Full text data of PCMT1
PCMT1
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Protein-L-isoaspartate(D-aspartate) O-methyltransferase; PIMT; 2.1.1.77 (L-isoaspartyl protein carboxyl methyltransferase; Protein L-isoaspartyl/D-aspartyl methyltransferase; Protein-beta-aspartate methyltransferase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Protein-L-isoaspartate(D-aspartate) O-methyltransferase; PIMT; 2.1.1.77 (L-isoaspartyl protein carboxyl methyltransferase; Protein L-isoaspartyl/D-aspartyl methyltransferase; Protein-beta-aspartate methyltransferase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00024989
IPI00024989 Protein-L-isoaspartate(D-aspartate) O-methyltransferase (EC 2.1.1.77) (Protein-beta-aspartate methyltransferase) (PIMT) Catalyzes the methyl esterification of L-isoaspartyl and D-aspartyl residues in peptides and proteins that result from spontaneous decomposition of normal L-aspartyl and L-asparaginyl residues. It plays a role in the repair and/or degradation of damaged proteins. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00024989 Protein-L-isoaspartate(D-aspartate) O-methyltransferase (EC 2.1.1.77) (Protein-beta-aspartate methyltransferase) (PIMT) Catalyzes the methyl esterification of L-isoaspartyl and D-aspartyl residues in peptides and proteins that result from spontaneous decomposition of normal L-aspartyl and L-asparaginyl residues. It plays a role in the repair and/or degradation of damaged proteins. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P22061
ID PIMT_HUMAN Reviewed; 227 AA.
AC P22061; A8K109; Q14661; Q16556; Q5VYC1; Q5VYC2; Q93061; Q96II9;
read moreAC Q99625; Q9BQV7; Q9BQV8; Q9NP03;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Protein-L-isoaspartate(D-aspartate) O-methyltransferase;
DE Short=PIMT;
DE EC=2.1.1.77;
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP PROTEIN SEQUENCE (ISOFORM 1).
RC TISSUE=Erythrocyte;
RX PubMed=2684970;
RA Ingrosso D., Fowler A.V., Bleibaum J., Clarke S.;
RT "Sequence of the D-aspartyl/L-isoaspartyl protein methyltransferase
RT from human erythrocytes. Common sequence motifs for protein, DNA, RNA,
RT and small molecule S-adenosylmethionine-dependent
RT methyltransferases.";
RL J. Biol. Chem. 264:20131-20139(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT ILE-120.
RC TISSUE=Brain cortex;
RX PubMed=1339271; DOI=10.1016/S0006-291X(05)80987-8;
RA Maclaren D.C., Kagan R.M., Clarke S.;
RT "Alternative splicing of the human isoaspartyl protein carboxyl
RT methyltransferase RNA leads to the generation of a C-terminal -RDEL
RT sequence in isozyme II.";
RL Biochem. Biophys. Res. Commun. 185:277-283(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=7592526;
RA Takeda R., Mizobuchi M., Murao K., Sato M., Takahara J.;
RT "Characterization of three cDNAs encoding two isozymes of an
RT isoaspartyl protein carboxyl methyltransferase from human erythroid
RT leukemia cells.";
RL J. Biochem. 117:683-685(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Shirasawa T., Takahashi H., Endoh R., Sakamoto K., Hirokawa K.,
RA Mori H.;
RT "Gene expression of carboxyl methyltransferase is altered in
RT Alzheimer's disease and the product is localized to neurofibrillary
RT tangles.";
RL Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ILE-120.
RC TISSUE=Muscle, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18.
RC TISSUE=Foreskin;
RX PubMed=8914929; DOI=10.1006/abbi.1996.0513;
RA Devry C.G., Tsai W., Clarke S.;
RT "Structure of the human gene encoding the protein repair L-isoaspartyl
RT (D-aspartyl) O-methyltransferase.";
RL Arch. Biochem. Biophys. 335:321-332(1996).
RN [9]
RP PROTEIN SEQUENCE OF 5-19; 44-60; 106-170; 179-198 AND 205-220.
RX PubMed=3167043; DOI=10.1021/bi00414a042;
RA Gilbert J.M., Fowler A., Bleibaum J., Clarke S.;
RT "Purification of homologous protein carboxyl methyltransferase
RT isozymes from human and bovine erythrocytes.";
RL Biochemistry 27:5227-5233(1988).
RN [10]
RP PROTEIN SEQUENCE OF 5-18; 25-37; 82-98; 114-144 AND 179-221, MASS
RP SPECTROMETRY, AND VARIANT ILE-120.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-53; 100-139 AND 169-224.
RX PubMed=8074695; DOI=10.1006/bbrc.1994.2209;
RA Tsai W., Clarke S.;
RT "Amino acid polymorphisms of the human L-isoaspartyl/D-aspartyl
RT methyltransferase involved in protein repair.";
RL Biochem. Biophys. Res. Commun. 203:491-497(1994).
