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Information on EC 2.1.1.233 - [phosphatase 2A protein]-leucine-carboxy methyltransferase
for references in articles please use BRENDA:EC2.1.1.233
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EC Tree 2 Transferases
2.1 Transferring one-carbon groups
2.1.1 Methyltransferases
2.1.1.233 [phosphatase 2A protein]-leucine-carboxy methyltransferase
IUBMB Comments
Methylates the C-terminal leucine of phosphatase 2A. A key regulator of protein phosphatase 2A. The methyl ester is hydrolysed by EC 3.1.1.89 (protein phosphatase methylesterase-1). Occurs mainly in the cytoplasm, Golgi region and late endosomes.
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 2.1.1.233
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demethylation
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holoenzyme
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methylesterase-1
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methylesterification
- tauopathies
Reaction Schemes
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[phosphatase 2A protein]-leucine
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[phosphatase 2A protein]-leucine methyl ester
Synonyms
pme-1, lcmt-1, lcmt1, pp2a methyltransferase, leucine carboxyl methyltransferase, leucine carboxyl methyltransferase-1, leucine carboxyl methyltransferase 1, ppm1p, pp2a-specific methyltransferase, leucine carboxyl methyl transferase 1, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
LCMT-1
LCMT1
leucine carboxy methyltransferase-1
leucine carboxyl methyltransferase
leucine carboxyl methyltransferase 1
leucine carboxyl methyltransferase 1 homolog
leucine carboxylmethyltransferase-1
PME-1
PP2A LCMT
PP2A methyltransferase
PP2A-methyltransferase
Ppm1p
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major phosphatase 2A protein methyltransferase in Saccharomyces cerevisiae
PPMT
protein phosphatase 2A leucine carboxyl methyltransferase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine = S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:[phosphatase 2A protein]-leucine O-methyltransferase
Methylates the C-terminal leucine of phosphatase 2A. A key regulator of protein phosphatase 2A. The methyl ester is hydrolysed by EC 3.1.1.89 (protein phosphatase methylesterase-1). Occurs mainly in the cytoplasm, Golgi region and late endosomes.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
S-adenosyl-L-methionine + [phosphatase 2A-C protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A-C protein]-leucine methyl ester
S-adenosyl-L-methionine + [protein phosphatase 4 catalytic subunit]-leucine
S-adenosyl-L-homocysteine + [protein phosphatase 4 catalytic subunit]-leucine methyl ester
S-adenosyl-L-methionine + [protein phosphatase 6 catalytic subunit]-leucine
S-adenosyl-L-homocysteine + [protein phosphatase 6 catalytic subunit]-leucine methyl ester
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
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Substrates: -
Products: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
Products: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
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Substrates: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
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Substrates: the enzyme LCMT1 methylates the terminal carboxyl group of the leucine 309 residue of protein phosphatase 2A protein
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
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Substrates: the enzyme exclusively methylates the carboxyl group of the C-terminal leucine residue of the catalytic subunit of protein phosphatase 2A (Leu309)
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
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Substrates: -
Products: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
Products: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
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Substrates: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: LCMT-1 is the major methyltransferase in embryonic fibroblasts for all three PP2A subfamily phosphatases, PP2Ac, PP4c, and PP6c
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
Products: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
Products: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
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Substrates: the enzyme catalyzes the methylation of the phosphatase 2A protein C subunit carboxyl-terminal leucine
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
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Substrates: the enzyme exclusively methylates the carboxyl group of the C-terminal leucine residue of the catalytic subunit of protein phosphatase 2A (Leu309)
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
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Substrates: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
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Substrates: absolut specific methylation of Leu309 in the C subunit of phosphatase 2A protein, no activity with Leu309DELTA PPA2 mutant
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
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Substrates: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
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Substrates: specific for
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
Substrates: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
Substrates: -
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S-adenosyl-L-methionine + [phosphatase 2A-C protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A-C protein]-leucine methyl ester
Substrates: -
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S-adenosyl-L-methionine + [phosphatase 2A-C protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A-C protein]-leucine methyl ester
Substrates: -
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S-adenosyl-L-methionine + [protein phosphatase 4 catalytic subunit]-leucine
S-adenosyl-L-homocysteine + [protein phosphatase 4 catalytic subunit]-leucine methyl ester
Substrates: LCMT-1 is the major methyltransferase in embryonic fibroblasts for all three PP2A subfamily phosphatases, PP2Ac, PP4c, and PP6c
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S-adenosyl-L-methionine + [protein phosphatase 4 catalytic subunit]-leucine
S-adenosyl-L-homocysteine + [protein phosphatase 4 catalytic subunit]-leucine methyl ester
Substrates: -
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S-adenosyl-L-methionine + [protein phosphatase 6 catalytic subunit]-leucine
S-adenosyl-L-homocysteine + [protein phosphatase 6 catalytic subunit]-leucine methyl ester
Substrates: LCMT-1 is the major methyltransferase in embryonic fibroblasts for all three PP2A subfamily phosphatases, PP2Ac, PP4c, and PP6c
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S-adenosyl-L-methionine + [protein phosphatase 6 catalytic subunit]-leucine
S-adenosyl-L-homocysteine + [protein phosphatase 6 catalytic subunit]-leucine methyl ester
Substrates: -
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additional information
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Substrates: no activity changes are observed upon methylation of dimeric and trimeric phosphatase 2A protein
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additional information
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Substrates: enzyme LCMT1 is a class 1 S-adenosylmethionine-dependent methyltransferase with PP2A as its only known substrate
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additional information
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Substrates: peptides mimicking the C-terminal tail of PP2A are not substrates of LCMT1
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additional information
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Substrates: no activity changes are observed upon methylation of dimeric and trimeric phosphatase 2A protein
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
S-adenosyl-L-methionine + [phosphatase 2A-C protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A-C protein]-leucine methyl ester
S-adenosyl-L-methionine + [protein phosphatase 4 catalytic subunit]-leucine
S-adenosyl-L-homocysteine + [protein phosphatase 4 catalytic subunit]-leucine methyl ester
Substrates: LCMT-1 is the major methyltransferase in embryonic fibroblasts for all three PP2A subfamily phosphatases, PP2Ac, PP4c, and PP6c
Products: -
Products: -
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S-adenosyl-L-methionine + [protein phosphatase 6 catalytic subunit]-leucine
S-adenosyl-L-homocysteine + [protein phosphatase 6 catalytic subunit]-leucine methyl ester
Substrates: LCMT-1 is the major methyltransferase in embryonic fibroblasts for all three PP2A subfamily phosphatases, PP2Ac, PP4c, and PP6c
Products: -
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additional information
?
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Substrates: enzyme LCMT1 is a class 1 S-adenosylmethionine-dependent methyltransferase with PP2A as its only known substrate
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: LCMT-1 is the major methyltransferase in embryonic fibroblasts for all three PP2A subfamily phosphatases, PP2Ac, PP4c, and PP6c
Products: -
Products: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
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Substrates: -
Products: -
Products: -
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S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
-
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + [phosphatase 2A-C protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A-C protein]-leucine methyl ester
Substrates: -
Products: -
Products: -
?
S-adenosyl-L-methionine + [phosphatase 2A-C protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A-C protein]-leucine methyl ester
Substrates: -
Products: -
Products: -
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
alpha-synuclein
alpha-syn, negatively regulates protein phosphatase 2A (PP2A) methylation via LCMT-1 and PME-1, whilst activation of LCMT-1 and inhibition of PME-1 reverses this process
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
stimulation of Gi-coupled adenosine type 1 receptors with N6-cyclopentyladenosine, and of other Gi-coupled receptors such as muscarinic M2 receptors (stimulated with carbachol) and angiotensin II AT2 receptors (stimulated with CGP42112) in adult rat ventricular myocytes, specifically induces methyltransferase LCMT-1 for PP2AC carboxylmethylation at Leu309 in a concentration-dependent manner. PI3K activity is upregulated in response to adenosine type 1 receptor stimulation
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
PME-1 modulates protein phosphatase 2A activity to promote the malignant phenotype of endometrial cancer cells.
Alzheimer Disease
Protein Phosphatase 2A and Its Methylation Modulating Enzymes LCMT-1 and PME-1 Are Dysregulated in Tauopathies of Progressive Supranuclear Palsy and Alzheimer Disease.
Alzheimer Disease
Reduced Expression of the PP2A Methylesterase, PME-1, or the PP2A Methyltransferase, LCMT-1, Alters Sensitivity to Beta-Amyloid-Induced Cognitive and Electrophysiological Impairments in Mice.
Astrocytoma
PME-1 protects extracellular signal-regulated kinase pathway activity from protein phosphatase 2A-mediated inactivation in human malignant glioma.
Carcinoma, Hepatocellular
Expression Pattern and Prognostic Utility of PME-1 in Patients with Hepatocellular Carcinoma.
Endometrial Neoplasms
Inhibition of protein methylesterase 1 decreased cancerous phenotypes in endometrial adenocarcinoma cell lines and xenograft tumor models.
Endometrial Neoplasms
PME-1 modulates protein phosphatase 2A activity to promote the malignant phenotype of endometrial cancer cells.
Glioblastoma
NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability.
Glioma
PME-1 protects extracellular signal-regulated kinase pathway activity from protein phosphatase 2A-mediated inactivation in human malignant glioma.
Memory Disorders
Methionine-Mediated Protein Phosphatase 2A Catalytic Subunit (PP2Ac) Methylation Ameliorates the Tauopathy Induced by Manganese in Cell and Animal Models.
methylenetetrahydrofolate dehydrogenase (nad+) deficiency
Altered protein phosphatase 2A methylation and Tau phosphorylation in the young and aged brain of methylenetetrahydrofolate reductase (MTHFR) deficient mice.
Neoplasm Metastasis
Expression Pattern and Prognostic Utility of PME-1 in Patients with Hepatocellular Carcinoma.
Neoplasms
Expression Pattern and Prognostic Utility of PME-1 in Patients with Hepatocellular Carcinoma.
Neoplasms
Inhibition of protein methylesterase 1 decreased cancerous phenotypes in endometrial adenocarcinoma cell lines and xenograft tumor models.
Neoplasms
PME-1 modulates protein phosphatase 2A activity to promote the malignant phenotype of endometrial cancer cells.
Neoplasms
PME-1 protects extracellular signal-regulated kinase pathway activity from protein phosphatase 2A-mediated inactivation in human malignant glioma.
Neoplasms
Protein phosphatase methylesterase-1 (PME-1) expression predicts a favorable clinical outcome in colorectal cancer.
Neoplasms
Relevance Rank Platform (RRP) for Functional Filtering of High Content Protein-Protein Interaction Data.
Neuroblastoma
Folate deficiency induces in vitro and mouse brain region-specific downregulation of leucine carboxyl methyltransferase-1 and protein phosphatase 2A B(alpha) subunit expression that correlate with enhanced tau phosphorylation.
Neuroblastoma
Leucine Carboxyl Methyltransferase 1 (LCMT1)-dependent Methylation Regulates the Association of Protein Phosphatase 2A and Tau Protein with Plasma Membrane Microdomains in Neuroblastoma Cells.
Neuroblastoma
Protein phosphatase 2A methyltransferase links homocysteine metabolism with tau and amyloid precursor protein regulation.
Neuroblastoma
Regulation of protein phosphatase 2A methylation by LCMT1 and PME-1 plays a critical role in differentiation of neuroblastoma cells.
Osteoporosis
Absorption and transport of a Mytilus edulis-derived peptide with the function of preventing osteoporosis.
Paralysis
Protein Phosphatase 2A and Its Methylation Modulating Enzymes LCMT-1 and PME-1 Are Dysregulated in Tauopathies of Progressive Supranuclear Palsy and Alzheimer Disease.
Rectal Neoplasms
Protein phosphatase methylesterase-1 (PME-1) expression predicts a favorable clinical outcome in colorectal cancer.
Starvation
Folate deficiency induces in vitro and mouse brain region-specific downregulation of leucine carboxyl methyltransferase-1 and protein phosphatase 2A B(alpha) subunit expression that correlate with enhanced tau phosphorylation.
Supranuclear Palsy, Progressive
Protein Phosphatase 2A and Its Methylation Modulating Enzymes LCMT-1 and PME-1 Are Dysregulated in Tauopathies of Progressive Supranuclear Palsy and Alzheimer Disease.
Tauopathies
Folate deficiency induces in vitro and mouse brain region-specific downregulation of leucine carboxyl methyltransferase-1 and protein phosphatase 2A B(alpha) subunit expression that correlate with enhanced tau phosphorylation.
Tauopathies
Protein Phosphatase 2A and Its Methylation Modulating Enzymes LCMT-1 and PME-1 Are Dysregulated in Tauopathies of Progressive Supranuclear Palsy and Alzheimer Disease.
[phosphatase 2a protein]-leucine-carboxy methyltransferase deficiency
Circumventing embryonic lethality with Lcmt1 deficiency: generation of hypomorphic Lcmt1 mice with reduced protein phosphatase 2A methyltransferase expression and defects in insulin signaling.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0018
[phosphatase 2A protein]-leucine
pH and temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
immunohistochemic analysis of LCMT-1 content in human postmortem brain sections, brain from humans with disease, such as progressive supranuclear palsy and Alzheimer's disease, clinical and neuropathological characteristics, overview
brenda
isolated from proximal caput, distal caput, and caudal regions of the epididymis
brenda
isolated from proximal caput, distal caput, and caudal regions of the epididymis
brenda
additional information
enzyme expression analysis in wild-type and mutant plant organs, overview
brenda
additional information
-
enzyme expression analysis in wild-type and mutant plant organs, overview
brenda
additional information
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enzyme expression analysis in wild-type and mutant plant organs, overview
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brenda
additional information
immunohistochemic enzyme detection in tissues
brenda
additional information
immunohistochemic enzyme detection in tissues
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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the enzyme is underrepresented in the nucleus and mainly localized to the cytoplasm, Golgi region and late endosomes
brenda
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the enzyme is underrepresented in the nucleus and mainly localized to the cytoplasm, Golgi region and late endosomes
brenda
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the enzyme is underrepresented in the nucleus and mainly localized to the cytoplasm, Golgi region and late endosomes
brenda
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LCMT1 and methylated phosphatase 2A protein are concentrated in rafts, whereas demethylated phosphatase 2A protein and small amounts of PME-1 are preferentially distributed in non-raft membrane microdomains
brenda
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the enzyme is underrepresented in the nucleus and mainly localized to the cytoplasm, Golgi region and late endosomes
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
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deletion of phosphatase 2A protein methyltransferase PPM1 greatly reduces Cdc55p, Tpd3p, and Rts1p binding and leads to nocodazole sensitivity
malfunction
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a dominant-negative leucine carboxyl methyltransferase 1 mutant attenuates the cell cycle without causing cell death, likely by inhibiting uncontrolled phosphatase activity
malfunction
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homozygous gene trap knock-out of leucine carboxyl methyltransferase-1 in mice results in embryonic lethality
malfunction
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leucine carboxyl methyltransferase-1 (LCMT-1) knockdown reduces the formation of protein phosphatase 2A heterotrimers containing the Balpha regulatory subunit and, in a subset of the cells, induces apoptosis, characterized by caspase activation, nuclear condensation/fragmentation, and membrane blebbing. LCMT-1 knockdown cells are more sensitive to the spindle-targeting drug nocodazole
malfunction
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hypomorphic Lcmt1 mice show reduced protein phosphatase 2A methyltransferase expression due to splicing around the insertion, Lcmt1 transcript and LCMT1 protein levels are reduced but not eliminated. LCMT1 activity and methylation of protein phosphatase 2A are reduced in a coordinate fashion, suggesting that LCMT1 is the only PP2A methyltransferase. The mice exhibit an insulin-resistance phenotype. Knockout of Lcmt1 in mice is lethal during embryonic development. Male Lcmt1-/- animals display increased glucose-stimulated insulin secretion, increased insulin resistance, and decreased methylation of phosphatase 2A protein
malfunction
