Sequence of the D-aspartyl/L-isoaspartyl protein methyltransferase from human erythrocytes. Common sequence motifs for protein, DNA, RNA, and small molecule S-adenosylmethionine-dependent methyltransferases.
A widely distributed protein methyltransferase catalyzes the transfer of a methyl group from S-adenosyl-methionine to the free carboxyl groups of D-aspartyl and/or L-isoaspartyl derivatives of L-aspartyl and L-asparaginyl residues. This enzyme has been postulated to function in the repair or the catabolism of age-damaged proteins. We present here the complete amino acid sequence of the more basic isozyme I of this enzyme from human erythrocytes. The sequence was determined by Edman degradation and mass spectral analysis of overlapping trypsin, Staphylococcus aureus V8 protease, Pseudomonas fragi endoproteinase Asp-N, cyanogen bromide, and hydroxylamine-generated fragments. The NH2-terminus is modified by acetylation and the protein contains 226 amino acids for a calculated molecular weight of 24,575. This value is in good agreement with the molecular weight determined for the purified protein by polyacrylamide gel electrophoresis in the presence of dodecyl sulfate and by gel filtration chromatography under nondenaturing conditions. The identification of 2 different amino acid residues at both positions 22 and 119 may indicate the presence of allelic variants or of two or more closely related structural genes. Finally, comparison of this sequence with those of methyltransferases for RNA, DNA, and small molecules, as well as other S-adenosylmethionine-utilizing enzymes, shows that many of these proteins share elements of three regions of sequence similarity and may be structurally or evolutionarily related.
Ingrosso
D
D
Department of Chemistry and Biochemistry, University of California, Los Angeles 90024-1569.
Fowler
A V
AV
Bleibaum
J
J
Clarke
S
S
D000595:Amino Acid Sequence; D003488:Cyanogen Bromide; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics*; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases; D010449:Peptide Mapping; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; D011496:Protein Methyltransferases / Q000097:blood / Q000235:genetics*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid
D007527:Isoenzymes; D012436:S-Adenosylmethionine; D008780:Methyltransferases; D011496:Protein Methyltransferases; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; D010447:Peptide Hydrolases; D003488:Cyanogen Bromide