RN [12]
RP PARTIAL PROTEIN SEQUENCE (ISOFORM 2), AND VARIANT ILE-120.
RC TISSUE=Erythrocyte;
RX PubMed=1998518; DOI=10.1016/S0006-291X(05)81242-2;
RA Ingrosso D., Kagan R.M., Clarke S.;
RT "Distinct C-terminal sequences of isozymes I and II of the human
RT erythrocyte L-isoaspartyl/D-aspartyl protein methyltransferase.";
RL Biochem. Biophys. Res. Commun. 175:351-358(1991).
RN [13]
RP VARIANT ILE-120.
RX PubMed=10496068; DOI=10.1007/s100380050161;
RA DeVry C.G., Clarke S.;
RT "Polymorphic forms of the protein L-isoaspartate (D-aspartate) O-
RT methyltransferase involved in the repair of age-damaged proteins.";
RL J. Hum. Genet. 44:275-288(1999).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=11792715; DOI=10.1074/jbc.M200229200;
RA Ryttersgaard C., Griffith S.C., Sawaya M.R., MacLaren D.C., Clarke S.,
RA Yeates T.O.;
RT "Crystal structure of human L-isoaspartyl methyltransferase.";
RL J. Biol. Chem. 277:10642-10646(2002).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
RX PubMed=11847284; DOI=10.1110/ps.37802;
RA Smith C.D., Carson M., Friedman A.M., Skinner M.M., Delucas L.,
RA Chantalat L., Weise L., Shirasawa T., Chattopadhyay D.;
RT "Crystal structure of human L-isoaspartyl-O-methyl-transferase with S-
RT adenosyl homocysteine at 1.6-A resolution and modeling of an
RT isoaspartyl-containing peptide at the active site.";
RL Protein Sci. 11:625-635(2002).
RN [16]
RP VARIANT [LARGE SCALE ANALYSIS] ILE-120, AND MASS SPECTROMETRY.
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Catalyzes the methyl esterification of L-isoaspartyl and
CC D-aspartyl residues in peptides and proteins that result from
CC spontaneous decomposition of normal L-aspartyl and L-asparaginyl
CC residues. It plays a role in the repair and/or degradation of
CC damaged proteins. Acts on microtubule-associated protein 2,
CC calreticulin, clathrin light chains a and b, Ubiquitin carboxyl-
CC terminal hydrolase isozyme L1, phosphatidylethanolamine-binding
CC protein 1, stathmin, beta-synuclein and alpha-synuclein (By
CC similarity).
CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + protein L-
CC isoaspartate = S-adenosyl-L-homocysteine + protein L-isoaspartate
CC alpha-methyl ester.
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC Self; NbExp=1; IntAct=EBI-353343, EBI-353343;
CC O60739:EIF1B; NbExp=1; IntAct=EBI-353343, EBI-1043343;
CC P23506:Pcmt1 (xeno); NbExp=1; IntAct=EBI-353343, EBI-2551550;
CC P40337:VHL; NbExp=1; IntAct=EBI-353343, EBI-301246;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P22061-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P22061-2; Sequence=VSP_004716;
CC -!- POLYMORPHISM: The allele frequencies for the polymorphism at codon
CC 120 differ between ethnic groups; in the Caucasian population Ile-
CC 120 is present at a frequency of 0.45, while it is found at a
CC frequency of 0.88 and 0.81 in the Asian and the African
CC populations respectively. Val-120 is found at a frequency of 0.55
CC in the Caucasians, 0.12 and 0.19 in the Asian and African
CC populations respectively. The Ile-120 variant has higher specific
CC activity and thermostability than the Val-120 variant. The Val-120
CC variant has a higher affinity for protein substrates.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. L-
CC isoaspartyl/D-aspartyl protein methyltransferase family.
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DR EMBL; M93008; AAA90934.1; -; mRNA.
DR EMBL; M93009; AAA90933.1; -; mRNA.
DR EMBL; D25545; BAA05028.1; -; mRNA.
DR EMBL; D25546; BAA05029.1; -; mRNA.
DR EMBL; D25547; BAA05030.1; -; mRNA.
DR EMBL; D13892; BAA02991.1; -; mRNA.
DR EMBL; AK289724; BAF82413.1; -; mRNA.
DR EMBL; AL355312; CAH72862.1; -; Genomic_DNA.
DR EMBL; AL355312; CAH72863.1; -; Genomic_DNA.
DR EMBL; BC007501; AAH07501.1; -; mRNA.
DR EMBL; BC008748; AAH08748.1; -; mRNA.
DR EMBL; U49740; AAB38386.1; -; Genomic_DNA.
DR EMBL; S73902; AAC60639.2; -; Genomic_DNA.
DR EMBL; S73903; AAC60640.1; -; Genomic_DNA.
DR EMBL; S73905; AAC60641.2; -; Genomic_DNA.
DR PIR; A34489; A34489.
DR PIR; JH0624; JH0624.
DR RefSeq; NP_001238978.1; NM_001252049.1.
