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Gene Review

HARS  -  histidyl-tRNA synthetase

Homo sapiens

Synonyms: HRS, HisRS, Histidine--tRNA ligase, cytoplasmic, Histidyl-tRNA synthetase, USH3B
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Disease relevance of HARS


Psychiatry related information on HARS

  • Concomitant psychopathology was monitored through the HARS and HDRS, and level of functioning through the GAS [6].
  • Furthermore, anxiety linked to the depressive syndrome decreased equally in both groups, as shown by the HARS measurements [7].
  • The clinical scales administered included the Hamilton Anxiety and Depression Rating Scale (HARS and HDRS), the Marks and Mathews Fears and Phobia Scale, Panic-Associated Symptom Scale (PASS), and a panic attack symptoms inventory [8].
  • Together, HARS and SHAS collect fairly comprehensive information of risk behaviors from persons with HIV infection and AIDS [9].

High impact information on HARS

  • Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity [10].
  • Prediction of the histidylation function of the new family of minimalist tRNA-like structures relates to the geometry of resected pseudoknots that allows proper presentation to histidyl-tRNA synthetase of analogues of the histidine identity determinants N-1 and N73 present in tRNAs [11].
  • We show here that anti-Jo-1 autoantibodies directed against histidyl-tRNA synthetase in the human autoimmune muscle disease polymyositis undergo, in addition to spectrotype broadening and class switching, the sine qua non of an immune response to the target antigen--affinity maturation to that antigen [12].
  • The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity [12].
  • Critical requirement for professional APCs in eliciting T cell responses to novel fragments of histidyl-tRNA synthetase (Jo-1) in Jo-1 antibody-positive polymyositis [13].

Chemical compound and disease context of HARS


Biological context of HARS


Anatomical context of HARS


Associations of HARS with chemical compounds

  • Triazolam-treated patients presented significantly more day-time-interdose anxiety than zopiclone as assessed by the weekly HARS and Clinical Global Assessment of Anxiety. Although daytime-interdose anxiety was observed with both drugs, this treatment emergent symptom was more frequent and severe with triazolam [23].
  • However, long-term treatment tended (P < 0.06) to increase basal plasma 5-HT concentrations, in covariation with decreases of MADRS (Montgomery-Asberg Depression Rating Scale) and HARS (Hamilton Anxiety Rating Scale) [24].
  • Oral treatment with 1800 mg pivagabine lasting 30 days showed in both groups a significant improvement of the psychic state with variations from 50 to 80% of the criteria reported in the Hamilton Rating Scale for Depression (HDRS) and for anxiety (HARS) and in the Self-rating Anxiety Scale (SAS) [25].
  • The subunit molecular weight of histidyl-tRNA synthetase is 50,000, as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate [26].
  • Indeed, the tsBN250 cell line had a single base change--guanine to adenine at the second position of the 362nd codon of hamster histidyl-tRNA-synthetase, converting arginine to histidine [27].

Regulatory relationships of HARS


Other interactions of HARS

  • In this report, we describe the genomic organization of the HARS/HARSL locus and map multiple transcripts originating from a bi-directional promoter controlling the differential expression of these genes [15].
  • The chromosomal gene (HRS) coding for hamster histidyl-tRNA synthetase, like many other housekeeping genes, lacks many of the features associated with promoters of RNA-polymerase-II-transcribed genes [28].
  • TFAM detects co-evolution of tRNA identity rules with lateral transfer of histidyl-tRNA synthetase [29].
  • Later, but not less than 1200 million years ago, the motif spread from histidyl-tRNA synthetase to the C and N terminals of glutamyl- and prolyl-tRNA synthetase, respectively, and then spread further during the evolution of the Chordate lineage to the N terminal of tryptophanyl-tRNA synthetase [30].
  • RESULTS: Using the histidyl tRNA synthetase (HtRNAS) gene as a housekeeping gene in the optimised multiplex RT-PCR, a significantly higher level of HERV-K10 gag mRNA expression was found in rheumatoid arthritis than in osteoarthritis (p = 0.01) or in the healthy controls (p = 0.02) [31].