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depletion of leucine carboxyl methyltransferase-1, LCMT1, or overexpression of protein phosphatase methylesterase-1, PME-1, lead to long spindles. In contrast, depletion of PME-1, pharmacological inhibition of PME-1 or overexpression of LCMT1 lead to short spindles. Perturbation of the LCMT1-PME-1 methylation equilibrium leads to mitotic arrest, spindle assembly checkpoint activation, defective cell divisions, induction of apoptosis and reduced cell viability, phenotype, overview
malfunction
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reduced methylation of phosphatase 2A protein through enzyme LCMT1, a major Tau phosphatase, occurs in Alzheimer disease. Altered phosphatase 2A protein and Tau membrane distribution can promote neuronal dysfunction and phospho-Tau pathology in Alzheimer disease. Methylation-incompetent L309DELTA mutant of PP2A C subunit is excluded from membrane rafts. Expression of the inactive LCMT1 mutant inhibits the accumulation of dephosphorylated and total Tau at the plasma membrane, whereas concomitantly enhancing Tau phosphorylation at the Ser422 phospho-epitope. Partial knockdown of LCMT1 in Neuro2a cells is associated with a 42-45% decrease in total amounts of membrane-associated Tau pools relative to controls
malfunction
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decreased phosphatase 2A protein catalytic subunit methylation is linked with decreased LCMT-1 expression causing human heart failure, overview
malfunction
mouse embryonic fibroblasts derived from LCMT-1 knock-out mouse embryos have reduced levels of PP2A B regulatory subunit and PP4R1 relative to control mouse embryonic fibroblasts, indicating that LCMT-1 is important for maintaining normal levels of these subunits. LCMT-1 homozygous knock-out mouse embryonic fibroblasts exhibit hyperphosphorylation of HDAC3, a reported target of the methylation-dependent PP4R1-PP4c complex
malfunction
alpha-synuclein (alpha-syn) overexpression induces increased alpha-syn phosphorylation at Ser129, and protein phosphatase 2A (PP2A) inhibition, in vitro and in vivo. alpha-Syn overexpression results in PP2A demethylation. This demethylation is mediated via downregulated leucine carboxyl methyltransferase (LCMT-1) expression, and upregulated protein phosphatase methylesterase (PME-1, EC 3.1.1.89) expression. Furthermore, LCMT-1 overexpression, or PME-1 inhibition, reverses alpha-syn-induced increases in alpha-syn phosphorylation and apoptosis
malfunction
the lcmt1 knockout mutant possesses essentially only unmethylated PP2A-C, has less dense rosettes, and earlier flowering compared to wild-type plants. Approximately 200 overlapping genes are 2fold upregulated, and 200 overlapping genes are 2fold downregulated in both lcmt1 and pme1 knockout mutants compared to wild-type. Differences between the 2 mutants, 97 genes are 2fold upregulated in pme1 compared with lcmt1, indicating that PME1 acts as a negative regulator for these genes. Arabidopsis thaliana plants with knocked out LCMT1 (sbi1 mutant) are void of methylated PP2A-C and have unmethylated catalytic subunit PP2A-C both in the microsomal and cytosolic fractions
malfunction
increased expression of NNMT selectively affects LCMT1 resulting in lower PP2A activation. Decreased LCMT1 expression or SAH concentration decreases endogenous activated PP2A
malfunction
Protein phosphatase 2A and its methylation modulating enzymes LCMT-1 and PME-1 are dysregulated in tauopathies of progressive supranuclear palsy and Alzheimer's disease, pathologic phenotype, overview. Analyses shows a decrease of methyl-PP2A and an increase of demethyl-PP2A with a concomitant reduction in the methyl/demethyl PP2A ratio in both PSP (74%) and AD (76%) brains. This is associated with a decrease in LCMT-1 and an increase in the demethylating enzyme, protein phosphatase methylesterase (PME-1), in both diseases. State of PP2A regulation in tauopathies, overview
malfunction
-
the lcmt1 knockout mutant possesses essentially only unmethylated PP2A-C, has less dense rosettes, and earlier flowering compared to wild-type plants. Approximately 200 overlapping genes are 2fold upregulated, and 200 overlapping genes are 2fold downregulated in both lcmt1 and pme1 knockout mutants compared to wild-type. Differences between the 2 mutants, 97 genes are 2fold upregulated in pme1 compared with lcmt1, indicating that PME1 acts as a negative regulator for these genes. Arabidopsis thaliana plants with knocked out LCMT1 (sbi1 mutant) are void of methylated PP2A-C and have unmethylated catalytic subunit PP2A-C both in the microsomal and cytosolic fractions
-
malfunction
-
alpha-synuclein (alpha-syn) overexpression induces increased alpha-syn phosphorylation at Ser129, and protein phosphatase 2A (PP2A) inhibition, in vitro and in vivo. alpha-Syn overexpression results in PP2A demethylation. This demethylation is mediated via downregulated leucine carboxyl methyltransferase (LCMT-1) expression, and upregulated protein phosphatase methylesterase (PME-1, EC 3.1.1.89) expression. Furthermore, LCMT-1 overexpression, or PME-1 inhibition, reverses alpha-syn-induced increases in alpha-syn phosphorylation and apoptosis
-
metabolism
-
past global read-outs of cellular PP2A activity more appropriately represent the collective activity of numerous individual PP2A holoenzymes, each displaying a specific subcellular localization (dictated by select PP2A regulatory subunits) as well as local specific post-translational catalytic subunit methylation and phosphorylation events that regulate local and rapid holoenzyme assembly/disassembly via leucine carboxymethyltransferase 1/phosphatase methylesterase 1 (LCMT-1/PME-1), PP2A regulation system involving nine different PP2A regulatory subunits (PPP2R2A, PPP2R2B, PPP2R3A, PPP2R4, PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, and PPP2R5E) in the heart. LCMT-1 and PME-1 show cell-type and disease-linked expressional regulation, overview
metabolism
protein phosphatase 2A catalytic subunit (PP2A-C) has a terminal leucine subjected to methylation, a regulatory mechanism conserved from yeast to mammals and plants. Two enzymes, leucine carboxyl methyltransferase (LCMT-1) and protein phosphatase methylesterase (PME-1, EC 3.1.1.89), methylate and demethylate PP2A-C, respectively, physiological importance of these posttranslational modifications. Regulation, overview. In addition to catalyzing demethylation of PP2A-C, PME1 has a function in stabilizing the PP2A complex, keeping part of the PP2AC pool in an inactive state
