Alternative splicing of the human isoaspartyl protein carboxyl methyltransferase RNA leads to the generation of a C-terminal -RDEL sequence in isozyme II.
We have isolated two cDNA clones that correspond to the mRNAs for two isozymes of the human L-isoaspartyl/D-aspartyl protein carboxyl methyltransferase (EC 2.1.1.77). The DNA sequence of one of these encodes the amino acid sequence of the C-terminal half of the human erythrocyte isozyme I. The other cDNA clone includes the complete coding region of the more acidic isozyme II. With the exception of potential polymorphic sites at amino acid residues 119 and 205, the deduced amino acid sequences differ only at the C-terminus, where the -RWK sequence of isozyme I is replaced by a -RDEL sequence in isozyme II. The latter sequence is identical to a mammalian endoplasmic reticulum retention signal. With the previous evidence for only a single gene for the L-isoaspartyl/D-aspartyl methyltransferase in humans, and with evidence for consensus sites for alternative splicing in corresponding mouse genomic clones, we suggest that alternative splicing reactions can generate the major isozymes previously identified in human erythrocytes. The presence of alternative splicing leads us to predict the existence of a third isozyme with a -R C-terminus. The calculated isoelectric point of this third form is similar to that of a previously detected but uncharacterized minor methyltransferase activity.
MacLaren
D C
DC
Department of Chemistry and Biochemistry, University of California, Los Angeles 90024-1569.
Kagan
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RM
Clarke
S
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004277:DNA, Single-Stranded; D004912:Erythrocytes / Q000201:enzymology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; D011496:Protein Methyltransferases / Q000096:biosynthesis / Q000235:genetics*; D012326:RNA Splicing; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D004277:DNA, Single-Stranded; D007527:Isoenzymes; D011496:Protein Methyltransferases; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase