TNFRSF10B (Mus musculus)
Description [+]
- Synonyms: TNFRSF10B, TNFRSF10B, TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 10B, DR5, KILLER, KILLER/DR5, LY98, TRAIL RECEPTOR, TRAIL-R2, TRAILR2, TRICK2A, TRICK2B, TRICKB
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Rodentia; Mus musculus
- Short gene description: Tumor necrosis factor receptor superfamily member 10B Precursor (Death receptor 5)(MK)(CD262 antigen) [Source:UniProtKB/Swiss-Prot;Acc:Q9QZM4]
- Family: Death receptor
- Process: apoptosis,
- Pathways: extrinsic pathway,
- Criteria: manually curated
- Curator comment: homolog of human TRAIL-R2
- WIKI: TNFRSF10B-M_musculus
References [+]
- 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.)
Source | Domain Name | Start | End |
---|---|---|---|
PFAM A | TNFR_c6 | 88 | 129 |
PFAM A | TNFR_c6 | 131 | 169 |
PFAM A | Death | 273 | 356 |
Protein sequence [+]
Tnfrsf10b | Mus musculus | 10090 | length:381
MEPPGPSTPTASAAARADHYTPGLRPLPKRRLLYSFALLLAVLQAVFVPVTANPAHNRPA
GLQRPEESPSRGPCLAGQYLSEGNCKPCREGIDYTSHSNHSLDSCILCTVCKEDKVVETR
CNITTNTVCRCKPGTFEDKDSPEICQSCSNCTDGEEELTSCTPRENRKCVSKTAWASWHK
LGLWIGLLVPVVLLIGALLVWKTGAWRQWLLCIKRGCERDPESANSVHSSLLDRQTSSTT
NDSNHNTEPGKTQKTGKKLLVPVNGNDSADDLKFIFEYCSDIVPFDSWNRLMRQLGLTDN
QIQMVKAETLVTREALYQMLLKWRHQTGRSASINHLLDALEAVEERDAMEKIEDYAVKSG
RFTYQNAAAQPETGPGGSQCV
GLQRPEESPSRGPCLAGQYLSEGNCKPCREGIDYTSHSNHSLDSCILCTVCKEDKVVETR
CNITTNTVCRCKPGTFEDKDSPEICQSCSNCTDGEEELTSCTPRENRKCVSKTAWASWHK
LGLWIGLLVPVVLLIGALLVWKTGAWRQWLLCIKRGCERDPESANSVHSSLLDRQTSSTT
NDSNHNTEPGKTQKTGKKLLVPVNGNDSADDLKFIFEYCSDIVPFDSWNRLMRQLGLTDN
QIQMVKAETLVTREALYQMLLKWRHQTGRSASINHLLDALEAVEERDAMEKIEDYAVKSG
RFTYQNAAAQPETGPGGSQCV
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:  
Explore tree at phylomeDB:   Click here.
Homologs list [+]
Name | Relationship | Species |
---|
DeathBase uses Jalview, an external application that requires Java. Please, check that you have the latest version of Java
installed and that Java is enabled in your browser. When correctly installed your browser should display the following examples properly. You can download the latest version of Java at Java Download Site.
Gene Ontology [+]
GO id | Name | Ontology type | Evidence |
---|---|---|---|
GO:0007165 | signal transduction | biological_proccess | IEA |
GO:0042981 | regulation of apoptosis | biological_proccess | RCA |
GO:0006915 | apoptosis | biological_proccess | RCA |
GO:0006955 | immune response | biological_proccess | IEA |
GO:0004872 | receptor activity | mollecular_function | IEA |
GO:0008656 | caspase activator activity | mollecular_function | RCA |
GO:0045569 | TRAIL binding | mollecular_function | RCA |
GO:0005515 | protein binding | mollecular_function | ISO |
GO:0004888 | transmembrane receptor activity | mollecular_function | IEA |
GO:0016020 | membrane | cell_component | IEA |
GO:0016021 | integral to membrane | cell_component | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Information from other databases [+]
- Gene info from MGI [?] MGI:1341090
- Ensembl genome browser [?] : ENSMUSG00000022074
- Expression info from Arrayexpress [?] : ENSMUSG00000022074
- Protein expression from Protein Atlas: [?] ENSMUSG00000022074
- Community gene edition from Wikigenes: [?] 21933
Click on [?] for more information.