PIMT_MOUSE
ID PIMT_MOUSE Reviewed; 227 AA.
AC P23506; Q810R4;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Protein-L-isoaspartate(D-aspartate) O-methyltransferase {ECO:0000305|PubMed:12023972};
DE Short=PIMT;
DE EC=2.1.1.77 {ECO:0000269|PubMed:12023972, ECO:0000269|PubMed:16923807};
DE AltName: Full=L-isoaspartyl protein carboxyl methyltransferase;
DE AltName: Full=Protein L-isoaspartyl/D-aspartyl methyltransferase;
DE AltName: Full=Protein-beta-aspartate methyltransferase;
GN Name=Pcmt1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=1511895; DOI=10.1016/0378-1119(92)90191-q;
RA Romanik E.A., Ladino C.A., Killoy L.C., D'Ardenne S.C., O'Connor C.M.;
RT "Genomic organization and tissue expression of the murine gene encoding the
RT protein beta-aspartate methyltransferase.";
RL Gene 118:217-222(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 82-98, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 186-227 (ISOFORM 2).
RX PubMed=8037467; DOI=10.1006/abbi.1994.1341;
RA Galus A., Lagos A., Romanik E.A., O'Connor C.M.;
RT "Structural analysis of transcripts for the protein L-isoaspartyl
RT methyltransferase reveals multiple transcription initiation sites and a
RT distinct pattern of expression in mouse testis: identification of a 5'-
RT flanking sequence with promoter activity.";
RL Arch. Biochem. Biophys. 312:524-533(1994).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=12023972; DOI=10.1074/jbc.m203911200;
RA Farrar C., Clarke S.;
RT "Altered levels of S-adenosylmethionine and S-adenosylhomocysteine in the
RT brains of L-isoaspartyl (D-Aspartyl) O-methyltransferase-deficient mice.";
RL J. Biol. Chem. 277:27856-27863(2002).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=16923807; DOI=10.1074/jbc.m605421200;
RA Vigneswara V., Lowenson J.D., Powell C.D., Thakur M., Bailey K., Clarke S.,
RA Ray D.E., Carter W.G.;
RT "Proteomic identification of novel substrates of a protein isoaspartyl
RT methyltransferase repair enzyme.";
RL J. Biol. Chem. 281:32619-32629(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION.
RX PubMed=20424163; DOI=10.1074/jbc.m110.120774;
RA Bidinosti M., Martineau Y., Frank F., Sonenberg N.;
RT "Repair of isoaspartate formation modulates the interaction of deamidated
RT 4E-BP2 with mTORC1 in brain.";
RL J. Biol. Chem. 285:19402-19408(2010).
CC -!- FUNCTION: Initiates the repair of damaged proteins by catalyzing methyl
CC esterification of L-isoaspartyl and D-aspartyl residues produced by
CC spontaneous isomerization and racemization of L-aspartyl and L-
CC asparaginyl residues in aging peptides and proteins (PubMed:12023972,
CC PubMed:16923807, PubMed:20424163). Acts on EIF4EBP2, microtubule-
CC associated protein 2, calreticulin, clathrin light chains a and b,
CC Ubiquitin C-terminal hydrolase isozyme L1, phosphatidylethanolamine-
CC binding protein 1, stathmin, beta-synuclein and alpha-synuclein
CC (PubMed:16923807, PubMed:20424163). {ECO:0000269|PubMed:12023972,
CC ECO:0000269|PubMed:16923807, ECO:0000269|PubMed:20424163}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-L-isoaspartate + S-adenosyl-L-methionine =
CC [protein]-L-isoaspartate alpha-methyl ester + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:12705, Rhea:RHEA-COMP:12143, Rhea:RHEA-
CC COMP:12144, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:90596,
CC ChEBI:CHEBI:90598; EC=2.1.1.77;
CC Evidence={ECO:0000269|PubMed:12023972, ECO:0000269|PubMed:16923807};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12706;
CC Evidence={ECO:0000269|PubMed:12023972};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P22061}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16923807}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P23506-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P23506-2; Sequence=VSP_004717;
CC -!- DISRUPTION PHENOTYPE: The survival of Pcmt1 homozygous knockout mice
CC drops significantly between the ages of 20 and 50 days compared to
CC their wild-type counterparts (PubMed:12023972). They have 20 times more
CC damaged aspartyl residues in their brains (PubMed:12023972).
