Identification of protein-arginine N-methyltransferase as 10-formyltetrahydrofolate dehydrogenase

J Biol Chem. 1998 Oct 16;273(42):27374-82. doi: 10.1074/jbc.273.42.27374.


S-Adenosylmethionine:protein-arginine N-methyltransferase (EC 2.1.1. 23; protein methylase I) transfers the methyl group of S-adenosyl-L-methionine to an arginine residue of a protein substrate. The homogeneous liver protein methylase I was subjected to tryptic digestion followed by reverse phase high performance liquid chromatography (HPLC) separation and either "on-line" mass spectrometric fragmentation or "off-line" Edman sequencing of selected fractions. Data base searching of both the mass spectrometric and Edman sequencing data from several peptides identified the protein methylase as 10-formyltetrahydrofolate dehydrogenase (EC; Cook, R. J., Lloyd, R. S., and Wagner, C. (1991) J. Biol. Chem. 266, 4965-4973; Swiss accession number). This identification was confirmed by comparative HPLC tryptic peptide mapping and affinity chromatography of the methylase on the 5-formyltetrahydrofolate-Sepharose affinity gel used to purify the dehydrogenase. The purified rat liver methylase had approximately 33% of the 10-formyltetrahydrofolate dehydrogenase and 36% of the aldehyde dehydrogenase activity as compared with the recombinant dehydrogenase, which also had protein methylase I activity. Polyclonal antibodies against recombinant dehydrogenase reacted with protein methylase I purified either by polyacrylamide gel electrophoresis or 5-formyltetrahydrofolate affinity chromatography. In each instance there was only a single immunoreactive band at a molecular weight of approximately 106,000. Together, these results confirm the co-identity of protein-arginine methyltransferase and 10-formyltetrahydrofolate dehydrogenase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Chromatography, Affinity
  • Chromatography, High Pressure Liquid
  • Gas Chromatography-Mass Spectrometry
  • Leucovorin / chemistry
  • Liver / enzymology
  • Molecular Sequence Data
  • Oxidoreductases Acting on CH-NH Group Donors / chemistry*
  • Oxidoreductases Acting on CH-NH Group Donors / genetics
  • Oxidoreductases Acting on CH-NH Group Donors / immunology
  • Oxidoreductases Acting on CH-NH Group Donors / metabolism
  • Peptide Mapping
  • Protein-Arginine N-Methyltransferases / chemistry*
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / immunology
  • Protein-Arginine N-Methyltransferases / metabolism
  • Rats
  • Recombinant Proteins / metabolism
  • Sepharose / chemistry
  • Sequence Analysis


  • Recombinant Proteins
  • Sepharose
  • Oxidoreductases Acting on CH-NH Group Donors
  • formyltetrahydrofolate dehydrogenase
  • Protein-Arginine N-Methyltransferases
  • Leucovorin