Information on EC 2.1.1.233 - [phosphatase 2A protein]-leucine-carboxy methyltransferase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.1.1.233
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RECOMMENDED NAME
GeneOntology No.
[phosphatase 2A protein]-leucine-carboxy methyltransferase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine = S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
show the reaction diagram
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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.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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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
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
show the reaction diagram
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
show the reaction diagram
additional information
?
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enzyme LCMT1 is a class 1 S-adenosylmethionine-dependent methyltransferase with PP2A as its only known substrate
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
S-adenosyl-L-methionine
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
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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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0000006
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crude extract, at 30°C in 20 mM Tris, 0.5 mM dithiothreitol, pH 7.4
0.0046
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purified enzyme, at 30°C in 20 mM Tris, 0.5 mM dithiothreitol, pH 7.4
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.7
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calculated from amino acid sequence
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
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
Manually annotated by BRENDA team
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the enzyme is underrepresented in the nucleus and mainly localized to the cytoplasm, Golgi region and late endosomes
Manually annotated by BRENDA team
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the enzyme is underrepresented in the nucleus and mainly localized to the cytoplasm, Golgi region and late endosomes
Manually annotated by BRENDA team
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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
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DEAE-cellulose column chromatography and Sephacryl S-200 gel filtration
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Ni-NTA column chromatography and Source 15S column chromatography
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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
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) and HeLa cells
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expressed in Escherichia coli BL21(DE3) cells
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expressed in Escherichia coli BL21(DE3) pLysS cells
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expressed in Escherichia coli XL-10 Gold cells
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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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C36A
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the mutant shows about wild type activity
D303R
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the mutant shows less than 10% activity compared to the wild type enzyme
E65R
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the mutant shows less than 10% activity compared to the wild type enzyme
F237D
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the mutant shows less than 10% activity compared to the wild type enzyme
K62E
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the mutant shows less than 10% activity compared to the wild type enzyme
N244A
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the mutant shows less than 40% activity compared to the wild type enzyme
R236D
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the mutant shows about 80% activity compared to the wild type enzyme
R73A
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inactive
T29V
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the mutant shows about 10% activity compared to the wild type enzyme
additional information