YARS2

Summary

Gene Symbol: YARS2
Description: tyrosyl-tRNA synthetase 2
Alias: CGI-04, MLASA2, MT-TYRRS, TYRRS, tyrosine--tRNA ligase, mitochondrial, tyrosine tRNA ligase 2, mitochondrial, tyrosyl-tRNA synthetase 2, mitochondrial
Species: human
Products:     YARS2

Top Publications

  1. Bonnefond L, Frugier M, Touzé E, Lorber B, Florentz C, Giege R, et al. Crystal structure of human mitochondrial tyrosyl-tRNA synthetase reveals common and idiosyncratic features. Structure. 2007;15:1505-16 pubmed
    We report the structure of a strictly mitochondrial human synthetase, namely tyrosyl-tRNA synthetase (mt-TyrRS), in complex with an adenylate analog at 2.2 A resolution...
  2. Bonnefond L, Fender A, Rudinger Thirion J, Giege R, Florentz C, Sissler M. Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS. Biochemistry. 2005;44:4805-16 pubmed
    ..Their sequence analysis confirms and further extends the view that, except for lysyl- and glycyl-tRNA synthetases, human mitochondrial and cytosolic enzymes are coded by two different sets of genes. ..
  3. Wei N, Zhang Q, Yang X. Neurodegenerative Charcot-Marie-Tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases. J Biol Chem. 2019;294:5321-5339 pubmed publisher
    ..With six currently known members (GlyRS, TyrRS, AlaRS, HisRS, TrpRS, and MetRS), aaRSs represent the largest protein family implicated in CMT etiology...
  4. Ravindranath Y, Johnson R, Goyette G, Buck S, Gadgeel M, Gallagher P. KLF1 E325K-associated Congenital Dyserythropoietic Anemia Type IV: Insights Into the Variable Clinical Severity. J Pediatr Hematol Oncol. 2018;40:e405-e409 pubmed publisher
    ..Hypomorphic alleles in SEC23B and YARS2 were also identified...
  5. Burrage L, Tang S, Wang J, Donti T, Walkiewicz M, Luchak J, et al. Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) plus associated with a novel de novo mutation (m.8969G>A) in the mitochondrial encoded ATP6 gene. Mol Genet Metab. 2014;113:207-12 pubmed publisher
    ..anemia (MLASA) is a rare mitochondrial disorder that has previously been associated with mutations in PUS1 and YARS2. In the present report, we describe a 6-year old male with an MLASA plus phenotype...
  6. Wei P, Zhuang B, Yu D, Sharipova A, Cai J, Huang L, et al. Cell-Free Expression of Unnatural Amino Acid Incorporated Aquaporin SS9 with Improved Separation Performance in Biomimetic Membranes. Biomed Res Int. 2018;2018:3560894 pubmed publisher
    ..P-AQP SS9) in vitro using a mutated Methanocaldococcus jannaschii tyrosyl-tRNA synthetase (TyrRS) and the cell-free expression system...
  7. Wei N, Shi Y, Truong L, Fisch K, Xu T, Gardiner E, et al. Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage. Mol Cell. 2014;56:323-32 pubmed publisher
    Tyrosyl-tRNA synthetase (TyrRS) is known for its essential aminoacylation function in protein synthesis. Here we report a function for TyrRS in DNA damage protection...
  8. Cheng G, Zhang H, Yang X, Tzima E, Ewalt K, Schimmel P, et al. Effect of mini-tyrosyl-tRNA synthetase on ischemic angiogenesis, leukocyte recruitment, and vascular permeability. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1138-46 pubmed publisher
    Mini-tyrosyl-tRNA synthetase (mini-TyrRS), the N-terminal domain of tyrosyl-tRNA synthetase, is a recently identified protein released by endothelial cells that exhibits angiogenic and leukocyte chemoattractant, ELR-motif (Glu-Leu-Arg)-..
  9. Sajish M, Schimmel P. A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. Nature. 2015;519:370-3 pubmed publisher
    ..Because human tyrosyl transfer-RNA (tRNA) synthetase (TyrRS) translocates to the nucleus under stress conditions, we considered the possibility that the tyrosine-like ..

