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Literature summary for 2.1.1.233 extracted from

  • 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 (2013), J. Biol. Chem., 288, 27396-27405.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of HA-tagged enzyme LCMT1 in Neuro-2a cells, coepression with Myc-tagged PME-1 Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information generation of LCMT1-R71DELTA, a catalytically inactive mutant of LCMT1 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
plasma membrane 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 Homo sapiens 5886
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Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309 Homo sapiens
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S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
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?

Organism

Organism UniProt Comment Textmining
Homo sapiens
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-
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Source Tissue

Source Tissue Comment Organism Textmining
brain
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Homo sapiens
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neuroblastoma cell
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Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309
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Homo sapiens S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
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?
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine309 absolut specific methylation of Leu309 in the C subunit of phosphatase 2A protein, no activity with Leu309DELTA PPA2 mutant Homo sapiens S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine309 methyl ester
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?

Synonyms

Synonyms Comment Organism
LCMT1
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Homo sapiens
leucine carboxyl methyltransferase 1
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Homo sapiens

Cofactor

Cofactor Comment Organism Structure
S-adenosyl-L-methionine
-
Homo sapiens

General Information

General Information Comment Organism
malfunction 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 Homo sapiens
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 Homo sapiens