human-PPME1
Homo sapiens (Human) protein phosphatase PP2A methylesterase-1 (EC 3.1.1.-) (pme-1)
Comment
PP2A dimethyl-esterase (PME-1). PME-1 Catalyzes the demethylation of protein phosphatases 2A (PP2A) and PP4 catalytic subunits to alter the composition of holoenzymes. Elevated PME-1 protein levels are observed in neurodegenerative diseases and cancer, suggesting the involvement of dysregulation of PP2A\/PP4 methylation. However, PME-1 also forms stable complexes with the catalytic subunit of PP2A to interfere with phosphatase activity. The loss of methylesterase activity due to the S156A mutation resulted in systemic apoptosis characterized by brain atrophy: the layers of the cerebellum collapsed with fewer Purkinje cells and more microglia. M335D mutant pups did not appear deformed and had intact brains but died about two days after birth with a demonstrated loss of olfaction and apoptosis in the olfactory epithelium (Ikeda et al. <\/A>)
Relationship
Family : PPase_methylesterase_euk
Block : X
Position in NCBI Life Tree : Homo sapiens
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)
> cellular organisms N E > Eukaryota N E > Opisthokonta N E > Metazoa N E > Eumetazoa N E > Bilateria N E > Deuterostomia N E > Chordata N E > Craniata N E > Vertebrata N E > Gnathostomata N E > Teleostomi N E > Euteleostomi N E > Sarcopterygii N E > Dipnotetrapodomorpha N E > Tetrapoda N E > Amniota N E > Mammalia N E > Theria N E > Eutheria N E > Boreoeutheria N E > Euarchontoglires N E > Primates N E > Haplorrhini N E > Simiiformes N E > Catarrhini N E > Hominoidea N E > Hominidae N E > Homininae N E > Homo N E > Homo sapiens N EMolecular evidence
No mutation
No kinetic
No disease
No substrate
Sequence
Peptide
MSALEKSMHL GRLPSRPPLP GSGGSQSGAK MRMGPGRKRD FSPVPWSQYF ESMEDVEVEN ETGKDTFRVY KSGSEGPVLL LLHGGGHSAL SWAVFTAAII SRVQCRIVAL DLRSHGETKV KNPEDLSAET MAKDVGNVVE AMYGDLPPPI MLIGHSMGGA IAVHTASSNL VPSLLGLCMI DVVEGTAMDA LNSMQNFLRG RPKTFKSLEN AIEWSVKSGQ IRNLESARVS MVGQVKQCEG ITSPEGSKSI VEGIIEEEEE DEEGSESISK RKKEDDMETK KDHPYTWRIE LAKTEKYWDG WFRGLSNLFL SCPIPKLLLL AGVDRLDKDL TIGQMQGKFQ MQVLPQCGHA VHEDAPDKVA EAVATFLIRH RFAEPIGGFQ CVFPGC
References (27)
| Title : Two Distinct Mechanisms of PP2A Regulation by Methylesterase PME-1 Are Both Essential for Mouse Development - Ikeda_2025_Faseb.j_39_e70554 |
| Author(s) : Ikeda S , Ando S , Kishida N , Tanaka K , Sakurai M , Sakai Y , Ayabe S , Mizuno-Iijima S , Yoshiki A , Nakashima K , Tsuji S , Asagiri M , Baba T , Takeda K , Sato K , Ohama T |
| Ref : Faseb j , 39 :e70554 , 2025 |
| Abstract : |
| PubMedSearch : Ikeda_2025_Faseb.j_39_e70554 |
| PubMedID: 40326231 |
| Gene_locus related to this paper: human-PPME1 , mouse-PPME1 |
| Title : PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers - Aakula_2023_Mol.Oncol_17_1007 |
| Author(s) : Aakula A , Isomursu A , Rupp C , Erickson A , Gupta N , Kauko O , Shah P , Padzik A , Pokharel YR , Kaur A , Li SP , Trotman L , Taimen P , Rannikko A , Lammerding J , Paatero I , Mirtti T , Ivaska J , Westermarck J |
| Ref : Mol Oncol , 17 :1007 , 2023 |
| Abstract : |
| PubMedSearch : Aakula_2023_Mol.Oncol_17_1007 |
| PubMedID: 36461911 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Transcriptome analysis revealed that PME-1 suppresses inflammatory signaling, activates PI3K\/Akt signaling, and promotes epithelial-mesenchymal transition - Ikeda_2023_Biochem.Biophys.Res.Commun_692_149148 |
