp120 primed hepatocytes by HCV core expressing hepatocytes
Title: TRAIL dependent fratricidal killing of gp120 primed hepatocytes by HCV core expressing hepatocytes.
Gli2 gene silencing sensitized SMMC-7721 cell to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by reducing the expression of the long and short isoform of c-FLIP and Bcl-2
Title: shRNA-mediated silencing of Gli2 gene inhibits proliferation and sensitizes human hepatocellular carcinoma cells towards TRAIL-induced apoptosis.
These results suggest that TRAIL, produced from myeloma cells, may play an important role in bone resorption of multiple myeloma patients
Title: TRAIL produced from multiple myeloma cells is associated with osteolytic markers.
Our data suggest that OPG through the TRAIL pathway, but not the RANKL pathway, plays a role in regulating anti-apoptosis during the development of infantile haemangioma
Title: Infantile haemangioma expresses tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors, osteoprotegerin and receptor activator for nuclear factor кB ligand (RANKL).
These data demonstrate that TRAIL and PKCepsilon must be reciprocally regulated to ensure physiological colon epithelial cell differentiation starting from the stem cell pool.
Title: TRAIL up-regulation must be accompanied by a reciprocal PKCε down-regulation during differentiation of colonic epithelial cell: implications for colorectal cancer cell differentiation.
TRAIL-induced redistribution of DR4 and DR5 in lipid rafts contributed to the sensitivity to TRAIL in TRAIL-sensitive NSCLC H460 cell line.
Title: Redistribution of DR4 and DR5 in lipid rafts accounts for the sensitivity to TRAIL in NSCLC cells.
YC-1 may confer a benefit in TRAIL treatment of epithelial ovarian adenocarcinoma.
Title: Guanylate cyclase activator YC-1 enhances TRAIL-induced apoptosis in human epithelial ovarian carcinoma cells via activation of apoptosis-related proteins.
transcript variants lose apoptotic activity but retain or enhance NF-kappaB activating potentials
Title: Novel transcript variants of TRAIL show different activities in activation of NF-κB and apoptosis.

Submit: New GeneRIF Correction See all (420)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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HIV-1 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
Tat	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
	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

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NC_000003.9	NP_004371.1	CREBBP	BIND	PubMed	CBP interacts with the TNFSF10 promoter.
NC_000003.9	NP_004955.2	HDAC1	BIND	PubMed	HDAC1 interacts with the TNFSF10 promoter.
NC_000003.9	NP_001518.1	HDAC2	BIND	PubMed	HDAC2 interacts with the TNFSF10 promoter.
NC_000003.9	NP_003874.2	HDAC3	BIND	PubMed	HDAC3 interacts with the TNFSF10 promoter.
NC_000003.9	NP_006028.1	HDAC4	BIND	PubMed	HDAC4 interacts with the TNFSF10 promoter.
NC_000003.9		HDAC5	BIND	PubMed	An unspecifed isoform of HDAC5 interacts with the TNFSF10 promoter.
NC_000003.9	NP_003484.1	HIST3H3	BIND	PubMed	Acetylated H3 interacts with the TNFSF10 promoter.
NC_000003.9	NP_612482.2	SP1	BIND	PubMed	SP1 interacts with the TNFSF10 promoter.
NC_000003.9	NP_003102.1	SP3	BIND	PubMed	SP3 interacts with the TNFSF10 promoter.
NC_000003.9			BIND	PubMed	RNA Pol II interacts with the TNFSF10 promoter.
NP_003801.1		IER3	BIND	PubMed	An unspecified isoform of IEX-1 interacts with TNFSF10.
NP_003801.1		TNFRSF10B	BIND	PubMed	TNFSF10 (TRAIL) interacts with TNFRSF10B (DR5).
P50591	P13686	ACP5	HPRD	PubMed
P50591	Hypothetical protein DKFZp564O0523	RBM48	HPRD	PubMed
P50591	O00220	TNFRSF10A	HPRD	PubMed
P50591	O14763	TNFRSF10B	HPRD	PubMed
P50591	O14798	TNFRSF10C	HPRD	PubMed
P50591	Q9UBN6	TNFRSF10D	HPRD	PubMed
P50591	O00300	TNFRSF11B	HPRD	PubMed
P50591	P50591	TNFSF10	HPRD	PubMed
BioGRID:114280	BioGRID:106570	ACP5	BioGRID	PubMed	Two-hybrid
BioGRID:114280	BioGRID:123855	RBM48	BioGRID	PubMed	Two-hybrid
BioGRID:114280	BioGRID:114325	TNFRSF10A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114280	BioGRID:114323	TNFRSF10B	BioGRID	PubMed	Affinity Capture-MS; Co-crystal Structure; Reconstituted Complex
BioGRID:114280	BioGRID:114321	TNFRSF10D	BioGRID	PubMed	Reconstituted Complex
BioGRID:114280	BioGRID:114280	TNFSF10	BioGRID	PubMed	Co-crystal Structure

