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Gene Review

TNFRSF12A  -  tumor necrosis factor receptor superfamily...

Homo sapiens

Synonyms: CD266, FGF-inducible 14, FN14, Fibroblast growth factor-inducible immediate-early response protein 14, TWEAKR, ...
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Disease relevance of TNFRSF12A


High impact information on TNFRSF12A

  • Five different assays demonstrate TWEAK-TweakR binding, and the interaction affinity constant (Kd) is within a physiologically relevant range of 2.3 +/- 0.1 nM [1].
  • The mature form of TweakR has only one hundred and two amino acids and six cysteine residues in its extracellular region [1].
  • By generating mice deficient in the TWEAK receptor Fn14, we further showed that Fn14-deficient primary myoblasts displayed significantly reduced proliferative capacity and altered myotube formation [3].
  • The crystal structure of human fibronectin (FN) type III repeats 12-14 reveals the primary heparin-binding site, a clump of positively charged residues in FN13, and a putative minor site approximately 60 A away in FN14 [4].
  • Recently, fibroblast growth factor-inducible 14 (Fn14) has been identified to be a TWEAK receptor, which was responsible for TWEAK-induced proliferation of endothelial cells and angiogenesis [5].

Biological context of TNFRSF12A


Anatomical context of TNFRSF12A


Analytical, diagnostic and therapeutic context of TNFRSF12A


  1. A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. Wiley, S.R., Cassiano, L., Lofton, T., Davis-Smith, T., Winkles, J.A., Lindner, V., Liu, H., Daniel, T.O., Smith, C.A., Fanslow, W.C. Immunity (2001) [Pubmed]
  2. Tweak induces mammary epithelial branching morphogenesis. Michaelson, J.S., Cho, S., Browning, B., Zheng, T.S., Lincecum, J.M., Wang, M.Z., Hsu, Y.M., Burkly, L.C. Oncogene (2005) [Pubmed]
  3. TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration. Girgenrath, M., Weng, S., Kostek, C.A., Browning, B., Wang, M., Brown, S.A., Winkles, J.A., Michaelson, J.S., Allaire, N., Schneider, P., Scott, M.L., Hsu, Y.M., Yagita, H., Flavell, R.A., Miller, J.B., Burkly, L.C., Zheng, T.S. EMBO J. (2006) [Pubmed]
  4. Crystal structure of a heparin- and integrin-binding segment of human fibronectin. Sharma, A., Askari, J.A., Humphries, M.J., Jones, E.Y., Stuart, D.I. EMBO J. (1999) [Pubmed]
  5. Fibroblast growth factor-inducible 14 mediates multiple pathways of TWEAK-induced cell death. Nakayama, M., Ishidoh, K., Kojima, Y., Harada, N., Kominami, E., Okumura, K., Yagita, H. J. Immunol. (2003) [Pubmed]
  6. Role of TWEAK and Fn14 in tumor biology. Winkles, J.A., Tran, N.L., Brown, S.A., Stains, N., Cunliffe, H.E., Berens, M.E. Front. Biosci. (2007) [Pubmed]
  7. TWEAK mediates signal transduction and differentiation of RAW264.7 cells in the absence of Fn14/TweakR. Evidence for a second TWEAK receptor. Polek, T.C., Talpaz, M., Darnay, B.G., Spivak-Kroizman, T. J. Biol. Chem. (2003) [Pubmed]
  8. Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes. Jin, L., Nakao, A., Nakayama, M., Yamaguchi, N., Kojima, Y., Nakano, N., Tsuboi, R., Okumura, K., Yagita, H., Ogawa, H. J. Invest. Dermatol. (2004) [Pubmed]
  9. Proinflammatory effects of tumour necrosis factor-like weak inducer of apoptosis (TWEAK) on human gingival fibroblasts. Hosokawa, Y., Hosokawa, I., Ozaki, K., Nakae, H., Matsuo, T. Clin. Exp. Immunol. (2006) [Pubmed]
  10. TWEAK/Fn14 interaction stimulates human bronchial epithelial cells to produce IL-8 and GM-CSF. Xu, H., Okamoto, A., Ichikawa, J., Ando, T., Tasaka, K., Masuyama, K., Ogawa, H., Yagita, H., Okumura, K., Nakao, A. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  11. TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages. Kim, S.H., Kang, Y.J., Kim, W.J., Woo, D.K., Lee, Y., Kim, D.I., Park, Y.B., Kwon, B.S., Park, J.E., Lee, W.H. Circ. J. (2004) [Pubmed]
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