TNFRSF10A tumor necrosis factor receptor superfamily, member 10a [Homo sapiens (human)] - Gene

Summary

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Official Symbol: TNFRSF10Aprovided by HGNC
Official Full Name: tumor necrosis factor receptor superfamily, member 10aprovided by HGNC
Primary source: HGNC:11904
See related: HPRD:04679; MIM:603611
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]

Genomic context

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Location :: 8p21

Sequence :: Chromosome: 8; NC_000008.10 (23048970..23082680, complement)

See TNFRSF10A in Epigenomics, MapViewer

Chromosome 8 - NC_000008.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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

endogenous MARCH-8 regulates the steady-state cell surface expression of TRAIL-R1.
Title: Ubiquitination by the membrane-associated RING-CH-8 (MARCH-8) ligase controls steady-state cell surface expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor 1.
the C626G polymorphism of DR4 may be associated with the risk and severity of lumbar disc degeneration in the Chinese Han population
Title: Association of the polymorphism of DR4 with the risk and severity of lumbar disc degeneration in the Chinese Han population.
Plumbagin alone could markedly up-regulate DR5 mRNA and protein expression, and slightly increase DR4 mRNA and protein expression in A375 cells.
Title: Plumbagin enhances TRAIL-mediated apoptosis through up-regulation of death receptor in human melanoma A375 cells.
Endometriosis is not associated with osteoprotegerin gene polymorphism.
Title: Association between endometriosis and polymorphisms in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptor and osteoprotegerin genes and their serum levels.
Data show that bufalin-induced down-regulation of Cbl-b contributed to the up-regulation of TRAIL Receptors DR4 and DR5.
Title: Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells.
DR4 is forming DISC complex to activate proximal caspases for apoptosis by TRAIL.
Title: Regulation in the targeting of TRAIL receptor 1 to cell surface via GODZ for TRAIL sensitivity in tumor cells.
we found that the TRAIL receptor I wild type with threonine at amino acid position 209 (626C) and alanine at position 228 (638A) is associated with an increased risk of Hepatocellular carcinoma in patients with chronic hepatitis C.
Title: TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients.
DR4, both as the complete form or as its new short isoform, is involved in TRAIL sensitivity in Ewing's sarcoma.
Title: A functional, new short isoform of death receptor 4 in Ewing's sarcoma cell lines may be involved in TRAIL sensitivity/resistance mechanisms.
A significant association of DR4 683A > C with a higher risk for ovarian cancer in carriers of BRCA1 mutations.
Title: Association of death receptor 4 variant (683A > C) with ovarian cancer risk in BRCA1 mutation carriers.
Data show that a higher expression of FAS receptor, FAS ligand, TrailR1 and TrailR2 on T cells or blasts of acute myeloid leukemia (AML) patients is associated with a better prognosis.
Title: Expression and prognostic value of FAS receptor/FAS ligand and TrailR1/TrailR2 in acute myeloid leukemia.

Submit: New GeneRIF Correction See all (107)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population.

HIV-1 protein interactions

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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 Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_003835.2	NP_071434.2	MOAP1	BIND	PubMed	TRAIL-R1 interacts with MAP-1.
NP_003835.2	NP_009113.3	RASSF1	BIND	PubMed	TRAIL-R1 interacts with RASSF1A.
O00220	O95999	BCL10	HPRD	PubMed
O00220	Q06187	BTK	HPRD	PubMed
O00220	Q14790	CASP8	HPRD	PubMed
O00220	P01730	CD4	HPRD	PubMed
O00220	P02458	COL2A1	HPRD	PubMed
O00220	P51398	DAP3	HPRD	PubMed
O00220	Q13158	FADD	HPRD	PubMed
O00220	Q8WXG6	MADD	HPRD	PubMed
O00220	Q96BY2	MOAP1	HPRD	PubMed
O00220	Q9NS23	RASSF1	HPRD	PubMed
O00220	Q13546	RIPK1	HPRD	PubMed
O00220	O00220	TNFRSF10A	HPRD	PubMed
O00220	O14763	TNFRSF10B	HPRD	PubMed
O00220	Q9UBN6	TNFRSF10D	HPRD	PubMed
O00220	P50591	TNFSF10	HPRD	PubMed
O00220	Q15628	TRADD	HPRD	PubMed
BioGRID:114325	BioGRID:114429	BCL10	BioGRID	PubMed	Two-hybrid
BioGRID:114325	BioGRID:107293	CASP10	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114325	BioGRID:107291	CASP8	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:114325	BioGRID:107315	CBL	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114325	BioGRID:114364	CFLAR	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114325	BioGRID:114030	CUL3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114325	BioGRID:113587	DAP3	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:114325	BioGRID:114302	FADD	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114325	BioGRID:114397	SQSTM1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114325	BioGRID:114323	TNFRSF10B	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114325	BioGRID:114280	TNFSF10	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114325	BioGRID:114257	TRADD	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114325	BioGRID:113038	TRAF2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114325	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western