DR RefSeq; NP_001238982.1; NM_001252053.1.
DR UniGene; Hs.279257; -.
DR PDB; 1I1N; X-ray; 1.50 A; A=2-227.
DR PDB; 1KR5; X-ray; 2.10 A; A=2-227.
DR PDBsum; 1I1N; -.
DR PDBsum; 1KR5; -.
DR ProteinModelPortal; P22061; -.
DR SMR; P22061; 3-226.
DR IntAct; P22061; 15.
DR MINT; MINT-234244; -.
DR BindingDB; P22061; -.
DR ChEMBL; CHEMBL4240; -.
DR PhosphoSite; P22061; -.
DR DMDM; 2507187; -.
DR OGP; P22061; -.
DR REPRODUCTION-2DPAGE; IPI00411680; -.
DR UCD-2DPAGE; P22061; -.
DR PaxDb; P22061; -.
DR PRIDE; P22061; -.
DR Ensembl; ENST00000367380; ENSP00000356350; ENSG00000120265.
DR GeneID; 5110; -.
DR KEGG; hsa:5110; -.
DR CTD; 5110; -.
DR GeneCards; GC06P150070; -.
DR HGNC; HGNC:8728; PCMT1.
DR HPA; HPA003239; -.
DR MIM; 176851; gene.
DR neXtProt; NX_P22061; -.
DR eggNOG; COG2518; -.
DR HOVERGEN; HBG004483; -.
DR KO; K00573; -.
DR PhylomeDB; P22061; -.
DR EvolutionaryTrace; P22061; -.
DR GeneWiki; PCMT1; -.
DR GenomeRNAi; 5110; -.
DR NextBio; 19718; -.
DR PRO; PR:P22061; -.
DR ArrayExpress; P22061; -.
DR Bgee; P22061; -.
DR Genevestigator; P22061; -.
DR GO; GO:0005783; C:endoplasmic reticulum; TAS:ProtInc.
DR GO; GO:0004719; F:protein-L-isoaspartate (D-aspartate) O-methyltransferase activity; TAS:UniProtKB.
DR GO; GO:0030091; P:protein repair; TAS:UniProtKB.
DR InterPro; IPR000682; PCMT.
DR PANTHER; PTHR11579; PTHR11579; 1.
DR Pfam; PF01135; PCMT; 1.
DR TIGRFAMs; TIGR00080; pimt; 1.
DR PROSITE; PS01279; PCMT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disulfide bond;
KW Methyltransferase; Polymorphism; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 227 Protein-L-isoaspartate(D-aspartate) O-
FT methyltransferase.
FT /FTId=PRO_0000111875.
FT ACT_SITE 60 60
FT MOD_RES 2 2 N-acetylalanine.
FT DISULFID 43 95 By similarity.
FT VAR_SEQ 226 227 WK -> DEL (in isoform 2).
FT /FTId=VSP_004716.
FT VARIANT 120 120 V -> I (in dbSNP:rs4816).
FT /FTId=VAR_006173.
FT CONFLICT 19 19 K -> G (in Ref. 9; AA sequence).
FT CONFLICT 23 23 I -> L (in Ref. 1; AA sequence).
FT CONFLICT 60 60 S -> A (in Ref. 9; AA sequence).
FT CONFLICT 102 102 C -> Q (in Ref. 1; AA sequence).
FT CONFLICT 168 168 A -> P (in Ref. 9; AA sequence).
FT CONFLICT 206 206 K -> R (in Ref. 2; AAA90933).
FT HELIX 10 19
FT HELIX 26 33
FT HELIX 37 39
FT STRAND 47 49
FT STRAND 51 54
FT STRAND 57 59
FT HELIX 62 71
FT TURN 72 75
FT STRAND 81 85
FT HELIX 91 100
FT TURN 101 103
FT STRAND 105 111
FT HELIX 113 126
FT HELIX 129 132
FT STRAND 134 141
FT HELIX 143 145
FT HELIX 148 150
FT STRAND 153 158
FT STRAND 160 164
FT HELIX 167 171
FT STRAND 173 184
FT STRAND 190 197
FT STRAND 203 211
FT HELIX 219 222
SQ SEQUENCE 227 AA; 24636 MW; 4EB1122379C8040A CRC64;
MAWKSGGASH SELIHNLRKN GIIKTDKVFE VMLATDRSHY AKCNPYMDSP QSIGFQATIS
APHMHAYALE LLFDQLHEGA KALDVGSGSG ILTACFARMV GCTGKVIGID HIKELVDDSV
NNVRKDDPTL LSSGRVQLVV GDGRMGYAEE APYDAIHVGA AAPVVPQALI DQLKPGGRLI
LPVGPAGGNQ MLEQYDKLQD GSIKMKPLMG VIYVPLTDKE KQWSRWK
//
ID PIMT_HUMAN Reviewed; 227 AA.