| Author(s) : Ikeda S , Sato K , Ohama T |
| Ref : Biochemical & Biophysical Research Communications , 692 :149148 , 2023 |
| Abstract : |
| PubMedSearch : Ikeda_2023_Biochem.Biophys.Res.Commun_692_149148 |
| PubMedID: 38043157 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition - Li_2022_Elife_11_e79736 |
| Author(s) : Li Y , Balakrishnan VK , Rowse M , Wu CG , Bravos AP , Yadav VK , Ivarsson Y , Strack S , Novikova IV , Xing Y |
| Ref : Elife , 11 : , 2022 |
| Abstract : |
| PubMedSearch : Li_2022_Elife_11_e79736 |
| PubMedID: 35924897 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Involvement of PP2A methylation in the adipogenic differentiation of bone marrow-derived mesenchymal stem cell - Ikeda_2020_J.Biochem_168_643 |
| Author(s) : Ikeda S , Tsuji S , Ohama T , Sato K |
| Ref : J Biochem , 168 :643 , 2020 |
| Abstract : |
| PubMedSearch : Ikeda_2020_J.Biochem_168_643 |
| PubMedID: 32663263 |
| Gene_locus related to this paper: human-PPME1 |
| Title : DNAH17-AS1 promotes pancreatic carcinoma by increasing PPME1 expression via inhibition of miR-432-5p - Xu_2020_World.J.Gastroenterol_26_1745 |
| Author(s) : Xu T , Lei T , Li SQ , Mai EH , Ding FH , Niu B |
| Ref : World J Gastroenterol , 26 :1745 , 2020 |
| Abstract : |
| PubMedSearch : Xu_2020_World.J.Gastroenterol_26_1745 |
| PubMedID: 32351291 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Glycogen synthase kinase-3beta suppresses the expression of protein phosphatase methylesterase-1 through beta-catenin - Jin_2019_Aging.(Albany.NY)_11_9672 |
| Author(s) : Jin N , Shi R , Jiang Y , Chu D , Gong CX , Iqbal K , Liu F |
| Ref : Aging (Albany NY) , 11 :9672 , 2019 |
| Abstract : |
| PubMedSearch : Jin_2019_Aging.(Albany.NY)_11_9672 |
| PubMedID: 31714894 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Hydrogen peroxide redistributes the localization of protein phosphatase methylesterase 1 - Tang_2018_Life.Sci_213_166 |
| Author(s) : Tang S , Lu C , Mo L , Wang X , Liang Z , Qin F , Liu Y , Huang H , Huang Y , Cai H , Xiao D , Guo S , Ouyang Y , Sun B , Li X |
| Ref : Life Sciences , 213 :166 , 2018 |
| Abstract : |
| PubMedSearch : Tang_2018_Life.Sci_213_166 |
| PubMedID: 30340029 |
| Gene_locus related to this paper: human-PPME1 |
| Title : PME-1 is regulated by USP36 in ERK and Akt signaling pathways - Kim_2018_FEBS.Lett_592_1575 |
| Author(s) : Kim SY , Choi J , Lee DH , Park JH , Hwang YJ , Baek KH |
| Ref : FEBS Letters , 592 :1575 , 2018 |
| Abstract : |
| PubMedSearch : Kim_2018_FEBS.Lett_592_1575 |
| PubMedID: 29577269 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Regulation of protein phosphatase 2A (PP2A) tumor suppressor function by PME-1 - Kaur_2016_Biochem.Soc.Trans_44_1683 |
| Author(s) : Kaur A , Westermarck J |
| Ref : Biochemical Society Transactions , 44 :1683 , 2016 |
| Abstract : |
| PubMedSearch : Kaur_2016_Biochem.Soc.Trans_44_1683 |
| PubMedID: 27913678 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Inhibition of protein methylesterase 1 decreased cancerous phenotypes in endometrial adenocarcinoma cell lines and xenograft tumor models - Pusey_2016_Tumour.Biol_37_11835 |
| Author(s) : Pusey M , Bail S , Xu Y , Buiakova O , Nestor M , Yang JJ , Rice LM |
| Ref : Tumour Biol , 37 :11835 , 2016 |
| Abstract : |
| PubMedSearch : Pusey_2016_Tumour.Biol_37_11835 |
| PubMedID: 27048286 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Protein Phosphatase Methyl-Esterase PME-1 Protects Protein Phosphatase 2A from Ubiquitin\/Proteasome Degradation - Yabe_2015_PLoS.One_10_e0145226 |