More Information

Publications46

  1. Italia J, Latour C, Wrobel C, Chatterjee A. Resurrecting the Bacterial Tyrosyl-tRNA Synthetase/tRNA Pair for Expanding the Genetic Code of Both E. coli and Eukaryotes. Cell Chem Biol. 2018;25:1304-1312.e5 pubmed publisher
    The bacteria-derived tyrosyl-tRNA synthetase (TyrRS)/tRNA pair was first used for unnatural amino acid (Uaa) mutagenesis in eukaryotic cells over 15 years ago...
  2. Zhu N, Lin Y, Li D, Gao N, Liu C, You X, et al. Identification of an anti-TB compound targeting the tyrosyl-tRNA synthetase. J Antimicrob Chemother. 2015;70:2287-94 pubmed publisher
    Drug-resistant Mycobacterium tuberculosis poses a great threat to human health. Tyrosyl-tRNA synthetase (TyrRS) is one of the aminoacyl tRNA synthetases that catalyse the attachment of amino acids to their cognate tRNAs and are essential ..
  3. Schiefner A, Nästle L, Landgraf M, Reichert A, Skerra A. Structural Basis for the Specific Cotranslational Incorporation of p-Boronophenylalanine into Biosynthetic Proteins. Biochemistry. 2018;57:2597-2600 pubmed publisher
    ..We describe the crystal structure of an aaRS specific for Bpa, which had been engineered on the basis of the TyrRS from Methanocaldococcus jannaschii, in complex with both Bpa and AMP...
  4. Riley L, Heeney M, Rudinger Thirion J, Frugier M, Campagna D, Zhou R, et al. The phenotypic spectrum of germline YARS2 variants: from isolated sideroblastic anemia to mitochondrial myopathy, lactic acidosis and sideroblastic anemia 2. Haematologica. 2018;103:2008-2015 pubmed publisher
    ..variants have previously been described in patients with myopathy, lactic acidosis and sideroblastic anemia 2 (MLASA2)...
  5. Rybak M, Kovalenko O, Tukalo M. The Dual Role of the 2'-OH Group of A76 tRNATyr in the Prevention of d-tyrosine Mistranslation. J Mol Biol. 2018;430:2670-2676 pubmed publisher
    ..Tyrosyl-tRNA synthetase (TyrRS) does not have such editing properties, but it shares weak stereospecificity in recognition of d-/l-tyrosine (Tyr)...
  6. Datt M, Sharma A. Novel and unique domains in aminoacyl-tRNA synthetases from human fungal pathogens Aspergillus niger, Candida albicans and Cryptococcus neoformans. BMC Genomics. 2014;15:1069 pubmed publisher
    ..Several fungal aaRSs have unique domain appendages of unknown function e.g. A. niger AsxRS and C. neoformans TyrRS have additional domains that are absent from human homologs...
  7. Liu F, Wang X, Du L, Wang D, Zhu Y, Geng Z, et al. Effect of NaCl Treatments on Tyramine Biosynthesis of Enterococcus faecalis. J Food Prot. 2015;78:940-5 pubmed publisher
    ..Relative gene expression of four genes in the tyrosine decarboxylase locus, namely, tyrRS, tyrDC, tyrP, and nhaC, was evaluated at different incubation times...
  8. Fournier G, Alm E. Ancestral Reconstruction of a Pre-LUCA Aminoacyl-tRNA Synthetase Ancestor Supports the Late Addition of Trp to the Genetic Code. J Mol Evol. 2015;80:171-85 pubmed publisher
    ..We observe that, since TrpRS and TyrRS are paralogous protein families retaining significant sequence similarity, the inferred sequence composition of ..
  9. Wang X, Wei W, Wang P, Yi L, Shi W, Xie Y, et al. Synthesis, molecular docking and biological evaluation of 3-arylfuran-2(5H)-ones as anti-gastric ulcer agent. Bioorg Med Chem. 2015;23:4860-5 pubmed publisher
    3-Arylfuran-2(5H)-one derivatives show good antibacterial activity and were determined as tyrosyl-tRNA synthetase (TyrRS) inhibitors...
  10. Xiao Z, Wei W, Wang P, Shi W, Zhu N, Xie M, et al. Synthesis and evaluation of new tyrosyl-tRNA synthetase inhibitors as antibacterial agents based on a N2-(arylacetyl)glycinanilide scaffold. Eur J Med Chem. 2015;102:631-8 pubmed publisher
    Tyrosyl-tRNA synthetase (TyrRS), an essential enzyme in bacterial protein biosynthesis, is an attractive therapeutic target for finding novel antibacterial agents, and a series of N2-(arylacetyl)glycinanilides has been herein synthesized ..
  11. Wei Z, Xu Z, Liu X, Lo W, Ye F, Lau C, et al. Alternative splicing creates two new architectures for human tyrosyl-tRNA synthetase. Nucleic Acids Res. 2016;44:1247-55 pubmed publisher
    ..we report analysis of two closely related, internally deleted, SVs of homodimeric human tyrosyl-tRNA synthetase (TyrRS)...
  12. Deng H, Mi M. Resveratrol Attenuates A?25-35 Caused Neurotoxicity by Inducing Autophagy Through the TyrRS-PARP1-SIRT1 Signaling Pathway. Neurochem Res. 2016;41:2367-79 pubmed publisher
    ..of poly (ADP-ribose) polymerase 1 (PARP1), as well as tyrosyl transfer-RNA (tRNA) synthetase (TyrRS)...
  13. Cao X, Li C, Xiao S, Tang Y, Huang J, Zhao S, et al. Acetylation promotes TyrRS nuclear translocation to prevent oxidative damage. Proc Natl Acad Sci U S A. 2017;114:687-692 pubmed publisher
    Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential aminoacylation function in protein synthesis. Recently, TyrRS has been shown to translocate to the nucleus and protect against DNA damage due to oxidative stress...
  14. Richardson C, First E. Altering the Enantioselectivity of Tyrosyl-tRNA Synthetase by Insertion of a Stereospecific Editing Domain. Biochemistry. 2016;55:1541-53 pubmed publisher
    ..polypeptide 1 (CP1) domain of Geobacillus stearothermophilus tyrosyl-tRNA synthetase (henceforth designated TyrRS-FRSed)...
  15. Rauch B, Porter J, Mehl R, Perona J. Improved Incorporation of Noncanonical Amino Acids by an Engineered tRNA(Tyr) Suppressor. Biochemistry. 2016;55:618-28 pubmed publisher
    The Methanocaldcoccus jannaschii tyrosyl-tRNA synthetase (TyrRS):tRNA(Tyr) cognate pair has been used to incorporate a large number of noncanonical amino acids (ncAAs) into recombinant proteins in Escherichia coli...
  16. Casas Tintó S, Lolo F, Moreno E. Active JNK-dependent secretion of Drosophila Tyrosyl-tRNA synthetase by loser cells recruits haemocytes during cell competition. Nat Commun. 2015;6:10022 pubmed publisher
    ..Here we show that apoptotic loser cells secrete Tyrosyl-tRNA synthetase (TyrRS), which is best known as a core component of the translational machinery...
  17. Hu J, Tian J, Li F, Xue B, Hu J, Cheng X, et al. Clone and functional analysis of Seryl-tRNA synthetase and Tyrosyl-tRNA synthetase from silkworm, Bombyx mori. Sci Rep. 2017;7:41563 pubmed publisher
    ..In this study, the seryl-tRNA synthetase (SerRS) and tyrosyl-tRNA synthetase (TyrRS) genes from silkworm were cloned...
  18. Gómez Ramos L, Smeekens J, Kovacs N, Bowman J, Wartell R, Wu R, et al. Yeast rRNA Expansion Segments: Folding and Function. J Mol Biol. 2016;428:4048-4059 pubmed publisher
    ..Seven synthetases, Ala-, Arg-, Asp-, Asn-, Leu-, Lys- and TyrRS, appear to associate with ES7...
