histidine trna ligase


Summary: An enzyme that activates histidine with its specific transfer RNA. EC

Top Publications

  1. Freist W, Verhey J, Rühlmann A, Gauss D, Arnez J. Histidyl-tRNA synthetase. Biol Chem. 1999;380:623-46 pubmed
    ..Successful attempts have been made to identify epitopes responsible for the complexation with such auto-antibodies. ..
  2. Chiu M, Mason T, Fink G. HTS1 encodes both the cytoplasmic and mitochondrial histidyl-tRNA synthetase of Saccharomyces cerevisiae: mutations alter the specificity of compartmentation. Genetics. 1992;132:987-1001 pubmed
    ..Taken together these studies show that the specificity of compartmentation of the Hts protein depends upon both the primary sequence and the concentration of the protein in the cell. ..
  3. Hawko S, Francklyn C. Covariation of a specificity-determining structural motif in an aminoacyl-tRNA synthetase and a tRNA identity element. Biochemistry. 2001;40:1930-6 pubmed
    ..The close interaction between enzyme loop and RNA sequence elements suggested by these experiments reflects a covariation between enzyme and tRNA that may have acted to preserve aminoacylation fidelity over evolutionary time. ..
  4. Bond J, Francklyn C. Proteobacterial histidine-biosynthetic pathways are paraphyletic. J Mol Evol. 2000;50:339-47 pubmed
    ..Our results suggest that horizontal gene transfer played an important role in the evolution of the regulation of histidine biosynthesis. ..
  5. Akashi K, Grandjean O, Small I. Potential dual targeting of an Arabidopsis archaebacterial-like histidyl-tRNA synthetase to mitochondria and chloroplasts. FEBS Lett. 1998;431:39-44 pubmed
    ..These observations suggest that the AtHisRS1 cDNA encodes both mitochondrial and chloroplast histidyl-tRNA synthetases. ..
  6. Natsoulis G, Hilger F, Fink G. The HTS1 gene encodes both the cytoplasmic and mitochondrial histidine tRNA synthetases of S. cerevisiae. Cell. 1986;46:235-43 pubmed
    ..These phenotypes can be explained if the longer message were to encode the mitochondrial synthetase and the shorter message were to encode the cytoplasmic histidine-tRNA synthetase. ..
  7. Yan W, Francklyn C. Cytosine 73 is a discriminator nucleotide in vivo for histidyl-tRNA in Escherichia coli. J Biol Chem. 1994;269:10022-7 pubmed
  8. Katsumata Y, Ridgway W, Oriss T, Gu X, Chin D, Wu Y, et al. Species-specific immune responses generated by histidyl-tRNA synthetase immunization are associated with muscle and lung inflammation. J Autoimmun. 2007;29:174-86 pubmed
    ..Corresponding to this self-reactivity, mice immunized with murine Jo-1 develop a striking combination of muscle and lung inflammation that replicates features of the human anti-synthetase syndrome. ..
  9. Connolly S, Rosen A, Musier Forsyth K, Francklyn C. G-1:C73 recognition by an arginine cluster in the active site of Escherichia coli histidyl-tRNA synthetase. Biochemistry. 2004;43:962-9 pubmed
    ..coli HisRS helps to further characterize the active site of this enzyme and improves our understanding of how the unique identity elements in the acceptor stem of tRNA(His) confer specificity. ..

More Information


  1. Guth E, Farris M, Bovee M, Francklyn C. Asymmetric amino acid activation by class II histidyl-tRNA synthetase from Escherichia coli. J Biol Chem. 2009;284:20753-62 pubmed publisher
    ..The results support an alternating site model for catalysis in HisRS that may prove to be common to other class II aminoacyl-tRNA synthetases. ..
  2. Augustine J, Francklyn C. Design of an active fragment of a class II aminoacyl-tRNA synthetase and its significance for synthetase evolution. Biochemistry. 1997;36:3473-82 pubmed
    ..The fusion of one or more accessory domains to a primordial catalytic domain may therefore have been a critical evolutionary step by which aminoacyl-tRNA synthetases acquired increased catalytic efficiency and substrate specificity. ..
  3. Huguet S, Sghiri R, Ballot E, Johanet C. [Analytic study of dot blotting for the detection of anti-Jo-1, anti-M2, anti-ribosomes and anti-LKM]. Ann Biol Clin (Paris). 2004;62:423-9 pubmed
    ..Results of this study are similar to those of Cyto-Dot HM010 for the three auto-antibodies already in use. Cyto-Dot 4 is a very good anti-LKM1 confirmation method as it is ID. ..
