TWEAK receptor | Tumour necrosis factor (TNF) receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

TWEAK receptor

Target id: 1884

Nomenclature: TWEAK receptor

Systematic Nomenclature: TNFRSF12A

Family: Tumour necrosis factor (TNF) receptor family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     TWEAK receptor has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - - TNFRSF12A TNF receptor superfamily member 12A
Mouse - - Tnfrsf12a tumor necrosis factor receptor superfamily, member 12a
Rat - - Tnfrsf12a TNF receptor superfamily member 12A
Previous and Unofficial Names
Fn14 | tumor necrosis factor receptor superfamily, member 12a | CD266 | FGF-inducible 14 | TweakR | tumor necrosis factor receptor superfamily, member 12A | tumor necrosis factor receptor superfamily
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
UniProtKB
Wikipedia
Adaptor proteins (Human)
TRAF1, TRAF2, TRAF3
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
TWEAK {Sp: Human} Hs - - -
Immunopharmacology Comments
The protein product of the TNFRSF12A gene (fibroblast growth factor-inducible 14, or TWEAK receptor) is a receptor for the endogenous ligand TNF-like weak inducer of apoptosis (TWEAK). TWEAK receptor expression is upregulated in response to tissue injury. TWEAK receptor activation results in modulation of expression of NF-κB-regulated genes associated with the resolution of tissue damage. Because of its proinflammatory signalling profile the TWEAK receptor/TWEAK system has been implicated in a number of pathologies, and is therefore considered a potential drug target for conditions including muscle atrophy, cerebral ischaemia [2], kidney injury, atherosclerosis and infarction, cancer, and autoimmune conditions such as autoimmune encephalitis, rheumatoid arthritis and inflammatory bowel disease [5]. An anti-TWEAK receptor monoclonal antibody (PDL192, enavatuzumab) has completed Phase 1 clinical trial (NCT00738764) in solid tumours [4] as a novel immuno-oncology therapeutic [1]. A TWEAK receptor targeting immunotoxin (PE38-P4A8, a fusion protein containing an anti-TWEAK receptor antibody scFv chain and the bacterial Pseudomonas exotoxin PE38) with anti-tumour activity has also been reported [3].
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0033209 tumor necrosis factor-mediated signaling pathway TAS

References

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1. Culp PA, Choi D, Zhang Y, Yin J, Seto P, Ybarra SE, Su M, Sho M, Steinle R, Wong MH et al.. (2010) Antibodies to TWEAK receptor inhibit human tumor growth through dual mechanisms. Clin. Cancer Res., 16 (2): 497-508. [PMID:20068083]

2. Haile WB, Echeverry R, Wu F, Guzman J, An J, Wu J, Yepes M. (2010) Tumor necrosis factor-like weak inducer of apoptosis and fibroblast growth factor-inducible 14 mediate cerebral ischemia-induced poly(ADP-ribose) polymerase-1 activation and neuronal death. Neuroscience, 171 (4): 1256-64. [PMID:20955770]

3. Keshtvarz M, Salimian J, Yaseri M, Bathaie SZ, Rezaie E, Aliramezani A, Norouzbabaei Z, Amani J, Douraghi M. (2017) Bioinformatic prediction and experimental validation of a PE38-based recombinant immunotoxin targeting the Fn14 receptor in cancer cells. Immunotherapy, 9 (5): 387-400. [PMID:28357912]

4. Purcell JW, Kim HK, Tanlimco SG, Doan M, Fox M, Lambert P, Chao DT, Sho M, Wilson KE, Starling GC et al.. (2014) Nuclear Factor κB is Required for Tumor Growth Inhibition Mediated by Enavatuzumab (PDL192), a Humanized Monoclonal Antibody to TweakR. Front Immunol, 4: 505. [PMID:24409185]

5. Xu WD, Zhao Y, Liu Y. (2016) Role of the TWEAK/Fn14 pathway in autoimmune diseases. Immunol. Res., 64 (1): 44-50. [PMID:26659091]

Contributors

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How to cite this page

David MacEwan.
Tumour necrosis factor (TNF) receptor family: TWEAK receptor. Last modified on 25/04/2017. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1884.