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 pro-apoptotic gene products	TAS Traceable Author Statement more info
apoptotic process	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
induction of apoptosis	TAS Traceable Author Statement more info	PubMed
induction of apoptosis by extracellular signals	TAS Traceable Author Statement more info
positive regulation of I-kappaB kinase/NF-kappaB cascade	IEP Inferred from Expression Pattern more info	PubMed
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info
positive regulation of extrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info
positive regulation of release of cytochrome c from mitochondria	IDA Inferred from Direct Assay more info
signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
extracellular region	TAS Traceable Author Statement more info
extracellular space	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
membrane	IEA Inferred from Electronic Annotation more info
soluble fraction	TAS Traceable Author Statement more info	PubMed

General protein information

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

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NCBI Reference Sequences (RefSeq)

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_001190942.1 → NP_001177871.1 tumor necrosis factor ligand superfamily member 10 isoform 2

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

Related

ENSP00000389931, OTTHUMP00000211019, ENST00000420541, OTTHUMT00000346602
NM_001190943.1 → 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
NM_003810.3 → NP_003801.1 tumor necrosis factor ligand superfamily member 10 isoform 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:122 – 278
Blast Score: 348

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

NR_033994.1 RNA Sequence

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: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000003.11 Reference GRCh37.p5 Primary Assembly

Range

172223298..172241297, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000135.1 Alternate HuRef

Range

169593908..169611904, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC007919.18 (1546..4273)	None
genomic	AC016938.24 (25758..41000)	None
genomic	AF178756.1	None
genomic	CH471052.2	EAW78465.1
		EAW78466.1
		EAW78467.1
genomic	CQ892411.1	CAH68809.1
genomic	CS276168.1	CAL33971.1
genomic	EF064708.1	ABK41891.1
genomic	HA637646.1	CAZ39545.1
genomic	JA362607.1	CCA94584.1
mRNA	AK296085.1	BAG58840.1
mRNA	AK312742.1	BAG35612.1
mRNA	AY312579.1	AAR16184.1
mRNA	BC009795.1	None
mRNA	BC020220.1	None
mRNA	BC032722.1	AAH32722.1
mRNA	BT019564.1	AAV38371.1
mRNA	CR456895.1	CAG33176.1
mRNA	DA041872.1	None
mRNA	DA969653.1	None
mRNA	DQ848564.1	ABI24016.1
mRNA	EU183231.1	ABW24658.1
mRNA	U37518.1	AAC50332.1
mRNA	U57059.1	AAB01233.1
other-genetic	DQ890873.2	ABM81799.1
other-genetic	DQ894029.2	ABM84955.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P50591.1	GenPept	UniProtKB/Swiss-Prot:P50591
Q6IBA9	GenPept	UniProtKB/TrEMBL:Q6IBA9
Q6JSD9	GenPept	UniProtKB/TrEMBL:Q6JSD9