| Author(s) : Yabe R , Miura A , Usui T , Mudrak I , Ogris E , Ohama T , Sato K |
| Ref : PLoS ONE , 10 :e0145226 , 2015 |
| Abstract : |
| PubMedSearch : Yabe_2015_PLoS.One_10_e0145226 |
| PubMedID: 26678046 |
| Gene_locus related to this paper: human-PPME1 , mouse-PPME1 |
| Title : A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size - Xia_2015_Cell.Cycle_14_1938 |
| Author(s) : Xia X , Gholkar A , Senese S , Torres JZ |
| Ref : Cell Cycle , 14 :1938 , 2015 |
| Abstract : |
| PubMedSearch : Xia_2015_Cell.Cycle_14_1938 |
| PubMedID: 25839665 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Interaction between salt-inducible kinase 2 and protein phosphatase 2A regulates the activity of calcium\/calmodulin-dependent protein kinase I and protein phosphatase methylesterase-1 - Lee_2014_J.Biol.Chem_289_21108 |
| Author(s) : Lee CW , Yang FC , Chang HY , Chou H , Tan BC , Lee SC |
| Ref : Journal of Biological Chemistry , 289 :21108 , 2014 |
| Abstract : |
| PubMedSearch : Lee_2014_J.Biol.Chem_289_21108 |
| PubMedID: 24841198 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Genetic amplification of PPME1 in gastric and lung cancer and its potential as a novel therapeutic target - Li_2014_Cancer.Biol.Ther_15_128 |
| Author(s) : Li J , Han S , Qian Z , Su X , Fan S , Fu J , Liu Y , Yin X , Gao Z , Zhang J , Yu DH , Ji Q |
| Ref : Cancer Biol Ther , 15 :128 , 2014 |
| Abstract : |
| PubMedSearch : Li_2014_Cancer.Biol.Ther_15_128 |
| PubMedID: 24253382 |
| Gene_locus related to this paper: human-PPME1 |
| Title : A high-throughput, multiplexed assay for superfamily-wide profiling of enzyme activity - Bachovchin_2014_Nat.Chem.Biol_10_656 |
| Author(s) : Bachovchin DA , Koblan LW , Wu W , Liu Y , Li Y , Zhao P , Woznica I , Shu Y , Lai JH , Poplawski SE , Kiritsy CP , Healey SE , DiMare M , Sanford DG , Munford RS , Bachovchin WW , Golub TR |
| Ref : Nat Chemical Biology , 10 :656 , 2014 |
| Abstract : |
| PubMedSearch : Bachovchin_2014_Nat.Chem.Biol_10_656 |
| PubMedID: 24997602 |
| Gene_locus related to this paper: human-PPME1 |
| Title : The biogenesis of active protein phosphatase 2A holoenzymes: a tightly regulated process creating phosphatase specificity - Sents_2013_Febs.j_280_644 |
| Author(s) : Sents W , Ivanova E , Lambrecht C , Haesen D , Janssens V |
| Ref : Febs J , 280 :644 , 2013 |
| Abstract : |
| PubMedSearch : Sents_2013_Febs.j_280_644 |
| PubMedID: 22443683 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Glycogen synthase kinase-3beta regulates leucine-309 demethylation of protein phosphatase-2A via PPMT1 and PME-1 - Yao_2012_FEBS.Lett_586_2522 |
| Author(s) : Yao XQ , Li XC , Zhang XX , Yin YY , Liu B , Luo DJ , Wang Q , Wang JZ , Liu GP |
| Ref : FEBS Letters , 586 :2522 , 2012 |
| Abstract : |
| PubMedSearch : Yao_2012_FEBS.Lett_586_2522 |
| PubMedID: 22732552 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors - Bachovchin_2011_Proc.Natl.Acad.Sci.U.S.A_108_6811 |
| Author(s) : Bachovchin DA , Mohr JT , Speers AE , Wang C , Berlin JM , Spicer TP , Fernandez-Vega V , Chase P , Hodder PS , Schurer SC , Nomura DK , Rosen H , Fu GC , Cravatt BF |
| Ref : Proc Natl Acad Sci U S A , 108 :6811 , 2011 |
| Abstract : |
| PubMedSearch : Bachovchin_2011_Proc.Natl.Acad.Sci.U.S.A_108_6811 |
| PubMedID: 21398589 |
| Gene_locus related to this paper: human-PPME1 |
| Title : PME-1 protects extracellular signal-regulated kinase pathway activity from protein phosphatase 2A-mediated inactivation in human malignant glioma - Puustinen_2009_Cancer.Res_69_2870 |
| Author(s) : Puustinen P , Junttila MR , Vanhatupa S , Sablina AA , Hector ME , Teittinen K , Raheem O , Ketola K , Lin S , Kast J , Haapasalo H , Hahn WC , Westermarck J |
| Ref : Cancer Research , 69 :2870 , 2009 |
| Abstract : |
| PubMedSearch : Puustinen_2009_Cancer.Res_69_2870 |
| PubMedID: 19293187 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Structural mechanism of demethylation and inactivation of protein phosphatase 2A - Xing_2008_Cell_133_154 |
| Author(s) : Xing Y , Li Z , Chen Y , Stock JB , Jeffrey PD , Shi Y |
| Ref : Cell , 133 :154 , 2008 |
| Abstract : |
| PubMedSearch : Xing_2008_Cell_133_154 |
| PubMedID: 18394995 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Spatial control of protein phosphatase 2A (de)methylation - Longin_2008_Exp.Cell.Res_314_68 |
| Author(s) : Longin S , Zwaenepoel K , Martens E , Louis JV , Rondelez E , Goris J , Janssens V |
| Ref : Experimental Cell Research , 314 :68 , 2008 |
| Abstract : |
| PubMedSearch : Longin_2008_Exp.Cell.Res_314_68 |
| PubMedID: 17803990 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Generation of active protein phosphatase 2A is coupled to holoenzyme assembly - Hombauer_2007_PLoS.Biol_5_e155 |
| Author(s) : Hombauer H , Weismann D , Mudrak I , Stanzel C , Fellner T , Lackner DH , Ogris E |
| Ref : PLoS Biol , 5 :e155 , 2007 |
| Abstract : |
| PubMedSearch : Hombauer_2007_PLoS.Biol_5_e155 |
| PubMedID: 17550305 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Methylation of the C-terminal leucine residue of the PP2A catalytic subunit is unnecessary for the catalytic activity and the binding of regulatory subunit (PR55\/B) - Ikehara_2007_Biochem.Biophys.Res.Commun_354_1052 |
| Author(s) : Ikehara T , Ikehara S , Imamura S , Shinjo F , Yasumoto T |
| Ref : Biochemical & Biophysical Research Communications , 354 :1052 , 2007 |
| Abstract : |
| PubMedSearch : Ikehara_2007_Biochem.Biophys.Res.Commun_354_1052 |
| PubMedID: 17274953 |
| Gene_locus related to this paper: human-PPME1 |
| Title : Carboxyl methylation regulates phosphoprotein phosphatase 2A by controlling the association of regulatory B subunits - Tolstykh_2000_EMBO.J_19_5682 |
| Author(s) : Tolstykh T , Lee J , Vafai S , Stock JB |
| Ref : EMBO Journal , 19 :5682 , 2000 |
| Abstract : |
| PubMedSearch : Tolstykh_2000_EMBO.J_19_5682 |
| PubMedID: 11060019 |
| Gene_locus related to this paper: human-PPME1 |
| Title : A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A - Ogris_1999_J.Biol.Chem_274_14382 |
| Author(s) : Ogris E , Du X , Nelson KC , Mak EK , Yu XX , Lane WS , Pallas DC |
| Ref : Journal of Biological Chemistry , 274 :14382 , 1999 |
| Abstract : |
| PubMedSearch : Ogris_1999_J.Biol.Chem_274_14382 |
| PubMedID: 10318862 |
| Gene_locus related to this paper: human-PPME1 , mouse-PPME1 |
| Title : A specific protein carboxyl methylesterase that demethylates phosphoprotein phosphatase 2A in bovine brain - Lee_1996_Proc.Natl.Acad.Sci.U.S.A_93_6043 |
| Author(s) : Lee J , Chen Y , Tolstykh T , Stock J |
| Ref : Proc Natl Acad Sci U S A , 93 :6043 , 1996 |
| Abstract : |
| PubMedSearch : Lee_1996_Proc.Natl.Acad.Sci.U.S.A_93_6043 |
| PubMedID: 8650216 |
| Gene_locus related to this paper: human-PPME1 |