  4. Franzolini N, Quartuccio L, De Marchi G, De Vita S. [Efficacy of ab initio immunosuppressive therapy and steroid-sparing effect in interstitial lung disease associated with antisynthetase antibody syndrome]. Reumatismo. 2007;59:202-8 pubmed
    ..Efficacy and safety of the aforementioned immunosuppressive approach were observed in our series, avoiding prolonged high-dose steroid administration. ..
  5. Pestronk A. Inflammatory and immune myopathies: concepts in diagnosis and treatment. J Child Neurol. 2002;17:205 pubmed
  6. Qiu H, Hu C, Dong J, Hinnebusch A. Mutations that bypass tRNA binding activate the intrinsically defective kinase domain in GCN2. Genes Dev. 2002;16:1271-80 pubmed
    ..Our results imply a two-step activation mechanism involving distinct conformational changes in the PK domain. ..
  7. Späth M, Schröder M, Schlotter Weigel B, Walter M, Hautmann H, Leinsinger G, et al. The long-term outcome of anti-Jo-1-positive inflammatory myopathies. J Neurol. 2004;251:859-64 pubmed
    ..An interdisciplinary therapeutic approach is necessary for best possible results in these patients. ..
  8. Sood R, Porter A, Olsen D, Cavener D, Wek R. A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2alpha. Genetics. 2000;154:787-801 pubmed
    ..Together, our studies identify a new mammalian eIF-2alpha kinase, GCN2, that can mediate translational control. ..
  9. Bovee M, Yan W, Sproat B, Francklyn C. tRNA discrimination at the binding step by a class II aminoacyl-tRNA synthetase. Biochemistry. 1999;38:13725-35 pubmed
  10. Qiu X, Janson C, Blackburn M, Chhohan I, Hibbs M, Abdel Meguid S. Cooperative structural dynamics and a novel fidelity mechanism in histidyl-tRNA synthetases. Biochemistry. 1999;38:12296-304 pubmed
    ..A dynamic and cooperative active site is most likely necessary for the proper functioning of the histidyl-tRNA synthetase, and suggests a novel mechanism for improving charging fidelity. ..
  11. von Kempis J, Kalden P, Gutfleisch J, Grimbacher B, Krause T, Uhl M, et al. Diagnosis of idiopathic myositis: value of 99mtechnetium pyrophosphate muscle scintigraphy and magnetic resonance imaging in targeted muscle biopsy. Rheumatol Int. 1998;17:207-13 pubmed
    ..Treatment with corticosteroids prior to histologic diagnosis may abolish inflammatory infiltrations in affected muscle tissue...
  12. Liu H, Gauld J. Substrate-assisted catalysis in the aminoacyl transfer mechanism of histidyl-tRNA synthetase: a density functional theory study. J Phys Chem B. 2008;112:16874-82 pubmed publisher
    ..Comparisons of these three mechanisms and reasons for the differences in barriers are also provided. ..
  13. Ascherman D. Role of Jo-1 in the Immunopathogenesis of the Anti-synthetase Syndrome. Curr Rheumatol Rep. 2015;17:56 pubmed publisher
  14. Meng X, Shi J, Liu X, Chen J. Prokaryotic expression and preparation of polyantibody of human histydyl-tRNA synthetase related gene. J Huazhong Univ Sci Technolog Med Sci. 2004;24:535-6, 555 pubmed
    ..The rabbits were inoculated with purified products. High-titer polyantibody was successfully prepared. Highly-purified expression product and prepared polyantibody may provide a good basis for further study. ..
  15. Lin J, Zhong J. Proteomic studies on anti-tumor agent ansamitocin P-3 producer Actinosynnema pretiosum in response to ammonium and isobutanol. Bioprocess Biosyst Eng. 2017;40:1133-1139 pubmed publisher
    ..basic medium. Based on the 2-DE data, exogenous L-serine which could inhibit the PGDH activity was added to the cultures with isobutanol, and a lower AP-3 production was confirmed under 2.5 mM serine addition (24 or 48 h). ..
  16. Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S. Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex. Biochem Biophys Res Commun. 2002;291:158-64 pubmed
    ..These data suggest that a systematic interaction network may exist between mammalian ARSs and EF-1 subunits probably to enhance the efficiency of in vivo protein synthesis. ..
  17. Kimura B, Takahashi H, Hokimoto S, Tanaka Y, Fujii T. Induction of the histidine decarboxylase genes of Photobacterium damselae subsp. damselae (formally P. histaminum) at low pH. J Appl Microbiol. 2009;107:485-97 pubmed publisher
    ..This is the first report of cloning the histidine decarboxylase gene cluster in gram-negative bacteria. Also, these genes were induced under acidic conditions and in the presence of excess histidine. ..
