Protein phosphatase methylesterase 1 (PPME1)
The protein contains 386 amino acids for an estimated molecular weight of 42315 Da.
Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme. (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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
(right-click above to access to more options from the contextual menu)
Biological Process
G2/M transition of mitotic cell cycle
Negative regulation of catalytic activity
Protein demethylation
Regulation of catalytic activity
Molecular Function
Cadherin binding
Protein C-terminal methylesterase activity
Protein kinase binding
Protein methylesterase activity
Protein phosphatase 2A binding
Protein phosphatase binding
Protein phosphatase inhibitor activity
Protein phosphatase regulator activity
Protein phosphatase type 2A regulator activity
The reference OMIM entry for this protein is 611117
Protein phosphatase methylesterase 1; ppme1
Pme1
DESCRIPTION
Protein phosphatase methylesterase-1 catalyzes the demethylation of the protein phosphatase-2A catalytic subunit (PPP2CA; 176915) (Ogris et al., 1999).CLONING
Using immunoprecipitation and characterization of stable protein complexes formed with catalytically inactive PPP2CA mutants H59Q and H118Q, Ogris et al. (1999) identified an approximately 44-kD PPP2CA-associated protein and cloned the cDNA, designated PPME1, from HeLa cell mRNA by RT-PCR. The deduced 386-amino acid protein shares 40% and 26% sequence identity with the C. elegans and S. cerevisiae homologs, respectively. Human PPME1 contains a highly charged stretch of amino acids, and all 3 PPME1 homologs contain a consensus sequence for lipases that use an active site serine.GENE FUNCTION
By immunoprecipitation analysis with wildtype and H59Q and H118Q mutant PPP2CA, Ogris et al. (1999) showed that PPME1 forms a stable complex with the catalytically inactive mutant subunits but not with the wildtype subunit. Expression of PPME1 in bacteria demonstrated that PPME1 has PPP2CA methylesterase activity that is inhibited by the PPP2CA inhibitor okadaic acid but not by the serine protease inhibitor PMSF. By coimmunoprecipitation experiments, Ogris et al. (1999) showed that the PPP2CA inhibitors okadaic acid, sodium fluoride, and sodium pyrophosphate decreased the association of PPME1 with the H59Q mutant.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PPME1 gene to chromosome 11 (TMAP RH11842).BIOCHEMICAL FEATURES
- Crystal Structure Xing et al. (2008) reported the crystal structure at 2.1-angstrom resolution of human PME1 by itself and in complex with a PP2A heterodimeric core enzyme, which consists of PPP2CA and PPP2R1A (605983). The structures revealed that PME1 directly binds to the active site of PP2A and that this interaction results in the activation of PME1 by rearranging its catalytic triad residues into an active conformation. This interaction also leads to inactivation of PP2A by evicting the manganese ions required for the phosphatase activity of PP2A. ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 611117 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed