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. 1991 Sep 15;278(Pt 3):809–816. doi: 10.1042/bj2780809

Evidence that gene G7a in the human major histocompatibility complex encodes valyl-tRNA synthetase.

S L Hsieh 1, R D Campbell 1
PMCID: PMC1151418  PMID: 1898367

Abstract

At least 36 genes have now been located in a 680 kb segment of DNA between the class I and class II multigene families within the class III region of the human major histocompatibility complex on chromosome 6p21.3. The complete nucleotide sequence of the 4.3 kb mRNA of one of these genes, G7a (or BAT6), has been determined from cDNA and genomic clones. The single-copy G7a gene encodes a 1265-amino-acid protein of molecular mass 140,457 Da. Comparison of the derived amino acid sequence of the G7a protein with the National Biomedical Research Foundation protein databases revealed 42% identity in a 250-amino-acid overlap with Bacillus stearothermophilus valyl-tRNA synthetase, 38.0% identity in a 993-amino-acid overlap with Escherichia coli valyl-tRNA synthetase (val RS), and 48.3% identity in a 1043-amino-acid overlap with Saccharomyces cerevisiae valyl-tRNA synthetase. The protein sequence of G7a contains two short consensus sequences, His-Ile-Gly-His and Lys-Met-Ser-Lys-Ser, which is the typical signature structure of class I tRNA synthetases and indicative of the presence of the Rossman fold. In addition, the molecular mass of the G7a protein is the same as that of other mammalian valyl-tRNA synthetases. These features and the high sequence identity with yeast valyl-tRNA synthetase strongly support the fact that the G7a gene, located within the major histocompatibility complex, encodes the human valyl-tRNA synthetase.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akins R. A., Lambowitz A. M. A protein required for splicing group I introns in Neurospora mitochondria is mitochondrial tyrosyl-tRNA synthetase or a derivative thereof. Cell. 1987 Jul 31;50(3):331–345. doi: 10.1016/0092-8674(87)90488-0. [DOI] [PubMed] [Google Scholar]
  2. Bec G., Kerjan P., Zha X. D., Waller J. P. Valyl-tRNA synthetase from rabbit liver. I. Purification as a heterotypic complex in association with elongation factor 1. J Biol Chem. 1989 Dec 15;264(35):21131–21137. [PubMed] [Google Scholar]
  3. Bec G., Waller J. P. Valyl-tRNA synthetase from rabbit liver. II. The enzyme derived from the high-Mr complex displays hydrophobic as well as polyanion-binding properties. J Biol Chem. 1989 Dec 15;264(35):21138–21143. [PubMed] [Google Scholar]
  4. Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
  5. Carroll M. C., Campbell R. D., Bentley D. R., Porter R. R. A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature. 1984 Jan 19;307(5948):237–241. doi: 10.1038/307237a0. [DOI] [PubMed] [Google Scholar]
  6. Carroll M. C., Campbell R. D., Porter R. R. Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man. Proc Natl Acad Sci U S A. 1985 Jan;82(2):521–525. doi: 10.1073/pnas.82.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carroll M. C., Katzman P., Alicot E. M., Koller B. H., Geraghty D. E., Orr H. T., Strominger J. L., Spies T. Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8535–8539. doi: 10.1073/pnas.84.23.8535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cherniack A. D., Garriga G., Kittle J. D., Jr, Akins R. A., Lambowitz A. M. Function of Neurospora mitochondrial tyrosyl-tRNA synthetase in RNA splicing requires an idiosyncratic domain not found in other synthetases. Cell. 1990 Aug 24;62(4):745–755. doi: 10.1016/0092-8674(90)90119-y. [DOI] [PubMed] [Google Scholar]
  9. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  10. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  11. Dunham I., Sargent C. A., Kendall E., Campbell R. D. Characterization of the class III region in different MHC haplotypes by pulsed-field gel electrophoresis. Immunogenetics. 1990;32(3):175–182. doi: 10.1007/BF02114970. [DOI] [PubMed] [Google Scholar]
  12. Dunham I., Sargent C. A., Kendall E., Campbell R. D. Characterization of the class III region in different MHC haplotypes by pulsed-field gel electrophoresis. Immunogenetics. 1990;32(3):175–182. doi: 10.1007/BF02114970. [DOI] [PubMed] [Google Scholar]
  13. Dunham I., Sargent C. A., Trowsdale J., Campbell R. D. Molecular mapping of the human major histocompatibility complex by pulsed-field gel electrophoresis. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7237–7241. doi: 10.1073/pnas.84.20.7237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Eisenberg D., Schwarz E., Komaromy M., Wall R. Analysis of membrane and surface protein sequences with the hydrophobic moment plot. J Mol Biol. 1984 Oct 15;179(1):125–142. doi: 10.1016/0022-2836(84)90309-7. [DOI] [PubMed] [Google Scholar]
  15. Eriani G., Delarue M., Poch O., Gangloff J., Moras D. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature. 1990 Sep 13;347(6289):203–206. doi: 10.1038/347203a0. [DOI] [PubMed] [Google Scholar]
  16. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  17. Gardiner-Garden M., Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261–282. doi: 10.1016/0022-2836(87)90689-9. [DOI] [PubMed] [Google Scholar]
  18. Heck J. D., Hatfield G. W. Valyl-tRNA synthetase gene of Escherichia coli K12. Primary structure and homology within a family of aminoacyl-TRNA synthetases. J Biol Chem. 1988 Jan 15;263(2):868–877. [PubMed] [Google Scholar]
  19. Herbert C. J., Labouesse M., Dujardin G., Slonimski P. P. The NAM2 proteins from S. cerevisiae and S. douglasii are mitochondrial leucyl-tRNA synthetases, and are involved in mRNA splicing. EMBO J. 1988 Feb;7(2):473–483. doi: 10.1002/j.1460-2075.1988.tb02835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jacobo-Molina A., Peterson R., Yang D. C. cDNA sequence, predicted primary structure, and evolving amphiphilic helix of human aspartyl-tRNA synthetase. J Biol Chem. 1989 Oct 5;264(28):16608–16612. [PubMed] [Google Scholar]
  21. Jordana X., Chatton B., Paz-Weisshaar M., Buhler J. M., Cramer F., Ebel J. P., Fasiolo F. Structure of the yeast valyl-tRNA synthetase gene (VASI) and the homology of its translated amino acid sequence with Escherichia coli isoleucyl-tRNA synthetase. J Biol Chem. 1987 May 25;262(15):7189–7194. [PubMed] [Google Scholar]
  22. Kellermann O., Tonetti H., Brevet A., Mirande M., Pailliez J. P., Waller J. P. Macromolecular complexes from sheep and rabbit containing seven aminoacyl-tRNA synthetases. I. Species specificity of the polypeptide composition. J Biol Chem. 1982 Sep 25;257(18):11041–11048. [PubMed] [Google Scholar]
  23. Kendall E., Sargent C. A., Campbell R. D. Human major histocompatibility complex contains a new cluster of genes between the HLA-D and complement C4 loci. Nucleic Acids Res. 1990 Dec 25;18(24):7251–7257. doi: 10.1093/nar/18.24.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kontis K. J., Arfin S. M. Isolation of a cDNA clone for human threonyl-tRNA synthetase: amplification of the structural gene in borrelidin-resistant cell lines. Mol Cell Biol. 1989 May;9(5):1832–1838. doi: 10.1128/mcb.9.5.1832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Myers A. M., Pape L. K., Tzagoloff A. Mitochondrial protein synthesis is required for maintenance of intact mitochondrial genomes in Saccharomyces cerevisiae. EMBO J. 1985 Aug;4(8):2087–2092. doi: 10.1002/j.1460-2075.1985.tb03896.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Natsoulis G., Hilger F., Fink G. R. The HTS1 gene encodes both the cytoplasmic and mitochondrial histidine tRNA synthetases of S. cerevisiae. Cell. 1986 Jul 18;46(2):235–243. doi: 10.1016/0092-8674(86)90740-3. [DOI] [PubMed] [Google Scholar]
  29. Pape L. K., Koerner T. J., Tzagoloff A. Characterization of a yeast nuclear gene (MST1) coding for the mitochondrial threonyl-tRNA1 synthetase. J Biol Chem. 1985 Dec 5;260(28):15362–15370. [PubMed] [Google Scholar]
