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Nucleic Acids Research, 1992, Vol. 20, No. 5 1075-1081
© 1992


MOLECULAR BIOLOGY

Human histidyl-tRNA synthetase: recognition of amino acid signature regions in class 2a aminoacyl-tRNA synthetases

Nina Raben, Frank Borriello*, Jay Amin+, Randy Horwitz§, David Fraser{Phi} and Paul Plotz

Connective Tissue Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, Bethesda, MD 20892, USA

Received December 3, 1991. Revised January 30, 1992. Accepted January 30, 1992.

We have determined the sequence of cDNA for the human histidyl-tRNA synthetase (HRS) in a hepatoma cell line and confirmed it in fetal myoblast and fibroblast cell lines. The newly determined sequence differs in 48 places, including insertions and deletions, from a previously published sequence. By sequence specific probing and by direct sequencing, we have established that only the newly determined sequence is present in genomic DNA and we have sequenced 500 hundred bases upstream of the translation start site. The predicted amino acid sequence now clearly demonstrates all three motifs recognized in class 2 aminoacyl-tRNA synthetases. Alignment of E. coli, yeast, and when available, mammalian predicted amino acid sequences for three of the four members of the class 2a subgroup (his, pro, ser, and thr) shows strong preservation of amino acid specific signature regions proximal to motif 2 and proximal to motif 3. These probably represent the active site binding regions for the proximal acceptor stem and for the amino acid. The first two exons of human HRS contain a 32 amino acid helical motif, first described in human QRS, a class 1 synthetase, which is found also in a yeast RNA polymerase, a rabbit termination factor, and both bovine and human WRS, suggesting that It may be an RNA binding motif.


*Present addresses: Department of Pathology, Brigham and Women's Hospital, Boston, MA,USA

+Present addresses: University of Connecticut School of Medicine, Farmington, CT.USA

§Present addresses: Department of Medicine, University Hospitals, Cleveland, OH,USA

{Phi}Present addresses: Department of Medicine, East Carolina School of Medicine, Greenville, NC, USA


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