Analytical, diagnostic and therapeutic context of HARS


  1. Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells. Howard, O.M., Dong, H.F., Yang, D., Raben, N., Nagaraju, K., Rosen, A., Casciola-Rosen, L., Härtlein, M., Kron, M., Yang, D., Yiadom, K., Dwivedi, S., Plotz, P.H., Oppenheim, J.J. J. Exp. Med. (2002) [Pubmed]
  2. Antiretroviral therapy and declining AIDS mortality in New York City. Wong, T., Chiasson, M.A., Reggy, A., Simonds, R.J., Heffess, J., Loo, V. Journal of urban health : bulletin of the New York Academy of Medicine. (2000) [Pubmed]
  3. Epitope studies indicate that histidyl-tRNA synthetase is a stimulating antigen in idiopathic myositis. Martin, A., Shulman, M.J., Tsui, F.W. FASEB J. (1995) [Pubmed]
  4. Proteobacterial histidine-biosynthetic pathways are paraphyletic. Bond, J.P., Francklyn, C. J. Mol. Evol. (2000) [Pubmed]
  5. Antiviral effect of the mammalian translation initiation factor 2alpha kinase GCN2 against RNA viruses. Berlanga, J.J., Ventoso, I., Harding, H.P., Deng, J., Ron, D., Sonenberg, N., Carrasco, L., de Haro, C. EMBO J. (2006) [Pubmed]
  6. Alcohol detoxification and social anxiety symptoms: a preliminary study of the impact of mirtazapine administration. Liappas, J., Paparrigopoulos, T., Tzavellas, E., Christodoulou, G. Journal of affective disorders. (2003) [Pubmed]
  7. The efficacy and safety of tianeptine in the treatment of depressive disorder: results of a controlled double-blind multicentre study vs. amitriptyline. Invernizzi, G., Aguglia, E., Bertolino, A., Casacchia, M., Ciani, N., Marchesi, G.F., Nardini, M., Rapisarda, V. Neuropsychobiology (1994) [Pubmed]
  8. Depersonalization in panic disorder: a clinical study. Seguí, J., Márquez, M., García, L., Canet, J., Salvador-Carulla, L., Ortiz, M. Comprehensive psychiatry. (2000) [Pubmed]
  9. HIV surveillance methods for the incarcerated population. Dean, H.D., Lansky, A., Fleming, P.L. AIDS education and prevention : official publication of the International Society for AIDS Education. (2002) [Pubmed]
  10. Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity. Mathews, M.B., Bernstein, R.M. Nature (1983) [Pubmed]
  11. Resected RNA pseudoknots and their recognition by histidyl-tRNA synthetase. Felden, B., Giegé, R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  12. The role of an autoantigen, histidyl-tRNA synthetase, in the induction and maintenance of autoimmunity. Miller, F.W., Waite, K.A., Biswas, T., Plotz, P.H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  13. Critical requirement for professional APCs in eliciting T cell responses to novel fragments of histidyl-tRNA synthetase (Jo-1) in Jo-1 antibody-positive polymyositis. Ascherman, D.P., Oriss, T.B., Oddis, C.V., Wright, T.M. J. Immunol. (2002) [Pubmed]
  14. Hepatorenal syndrome and its treatment today. Gentilini, P., La Villa, G., Casini-Raggi, V., Romanelli, R.G. European journal of gastroenterology & hepatology. (1999) [Pubmed]
  15. Genomic organization, transcriptional mapping, and evolutionary implications of the human bi-directional histidyl-tRNA synthetase locus (HARS/HARSL). O'Hanlon, T.P., Miller, F.W. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  16. Chromosomal localization of human gene for histidyl-tRNA synthetase: clustering of genes encoding aminoacyl-tRNA synthetases on human chromosome 5. Wasmuth, J.J., Carlock, L.R. Somat. Cell Mol. Genet. (1986) [Pubmed]
  17. Epitope mapping of the cloned human autoantigen, histidyl-tRNA synthetase. Analysis of the myositis-associated anti-Jo-1 autoimmune response. Ramsden, D.A., Chen, J., Miller, F.W., Misener, V., Bernstein, R.M., Siminovitch, K.A., Tsui, F.W. J. Immunol. (1989) [Pubmed]
  18. Localization of histidyl-tRNA synthetase (Jo-1) in human laryngeal epithelial carcinoma cell line (HEp-2 cells). Vázquez-Abad, D., Carson, J.H., Rothfield, N. Cell Tissue Res. (1996) [Pubmed]