  30. Pape L. K., Tzagoloff A. Cloning and characterization of the gene for the yeast cytoplasmic threonyl-tRNA synthetase. Nucleic Acids Res. 1985 Sep 11;13(17):6171–6183. doi: 10.1093/nar/13.17.6171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ragoussis J., Monaco A., Mockridge I., Kendall E., Campbell R. D., Trowsdale J. Cloning of the HLA class II region in yeast artificial chromosomes. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3753–3757. doi: 10.1073/pnas.88.9.3753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sargent C. A., Dunham I., Campbell R. D. Identification of multiple HTF-island associated genes in the human major histocompatibility complex class III region. EMBO J. 1989 Aug;8(8):2305–2312. doi: 10.1002/j.1460-2075.1989.tb08357.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schimmel P. R., Söll D. Aminoacyl-tRNA synthetases: general features and recognition of transfer RNAs. Annu Rev Biochem. 1979;48:601–648. doi: 10.1146/annurev.bi.48.070179.003125. [DOI] [PubMed] [Google Scholar]
  35. Schimmel P. Alanine transfer RNA synthetase: structure-function relationships and molecular recognition of transfer RNA. Adv Enzymol Relat Areas Mol Biol. 1990;63:233–270. doi: 10.1002/9780470123096.ch4. [DOI] [PubMed] [Google Scholar]
  36. Schimmel P. Aminoacyl tRNA synthetases: general scheme of structure-function relationships in the polypeptides and recognition of transfer RNAs. Annu Rev Biochem. 1987;56:125–158. doi: 10.1146/annurev.bi.56.070187.001013. [DOI] [PubMed] [Google Scholar]
  37. Seed B. An LFA-3 cDNA encodes a phospholipid-linked membrane protein homologous to its receptor CD2. 1987 Oct 29-Nov 4Nature. 329(6142):840–842. doi: 10.1038/329840a0. [DOI] [PubMed] [Google Scholar]
  38. Simmons D., Seed B. Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid progenitor cells. J Immunol. 1988 Oct 15;141(8):2797–2800. [PubMed] [Google Scholar]
  39. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  40. Spies T., Bresnahan M., Bahram S., Arnold D., Blanck G., Mellins E., Pious D., DeMars R. A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature. 1990 Dec 20;348(6303):744–747. doi: 10.1038/348744a0. [DOI] [PubMed] [Google Scholar]
  41. Spies T., Bresnahan M., Strominger J. L. Human major histocompatibility complex contains a minimum of 19 genes between the complement cluster and HLA-B. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8955–8958. doi: 10.1073/pnas.86.22.8955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Spies T., Morton C. C., Nedospasov S. A., Fiers W., Pious D., Strominger J. L. Genes for the tumor necrosis factors alpha and beta are linked to the human major histocompatibility complex. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8699–8702. doi: 10.1073/pnas.83.22.8699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Staden R. The current status and portability of our sequence handling software. Nucleic Acids Res. 1986 Jan 10;14(1):217–231. doi: 10.1093/nar/14.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Trowsdale J. Genetics and polymorphism: class II antigens. Br Med Bull. 1987 Jan;43(1):15–36. doi: 10.1093/oxfordjournals.bmb.a072168. [DOI] [PubMed] [Google Scholar]
  45. Trowsdale J., Hanson I., Mockridge I., Beck S., Townsend A., Kelly A. Sequences encoded in the class II region of the MHC related to the 'ABC' superfamily of transporters. Nature. 1990 Dec 20;348(6303):741–744. doi: 10.1038/348741a0. [DOI] [PubMed] [Google Scholar]
  46. Tsui F. W., Siminovitch L. Isolation, structure and expression of mammalian genes for histidyl-tRNA synthetase. Nucleic Acids Res. 1987 Apr 24;15(8):3349–3367. doi: 10.1093/nar/15.8.3349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Ussery M. A., Tanaka W. K., Hardesty B. Subcellular distribution of aminoacyl-tRNA synthetases in various eukaryotic cells. Eur J Biochem. 1977 Feb;72(3):491–500. doi: 10.1111/j.1432-1033.1977.tb11272.x. [DOI] [PubMed] [Google Scholar]
  48. Vellekamp G., Deutscher M. P. A basic NH2-terminal extension of rat liver arginyl-tRNA synthetase required for its association with high molecular weight complexes. J Biol Chem. 1987 Jul 25;262(21):9927–9930. [PubMed] [Google Scholar]
  49. White P. C., Grossberger D., Onufer B. J., Chaplin D. D., New M. I., Dupont B., Strominger J. L. Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1089–1093. doi: 10.1073/pnas.82.4.1089. [DOI] [PMC free article] [PubMed] [Google Scholar]

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