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p(HGNC:PPME1)

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Entity

Name
PPME1
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 3

Assembly and structure of protein phosphatase 2A v1.0.0

Protein phosphatase 2A dysfunction in Alzheimer’s disease v1.0.0

PP2A and Alzheimer Disease v1.0.0

In-Edges 12

complex(a(GO:"protein phosphatase type 2A complex"), p(HGNC:PPME1)) increases act(p(HGNC:PPME1)) View Subject | View Object

Thus, PME-1 appears to exist in an inactive conformation in the absence of PP2A binding. PubMed:19277525

Appears in Networks:

composite(p(HGNC:PPME1), p(HGNC:PPP2CA), p(HGNC:PPP2R1A)) hasComponent p(HGNC:PPME1) View Subject | View Object

Appears in Networks:

a(CHEBI:"microcystin-LR") decreases act(p(HGNC:PPME1)) View Subject | View Object

The structural feature that PME-1 binds directly to the PP2A active site, overlapping the binding sites for OA and MCLR, also explains why these phosphatase inhibitors blocked the methylesterase activity of PME-1 PubMed:19277525

Appears in Networks:

a(CHEBI:"okadaic acid") decreases act(p(HGNC:PPME1)) View Subject | View Object

The structural feature that PME-1 binds directly to the PP2A active site, overlapping the binding sites for OA and MCLR, also explains why these phosphatase inhibitors blocked the methylesterase activity of PME-1 PubMed:19277525

Appears in Networks:

complex(a(GO:"protein phosphatase type 2A complex"), p(HGNC:PPME1)) hasComponent p(HGNC:PPME1) View Subject | View Object

Appears in Networks:

complex(a(GO:"protein phosphatase type 2A complex"), p(HGNC:PPME1)) increases act(p(HGNC:PPME1)) View Subject | View Object

Structural analysis of the heterotrimeric PME-1-PP2A complex showed that PME-1 is only activated upon binding to PP2A (Figure 4, left panel). PubMed:19277525

Appears in Networks:

complex(a(GO:"protein phosphatase type 2A complex"), p(HGNC:PPME1)) increases act(p(HGNC:PPME1)) View Subject | View Object

Interestingly, although PME-1 is activated by PP2A binding, the catalytic subunit of PP2A is inactivated in this process, not just through demethylation but also by loss of the catalytic metal ions PubMed:19277525

Appears in Networks:

act(p(HGNC:LCMT1)) negativeCorrelation act(p(HGNC:PPME1)) View Subject | View Object

PME-1 catalyzes removal of the methyl group, thus reversing the activity of LCMT1 PubMed:19277525

Appears in Networks:

act(complex(GO:"protein phosphatase type 2A complex")) negativeCorrelation p(HGNC:PPME1) View Subject | View Object

For example, PME-1 stabilizes a nuclear pool of inactive PP2A enzymes (Longin et al., 2008), while methylation by LCMT1 influences the amounts of PP2A enzymes bound to plasma membrane microdomains (Sontag et al.,2013). PubMed:24653673

Appears in Networks:
Annotations
MeSH
Cell Nucleus

act(p(HGNC:GSK3B)) increases act(p(HGNC:PPME1)) View Subject | View Object

For instance, activated GSK3β has been reported to induce PP2A inactivation via several mechanisms: phosphorylation of PP2A on Tyr307 (Yao et al.,2011); demethylation of PP2A on Leu309 through inhibition of LCMT1 and up-regulation of PME1 (Yao et al.,2012); and accumulation of I2 PP2A (Liu et al.,2008a). PubMed:24653673

Appears in Networks:

complex(p(HGNC:PPME1), p(HGNC:PPP2CA)) hasComponent p(HGNC:PPME1) View Subject | View Object

Appears in Networks:

complex(p(HGNC:PPME1), p(HGNC:PPP2CB)) hasComponent p(HGNC:PPME1) View Subject | View Object

Appears in Networks:

Out-Edges 12

p(HGNC:PPME1) decreases p(HGNC:PPP2CA, pmod(Me, Leu, 309)) View Subject | View Object

Reversible methylation of PP2A is catalyzed by two highly conserved and PP2A-specific enzymes, leucine carboxyl methyltransferase (LCMT1)[21,33] and PP2A methylesterase (PME-1)[17] (Figure 1). PubMed:19277525