metabolism
nicotinamide-N-methyltransferase (NNMT, EC 2.1.1.1) outcompetes leucine carboxyl methyl transferase 1 (LCMT1) for methyl transfer from principal methyl donor SAM in biological systems, because NNMT has a higher affinity for SAM as compared to LCMT1. Inhibiting NNMT increases the availability of methyl groups for LCMT1 to methylate protein phosphatase 2A (PP2A) resulting in the inhibition of oncogenic serine/threonine kinases (STKs, EC 2.7.11.). Even if there are methylated products in the system by LCMT1, which is a O-methylating enzyme, they can potentially be reversed to unmethylated form due to their reversible nature and availability of demethylases such as PME1. In contrast, N-methylating NNMT enzyme product MNA which is stable and acts as methylation sink further favoring methyl transfer by NNMT compared to LCMT1. The NNMT-PME1-LCMT1 signaling axis is one mechanism by which the activity of the MAPK/Akt pathways are maintained in cancer cells
metabolism
in vivo demethylation of sperm PP2A in the epididymis, regulation of protein phosphatase activity in sperm
metabolism
in vivo demethylation of sperm PP2A in the epididymis, regulation of protein phosphatase activity in sperm
metabolism
-
protein phosphatase 2A catalytic subunit (PP2A-C) has a terminal leucine subjected to methylation, a regulatory mechanism conserved from yeast to mammals and plants. Two enzymes, leucine carboxyl methyltransferase (LCMT-1) and protein phosphatase methylesterase (PME-1, EC 3.1.1.89), methylate and demethylate PP2A-C, respectively, physiological importance of these posttranslational modifications. Regulation, overview. In addition to catalyzing demethylation of PP2A-C, PME1 has a function in stabilizing the PP2A complex, keeping part of the PP2AC pool in an inactive state
-
physiological function
-
carboxymethylation of the PP2A catalytic subunit by phosphatase 2A protein methyltransferase PPM1 in Saccharomyces cerevisiae is required for efficient interaction with the B-type subunits Cdc55p and Rts1p
physiological function
-
regulation of protein phosphatase 2A methylation by leucine carboxy methyltransferase-1 (LCMT1) plays a critical role in differentiation of neuroblastoma cells. Enhanced expression of LCMT1 in cultured N2a neuroblastoma cells induces changes in F-actin organization. Expression of LCMT1 promotes the formation of elongated neurite-like processes
physiological function
-
the enzyme tightly controls phosphatase 2A protein function, important for the cell cycle and cell survival
physiological function
-
methylation by PP2A methyltransferase regulates PP2A phosphatase activity by promoting holoenzyme assembly
physiological function
-
leucine carboxyl methyltransferase-1 (LCMT-1) is essential for embryonic development in mice. LCMT-1 is important for spindle checkpoint
physiological function
-
leucine carboxyl methyltransferase-1 (LCMT-1) is necessary for normal progression through mitosis and cell survival. LCMT-1 is important for spindle checkpoint
physiological function
the enzyme regulates the activity and subcellular localisation of type 2A protein phosphatase, PP2A, by reversible carboxylmethylation of its C-terminal leucine 309 residue. Stimulation of adenosine type 1 receptors induces PP2AC carboxylmethylation via PI3K and alters subcellular distribution in adult rat ventricular myocytes
physiological function
-
protein phosphatase 2A is the major serine/threonine phosphatase in eukaryotic cells, its assembly is governed by a variety of mechanisms, one of which is carboxyl-terminal methylation of the catalytic subunit by the leucine carboxyl methyltransferase LCMT1. Protein phosphatase 2A is nearly stoichiometrically methylated in the cytosol. Role for this methyltransferase in signaling in insulin-sensitive tissues
physiological function
-
leucine carboxyl methyltransferase-1, LCMT1, and protein phosphatase methylesterase-1, PME-1, are essential enzymes that regulate the methylation of the protein phosphatase 2A catalytic subunit. The two enzymes have been linked to the regulation of cell growth and proliferation, and a role of LCMT1-PME-1 methylation equilibrium in controlling mitotic spindle size. The LCMT1-PME-1 methylation equilibrium is critical for regulating mitotic spindle size and thereby proper cell division
physiological function
-
leucine carboxyl methyltransferase 1-dependent methylation regulates the association of protein phosphatase 2A and Tau protein with plasma membrane microdomains in neuroblastoma cells
physiological function
the enzyme coordinately regulates the carboxyl methylation of PP2A-related phosphatases and, consequently, their holoenzyme assembly and function
physiological function
generation of transgenic mice that overexpress the leucine carboxylmethyltransferase-1 (LCMT-1). LCMT-1 overexpression protected against behavioral and electrophysiological impairments caused by exogenous Abeta exposure
physiological function
LCMT-1 overexpression or protein phosphatase methylesterase (PME-1, EC 3.1.1.89) inhibition protects against alpha-syn-induced protein phosphatase 2A (PP2A) inhibition, and increases in apoptosis of SK-N-SH cells
physiological function
protein phosphatase 2A catalytic subunit (PP2A-C) has a terminal leucine subjected to methylation, a regulatory mechanism conserved from yeast to mammals and plants. Two enzymes, leucine carboxyl methyltransferase (LCMT-1) and protein phosphatase methylesterase (PME-1, EC 3.1.1.89), methylate and demethylate PP2A-C, respectively, physiological importance of these posttranslational modifications. Active LCMT1 methylates all PP2A-C in microsomes
physiological function
methylation of protein phosphatase 2A (PP2A) activates PP2A activity
physiological function
the enzyme PP2A methyl transferase, LCMT1 responsible for transferring the methyl group from S-adenosyl methionine specifically to PP2A
physiological function
the enzyme PP2A methyl transferase, LCMT1 responsible for transferring the methyl group from S-adenosyl methionine specifically to PP2A
physiological function
