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Gene Review

WARS2  -  tryptophanyl tRNA synthetase 2, mitochondrial

Homo sapiens

Synonyms: (Mt)TrpRS, TrpRS, Tryptophan--tRNA ligase, mitochondrial, Tryptophanyl-tRNA synthetase
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Disease relevance of WARS2


High impact information on WARS2

  • A Minimal TrpRS Catalytic Domain Supports Sense/Antisense Ancestry of Class I and II Aminoacyl-tRNA Synthetases [4].
  • Until now the human cytoplasmic tryptophanyl-tRNA synthetase (hTrpRS) was thought to function as the h(mt)TrpRS, possibly in the form of a splice variant [5].
  • Tryptophanyl-tRNA synthetase (TrpRS) is an interferon-induced phosphoprotein with autoantigenic and cytokine activities detected in addition to its canonical function in tRNA aminoacylation [2].
  • Here it is shown that expression of cytoplasmic-TrpRS is inversely correlated with neurofibrillary degeneration, whereas a nonionic detergent-insoluble presumably aggregated TrpRS is simultaneously accumulated in human cells treated by tryptamine, a metabolic tryptophan analog that acts as a competitive inhibitor of TrpRS [3].
  • Tryptophan-dependent tRNAtrp aminoacylation catalyzed by TrpRS can be inhibited by its substrate tryptophan at physiological concentrations was demonstrated [3].

Biological context of WARS2


Other interactions of WARS2


Analytical, diagnostic and therapeutic context of WARS2

  • In immunoblotting, the 6C10 mAb reacts preferably with (i) oligomer than monomer, and (ii) bound than free TrpRS forms [2].
  • For epitope mapping of mAb 6C10, the affinity selected phage-displayed peptides were used as a database for prediction of conformational discontinuous epitopes within hTrpRS crystal structure [2].


  1. Interferons induce accumulation of diadenosine triphosphate (Ap3A) in human cultured cells. Vartanian, A., Narovlyansky, A., Amchenkova, A., Turpaev, K., Kisselev, L. FEBS Lett. (1996) [Pubmed]
  2. Mapping and molecular characterization of novel monoclonal antibodies to conformational epitopes on NH2 and COOH termini of mammalian tryptophanyl-tRNA synthetase reveal link of the epitopes to aggregation and Alzheimer's disease. Paley, E.L., Smelyanski, L., Malinovskii, V., Subbarayan, P.R., Berdichevsky, Y., Posternak, N., Gershoni, J.M., Sokolova, O., Denisova, G. Mol. Immunol. (2007) [Pubmed]
  3. Tryptamine Induces Tryptophanyl-tRNA Synthetase-Mediated Neurodegeneration With Neurofibrillary Tangles in Human Cell and Mouse Models. Paley, E.L., Denisova, G., Sokolova, O., Posternak, N., Wang, X., Brownell, A.L. Neuromolecular Med. (2007) [Pubmed]
  4. A Minimal TrpRS Catalytic Domain Supports Sense/Antisense Ancestry of Class I and II Aminoacyl-tRNA Synthetases. Pham, Y., Li, L., Kim, A., Erdogan, O., Weinreb, V., Butterfoss, G.L., Kuhlman, B., Carter, C.W. Mol. Cell (2007) [Pubmed]
  5. Identification and characterization of human mitochondrial tryptophanyl-tRNA synthetase. Jorgensen, R., Søgaard, T.M., Rossing, A.B., Martensen, P.M., Justesen, J. J. Biol. Chem. (2000) [Pubmed]
  6. A new gamma-interferon-inducible promoter and splice variants of an anti-angiogenic human tRNA synthetase. Liu, J., Shue, E., Ewalt, K.L., Schimmel, P. Nucleic Acids Res. (2004) [Pubmed]
  7. Assignment of the human mitochondrial tryptophanyl-tRNA synthetase (WARS2) to 1p13.3-->p13.1 by radiation hybrid mapping. Martinez-Dominguez, M.T., Justesen, J., Kruse, T.A., Hansen, L.L. Cytogenet. Cell Genet. (1998) [Pubmed]
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