Appears in Networks:

p(HGNC:PPME1) decreases p(HGNC:PPP2CA, pmod(Me, Leu, 309)) View Subject | View Object

PME-1 catalyzes removal of the methyl group, thus reversing the activity of LCMT1 PubMed:19277525

Appears in Networks:

p(HGNC:PPME1) decreases p(HGNC:PPP2CA, pmod(Me, Leu, 309)) View Subject | View Object

Recent evidence suggests a broader role for PME-1 than just being a demethylating enzyme for the catalytic subunit of PP2A PubMed:19277525

Appears in Networks:

act(p(HGNC:PPME1)) negativeCorrelation act(p(HGNC:LCMT1)) View Subject | View Object

PME-1 catalyzes removal of the methyl group, thus reversing the activity of LCMT1 PubMed:19277525

Appears in Networks:

p(HGNC:PPME1) increases complex(a(GO:"protein phosphatase type 2A complex"), p(HGNC:PPME1)) View Subject | View Object

A portion of cellular PP2A stably associated with PME-1 and was catalytically inactive [80]; intriguingly, this inactive portion of PP2A could be re-activated by PP2A phosphatase activator (PTPA), but not by LCMT1, ruling out the possibility that inactivation was solely caused by demethylation PubMed:19277525

Appears in Networks:

p(HGNC:PPME1) directlyIncreases complex(a(GO:"protein phosphatase type 2A complex"), p(HGNC:PPME1)) View Subject | View Object

The structural feature that PME-1 binds directly to the PP2A active site, overlapping the binding sites for OA and MCLR, also explains why these phosphatase inhibitors blocked the methylesterase activity of PME-1 PubMed:19277525

Appears in Networks:

p(HGNC:PPME1) decreases act(complex(GO:"protein phosphatase type 2A complex")) View Subject | View Object

Structural observations clearly indicate that PME-1 inactivates the phosphatase activity of PP2A PubMed:19277525

Appears in Networks:

p(HGNC:PPME1) increases complex(p(HGNC:PPME1), p(HGNC:PPP2CA)) View Subject | View Object

Conversely, the PP2A-specific methylesterase PME-1 can directly bind to the active site of the catalytic subunit, remove the methyl group and inactivate PP2A by evicting manganese ions required for phosphatase activity (Xing et al.,2008). PubMed:24653673

Appears in Networks:

p(HGNC:PPME1) increases complex(p(HGNC:PPME1), p(HGNC:PPP2CB)) View Subject | View Object

Conversely, the PP2A-specific methylesterase PME-1 can directly bind to the active site of the catalytic subunit, remove the methyl group and inactivate PP2A by evicting manganese ions required for phosphatase activity (Xing et al.,2008). PubMed:24653673

Appears in Networks:

p(HGNC:PPME1) negativeCorrelation act(complex(GO:"protein phosphatase type 2A complex")) View Subject | View Object

For example, PME-1 stabilizes a nuclear pool of inactive PP2A enzymes (Longin et al., 2008), while methylation by LCMT1 influences the amounts of PP2A enzymes bound to plasma membrane microdomains (Sontag et al.,2013). PubMed:24653673

Appears in Networks:
Annotations
MeSH
Cell Nucleus

act(p(HGNC:PPME1)) decreases p(HGNC:PPP2CA, pmod(Me, Leu, 309)) View Subject | View Object

For instance, activated GSK3β has been reported to induce PP2A inactivation via several mechanisms: phosphorylation of PP2A on Tyr307 (Yao et al.,2011); demethylation of PP2A on Leu309 through inhibition of LCMT1 and up-regulation of PME1 (Yao et al.,2012); and accumulation of I2 PP2A (Liu et al.,2008a). PubMed:24653673

Appears in Networks:

p(HGNC:PPME1) decreases p(FPLX:PPP2C, pmod(Me)) View Subject | View Object

Car- boxyl methylation of the catalytic subunit is required for efficient in vivo assembly of the trimer C, A, and B [63-65]; a process that is balanced by the opposite actions of methyl- transferase type IV (PPMT) and the methylesterase PME-1 [66-70]. PubMed:22299660

Appears in Networks:

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.