TRAIL-R4, TNFRSF10D (Homo sapiens)
- Synonyms: TRAIL-R4, TNFRSF10D, TNFRSF10D, TRAIL-R4, DCR2, TRUNDD, CD264
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: (TNF-related apoptosis-inducing ligand receptor 4)(TRAIL receptor 4)(TRAIL-R4) Tumor necrosis factor receptor superfamily member 10D Precursor (Decoy receptor 2)(DcR2) (TRAIL receptor with a truncated death domain)(CD264 antigen) [Source:UniProtKB/Swiss-Prot;Acc:Q9UBN6]
- Family: Death receptor
- Process: apoptosis,
- Pathways: extrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Tnfrsf10b
- WIKI: TRAIL-R4, TNFRSF10D-H_sapiens
- A novel receptor for Apo2L/TRAIL contains a truncated death domain.
- Marsters SA, Sheridan JP, Pitti RM, Huang A, Skubatch M, Baldwin D, Yuan J, Gurney A, Goddard AD, Godowski P, Ashkenazi A
- Apo2 ligand (Apo2L , also called TRAIL for tumor necrosis factor (TNF)-related apoptosis-inducing ligand ) belongs to the TNF family and activates apoptosis in tumor cells. Three closely related receptors bind Apo2L: DR4 and DR5, which contain cytoplasmic death domains and signal apoptosis, and DcR1, a decoy receptor that lacks a cytoplasmic tail and inhibits Apo2L function [3-5]. By cross-hybridization with DcR1, we have identified a fourth Apo2L receptor, which contains a cytoplasmic region with a truncated death domain. We subsequently named this protein decoy receptor 2 (DcR2). The DcR2 gene mapped to human chromosome 8p21, as did the genes encoding DR4, DR5 and DcR1. A single DcR2 mRNA transcript showed a unique expression pattern in human tissues and was particularly abundant in fetal liver and adult testis. Upon overexpression, DcR2 did not activate apoptosis or nuclear factor-kappaB; however, it substantially reduced cellular sensitivity to Apo2L-induced apoptosis. These results suggest that DcR2 functions as an inhibitory Apo2L receptor. Curr Biol. 1997 Dec 1;7(12):1003-6.
- 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-R4, TNFRSF10D | Homo sapiens | 9606 | length:386
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Homologs list [+]
|TRAIL-R3 / TNFSF10C||paralogy||Human|
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Gene Ontology [+]
|GO id||Name||Ontology type||Evidence|
|GO:0004888||transmembrane receptor activity||mollecular_function||TAS|
|GO:0016021||integral to membrane||cell_component||IEA|
Check GO Evidence Codes here
KEGG Pathways [+]
Curated Isoforms [+]
Information from other databases [+]
- OMIM gene information: 603614
- OMIM disease information:
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