AC P22061; A8K109; Q14661; Q16556; Q5VYC1; Q5VYC2; Q93061; Q96II9;
read moreAC Q99625; Q9BQV7; Q9BQV8; Q9NP03;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Protein-L-isoaspartate(D-aspartate) O-methyltransferase;
DE Short=PIMT;
DE EC=2.1.1.77;
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP PROTEIN SEQUENCE (ISOFORM 1).
RC TISSUE=Erythrocyte;
RX PubMed=2684970;
RA Ingrosso D., Fowler A.V., Bleibaum J., Clarke S.;
RT "Sequence of the D-aspartyl/L-isoaspartyl protein methyltransferase
RT from human erythrocytes. Common sequence motifs for protein, DNA, RNA,
RT and small molecule S-adenosylmethionine-dependent
RT methyltransferases.";
RL J. Biol. Chem. 264:20131-20139(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT ILE-120.
RC TISSUE=Brain cortex;
RX PubMed=1339271; DOI=10.1016/S0006-291X(05)80987-8;
RA Maclaren D.C., Kagan R.M., Clarke S.;
RT "Alternative splicing of the human isoaspartyl protein carboxyl
RT methyltransferase RNA leads to the generation of a C-terminal -RDEL
RT sequence in isozyme II.";
RL Biochem. Biophys. Res. Commun. 185:277-283(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=7592526;
RA Takeda R., Mizobuchi M., Murao K., Sato M., Takahara J.;
RT "Characterization of three cDNAs encoding two isozymes of an
RT isoaspartyl protein carboxyl methyltransferase from human erythroid
RT leukemia cells.";
RL J. Biochem. 117:683-685(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Shirasawa T., Takahashi H., Endoh R., Sakamoto K., Hirokawa K.,
RA Mori H.;
RT "Gene expression of carboxyl methyltransferase is altered in
RT Alzheimer's disease and the product is localized to neurofibrillary
RT tangles.";
RL Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ILE-120.
RC TISSUE=Muscle, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18.
RC TISSUE=Foreskin;
RX PubMed=8914929; DOI=10.1006/abbi.1996.0513;
RA Devry C.G., Tsai W., Clarke S.;
RT "Structure of the human gene encoding the protein repair L-isoaspartyl
RT (D-aspartyl) O-methyltransferase.";
RL Arch. Biochem. Biophys. 335:321-332(1996).
RN [9]
RP PROTEIN SEQUENCE OF 5-19; 44-60; 106-170; 179-198 AND 205-220.
RX PubMed=3167043; DOI=10.1021/bi00414a042;
RA Gilbert J.M., Fowler A., Bleibaum J., Clarke S.;
RT "Purification of homologous protein carboxyl methyltransferase
RT isozymes from human and bovine erythrocytes.";
RL Biochemistry 27:5227-5233(1988).
RN [10]
RP PROTEIN SEQUENCE OF 5-18; 25-37; 82-98; 114-144 AND 179-221, MASS
RP SPECTROMETRY, AND VARIANT ILE-120.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-53; 100-139 AND 169-224.
RX PubMed=8074695; DOI=10.1006/bbrc.1994.2209;
RA Tsai W., Clarke S.;
RT "Amino acid polymorphisms of the human L-isoaspartyl/D-aspartyl
RT methyltransferase involved in protein repair.";
RL Biochem. Biophys. Res. Commun. 203:491-497(1994).
RN [12]
RP PARTIAL PROTEIN SEQUENCE (ISOFORM 2), AND VARIANT ILE-120.
RC TISSUE=Erythrocyte;
RX PubMed=1998518; DOI=10.1016/S0006-291X(05)81242-2;
RA Ingrosso D., Kagan R.M., Clarke S.;
RT "Distinct C-terminal sequences of isozymes I and II of the human
RT erythrocyte L-isoaspartyl/D-aspartyl protein methyltransferase.";
RL Biochem. Biophys. Res. Commun. 175:351-358(1991).
RN [13]
RP VARIANT ILE-120.
RX PubMed=10496068; DOI=10.1007/s100380050161;
RA DeVry C.G., Clarke S.;
RT "Polymorphic forms of the protein L-isoaspartate (D-aspartate) O-
RT methyltransferase involved in the repair of age-damaged proteins.";
RL J. Hum. Genet. 44:275-288(1999).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=11792715; DOI=10.1074/jbc.M200229200;
RA Ryttersgaard C., Griffith S.C., Sawaya M.R., MacLaren D.C., Clarke S.,
RA Yeates T.O.;
RT "Crystal structure of human L-isoaspartyl methyltransferase.";
RL J. Biol. Chem. 277:10642-10646(2002).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
RX PubMed=11847284; DOI=10.1110/ps.37802;
RA Smith C.D., Carson M., Friedman A.M., Skinner M.M., Delucas L.,
RA Chantalat L., Weise L., Shirasawa T., Chattopadhyay D.;
RT "Crystal structure of human L-isoaspartyl-O-methyl-transferase with S-
RT adenosyl homocysteine at 1.6-A resolution and modeling of an
RT isoaspartyl-containing peptide at the active site.";
RL Protein Sci. 11:625-635(2002).
RN [16]
RP VARIANT [LARGE SCALE ANALYSIS] ILE-120, AND MASS SPECTROMETRY.
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Catalyzes the methyl esterification of L-isoaspartyl and
CC D-aspartyl residues in peptides and proteins that result from
CC spontaneous decomposition of normal L-aspartyl and L-asparaginyl
CC residues. It plays a role in the repair and/or degradation of
CC damaged proteins. Acts on microtubule-associated protein 2,
CC calreticulin, clathrin light chains a and b, Ubiquitin carboxyl-
CC terminal hydrolase isozyme L1, phosphatidylethanolamine-binding
CC protein 1, stathmin, beta-synuclein and alpha-synuclein (By
CC similarity).
CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + protein L-
CC isoaspartate = S-adenosyl-L-homocysteine + protein L-isoaspartate
CC alpha-methyl ester.
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC Self; NbExp=1; IntAct=EBI-353343, EBI-353343;
CC O60739:EIF1B; NbExp=1; IntAct=EBI-353343, EBI-1043343;
CC P23506:Pcmt1 (xeno); NbExp=1; IntAct=EBI-353343, EBI-2551550;
CC P40337:VHL; NbExp=1; IntAct=EBI-353343, EBI-301246;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P22061-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P22061-2; Sequence=VSP_004716;
CC -!- POLYMORPHISM: The allele frequencies for the polymorphism at codon
CC 120 differ between ethnic groups; in the Caucasian population Ile-
CC 120 is present at a frequency of 0.45, while it is found at a
CC frequency of 0.88 and 0.81 in the Asian and the African
CC populations respectively. Val-120 is found at a frequency of 0.55
CC in the Caucasians, 0.12 and 0.19 in the Asian and African
CC populations respectively. The Ile-120 variant has higher specific
CC activity and thermostability than the Val-120 variant. The Val-120
CC variant has a higher affinity for protein substrates.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. L-
CC isoaspartyl/D-aspartyl protein methyltransferase family.
CC -----------------------------------------------------------------------
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DR EMBL; M93008; AAA90934.1; -; mRNA.
DR EMBL; M93009; AAA90933.1; -; mRNA.
DR EMBL; D25545; BAA05028.1; -; mRNA.
DR EMBL; D25546; BAA05029.1; -; mRNA.
DR EMBL; D25547; BAA05030.1; -; mRNA.
DR EMBL; D13892; BAA02991.1; -; mRNA.
DR EMBL; AK289724; BAF82413.1; -; mRNA.
DR EMBL; AL355312; CAH72862.1; -; Genomic_DNA.
DR EMBL; AL355312; CAH72863.1; -; Genomic_DNA.
DR EMBL; BC007501; AAH07501.1; -; mRNA.
DR EMBL; BC008748; AAH08748.1; -; mRNA.
DR EMBL; U49740; AAB38386.1; -; Genomic_DNA.
DR EMBL; S73902; AAC60639.2; -; Genomic_DNA.
DR EMBL; S73903; AAC60640.1; -; Genomic_DNA.
DR EMBL; S73905; AAC60641.2; -; Genomic_DNA.
DR PIR; A34489; A34489.
DR PIR; JH0624; JH0624.
DR RefSeq; NP_001238978.1; NM_001252049.1.
DR RefSeq; NP_001238982.1; NM_001252053.1.
DR UniGene; Hs.279257; -.
DR PDB; 1I1N; X-ray; 1.50 A; A=2-227.
DR PDB; 1KR5; X-ray; 2.10 A; A=2-227.
DR PDBsum; 1I1N; -.
DR PDBsum; 1KR5; -.
DR ProteinModelPortal; P22061; -.
DR SMR; P22061; 3-226.
DR IntAct; P22061; 15.
DR MINT; MINT-234244; -.
DR BindingDB; P22061; -.
DR ChEMBL; CHEMBL4240; -.
DR PhosphoSite; P22061; -.
DR DMDM; 2507187; -.
DR OGP; P22061; -.
DR REPRODUCTION-2DPAGE; IPI00411680; -.
DR UCD-2DPAGE; P22061; -.
DR PaxDb; P22061; -.
DR PRIDE; P22061; -.
DR Ensembl; ENST00000367380; ENSP00000356350; ENSG00000120265.
DR GeneID; 5110; -.
DR KEGG; hsa:5110; -.
DR CTD; 5110; -.
DR GeneCards; GC06P150070; -.
DR HGNC; HGNC:8728; PCMT1.
DR HPA; HPA003239; -.
DR MIM; 176851; gene.
DR neXtProt; NX_P22061; -.
DR eggNOG; COG2518; -.
DR HOVERGEN; HBG004483; -.
DR KO; K00573; -.
DR PhylomeDB; P22061; -.
DR EvolutionaryTrace; P22061; -.
DR GeneWiki; PCMT1; -.
DR GenomeRNAi; 5110; -.
DR NextBio; 19718; -.
DR PRO; PR:P22061; -.
DR ArrayExpress; P22061; -.
DR Bgee; P22061; -.
DR Genevestigator; P22061; -.
DR GO; GO:0005783; C:endoplasmic reticulum; TAS:ProtInc.
DR GO; GO:0004719; F:protein-L-isoaspartate (D-aspartate) O-methyltransferase activity; TAS:UniProtKB.
DR GO; GO:0030091; P:protein repair; TAS:UniProtKB.
DR InterPro; IPR000682; PCMT.
DR PANTHER; PTHR11579; PTHR11579; 1.
DR Pfam; PF01135; PCMT; 1.
DR TIGRFAMs; TIGR00080; pimt; 1.
DR PROSITE; PS01279; PCMT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disulfide bond;
KW Methyltransferase; Polymorphism; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 227 Protein-L-isoaspartate(D-aspartate) O-
FT methyltransferase.
FT /FTId=PRO_0000111875.
FT ACT_SITE 60 60
FT MOD_RES 2 2 N-acetylalanine.
FT DISULFID 43 95 By similarity.
FT VAR_SEQ 226 227 WK -> DEL (in isoform 2).
FT /FTId=VSP_004716.
FT VARIANT 120 120 V -> I (in dbSNP:rs4816).
FT /FTId=VAR_006173.
FT CONFLICT 19 19 K -> G (in Ref. 9; AA sequence).
FT CONFLICT 23 23 I -> L (in Ref. 1; AA sequence).
FT CONFLICT 60 60 S -> A (in Ref. 9; AA sequence).
FT CONFLICT 102 102 C -> Q (in Ref. 1; AA sequence).
FT CONFLICT 168 168 A -> P (in Ref. 9; AA sequence).
FT CONFLICT 206 206 K -> R (in Ref. 2; AAA90933).
FT HELIX 10 19
FT HELIX 26 33
FT HELIX 37 39
FT STRAND 47 49
FT STRAND 51 54
FT STRAND 57 59
FT HELIX 62 71
FT TURN 72 75
FT STRAND 81 85
FT HELIX 91 100
FT TURN 101 103
FT STRAND 105 111
FT HELIX 113 126
FT HELIX 129 132
FT STRAND 134 141
FT HELIX 143 145
FT HELIX 148 150
FT STRAND 153 158
FT STRAND 160 164
FT HELIX 167 171
FT STRAND 173 184
FT STRAND 190 197
FT STRAND 203 211
FT HELIX 219 222
SQ SEQUENCE 227 AA; 24636 MW; 4EB1122379C8040A CRC64;
MAWKSGGASH SELIHNLRKN GIIKTDKVFE VMLATDRSHY AKCNPYMDSP QSIGFQATIS
APHMHAYALE LLFDQLHEGA KALDVGSGSG ILTACFARMV GCTGKVIGID HIKELVDDSV
NNVRKDDPTL LSSGRVQLVV GDGRMGYAEE APYDAIHVGA AAPVVPQALI DQLKPGGRLI
LPVGPAGGNQ MLEQYDKLQD GSIKMKPLMG VIYVPLTDKE KQWSRWK
//
MIM
176851
*RECORD*
*FIELD* NO
176851
*FIELD* TI
*176851 PROTEIN CARBOXYL METHYLTRANSFERASE 1; PCMT1
;;L-ISOASPARTYL/D-ASPARTYL PROTEIN METHYLTRANSFERASE
read more*FIELD* TX
DESCRIPTION
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.
CLONING
L-isoaspartyl-D-aspartyl methyltransferase is a cytosolic monomer of
about 25 kD. Ingrosso et al. (1991) and MacLaren et al. (1992) showed
that 2 major isozymes of this transferase result by alternative splicing
of a single gene product.
MAPPING
By a combination of Southern blot analysis of DNA from a panel of
mouse/human somatic cell hybrids and in situ hybridization, MacLaren et
al. (1992) mapped the PCMT1 gene to 6q22.3-q24. By study of an RFLV in
interspecific backcrosses, they localized the gene to mouse chromosome
10, at a position approximately 8.2 cM proximal to the Myb locus, in a
region homologous to human 6q24.
By radiation hybrid analysis, DeVry and Clarke (1999) mapped the PCMT1
gene to a more telomeric position in the 6q24-q25 region.
ANIMAL MODEL
Kim et al. (1999) developed Pcmt1-null mice. These mice manifested 2
phenotypes, a fatal seizure disorder and retarded growth. Continuous
electroencephalogram monitoring of Pcmt1-null mice revealed that
abnormal cortical activity occurred for about half of each 24-hour
period, even in mice that had no visible evidence of convulsions.
Antiepileptic therapy mitigated but did not eliminate the seizure
disorder. It did, however, normalize the growth of Pcmt1-null mice,
suggesting that the growth retardation was due to seizures rather than a
global disturbance in growth at the cellular level. Consistent with
this, the growth rate of Pcmt1-null fibroblasts was indistinguishable
from that of wildtype fibroblasts.