in MDCK cells, overexpression of LCMT1, enhances cellular PP2A methylation, inhibits tight junction formation, induces tight junction ruffling, and decreases tight junction barrier function. LCMT1 delays the initial redistribution of ZO-1, occludin and Par3 to cell-cell contacts during Ca2+-induced tight junctions assembly and inhibits the development of tight junctions barrier function
physiological function
in a liver-specific LCMT1 knockout mouse model, hepatic glycogen synthesis and glycogen accumulation in liver are upregulated. The knockout improves high fat diet-induced glucose intolerance and insulin resistance
physiological function
in a strain lacking LCMT1, phosphatase 2A activity is reduced by about 40%. Contrary to wild-type, the number of lateral roots do not change significantly in response to Pseudomonas simiae. The mutant strain originally has low chlorophyll content compared with wild-type, but after inoculation with P. simiae reaches wild-type values
physiological function
-
protein phosphatase 2A catalytic subunit (PP2A-C) has a terminal leucine subjected to methylation, a regulatory mechanism conserved from yeast to mammals and plants. Two enzymes, leucine carboxyl methyltransferase (LCMT-1) and protein phosphatase methylesterase (PME-1, EC 3.1.1.89), methylate and demethylate PP2A-C, respectively, physiological importance of these posttranslational modifications. Active LCMT1 methylates all PP2A-C in microsomes
-
physiological function
-
the enzyme regulates the activity and subcellular localisation of type 2A protein phosphatase, PP2A, by reversible carboxylmethylation of its C-terminal leucine 309 residue. Stimulation of adenosine type 1 receptors induces PP2AC carboxylmethylation via PI3K and alters subcellular distribution in adult rat ventricular myocytes
-
physiological function
-
LCMT-1 overexpression or protein phosphatase methylesterase (PME-1, EC 3.1.1.89) inhibition protects against alpha-syn-induced protein phosphatase 2A (PP2A) inhibition, and increases in apoptosis of SK-N-SH cells
-
Show AA Sequence and Transmembrane Helices (4322 entries)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
38000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme in isolation and in complex with phosphatase 2A protein stabilized by a cofactor mimic, hanging drop vapor diffusion method, using 17-19% (w/v) PEG2000 monomethyl ether, 150 mM triethylamine N-oxide, and 5 mM dithiothreitol
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in complex with the cofactor S-adenosylmethionine, hanging drop vapor diffusion method
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native protein alone or in complexes with the S-adenosyl-L-methionine methyl donor and the S-adenosyl-L-homocysteine product and inhibitor, hanging drop vapor diffusion method, using 15% (w/v) PEG 8000 and 0.1 M potassium or sodium phosphate, pH 4.6, or 20% (w/v) PEG 8000, 0.1 M sodium acetate, and 0.1 M MES, pH 5.6, or 24% (w/v) PEG 4000, 0.2 M magnesium chloride, and 0.1 M Tris-HCl, pH 8.5
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D303R
-
the mutant shows less than 10% activity compared to the wild type enzyme
F237D
-
the mutant shows less than 10% activity compared to the wild type enzyme
N244A
-
the mutant shows less than 40% activity compared to the wild type enzyme
additional information
additional information
generation of a knockout lcmt1 mutant sbi1, phenotype, overview. PP2A-C methylation status in wild-type and lcmt1 mutant seedlings under control conditions
additional information
-
generation of a knockout lcmt1 mutant sbi1, phenotype, overview. PP2A-C methylation status in wild-type and lcmt1 mutant seedlings under control conditions
additional information
-
generation of a knockout lcmt1 mutant sbi1, phenotype, overview. PP2A-C methylation status in wild-type and lcmt1 mutant seedlings under control conditions
-
additional information
-
generation of LCMT1-R71DELTA, a catalytically inactive mutant of LCMT1
additional information
-
generation of hypomorphic Lcmt1 mice with reduced protein phosphatase 2A methyltransferase expression and defects in insulin signaling, circumventing embryonic lethality with Lcmt1 deficiency
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni2+ affinity column chromatography and Superdex 75 gel filtration
phenyl Sepharose column chromatography, DEAE cellulose column chromatography, Poros ion exchange column chromatography, DEAE Sephacelcolumn chromatography, and Sephadex G-75 gel filtration
phenyl Sepharose column chromatography, DEAE cellulose column chromatography, Poros ion exchange column chromatography, DEAE Sephacelcolumn chromatography, and Sephadex G-75 gel filtration
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phenyl Sepharose column chromatography, DEAE cellulose column chromatography, Poros ion exchange column chromatography, DEAE Sephacelcolumn chromatography, and Sephadex G-75 gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene lcmt1, DNA and amino acid sequence determination and analysis, quantitative expression analysis in wild-type and mutant mice
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recombinant expression of HA-tagged enzyme LCMT1 in Neuro-2a cells, coepression with Myc-tagged PME-1
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
alpha-syn overexpression results in PP2A demethylation. This demethylation is mediated via downregulated leucine carboxyl methyltransferase (LCMT-1) expression
alpha-syn overexpression results in PP2A demethylation. This demethylation is mediated via downregulated leucine carboxyl methyltransferase (LCMT-1) expression
alpha-syn overexpression results in PP2A demethylation. This demethylation is mediated via downregulated leucine carboxyl methyltransferase (LCMT-1) expression
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
LMCT-1 may participate in the molecular pathogenesis of Alzheimer's disease. In Tg2576 mice with chronic overexpression of mutant human amyloid-binding protein, LCMT-1 overexpression prevents impairments in short-term spatial memory and synaptic plasticity, without altering amyloid-binding protein expression or soluble Abeta levels
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tolstykh, T.; Lee, J.; Vafai, S.; Stock, J.B.
Carboxyl methylation regulates phosphoprotein phosphatase 2A by controlling the association of regulatory B subunits
EMBO J.
19
5682-5691
2000
Bos taurus
brenda
Tsai, M.; Cronin, N.; Djordjevic, S.
The structure of human leucine carboxyl methyltransferase 1 that regulates protein phosphatase PP2A
Acta Crystallogr. Sect. D
67
14-24
2011
Homo sapiens
brenda
De Baere, I.; Derua, R.; Janssens, V.; Van Hoof, C.; Waelkens, E.; Merlevede, W.; Goris, J.
Purification of porcine brain protein phosphatase 2A leucine carboxyl methyltransferase and cloning of the human homologue
Biochemistry
38
16539-16547
1999
Homo sapiens, Sus scrofa
brenda
Longin, S.; Zwaenepoel, K.; Martens, E.; Louis, J.; Rondelez, E.; Goris, J.; Janssens, V.
Spatial control of protein phosphatase 2A (de)methylation
Exp. Cell Res.
314
68-81
2008
Homo sapiens
brenda
Xie, H.; Clarke, S.
Protein phosphatase 2A is reversibly modified by methyl esterification at its C-terminal leucine residue in bovine brain
J. Biol. Chem.
269
1981-1984
1994
Bos taurus
brenda
Wei, H.; Ashby, D.; Moreno, C.; Ogris, E.; Yeong, F.; Corbett, A.; Pallas, D.
Carboxymethylation of the PP2A catalytic subunit in Saccharomyces cerevisiae is required for efficient interaction with the B-type subunits Cdc55p and Rts1p
J. Biol. Chem.
276
1570-1577
2001
Saccharomyces cerevisiae
brenda
Leulliot, N.; Quevillon-Cheruel, S.; Sorel, I.; De La Sierra-Gallay, I.; Collinet, B.; Graille, M.; Blondeau, K.; Bettache, N.; Poupon, A.; Janin, J.; Van Tilbeurgh, H.
Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl methyltransferase involved in the regulation of protein phosphatase 2A activity
J. Biol. Chem.
279
8351-8358
2004
Saccharomyces cerevisiae (Q04081), Saccharomyces cerevisiae
brenda
Lee, J.; Pallas, D.
Leucine carboxyl methyltransferase-1 is necessary for normal progression through mitosis in mammalian cells
J. Biol. Chem.
282
30974-30984
2007
Homo sapiens, Mus musculus
brenda
Sontag, J.; Nunbhakdi-Craig, V.; Mitterhuber, M.; Ogris, E.; Sontag, E.
Regulation of protein phosphatase 2A methylation by LCMT1 and PME-1 plays a critical role in differentiation of neuroblastoma cells
J. Neurochem.
115
1455-1465
2010
Mus musculus
brenda
Stanevich, V.; Jiang, L.; Satyshur, K.; Li, Y.; Jeffrey, P.; Li, Z.; Menden, P.; Semmelhack, M.; Xing, Y.
The structural basis for tight control of PP2A methylation and function by LCMT-1
Mol. Cell.
41
331-342
2011
Homo sapiens
brenda
DeGrande, S.; Little, S.; Nixon, D.; Wright, P.; Snyder, J.; Dun, W.; Murphy, N.; Kilic, A.; Higgins, R.; Binkley, P.; Boyden, P.; Carnes, C.; Anderson, M.; Hund, T.; Mohler, P.
Molecular mechanisms underlying cardiac protein phosphatase 2A regulation in heart
J. Biol. Chem.
288
1032-1046
2013
Homo sapiens
brenda
Longman, M.; Ranieri, A.; Avkiran, M.; Snabaitis, A.
Regulation of PP2AC carboxylmethylation and cellular localisation by inhibitory class G-protein coupled receptors in cardiomyocytes
PLoS ONE
9
e86234
2014
Rattus norvegicus (Q6P4Z6), Rattus norvegicus Wistar (Q6P4Z6)
brenda
Xia, X.; Gholkar, A.; Senese, S.; Torres, J.Z.
A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size
Cell Cycle
14
1938-1947
2015
Homo sapiens
brenda
Sontag, J.M.; Nunbhakdi-Craig, V.; Sontag, E.
Leucine carboxyl methyltransferase 1 (LCMT1)-dependent methylation regulates the association of protein phosphatase 2A and Tau protein with plasma membrane microdomains in neuroblastoma cells
J. Biol. Chem.
288
27396-27405
2013
Homo sapiens
brenda
MacKay, K.B.; Tu, Y.; Young, S.G.; Clarke, S.G.
Circumventing embryonic lethality with Lcmt1 deficiency: generation of hypomorphic Lcmt1 mice with reduced protein phosphatase 2A methyltransferase expression and defects in insulin signaling
PLoS ONE
8
e65967
2013
Mus musculus
brenda
Tian, H.; Lu, Y.; Liu, J.; Liu, W.; Lu, L.; Duan, C.; Gao, G.; Yang, H.
Leucine carboxyl methyltransferase downregulation and protein phosphatase methylesterase upregulation contribute toward the inhibition of protein phosphatase 2A by alpha-synuclein
Front. Aging Neurosci.
10
173
2018
Mus musculus (A0A0U1RNF2), Mus musculus, Mus musculus C57BL/6N (A0A0U1RNF2)
brenda
Hwang, J.; Lee, J.A.; Pallas, D.C.
Leucine carboxyl methyltransferase 1 (LCMT-1) methylates protein phosphatase 4 (PP4) and protein phosphatase 6 (PP6) and differentially regulates the stable formation of different PP4 holoenzymes
J. Biol. Chem.
291
21008-21019
2016
Mus musculus (A2RTH5), Mus musculus
brenda
Nicholls, R.E.; Sontag, J.M.; Zhang, H.; Staniszewski, A.; Yan, S.; Kim, C.Y.; Yim, M.; Woodruff, C.M.; Arning, E.; Wasek, B.; Yin, D.; Bottiglieri, T.; Sontag, E.; Kandel, E.R.; Arancio, O.
PP2A methylation controls sensitivity and resistance to beta-amyloid-induced cognitive and electrophysiological impairments
Proc. Natl. Acad. Sci. USA
113
3347-3352
2016
Mus musculus (A2RTH5), Mus musculus
brenda
Palanichamy, K.; Kanji, S.; Gordon, N.; Thirumoorthy, K.; Jacob, J.R.; Litzenberg, K.T.; Patel, D.; Chakravarti, A.
NNMT silencing activates tumor suppressor PP2A, inactivates oncogenic STKs, and inhibits tumor forming ability
Clin. Cancer Res.
23
2325-2334
2017
Homo sapiens (Q9UIC8)
brenda
Park, H.J.; Lee, K.W.; Oh, S.; Yan, R.; Zhang, J.; Beach, T.G.; Adler, C.H.; Voronkov, M.; Braithwaite, S.P.; Stock, J.B.; Mouradian, M.M.
Protein phosphatase 2A and its methylation modulating enzymes LCMT-1 and PME-1 are dysregulated in tauopathies of progressive supranuclear palsy and Alzheimer disease
J. Neuropathol. Exp. Neurol.
77
139-148
2018
Homo sapiens (Q9UIC8)
brenda
Creighton, M.T.; Kolton, A.; Kataya, A.R.A.; Maple-Grodem, J.; Averkina, I.O.; Heidari, B.; Lillo, C.
Methylation of protein phosphatase 2A - influence of regulators and environmental stress factors
Plant Cell Environ.
40
2347-2358
2017
Arabidopsis thaliana (Q8VY08), Arabidopsis thaliana, Arabidopsis thaliana Col-0 (Q8VY08)
brenda
Dudiki, T.; Kadunganattil, S.; Ferrara, J.; Kline, D.; Vijayaraghavan, S.
Changes in carboxy methylation and tyrosine phosphorylation of protein phosphatase PP2A are associated with epididymal sperm maturation and motility
PLoS ONE
10
e0141961
2015
Bos taurus (Q3T0H0), Mus musculus (A0A0U1RNF2)
brenda
Schuhmacher, D.; Sontag, J.M.; Sontag, E.
A novel role of PP2A methylation in the regulation of tight junction assembly and integrity
Front. Cell Dev. Biol.
10
911279
2022
Canis lupus familiaris (A0A8C0RW18)
brenda
Gnanaprakash, M.; Staniszewski, A.; Zhang, H.; Pitstick, R.; Kavanaugh, M.P.; Arancio, O.; Nicholls, R.E.
Leucine carboxyl methyltransferase 1 overexpression protects against cognitive and electrophysiological impairments in Tg2576 APP transgenic mice
J. Alzheimers Dis.
79
1813-1829
2021
Mus musculus (A2RTH5)
brenda
Mo, J.; Wang, X.; Liang, N.; Zhang, N.; Li, Y.; Zheng, Z.; Ao, Q.; Wu, Y.; Tang, T.; Liao, S.; Lei, Y.; Ding, H.; Du, B.; Feng, M.; Chen, C.; Shi, Q.; Wei, L.; Huang, Y.; Lu, C.; Tang, S.; Li, X.
Hepatic leucine carboxyl methyltransferase 1 (LCMT1) contributes to high fat diet-induced glucose intolerance through regulation of glycogen metabolism
J. Nutr. Biochem.
117
109321
2023
Mus musculus (A2RTH5)
brenda
Averkina, I.; Paponov, I.; Sanchez-Serrano, J.; Lillo, C.
Specific PP2A catalytic subunits are a prerequisite for positive growth effects in arabidopsis co-cultivated with Azospirillum brasilense and Pseudomonas simiae
Plants (Basel)
10
66
2021
Arabidopsis thaliana (Q8VY08)
brenda
EXTERNAL LINKS (specific for EC-Number 2.1.1.233)
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