  19. Facial atrophy in HIV-related fat redistribution syndrome: anatomic evaluation and surgical reconstruction. Talmor, M., Hoffman, L.A., LaTrenta, G.S. Annals of plastic surgery. (2002) [Pubmed]
  20. The influence of surgical stress on the psychoneuro-endocrine-immune axis. Dahanukar, S.A., Thatte, U.M., Deshmukh, U.D., Kulkarni, M.K., Bapat, R.D. Journal of postgraduate medicine. (1996) [Pubmed]
  21. An enzyme-linked immunosorbent assay for the detection and quantitation of anti-Jo-1 antibody in human serum. Biswas, T., Miller, F.W., Takagaki, Y., Plotz, P.H. J. Immunol. Methods (1987) [Pubmed]
  22. Presence of role of the 5SrRNA-L5 protein complex (5SRNP) in the threonyl- and histidyl-tRNA synthetase complex in rat liver cytosol. Ogata, K., Kurahashi, A., Nishiyama, C., Terao, K. Biochim. Biophys. Acta (1994) [Pubmed]
  23. Zopiclone and triazolam in insomnia associated with generalized anxiety disorder: a placebo-controlled evaluation of efficacy and daytime anxiety. Fontaine, R., Beaudry, P., Le Morvan, P., Beauclair, L., Chouinard, G. International clinical psychopharmacology. (1990) [Pubmed]
  24. Effects of the antidepressant drug tianeptine on plasma and platelet serotonin of depressive patients and healthy controls. Ortiz, J., Mariscot, C., Alvarez, E., Artigas, F. Journal of affective disorders. (1993) [Pubmed]
  25. Clinical evaluation of the efficacy of pivagabine in the treatment of mood and adjustment disorders. Terranova, R., Gilotta, S.M., Luca, S. Arzneimittel-Forschung. (1997) [Pubmed]
  26. Purification of mammalian histidyl-tRNA synthetase and its interaction with myositis-specific anti-Jo-1 antibodies. Fahoum, S.K., Yang, D.C. Biochemistry (1987) [Pubmed]
  27. A hamster temperature-sensitive G1 mutant, tsBN250 has a single point mutation in histidyl-tRNA synthetase that inhibits an accumulation of cyclin D1. Motomura, S., Fukushima, K., Nishitani, H., Nawata, H., Nishimoto, T. Genes Cells (1996) [Pubmed]
  28. Structural analysis of the 5' region of the chromosomal gene for hamster histidyl-tRNA synthetase. Tsui, F.W., Siminovitch, L. Gene (1987) [Pubmed]
  29. TFAM detects co-evolution of tRNA identity rules with lateral transfer of histidyl-tRNA synthetase. Ardell, D.H., Andersson, S.G. Nucleic Acids Res. (2006) [Pubmed]
  30. Intron positions delineate the evolutionary path of a pervasively appended peptide in five human aminoacyl-tRNA synthetases. Shiba, K. J. Mol. Evol. (2002) [Pubmed]
  31. The potential role of human endogenous retrovirus K10 in the pathogenesis of rheumatoid arthritis: a preliminary study. Ejtehadi, H.D., Freimanis, G.L., Ali, H.A., Bowman, S., Alavi, A., Axford, J., Callaghan, R., Nelson, P.N. Ann. Rheum. Dis. (2006) [Pubmed]
  32. Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex. Sang Lee, J., Gyu Park, S., Park, H., Seol, W., Lee, S., Kim, S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  33. Increasing trend of Cesarean deliveries in HIV-infected women in the United States from 1994 to 2000. Dominguez, K.L., Lindegren, M.L., D'Almada, P.J., Peters, V.B., Frederick, T., Rakusan, T.A., Ortiz, I.R., Hsu, H.W., Melville, S.K., Sadek, R., Fowler, M.G. J. Acquir. Immune Defic. Syndr. (2003) [Pubmed]
  34. Kleptomania: comorbid psychiatric diagnosis in patients and their families. Dannon, P.N., Lowengrub, K.M., Iancu, I., Kotler, M. Psychopathology. (2004) [Pubmed]
  35. Measurement of antibody to Jo-1 by ELISA and comparison to enzyme inhibitory activity. Targoff, I.N., Reichlin, M. J. Immunol. (1987) [Pubmed]
  36. Improved detection of anti-Jo-1 antibody, a marker for myositis, using purified histidyl-tRNA synthetase. Walker, E.J., Tymms, K.E., Webb, J., Jeffrey, P.D. J. Immunol. Methods (1987) [Pubmed]
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