TRAIL-R3 / TNFSF10C (Homo sapiens)
- Synonyms: TRAIL-R3 / TNFSF10C, TNFRSF10C, TRAIL-R3, DCR1, LIT, TRID, CD263
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Tumor necrosis factor receptor superfamily member 10C Precursor (Decoy receptor 1)(DcR1)(Decoy TRAIL receptor without death domain)(TNF-related apoptosis-inducing ligand receptor 3)(TRAIL receptor 3)(TRAIL-R3)(Trail receptor without an intracellular domain)(Lymphocyte inhibitor of TRAIL)(Antagonist decoy receptor for TRAIL/Apo-2L)(CD263 antigen) [Source:UniProtKB/Swiss-Prot;Acc:O14798]
- Family: Other
- Process: apoptosis,
- Pathways: extrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Tnfrsf10b
- WIKI: TRAIL-R3 / TNFSF10C-H_sapiens
- Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family.
- Degli-Esposti MA, Smolak PJ, Walczak H, Waugh J, Huang CP, DuBose RF, Goodwin RG, Smith CA
- TRAIL-R3, a new member of the TRAIL receptor family, has been cloned and characterized. TRAIL-R3 encodes a 299 amino acid protein with 58 and 54% overall identity to TRAIL-R1 and -R2, respectively. Transient expression and quantitative binding studies show TRAIL-R3 to be a plasma membrane-bound protein capable of high affinity interaction with the TRAIL ligand. The TRAIL-R3 gene maps to human chromosome 8p22-21, clustered with the genes encoding two other TRAIL receptors. In contrast to TRAIL-R1 and -R2, this receptor shows restricted expression, with transcripts detectable only in peripheral blood lymphocytes and spleen. The structure of TRAIL-R3 is unique when compared to the other TRAIL receptors in that it lacks a cytoplasmic domain and appears to be glycosyl-phosphatidylinositol-linked. Moreover, unlike TRAIL-R1 and -R2, in a transient overexpression system TRAIL-R3 does not induce apoptosis. J Exp Med. 1997 Oct 6;186(7):1165-70.
- References from Mouse ortholog(s):
- TRAIL-R deficiency in mice promotes susceptibility to chronic inflammation and tumorigenesis.
- Finnberg N, Klein-Szanto AJ, El-Deiry WS
- Preclinical data support the potential of the death-signaling receptors for TRAIL as targets for cancer therapy. However, it is unclear whether these death-signaling receptors suppress the emergence and growth of malignant tumors in vivo. Herein we show that TNF-related apoptosis-inducing ligand receptor (TRAIL-R), the only proapoptotic death-signaling receptor for TRAIL in the mouse, suppresses inflammation and tumorigenesis. Loss of a single TRAIL-R allele on the lymphoma-prone Emu-myc genetic background significantly reduced median lymphoma-free survival. TRAIL-R-deficient lymphomas developed with equal frequency irrespective of mono- or biallelic loss of TRAIL-R, had increased metastatic potential, and showed apoptotic defects relative to WT littermates. In addition, TRAIL-R-/- mice showed decreased long-term survival following a sublethal dose of ionizing radiation. Histological evaluation of moribund irradiated TRAIL-R-/- animals showed hallmarks of bronchopneumonia as well as tumor formation with increased NF-kappaB p65 expression. TRAIL-R also suppressed diethylnitrosamine-induced (DEN-induced) hepatocarcinogenesis, as an increased number of large tumors with apoptotic defects developed in the livers of DEN-treated TRAIL-R-/- mice. Thus TRAIL-R may function as an inflammation and tumor suppressor in multiple tissues in vivo. J Clin Invest. 2008 Jan;118(1):111-23.
- Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor.
- Wu GS, Burns TF, Zhan Y, Alnemri ES, El-Deiry WS
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors are members of the tumor necrosis factor superfamily. TRAIL selectively kills cancer cells but not normal cells. We report here the cloning of the mouse homologue of the TRAIL receptor KILLER/DR5 (MK). The cDNA of MK is 1146 bp in length and encodes a protein of 381 amino acids. MK contains an extracellular cysteine-rich domain, a transmembrane domain, and a cytoplasmic death-domain characteristic of Fas, tumor necrosis factor, and human TRAIL receptors. MK is highly homologous and binds TRAIL with similar affinity as human DR4 and KILLER/DR5. MK induces apoptosis in mouse and human cells and inhibits colony growth of NIH3T3 cells. Expression of MK is p53-dependent and up-regulated by tumor suppressor p53 and by DNA damaging agents in mouse cells undergoing apoptosis. This is the first report describing a mouse TRAIL receptor gene and also demonstrating that the p53-dependent regulation of KILLER/DR5-mediated apoptosis is conserved between human and mouse. Cancer Res. 1999 Jun 15;59(12):2770-5.
- DR5 knockout mice are compromised in radiation-induced apoptosis.
- Finnberg N, Gruber JJ, Fei P, Rudolph D, Bric A, Kim SH, Burns TF, Ajuha H, Page R, Wu GS, Chen Y, McKenna WG, Bernhard E, Lowe S, Mak T, El-Deiry WS
- DR5 (also called TRAIL receptor 2 and KILLER) is an apoptosis-inducing membrane receptor for tumor necrosis factor-related apoptosis-inducing ligand (also called TRAIL and Apo2 ligand). DR5 is a transcriptional target of p53, and its overexpression induces cell death in vitro. However, the in vivo biology of DR5 has remained largely unexplored. To better understand the role of DR5 in development and in adult tissues, we have created a knockout mouse lacking DR5. This mouse is viable and develops normally with the exception of having an enlarged thymus. We show that DR5 is not expressed in developing embryos but is present in the decidua and chorion early in development. DR5-null mouse embryo fibroblasts expressing E1A are resistant to treatment with TRAIL, suggesting that DR5 may be the primary proapoptotic receptor for TRAIL in the mouse. When exposed to ionizing radiation, DR5-null tissues exhibit reduced amounts of apoptosis compared to wild-type thymus, spleen, Peyer's patches, and the white matter of the brain. In the ileum, colon, and stomach, DR5 deficiency was associated with a subtle phenotype of radiation-induced cell death. These results indicate that DR5 has a limited role during embryogenesis and early stages of development but plays an organ-specific role in the response to DNA-damaging stimuli. Mol Cell Biol. 2005 Mar;25(5):2000-13.
Structure & Sequence [+]
Pfam domains: (Pfam is a large collection of protein families.)
Protein sequence [+]
TRAIL-R3 / TNFSF10C | Homo sapiens | 9606 | length:299
View protein alignment and tree with Jalview:
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Homologs list [+]
|NGFR (2 of 2)||paralogy||Fugu|
|NGFR (2 of 2)||paralogy||Gasterosteus|
|NGFR (1 of 2)||paralogy||Gasterosteus|
|NGFR (1 of 2)||paralogy||Medaka|
|NGFR (2 of 2)||paralogy||Tetraodon|
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Gene Ontology [+]
|GO id||Name||Ontology type||Evidence|
|GO:0004888||transmembrane receptor activity||mollecular_function||TAS|
|GO:0005887||integral to plasma membrane||cell_component||TAS|
|GO:0031225||anchored to membrane||cell_component||IEA|
Check GO Evidence Codes here
KEGG Pathways [+]
Curated Isoforms [+]
Information from other databases [+]
- OMIM gene information: 603613
- OMIM disease information:
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