Lowenson et al. (2001) noted that Pcmt1-null mice died at a mean age of
42 days due to massive tonic-clonic seizures. In order to extend the
lives of the knockout mice and to study the long-term effects of damaged
amino acid accumulation, Lowenson et al. (2001) produced transgenic mice
with Pcmt1 cDNA under the control of a neuron-specific promoter. These
mice showed low but measurable Pcmt1 activity in brain tissue, but
little or no activity in other tissues. The transgenic mice lived on
average 5-fold longer than nontransgenic Pcmt1-null mice, and they
accumulated only half as many damaged aspartyl residues in their brain
proteins. The concentration of damaged residues in heart, testis, and
brain proteins in transgenic mice initially increased with age, then
reached a plateau by 100 days of age. Lowenson et al. (2001) suggested
that proteolysis may limit the intracellular accumulation of damaged
proteins, but less efficiently than in wildtype mice having
Pcmt1-mediated repair.
In the course of the repair reaction that generates L-aspartic acid,
PCMT1 converts the methyl donor S-adenosylmethionine (AdoMet) to
S-adenosylhomocysteine (AdoHcy). Farrar and Clarke (2002) measured these
metabolites in the brains of Pcmt1-null, Pcmt1 heterozygous, and
wildtype mice. Highest levels of AdoMet and lower levels of AdoHcy were
found in the brains of Pcmt1-null mice, and to a lesser extent in the
heterozygous mice, when compared with wildtype mice. These levels were
most significantly altered in the hippocampus. Farrar and Clarke (2002)
concluded that the AdoMet/AdoHcy ratio could potentially alter the
overall excitatory state of the brain and may play a role in the
progressive epilepsy seen in Pcmt1-null mice.
*FIELD* SA
MacLaren et al. (1992); Ota et al. (1988)
*FIELD* RF
1. DeVry, C. G.; 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:
130-131, 1999.
2. Farrar, C.; Clarke, S.: Altered levels of S-adenosylmethionine
and S-adenosylhomocysteine in the brains of L-isoaspartyl (D-aspartyl)
O-methyltransferase-deficient mice. J. Biol. Chem. 277: 27856-27863,
2002.
3. Ingrosso, D.; Kagan, R. M.; 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: 351-358,
1991. Note: Erratum: Biochem. Biophys. Res. Commun. 176: 549 only,
1991.
4. Kim, E.; Lowenson, J. D.; Clarke, S.; Young, S. G.: Phenotypic
analysis of seizure-prone mice lacking L-isoaspartate (D-aspartate)
O-methyltransferase. J. Biol. Chem. 274: 20671-20678, 1999.
5. Lowenson, J. D.; Kim, E.; Young, S. G.; Clarke, S.: Limited accumulation
of damaged proteins in L-isoaspartyl (D-aspartyl) O-methyltransferase-deficient
mice. J. Biol. Chem. 276: 20695-20702, 2001.
6. MacLaren, D. C.; Kagan, R. M.; Clarke, S.: Alternative splicing
of the human isoaspartyl protein carboxyl methyltransferase leads
to the generation of a C-terminal -RDEL sequence in isozyme II. Biochem.
Biophys. Res. Commun. 185: 277-283, 1992.
7. MacLaren, D. C.; O'Connor, C. M.; Xia, Y.-R.; Mehrabian, M.; Klisak,
I.; Sparkes, R. S.; Clarke, S.; Lusis, A. J.: 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: 852-856,
1992.
8. Ota, I. M.; Gilbert, J. M.; Clarke, S.: Two major isozymes of
the protein D-aspartyl/L-isoaspartyl methyltransferase from human
erythrocytes. Biochem. Biophys. Res. Commun. 151: 1136-1143, 1988.
*FIELD* CN
Patricia A. Hartz - updated: 10/3/2002
*FIELD* CD
Victor A. McKusick: 1/14/1993
*FIELD* ED
terry: 12/20/2012
terry: 3/16/2005
mgross: 10/3/2002
carol: 2/11/1993
carol: 1/14/1993
*RECORD*
*FIELD* NO
176851
*FIELD* TI
*176851 PROTEIN CARBOXYL METHYLTRANSFERASE 1; PCMT1
;;L-ISOASPARTYL/D-ASPARTYL PROTEIN METHYLTRANSFERASE
read more*FIELD* TX
DESCRIPTION
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.
CLONING
L-isoaspartyl-D-aspartyl methyltransferase is a cytosolic monomer of
about 25 kD. Ingrosso et al. (1991) and MacLaren et al. (1992) showed
that 2 major isozymes of this transferase result by alternative splicing
of a single gene product.
MAPPING
By a combination of Southern blot analysis of DNA from a panel of
mouse/human somatic cell hybrids and in situ hybridization, MacLaren et
al. (1992) mapped the PCMT1 gene to 6q22.3-q24. By study of an RFLV in
interspecific backcrosses, they localized the gene to mouse chromosome
10, at a position approximately 8.2 cM proximal to the Myb locus, in a
region homologous to human 6q24.
