Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT1)
The protein contains 227 amino acids for an estimated molecular weight of 24636 Da.
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. Acts on EIF4EBP2, microtubule-associated protein 2, calreticulin, clathrin light chains a and b, Ubiquitin carboxyl-terminal hydrolase isozyme L1, phosphatidylethanolamine-binding protein 1, stathmin, beta-synuclein and alpha-synuclein. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs4816 |
Cellular Component
Cytoplasm
Cytosol
Endoplasmic reticulum
Extracellular exosome
Extracellular vesicle
Vesicle
The reference OMIM entry for this protein is 176851
Protein carboxyl methyltransferase 1; pcmt1
L-isoaspartyl/d-aspartyl protein methyltransferase
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 PCMT
1 (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 PCMT
1 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 PCMT
1 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, PCMT
1 converts the methyl donor S-adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy). Farrar and Clarke (2002) measured these metabol ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 176851 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed