TWEAK receptor

Immunopharmacology Ligand Target has curated data in GtoImmuPdb

Target id: 1884

Nomenclature: TWEAK receptor

Systematic Nomenclature: TNFRSF12A

Family: Tumour necrosis factor (TNF) receptor family

Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	1	129	16p13.3	TNFRSF12A	TNF receptor superfamily member 12A
Mouse	1	129	17 A3.3	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
Alphafold	Q9NP84 (Hs), Q9CR75 (Mm)
ChEMBL Target	CHEMBL3712850 (Hs)
Ensembl Gene	ENSG00000006327 (Hs), ENSMUSG00000023905 (Mm), ENSRNOG00000003546 (Rn)
Entrez Gene	51330 (Hs), 27279 (Mm), 302965 (Rn)
Human Protein Atlas	ENSG00000006327 (Hs)
KEGG Gene	hsa:51330 (Hs), mmu:27279 (Mm), rno:302965 (Rn)
OMIM	605914 (Hs)
Pharos	Q9NP84 (Hs)
UniProtKB	Q9NP84 (Hs), Q9CR75 (Mm)
Wikipedia	TNFRSF12A (Hs)

Natural/Endogenous Ligands
TWEAK {Sp: Human}

Adaptor proteins (Human)
TRAF1, TRAF2, TRAF3

Adaptor proteins (Human)

TRAF1, TRAF2, TRAF3

Other Binding Ligands

Key to terms and symbols

Click column headers to sort

Ligand											Sp.	Action	Value	Parameter	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].

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

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]