By radiation hybrid analysis, DeVry and Clarke (1999) mapped the PCMT1
gene to a more telomeric position in the 6q24-q25 region.
ANIMAL MODEL
Kim et al. (1999) developed Pcmt1-null mice. These mice manifested 2
phenotypes, a fatal seizure disorder and retarded growth. Continuous
electroencephalogram monitoring of Pcmt1-null mice revealed that
abnormal cortical activity occurred for about half of each 24-hour
period, even in mice that had no visible evidence of convulsions.
Antiepileptic therapy mitigated but did not eliminate the seizure
disorder. It did, however, normalize the growth of Pcmt1-null mice,
suggesting that the growth retardation was due to seizures rather than a
global disturbance in growth at the cellular level. Consistent with
this, the growth rate of Pcmt1-null fibroblasts was indistinguishable
from that of wildtype fibroblasts.
Lowenson et al. (2001) noted that Pcmt1-null mice died at a mean age of
42 days due to massive tonic-clonic seizures. In order to extend the
lives of the knockout mice and to study the long-term effects of damaged
amino acid accumulation, Lowenson et al. (2001) produced transgenic mice
with Pcmt1 cDNA under the control of a neuron-specific promoter. These
mice showed low but measurable Pcmt1 activity in brain tissue, but
little or no activity in other tissues. The transgenic mice lived on
average 5-fold longer than nontransgenic Pcmt1-null mice, and they
accumulated only half as many damaged aspartyl residues in their brain
proteins. The concentration of damaged residues in heart, testis, and
brain proteins in transgenic mice initially increased with age, then
reached a plateau by 100 days of age. Lowenson et al. (2001) suggested
that proteolysis may limit the intracellular accumulation of damaged
proteins, but less efficiently than in wildtype mice having
Pcmt1-mediated repair.
In the course of the repair reaction that generates L-aspartic acid,
PCMT1 converts the methyl donor S-adenosylmethionine (AdoMet) to
S-adenosylhomocysteine (AdoHcy). Farrar and Clarke (2002) measured these
metabolites in the brains of Pcmt1-null, Pcmt1 heterozygous, and
wildtype mice. Highest levels of AdoMet and lower levels of AdoHcy were
found in the brains of Pcmt1-null mice, and to a lesser extent in the
heterozygous mice, when compared with wildtype mice. These levels were
most significantly altered in the hippocampus. Farrar and Clarke (2002)
concluded that the AdoMet/AdoHcy ratio could potentially alter the
overall excitatory state of the brain and may play a role in the
progressive epilepsy seen in Pcmt1-null mice.
*FIELD* SA
MacLaren et al. (1992); Ota et al. (1988)
*FIELD* RF
1. DeVry, C. G.; 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:
130-131, 1999.
2. Farrar, C.; Clarke, S.: Altered levels of S-adenosylmethionine
and S-adenosylhomocysteine in the brains of L-isoaspartyl (D-aspartyl)
O-methyltransferase-deficient mice. J. Biol. Chem. 277: 27856-27863,
2002.
3. Ingrosso, D.; Kagan, R. M.; 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: 351-358,
1991. Note: Erratum: Biochem. Biophys. Res. Commun. 176: 549 only,
1991.
4. Kim, E.; Lowenson, J. D.; Clarke, S.; Young, S. G.: Phenotypic
analysis of seizure-prone mice lacking L-isoaspartate (D-aspartate)
O-methyltransferase. J. Biol. Chem. 274: 20671-20678, 1999.
5. Lowenson, J. D.; Kim, E.; Young, S. G.; Clarke, S.: Limited accumulation
of damaged proteins in L-isoaspartyl (D-aspartyl) O-methyltransferase-deficient
mice. J. Biol. Chem. 276: 20695-20702, 2001.
6. MacLaren, D. C.; Kagan, R. M.; Clarke, S.: Alternative splicing
of the human isoaspartyl protein carboxyl methyltransferase leads
to the generation of a C-terminal -RDEL sequence in isozyme II. Biochem.
Biophys. Res. Commun. 185: 277-283, 1992.
7. MacLaren, D. C.; O'Connor, C. M.; Xia, Y.-R.; Mehrabian, M.; Klisak,
I.; Sparkes, R. S.; Clarke, S.; Lusis, A. J.: 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: 852-856,
1992.
8. Ota, I. M.; Gilbert, J. M.; Clarke, S.: Two major isozymes of
the protein D-aspartyl/L-isoaspartyl methyltransferase from human
erythrocytes. Biochem. Biophys. Res. Commun. 151: 1136-1143, 1988.
*FIELD* CN
Patricia A. Hartz - updated: 10/3/2002
*FIELD* CD
Victor A. McKusick: 1/14/1993
*FIELD* ED
terry: 12/20/2012
terry: 3/16/2005
mgross: 10/3/2002
carol: 2/11/1993
carol: 1/14/1993