  19. Druart K, Guennec M, Palmai Z, Simonson T. Probing the stereospecificity of tyrosyl- and glutaminyl-tRNA synthetase with molecular dynamics. J Mol Graph Model. 2017;71:192-199 pubmed publisher
    ..dynamics simulations to probe the stereospecificity of the class I tyrosyl- and glutaminyl-tRNA synthetases (TyrRS, GlnRS), including wildtype enzymes and three point mutants suggested by three different protein design methods...
  20. Tsukahara T, Yamagishi S, Neyama H, Ueda H. Tyrosyl-tRNA synthetase: A potential kyotorphin synthetase in mammals. Peptides. 2018;101:60-68 pubmed publisher
    ..However, the latter has never been identified. We aimed to test the hypothesis that tyrosyl-tRNA synthetase (TyrRS) is also KTP synthetase...
  21. Käser S, Glauser I, Rettig J, Schneider A. The pseudo-dimeric tyrosyl-tRNA synthetase of T. brucei aminoacylates cytosolic and mitochondrial tRNATyr and requires both monomeric units for activity. Mol Biochem Parasitol. 2018;221:52-55 pubmed publisher
    Aminoacyl-tRNA synthetases are essential for protein synthesis. The single-copy tyrosyl-tRNA synthetase (Tb-TyrRS) of T. brucei has an unusual structure and forms a pseudo-dimer...
  22. Chen L, Wang P, Tang D, Tao X, Man R, Qiu H, et al. Metronidazole containing pyrazole derivatives potently inhibit tyrosyl-tRNA synthetase: design, synthesis, and biological evaluation. Chem Biol Drug Des. 2016;88:592-8 pubmed publisher
    As an important enzyme in bacterial protein biosynthesis, tyrosyl-tRNA synthetase (TyrRS) has been an absorbing therapeutic target for exploring novel antibacterial agents...
  23. Wei W, Liu Q, Li Z, Shi W, Fu X, Liu J, et al. Synthesis and evaluation of adenosine containing 3-arylfuran-2(5H)-ones as tyrosyl-tRNA synthetase inhibitors. Eur J Med Chem. 2017;133:62-68 pubmed publisher
    Tyrosyl-tRNA synthetase (TyrRS) is an aminoacyl-tRNA synthetase family protein that possesses an essential role in bacterial protein synthesis...
  24. Blocquel D, Li S, Wei N, Daub H, Sajish M, Erfurth M, et al. Alternative stable conformation capable of protein misinteraction links tRNA synthetase to peripheral neuropathy. Nucleic Acids Res. 2017;45:8091-8104 pubmed publisher
    ..Here, we study the structural effect of three CMT-causing mutations in tyrosyl-tRNA synthetase (TyrRS or YARS)...
  25. Paukstelis P, Chari N, Lambowitz A, Hoffman D. NMR Structure of the C-terminal domain of a tyrosyl-tRNA synthetase that functions in group I intron splicing. Biochemistry. 2011;50:3816-26 pubmed publisher
    ..Here, we determined an NMR structure of the isolated C-terminal domain of the Aspergillus nidulans mt TyrRS, which is closely related to but smaller than CYT-18's...
  26. Baumann T, Exner M, Budisa N. Orthogonal Protein Translation Using Pyrrolysyl-tRNA Synthetases for Single- and Multiple-Noncanonical Amino Acid Mutagenesis. Adv Biochem Eng Biotechnol. 2018;162:1-19 pubmed publisher
    ..noncanonical amino acid (ncAA) incorporation via orthogonal translation are based on the Methanococcus jannaschii TyrRS/tRNA CUATyr and the Methanosarcina barkeri/Methanosarcina mazei PylRS/tRNA CUA<..
  27. Mukai T, Reynolds N, Crnkovic A, Soll D. Bioinformatic Analysis Reveals Archaeal tRNATyr and tRNATrp Identities in Bacteria. Life (Basel). 2017;7: pubmed publisher
    ..These bacteria possess genes for tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase (TrpRS) predicted to be derived from DPANN superphylum archaea, while the ..
  28. Guo Z, Yin Y, Wang C, Wang P, Zhang X, Wang Z, et al. Design, synthesis and molecular docking of salicylic acid derivatives containing metronidazole as a new class of antimicrobial agents. Bioorg Med Chem. 2015;23:6148-56 pubmed publisher
    ..of novel salicylic acid derivatives containing metronidazole as Staphylococcus aureus Tyrosyl-tRNA synthetase (TyrRS) inhibitors have been synthesized and evaluated their biology activities as potential antibacterial agents...
  29. Kunjapur A, Stork D, Kuru E, Vargas Rodriguez O, Landon M, Soll D, et al. Engineering posttranslational proofreading to discriminate nonstandard amino acids. Proc Natl Acad Sci U S A. 2018;115:619-624 pubmed publisher
    ..proofreading system to further evolve a Methanocaldococcus jannaschii tyrosyl-tRNA synthetase (TyrRS) variant and a tRNATyr species for improved specificity of the nsAA biphenylalanine in vitro and in ..
  30. Sommerville E, Ng Y, Alston C, Dallabona C, Gilberti M, He L, et al. Clinical Features, Molecular Heterogeneity, and Prognostic Implications in YARS2-Related Mitochondrial Myopathy. JAMA Neurol. 2017;74:686-694 pubmed publisher
    b>YARS2 mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations...
  31. Riley L, Menezes M, Rudinger Thirion J, Duff R, de Lonlay P, Rotig A, et al. Phenotypic variability and identification of novel YARS2 mutations in YARS2 mitochondrial myopathy, lactic acidosis and sideroblastic anaemia. Orphanet J Rare Dis. 2013;8:193 pubmed publisher
    Mutations in the mitochondrial tyrosyl-tRNA synthetase (YARS2) gene have previously been identified as a cause of the tissue specific mitochondrial respiratory chain (RC) disorder, Myopathy, Lactic Acidosis, Sideroblastic Anaemia (MLASA)...
  32. Richardson C, First E. Hyperactive Editing Domain Variants Switch the Stereospecificity of Tyrosyl-tRNA Synthetase. Biochemistry. 2016;55:2526-37 pubmed publisher
    ..We previously altered the enantioselectivity of tyrosyl-tRNA synthetase (TyrRS) by inserting the editing domain from phenylalanyl-tRNA synthetase (FRSed) between Gly 161 and Ile 162 in tyrosyl-..
  33. Sasarman F, Nishimura T, Thiffault I, Shoubridge E. A novel mutation in YARS2 causes myopathy with lactic acidosis and sideroblastic anemia. Hum Mutat. 2012;33:1201-6 pubmed publisher
    ..Here, we report a novel missense mutation (c.137G>A, p.Gly46Asp) in the catalytic domain of YARS2, which codes for the mitochondrial tyrosyl-tRNA synthetase, in a subject with myopathy, lactic acidosis, and ..
  34. Riley L, Cooper S, Hickey P, Rudinger Thirion J, McKenzie M, Compton A, et al. Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome. Am J Hum Genet. 2010;87:52-9 pubmed publisher
    ..We have identified a pathogenic mutation (c.156C>G [p.F52L]) in YARS2, located at chromosome 12p11...
  35. Bonnefond L, Frugier M, Giege R, Rudinger Thirion J. Human mitochondrial TyrRS disobeys the tyrosine identity rules. RNA. 2005;11:558-62 pubmed
    Human tyrosyl-tRNA synthetase from mitochondria (mt-TyrRS) presents dual sequence features characteristic of eubacterial and archaeal TyrRSs, especially in the region containing amino acids recognizing the N1-N72 tyrosine identity pair...
  36. Lolo F, Rius C, Casas Tinto S. Elimination of classically-activated macrophages in tumor-conditioned medium by alternatively-activated macrophages. Biol Open. 2017;6:1897-1903 pubmed publisher
    ..M1 macrophages in tumoral medium upregulated markers of a suboptimal condition, such as Sparc and TyrRS, and undergo apoptosis...
  37. Jiang P, Jin X, Peng Y, Wang M, Liu H, Liu X, et al. The exome sequencing identified the mutation in YARS2 encoding the mitochondrial tyrosyl-tRNA synthetase as a nuclear modifier for the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation. Hum Mol Genet. 2016;25:584-96 pubmed publisher
    ..572G>T, p.191Gly>Val) in YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase, which interacts with m...