  18. Kashiwabara K, Ota K. Rapidly progressive interstitial lung disease in a dermatomyositis patient with high levels of creatine phosphokinase, severe muscle symptoms and positive anti-Jo-1 antibody. Intern Med. 2002;41:584-8 pubmed
    ..However, if corticosteroid treatment is not effective, additional administration of cyclosporine in the early period of rapidly progressive ILD may rescue deteriorating cases. ..
  19. Kamei H. Intracellular localization of histidyl-tRNA synthetase/Jo-1 antigen in T24 cells and some other cells. J Autoimmun. 2004;22:201-10 pubmed
    ..These results indicate that HisRS would localize predominantly in the cytoplasm. The possible nuclear antigens other than HisRS that might be detected by anti-Jo-1 antisera are discussed. ..
  20. Banik S, Nandi N. Orientation and distance dependent chiral discrimination in the first step of the aminoacylation reaction: integrated molecular orbital and semi-empirical method (ONIOM) based calculation. Colloids Surf B Biointerfaces. 2009;74:468-76 pubmed publisher
    ..The study provides a molecular mechanism of the retention of biological homochirality. ..
  21. Ardell D, Andersson S. TFAM detects co-evolution of tRNA identity rules with lateral transfer of histidyl-tRNA synthetase. Nucleic Acids Res. 2006;34:893-904 pubmed
    ..Our results demonstrate that TFAM is an effective tool for the bioinformatics, comparative genomics and evolutionary study of tRNA identity. ..
  22. Englert M, Vargas Rodriguez O, Reynolds N, Wang Y, Soll D, Umehara T. A genomically modified Escherichia coli strain carrying an orthogonal E. coli histidyl-tRNA synthetase•tRNAHis pair. Biochim Biophys Acta Gen Subj. 2017;1861:3009-3015 pubmed publisher
    ..coli HisRS that should facilitate GCE in E. coli. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. ..
  23. Levine S, Raben N, Xie D, Askin F, Tuder R, Mullins M, et al. Novel conformation of histidyl-transfer RNA synthetase in the lung: the target tissue in Jo-1 autoantibody-associated myositis. Arthritis Rheum. 2007;56:2729-39 pubmed
    ..A proteolytically sensitive conformation of HisRS exists in the lung, the target tissue associated with this autoantibody response. We thus propose that autoimmunity to HisRS is initiated and propagated in the lung. ..
  24. Bergoin C, Bure M, Tavernier J, Lamblin C, Maurage C, Remy Jardin M, et al. [The anti-synthetase syndrome]. Rev Mal Respir. 2002;19:371-4 pubmed
    ..Immuno-suppressive treatment with cortico-steroids and cyclophosphamide lead to a symptomatic improvement, regression of the radiological changes and improvement in the measurements of pulmonary function. ..
  25. Kalogerakos T, Hountondji C, Berne P, Dukta S, Blanquet S. Modification of aminoacyl-tRNA synthetases with pyridoxal-5'-phosphate. Identification of the labeled amino acid residues. Biochimie. 1994;76:33-44 pubmed
    ..It is concluded that these residues participate to the binding sites of the phosphates of ATP on the studied synthetases. ..
  26. Polosa R, Di Mauro C, Spampinato B, Castelli L, D Amico G, Edwards C, et al. A patient with antihistidyl-tRNA synthetase positive polymyositis presenting as acute respiratory distress syndrome. J Clin Rheumatol. 2008;14:219-21 pubmed publisher
    ..One year after onset, PM has been maintained in remission with oral prednisone and azathioprine. This is the first report of a patient in whom ARDS was the presenting feature of anti-Jo-1 positive PM. ..
  27. Rosen A, Musier Forsyth K. Recognition of G-1:C73 atomic groups by Escherichia coli histidyl-tRNA synthetase. J Am Chem Soc. 2004;126:64-5 pubmed
    ..Additionally, the C73 and G-1 bases contain major groove exocyclic atomic groups that contribute to HisRS recognition. ..
  28. Baker J, Franklin D, Parker J. Sequence and characterization of the gcpE gene of Escherichia coli. FEMS Microbiol Lett. 1992;73:175-80 pubmed
    ..The probable transcription terminator of gcpE overlaps the hisS promoter. Haploid cells containing a disrupted gcpE could not be obtained, suggesting that the gcpE gene is essential. ..
  29. Chaudhary R, Winterø A, Fredholm M, Chowdhary B. FISH mapping of seven cDNA sequences in the pig. Chromosome Res. 1997;5:545-9 pubmed
    ..These localizations contribute to the transcript map in pig and are significant as comparative markers. Difficulties associated with the mapping of small sequences using FISH are discussed. ..
