Death receptor 6

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"DR6" redirects here. For the highway in the Dominican Republic, see DR-6. For the debug register, see DR6 register.
Protein TNFRSF21 PDB 2dbh.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases TNFRSF21, BM-018, CD358, DR6, tumor necrosis factor receptor superfamily member 21
External IDs MGI: 2151075 HomoloGene: 8696 GeneCards: 27242
Genetically Related Diseases
Disease Name References
panic disorder
RNA expression pattern
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More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 6: 47.23 – 47.31 Mb Chr 17: 43.02 – 43.09 Mb
PubMed search [2] [3]
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Death receptor 6 (DR6), also known as tumor necrosis factor receptor superfamily member 21 (TNFRSF21), is a cell surface receptor of the tumor necrosis factor receptor superfamily which activates the JNK and NF-κB pathways.[4][5] It is mostly expressed in the thymus, spleen and white blood cells.[6]


The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been shown to activate NF-κB and MAPK8/JNK, and induce cell apoptosis. Through its death domain, this receptor interacts with TRADD protein, which is known to serve as an adaptor that mediates signal transduction of TNF-receptors. Knockout studies in mice suggested that this gene plays a role in T helper cell activation, and may be involved in inflammation and immune regulation.[5]

Clinical significance[edit]

DR6 is also thought to be involved in neurodegeneration in the brain that causes Alzheimer's disease as well as signal transduction in stress response and cellular survival.[7] DR6 induces apoptosis when it is over expressed, however the manner in which the death signal is intracellularly transduced is currently unknown. It has been determined that Bax translocation is necessary for the apoptosis triggered by DR6, but through an unknown pathway instead of the traditional pathways of intrinsic versus extrinsic.[8] APP (amyloid precursor protein) is the natural ligand of DR6 and is first cleaved into and N-APP. N-APP is the fragment that interacts with DR6 to trigger axonal degradation in Alzheimer's patients.[9] This pathway is essentially "hi-jacked" in the aging brain.


  1. ^ "". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ Pan G, Bauer JH, Haridas V, Wang S, Liu D, Yu G, Vincenz C, Aggarwal BB, Ni J, Dixit VM (July 1998). "Identification and functional characterization of DR6, a novel death domain-containing TNF receptor". FEBS Lett. 431 (3): 351–356. doi:10.1016/S0014-5793(98)00791-1. PMID 9714541. 
  5. ^ a b "Entrez Gene: TNFRSF21 tumor necrosis factor receptor superfamily, member 21". 
  6. ^ Salido, Ginés María; Rosado, Juan Antonio (2009). Apoptosis: Involvement of Oxidative Stress and Intracellular Ca2+ Homeostasis. Heidelberg, Germany: Springer. p. 37. 
  7. ^ Kuester M, Kemmerzehl S, Dahms SO, Roeser D, Than ME (June 2011). "The crystal structure of death receptor 6 (DR6): a potential receptor of the amyloid precursor protein (APP)". J. Mol. Biol. 409 (2): 189–201. doi:10.1016/j.jmb.2011.03.048. PMID 21463639. 
  8. ^ Cetin F (2012). "Role of oxidative stress in Aβ animal model of Alzheimer's disease: Vicious circle of apoptosis, nitric oxide and age". INTECH. 
  9. ^ Osherovich L (2009). "Genentech's new parADigm". Science-Business eXchange. 2 (8): 1–5. doi:10.1038/scibx.2009.300. 

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.