Pathways from BioSystems

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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 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...
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 ...
Direct p53 effectors, organism-specific biosystem (from Pathway Interaction Database)
Direct p53 effectors, organism-specific biosystem
Direct p53 effectors
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 ...
Kit Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
Kit Receptor Signaling Pathway, organism-specific biosystemKit is a receptor protein tyrosine kinase, which is a receptor for stem cell factor or kit ligand. Signaling through Kit is important for formation of red cells, lymphocytes, mast cells and platelets...
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...
TRAIL signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
TRAIL signaling pathway, organism-specific biosystem
TRAIL signaling pathway

General gene information

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Markers

RH67885 (e-PCR)
- UniSTS:55396

TNFRSF10A_2005 (e-PCR)
- UniSTS:281061

Genotypes

See TNFRSF10A SNP Geneview Report
See TNFRSF10A SNP Genotype Report
See TNFRSF10A SNP Variation Viewer Report

Homology

Homologs of the TNFRSF10A gene: The TNFRSF10A gene is conserved in chimpanzee, Rhesus monkey, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

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
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

Process	Evidence Code	Pubs
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	NAS Non-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
extrinsic apoptotic signaling pathway via death domain receptors	NAS Non-traceable Author Statement more info	PubMed
induction of apoptosis	NAS Non-traceable Author Statement more info	PubMed
signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
integral to membrane	IC Inferred by Curator more info	PubMed

General protein information

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Preferred Names: tumor necrosis factor receptor superfamily member 10A

Names: tumor necrosis factor receptor superfamily member 10A; TRAIL-R1; TRAIL receptor 1; death receptor 4; cytotoxic TRAIL receptor; TNF-related apoptosis-inducing ligand receptor 1; tumor necrosis factor receptor superfamily member 10a variant 2

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.

Genomic

NG_032107.1 RefSeqGene

Range

5001..38711

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Status: REVIEWED

Source sequence(s)

BC012866, CN423254, DB101031

Consensus CDS

CCDS6039.1

UniProtKB/Swiss-Prot

O00220

Conserved Domains (3) summary

cd00185
Location:119 – 208
Blast Score: 216

TNFR; Tumor necrosis factor receptor (TNFR) domain; superfamily of TNF-like receptor domains. When bound to TNF-like cytokines, TNFRs trigger multiple signal transduction pathways, they are involved in inflammation response, apoptosis, autoimmunity and ...

smart00208
Location:190 – 229
Blast Score: 118

TNFR; Tumor necrosis factor receptor / nerve growth factor receptor repeats.

cd08315
Location:359 – 454
Blast Score: 430

Death_TRAILR_DR4_DR5; Death domain of Tumor necrosis factor-Related Apoptosis-Inducing Ligand Receptors

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000008.10 Reference GRCh37.p10 Primary Assembly

Range

23048970..23082680, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000140.1 Alternate HuRef

Range

21594946..21628637, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018919.1 Alternate CHM1_1.0

Range

23303188..23336897, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01005539.1 (21407..55098)	None
genomic	AC100861.2 (54141..87810)	None
genomic	AMYH01018573.1 (28346..62055)	None
genomic	CH471080.2	EAW63636.1
genomic	EF064713.1	ABK41896.1
genomic	JA362578.1	CCA94571.1
mRNA	AK291299.1	BAF83988.1
mRNA	BC012866.1	AAH12866.1
mRNA	BT006906.1	AAP35552.1
mRNA	CN423254.1	None
mRNA	DB101031.1	None
mRNA	FJ795027.1	ACO37639.1
mRNA	JF729355.1	AEB77762.1
mRNA	U90875.1	AAC51226.1
other-genetic	DQ891791.2	ABM82717.1
other-genetic	DQ894973.2	ABM85899.1