  30. Barbasso Helmers S, Englund P, Engstrom M, Ahlin E, Fathi M, Janciauskiene S, et al. Sera from anti-Jo-1-positive patients with polymyositis and interstitial lung disease induce expression of intercellular adhesion molecule 1 in human lung endothelial cells. Arthritis Rheum. 2009;60:2524-30 pubmed publisher
    ..The EC-activating factors are not the autoantibodies themselves, but might be systemic factors associated with these autoantibodies. ..
  31. Airas R. Differences in the magnesium dependences of the class I and class II aminoacyl-tRNA synthetases from Escherichia coli. Eur J Biochem. 1996;240:223-31 pubmed
    ..The binding of ATP to the E. aminoacyl-tRNA complex also speeds up the dissociation of the aminoacyl-tRNA from most of these enzymes. ..
  32. Martín M, Fernandez M, Linares D, Alvarez M. Sequencing, characterization and transcriptional analysis of the histidine decarboxylase operon of Lactobacillus buchneri. Microbiology. 2005;151:1219-28 pubmed
    ..buchneri). The expression of hisS depends on the histidine concentration of the growth medium, and it can be transcribed as monocistronic or hdcA-hdcB-hisS polycistronic mRNA. ..
  33. Zampieri S, Biral D, Adami N, Ghirardello A, Rampudda M, Tonello M, et al. Expression of myositis specific autoantigens during post-natal myogenesis. Neurol Res. 2008;30:145-8 pubmed publisher
  34. Tsui F, Siminovitch L. Isolation, structure and expression of mammalian genes for histidyl-tRNA synthetase. Nucleic Acids Res. 1987;15:3349-67 pubmed
    ..These studies provide the basis for future structural and functional analysis of the gene for HRS. In particular, it will be of interest to examine if different exons of HRS correlate to different domains of the HRS polypeptide. ..
  35. Sibilia J, Chatelus E, Meyer A, Gottenberg J, Sordet C, Goetz J. [How can we diagnose and better understand inflammatory myopathies? The usefulness of auto-antibodies]. Presse Med. 2010;39:1010-25 pubmed publisher
  36. Shi M, Tsui F, Rubin L. Cellular localization of the target structures recognized by the anti-Jo-1 antibody: immunofluorescence studies on cultured human myoblasts. J Rheumatol. 1991;18:252-8 pubmed
    ..Given the importance of aminoacyl tRNA synthetases such as HRS to intracellular protein assembly, intracytoplasmic binding and enzyme inhibition in vivo may potentially contribute to the pathogenesis of autoimmune muscle damage in PM. ..
  37. Meng X, Chen J, Yang Q, Wang S, Chao Y, Ying K, et al. Cloning and identification of a novel cDNA which may be associated with FKBP25. Biochem Genet. 2002;40:303-10 pubmed
    ..The gene encodes a putative protein with an unknown domain conserved in many species and is similar to bacterial histidyl-tRNA synthetase, and so it is named human histidyl-tRNA-synthetase-related gene. ..
  38. Merritt E, Arakaki T, Gillespie J, Larson E, Kelley A, Mueller N, et al. Crystal structures of trypanosomal histidyl-tRNA synthetase illuminate differences between eukaryotic and prokaryotic homologs. J Mol Biol. 2010;397:481-94 pubmed publisher
    ..The essentiality of the single HisRS gene in T. brucei is shown by a severe depression of parasite growth rate that results from even partial suppression of expression by RNA interference...
  39. Abbott J, Meyer Schuman R, Lupo V, Feely S, Mademan I, Oprescu S, et al. Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy. Hum Mutat. 2017;: pubmed publisher
    ..This article is protected by copyright. All rights reserved...
  40. Safka Brožková D, Deconinck T, Griffin L, Ferbert A, Haberlova J, Mazanec R, et al. Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies. Brain. 2015;138:2161-72 pubmed publisher
    ..This study demonstrates the role of HARS mutations in peripheral neuropathy and expands the genetic and clinical spectrum of aminoacyl-tRNA synthetase-related human disease. ..
  41. Raben N, Borriello F, Amin J, Horwitz R, Fraser D, Plotz P. Human histidyl-tRNA synthetase: recognition of amino acid signature regions in class 2a aminoacyl-tRNA synthetases. Nucleic Acids Res. 1992;20:1075-81 pubmed
  42. Mimori T, Imura Y, Nakashima R, Yoshifuji H. Autoantibodies in idiopathic inflammatory myopathy: an update on clinical and pathophysiological significance. Curr Opin Rheumatol. 2007;19:523-9 pubmed
    ..To understand the etiopathogenic mechanisms of the disease it is particularly important to elucidate the nature of target autoantigens recognized by these myositis-specific autoantibodies. ..
  43. Ogata K, Kurahashi A, Nishiyama C, Terao K. Presence of role of the 5SrRNA-L5 protein complex (5SRNP) in the threonyl- and histidyl-tRNA synthetase complex in rat liver cytosol. Biochim Biophys Acta. 1994;1218:388-400 pubmed
    ..This activity was inhibited by an antibody against protein L5, and the inhibition was reversed by addition of 5SRNP. These results indicate that 5SRNP plays a role as a positive effector of Thr-RS in the complex. ..
  44. Aberg A, Yaremchuk A, Tukalo M, Rasmussen B, Cusack S. Crystal structure analysis of the activation of histidine by Thermus thermophilus histidyl-tRNA synthetase. Biochemistry. 1997;36:3084-94 pubmed
    ..Arg-259 thus substitutes for the divalent cation observed in seryl-tRNA synthetase and plays a crucial catalytic role in the mechanism of histidine activation. ..
  45. Yaremchuk A, Tukalo M, Grøtli M, Cusack S. A succession of substrate induced conformational changes ensures the amino acid specificity of Thermus thermophilus prolyl-tRNA synthetase: comparison with histidyl-tRNA synthetase. J Mol Biol. 2001;309:989-1002 pubmed
    ..T. thermophilus prolyl-tRNA synthetase appears to be the second class II aminoacyl-tRNA synthetase, after HisRS, to use a positively charged amino acid instead of a divalent cation to catalyse the amino acid activation reaction. ..
  46. O Hanlon T, Raben N, Miller F. A novel gene oriented in a head-to-head configuration with the human histidyl-tRNA synthetase (HRS) gene encodes an mRNA that predicts a polypeptide homologous to HRS. Biochem Biophys Res Commun. 1995;210:556-66 pubmed
    ..RNA blot analysis revealed that HRS (2.0 kb) and HO3 (2.5 kb) exhibit distinct patterns of steady-state mRNA expression among multiple human tissues. ..
  47. Arnez J, Harris D, Mitschler A, Rees B, Francklyn C, Moras D. Crystal structure of histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate. EMBO J. 1995;14:4143-55 pubmed
    ..The modular domain organization of histidyl-tRNA synthetase reiterates a repeated theme in aaRS, and its structure should provide insight into the ability of certain aaRS to aminoacylate minihelices and other non-tRNA molecules. ..
  48. Katsuki Y, Hirakata M. [Immunologic tests: Anti-Jo-l antibody (anti-histidyl transfer RNA synthetase antibody)]. Nihon Rinsho. 2005;63 Suppl 7:505-7 pubmed
  49. Rühlmann A, Cramer F, Englisch U. Isolation and analysis of mutated histidyl-tRNA synthetases from Escherichia coli. Biochem Biophys Res Commun. 1997;237:192-201 pubmed
    ..The experiments shown identify a highly conserved N-terminal R/KG-patch in front of MOTIF 1 as well as R259 as vital for full enzymatic activity. ..
  50. Guth E, Connolly S, Bovee M, Francklyn C. A substrate-assisted concerted mechanism for aminoacylation by a class II aminoacyl-tRNA synthetase. Biochemistry. 2005;44:3785-94 pubmed
    ..These experiments support a substrate-assisted concerted mechanism for HisRS, a feature that may generalize to other aaRS, as well as the peptidyl transferase center. ..
  51. Tsai C, Tsai Y, Kuo H, Chou C. A woman with anti-histidyl-aminoacyl-tRNA synthetase (Jo-1 antibodies), myositis, hyperglycemia, interstitial lung disease, and morbilliform rashes. Rheumatol Int. 2005;25:156-7 pubmed
  52. Francklyn C, Schimmel P. Enzymatic aminoacylation of an eight-base-pair microhelix with histidine. Proc Natl Acad Sci U S A. 1990;87:8655-9 pubmed
    ..Alanine- and histidine-specific microhelices may resemble a system that arose early in the evolution of charging and coding. ..
  53. Warrington R. L-histidinol in experimental cancer chemotherapy: improving the selectivity and efficacy of anticancer drugs, eliminating metastatic disease and reversing the multidrug-resistant phenotype. Biochem Cell Biol. 1992;70:365-75 pubmed
    ..The establishment of a connection between the latter mechanism and the capacity to modulate anticancer drug action has resulted in a clinical trial in the treatment of human cancer...