PCMT1 explained

Protein-L-isoaspartate(D-aspartate) O-methyltransferase is an enzyme that in humans is encoded by the PCMT1 gene.^{[1] [2]}

Three classes of protein carboxyl methyltransferases, distinguished by their methyl-acceptor substrate specificity, have been found in prokaryotic and eukaryotic cells. The type II enzyme catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to the free carboxyl groups of D-aspartyl and L-isoaspartyl residues. These methyl-accepting residues result from the spontaneous deamidation, isomerization, and racemization of normal L-aspartyl and L-asparaginyl residues and represent sites of covalent damage to aging proteins PCMT1 (EC 2.1.1.77) is a protein repair enzyme that initiates the conversion of abnormal D-aspartyl and L-isoaspartyl residues to the normal L-aspartyl form.[supplied by OMIM]^[3]

Further reading

• MacLaren DC, Kagan RM, Clarke S . Alternative splicing of the human isoaspartyl protein carboxyl methyltransferase RNA leads to the generation of a C-terminal -RDEL sequence in isozyme II . Biochem. Biophys. Res. Commun. . 185 . 1 . 277–83 . 1992 . 1339271 . 10.1016/S0006-291X(05)80987-8 .
• Ingrosso D, Kagan RM, Clarke S . Distinct C-terminal sequences of isozymes I and II of the human erythrocyte L-isoaspartyl/D-aspartyl protein methyltransferase . Biochem. Biophys. Res. Commun. . 175 . 1 . 351–8 . 1991 . 1998518 . 10.1016/S0006-291X(05)81242-2 .
• Ingrosso D, Fowler AV, Bleibaum J, Clarke S . 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 . J. Biol. Chem. . 264 . 33 . 20131–9 . 1989 . 10.1016/S0021-9258(19)47228-1 . 2684970 . free .
• Gilbert JM, Fowler A, Bleibaum J, Clarke S . Purification of homologous protein carboxyl methyltransferase isozymes from human and bovine erythrocytes . Biochemistry . 27 . 14 . 5227–33 . 1988 . 3167043 . 10.1021/bi00414a042 .
• Ota IM, Gilbert JM, Clarke S . Two major isozymes of the protein D-aspartyl/L-isoaspartyl methyltransferase from human erythrocytes . Biochem. Biophys. Res. Commun. . 151 . 3 . 1136–43 . 1988 . 3355545 . 10.1016/S0006-291X(88)80484-4 .
• Takeda R, Mizobuchi M, Murao K, etal . Characterization of three cDNAs encoding two isozymes of an isoaspartyl protein carboxyl methyltransferase from human erythroid leukemia cells . J. Biochem. . 117 . 4 . 683–5 . 1995 . 7592526 . 10.1093/jb/117.2.267 . free .
• Tsai W, Clarke S . Amino acid polymorphisms of the human L-isoaspartyl/D-aspartyl methyltransferase involved in protein repair . Biochem. Biophys. Res. Commun. . 203 . 1 . 491–7 . 1994 . 8074695 . 10.1006/bbrc.1994.2209 .
• DeVry CG, Tsai W, Clarke S . Structure of the human gene encoding the protein repair L-isoaspartyl (D-aspartyl) O-methyltransferase . Arch. Biochem. Biophys. . 335 . 2 . 321–32 . 1997 . 8914929 . 10.1006/abbi.1996.0513 . 10.1.1.630.8527 .
• DeVry CG, Clarke S . Polymorphic forms of the protein L-isoaspartate (D-aspartate) O-methyltransferase involved in the repair of age-damaged proteins . J. Hum. Genet. . 44 . 5 . 275–88 . 1999 . 10496068 . 10.1007/s100380050161 . free .
• Ryttersgaard C, Griffith SC, Sawaya MR, etal . Crystal structure of human L-isoaspartyl methyltransferase . J. Biol. Chem. . 277 . 12 . 10642–6 . 2002 . 11792715 . 10.1074/jbc.M200229200 . free .
• Smith CD, Carson M, Friedman AM, etal . Crystal structure of human L-isoaspartyl-O-methyl-transferase with S-adenosyl homocysteine at 1.6-Å resolution and modeling of an isoaspartyl-containing peptide at the active site . Protein Sci. . 11 . 3 . 625–35 . 2002 . 11847284 . 10.1110/ps.37802 . 2373461 .
• Misra P, Qi C, Yu S, etal . Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation . J. Biol. Chem. . 277 . 22 . 20011–9 . 2002 . 11912212 . 10.1074/jbc.M201739200 . free.
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Enünlü I, Pápai G, Cserpán I, etal . Different isoforms of PRIP-interacting protein with methyltransferase domain/trimethylguanosine synthase localizes to the cytoplasm and nucleus . Biochem. Biophys. Res. Commun. . 309 . 1 . 44–51 . 2003 . 12943661 . 10.1016/S0006-291X(03)01514-6 .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Zhu H, Yang W, Lu W, etal . A known functional polymorphism (Ile120Val) of the human PCMT1 gene and risk of spina bifida . Mol. Genet. Metab. . 87 . 1 . 66–70 . 2006 . 16256389 . 2947858 . 10.1016/j.ymgme.2005.09.008 .
• Lanthier J, Desrosiers RR . Regulation of protein L-isoaspartyl methyltransferase by cell-matrix interactions: involvement of integrin alphavbeta3, PI 3-kinase, and the proteasome . Biochem. Cell Biol. . 84 . 5 . 684–94 . 2007 . 17167531 . 10.1139/o06-055 .
• Ewing RM, Chu P, Elisma F, etal . Large-scale mapping of human protein–protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1. 89 . 2007 . 17353931 . 10.1038/msb4100134 . 1847948 .

Notes and References

1. MacLaren DC, O'Connor CM, Xia YR, Mehrabian M, Klisak I, Sparkes RS, Clarke S, Lusis AJ . The L-isoaspartyl/D-aspartyl protein methyltransferase gene (PCMT1) maps to human chromosome 6q22.3-6q24 and the syntenic region of mouse chromosome 10 . Genomics . 14 . 4 . 852–6 . Feb 1993 . 1478665 . 10.1016/S0888-7543(05)80104-1 .
2. DeVry CG, Clarke S . Assignment of the protein L-isoaspartate (D-aspartate) O-methyltransferase gene (PCMT1) to human chromosome bands 6q24→q25 with radiation hybrid mapping . Cytogenet Cell Genet . 84 . 1–2 . 130–1 . Jun 1999 . 10343128 . 10.1159/000015239 . 38976877 .
3. Web site: Entrez Gene: PCMT1 protein-L-isoaspartate (D-aspartate) O-methyltransferase.