CC {ECO:0000269|PubMed:12023972}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. L-
CC isoaspartyl/D-aspartyl protein methyltransferase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH49613.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M60320; AAA92742.1; ALT_SEQ; mRNA.
DR EMBL; M84684; AAA74565.1; -; Genomic_DNA.
DR EMBL; BC049613; AAH49613.1; ALT_INIT; mRNA.
DR EMBL; BC058966; AAH58966.1; -; mRNA.
DR EMBL; S72473; AAB31369.1; -; mRNA.
DR PIR; JC1248; JC1248.
DR AlphaFoldDB; P23506; -.
DR SMR; P23506; -.
DR IntAct; P23506; 2.
DR MINT; P23506; -.
DR STRING; 10090.ENSMUSP00000124932; -.
DR iPTMnet; P23506; -.
DR PhosphoSitePlus; P23506; -.
DR REPRODUCTION-2DPAGE; P23506; -.
DR EPD; P23506; -.
DR jPOST; P23506; -.
DR MaxQB; P23506; -.
DR PaxDb; P23506; -.
DR PRIDE; P23506; -.
DR ProteomicsDB; 288164; -. [P23506-1]
DR ProteomicsDB; 288165; -. [P23506-2]
DR MGI; MGI:97502; Pcmt1.
DR eggNOG; KOG1661; Eukaryota.
DR InParanoid; P23506; -.
DR Reactome; R-MMU-5676934; Protein repair.
DR ChiTaRS; Pcmt1; mouse.
DR PRO; PR:P23506; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P23506; protein.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0004719; F:protein-L-isoaspartate (D-aspartate) O-methyltransferase activity; IDA:MGI.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; ISO:MGI.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0006479; P:protein methylation; IDA:MGI.
DR GO; GO:0046498; P:S-adenosylhomocysteine metabolic process; ISO:MGI.
DR GO; GO:0046500; P:S-adenosylmethionine metabolic process; ISO:MGI.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR000682; PCMT.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR11579; PTHR11579; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR00080; pimt; 1.
DR PROSITE; PS01279; PCMT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P22061"
FT CHAIN 2..227
FT /note="Protein-L-isoaspartate(D-aspartate) O-
FT methyltransferase"
FT /id="PRO_0000111876"
FT ACT_SITE 60
FT /evidence="ECO:0000250|UniProtKB:Q27869"
FT BINDING 57..60
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000250|UniProtKB:P22061"
FT BINDING 65
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000250|UniProtKB:P22061"
FT BINDING 89
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000250|UniProtKB:P22061"
FT BINDING 110..111
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000250|UniProtKB:P22061"
FT BINDING 142..143
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000250|UniProtKB:P22061"
FT BINDING 217
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000250|UniProtKB:P22061"
FT BINDING 222
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000250|UniProtKB:P22061"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P22061"
FT VAR_SEQ 226..227
FT /note="WK -> DEL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8037467"
FT /id="VSP_004717"
SQ SEQUENCE 227 AA; 24634 MW; 954E2491A9DA9249 CRC64;
MAWKSGGASH SELIHNLRKN GIIKTDKVFE VMLATDRSHY AKSNPYMDSP QSIGFQATIS
APHMHAYALE LLFDQLHEGA KALDVGSGSG ILTACFARMV GNSGKVIGID HIKELVDDSI
TNVKKDDPML LSSGRVRLVV GDGRMGYAEE APYDAIHVGA AAPVVPQALI DQLKPGGRLI
LPVGPAGGNQ MLEQYDKLQD GSVKMKPLMG VIYVPLTDKE KQWSRWK
