1. Catalog
  2. Nodes
  3. p(HGNC:PPP2CA)

p(HGNC:PPP2CA)

Equivalencies: 0 | Classes: 1 | Children: 0 | Explore

Entity

Name
PPP2CA
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 8

Clearance of Amyloid Beta and Tau in Alzheimer’s Disease:from Mechanisms to Therapy v1.0.1

TAU and Interaction Partners v1.2.5

TAU Interactions Section of NESTOR

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer v1.0.0

Assembly and structure of protein phosphatase 2A v1.0.0

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

Caenorhabditis elegans models of tauopathy v1.0.0

Tau in physiology and pathology v1.0.0

In-Edges 43

complex(a(PUBCHEM:6913994), p(HGNC:PPP2CA)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

a(MESH:"Cell Membrane") association p(HGNC:PPP2CA) View Subject | View Object

The isoform C α is predominantly expressed in the plasma membrane and C β in the cytoplasm and nucleus. PubMed:23454242

Appears in Networks:

complex(GO:microtubule) association p(HGNC:PPP2CA) View Subject | View Object

ABaC binds directly to MTs through a site that encompasses its catalytic subunit and is distinct from its binding site for tau, and ABaC and tau bind to different domains on MTs. PubMed:10464280

Appears in Networks:

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

Appears in Networks:

a(CHEBI:"quinolinic acid") decreases p(HGNC:PPP2CA) View Subject | View Object

Kynurenic pathway is overactive in AD. QA is co-localized with hyperphosphorylated tau within cortical neurons in AD brain. In primary cultures of human neurons, QA treatment increased tau phosphorylation at serine 199/202, threonine 231 and serine 396/404 in a dose dependent manner. This increase in tau phosphorylation was paralleled by a substantial decrease in the total protein phosphatase activity, mostly in PP2A expression and modest in PP1. PubMed:19623258

Appears in Networks:

a(CHEBI:resveratrol) directlyIncreases act(p(HGNC:PPP2CA)) View Subject | View Object

Here we show that resveratrol treatment directly interferes with the MID1-α4-PP2A degradation complex by reducing MID1 protein expression in vitro and in vivo. This leads to an increase of microtubule-associated PP2A activity and a time- and dose-dependent dephosphorylation of Tau. Interestingly, we further show that MID1 expression is elevated in AD tissue. PubMed:29062069

Appears in Networks:

p(HGNC:MAPT, pmod(Ph)) negativeCorrelation act(p(HGNC:PPP2CA)) View Subject | View Object

Here we show that resveratrol treatment directly interferes with the MID1-α4-PP2A degradation complex by reducing MID1 protein expression in vitro and in vivo. This leads to an increase of microtubule-associated PP2A activity and a time- and dose-dependent dephosphorylation of Tau. Interestingly, we further show that MID1 expression is elevated in AD tissue. PubMed:29062069

Appears in Networks:

p(HGNC:MID1) decreases act(p(HGNC:PPP2CA)) View Subject | View Object

Here we show that resveratrol treatment directly interferes with the MID1-α4-PP2A degradation complex by reducing MID1 protein expression in vitro and in vivo. This leads to an increase of microtubule-associated PP2A activity and a time- and dose-dependent dephosphorylation of Tau. Interestingly, we further show that MID1 expression is elevated in AD tissue. PubMed:29062069

Appears in Networks:

act(p(HGNC:PIN1)) positiveCorrelation act(p(HGNC:PPP2CA)) View Subject | View Object

Pin1 is indicated to facilitate Tau dephosphorylation via PP2A by binding to the phospho-Thr-231-Pro or phospho-Thr-212-Pro site PubMed:19401603

Appears in Networks:

p(HGNC:PPP2CA, pmod(Me)) increases act(p(HGNC:PPP2CA)) View Subject | View Object

These findings suggest a scenario in which MC-LR-mediated demethylation of PP2Ac is associated with GSK-3β phosphorylation at Ser9 and contributes to dissociation of Bα from PP2Ac, which would result in Bα degradation and disruption of PP2A/Bα-tau interactions, thus promoting tau hyperphosphorylation and paired helical filaments-tau accumulation and, consequently, axonal degeneration and cell death. PubMed:29228318

Appears in Networks:

complex(p(HGNC:PPP2CA), p(INTERPRO:"Protein phosphatase 2A regulatory subunit PR55")) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:PPP2CA), p(INTERPRO:"Protein phosphatase 2A, regulatory B subunit, B56")) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

act(p(HGNC:PPP2R1A)) increases act(p(HGNC:PPP2CA)) View Subject | View Object

Second, conformational flexibility of the scaffold subunit might be important for the phosphatase activity of the catalytic subunit PubMed:19277525

Appears in Networks:

complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(HGNC:PPP2R3A)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:PPP2CA), p(INTERPRO:"HEAT repeat")) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

p(FPLX:PPP2C) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

a(CHEBI:"okadaic acid") decreases act(p(HGNC:PPP2CA)) View Subject | View Object

The catalytic subunit of PP2A is the primary cellular target of OA PubMed:19277525

Appears in Networks:

complex(GO:"protein phosphatase type 2A complex") hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(a(GO:"protein phosphatase type 2A complex"), p(HGNC:PPME1)) decreases act(p(HGNC:PPP2CA)) 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:

complex(a(GO:"protein phosphatase type 2A complex"), p(HGNC:PPME1)) decreases act(p(HGNC:PPP2CA)) 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:

complex(p(HGNC:IGBP1), p(HGNC:PPP2CA)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(HGNC:PPP2R3B)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(HGNC:SGO1), p(INTERPRO:"Protein phosphatase 2A, regulatory B subunit, B56")) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(HGNC:STRN)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(HGNC:STRN3)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(INTERPRO:"Protein phosphatase 2A regulatory subunit PR55")) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(INTERPRO:"Protein phosphatase 2A, regulatory B subunit, B56")) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(UNIPROT:P03081)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

p(HGNC:PPP2CA, pmod(Me, Leu, 309)) increases act(p(HGNC:PPP2CA)) 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:

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

Appears in Networks:

act(complex(GO:"protein phosphatase type 2A complex")) association p(HGNC:PPP2CA) View Subject | View Object

Deficits in PP2A activity are in line with the reported down-regulation of PP2A catalytic C subunit at the gene (Loring et al.,2001), mRNA (Vogelsberg-Ragaglia et al.,2001) and protein (Sontag et al.,2004b) expression levels in AD. PubMed:24653673

Appears in Networks:

complex(a(CHEBI:"okadaic acid"), p(HGNC:PPP2CA)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(a(PUBCHEM:5311365), p(HGNC:PPP2CA)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:ANP32A), p(HGNC:PPP2CA)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:LCMT1), p(HGNC:PPP2CA)) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

complex(p(HGNC:MAPT), p(HGNC:PPP2CA), p(HGNC:PPP2R1A), p(INTERPRO:"Protein phosphatase 2A regulatory subunit PR55")) hasComponent p(HGNC:PPP2CA) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

p(HGNC:IGBP1, frag("?")) positiveCorrelation deg(p(HGNC:PPP2CA)) View Subject | View Object

Lastly, increased calpain-mediated cleavage of alpha4, which critically modulates PP2A stability, could be responsible for increased degradation of PP2A catalytic subunit in AD (Watkins et al., 2012). PubMed:24653673

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") negativeCorrelation p(HGNC:PPP2CA) View Subject | View Object

Deficits in PP2A activity are in line with the reported down-regulation of PP2A catalytic C subunit at the gene (Loring et al.,2001), mRNA (Vogelsberg-Ragaglia et al.,2001) and protein (Sontag et al.,2004b) expression levels in AD. PubMed:24653673

Appears in Networks:

path(MESH:"Alzheimer Disease") negativeCorrelation act(p(HGNC:PPP2CA)) View Subject | View Object

Among them, PP2A is the main phosphatase:it accounts for ~70% of the human brain tau phosphatase activity, and its activity is reduced in the AD brain (by ~20% and ~40% in the grey and white matter, respectively) PubMed:26631930

Appears in Networks:

Out-Edges 27

p(HGNC:PPP2CA) directlyDecreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Protein phosphatase 1 (PP1), PP2A, PP2B, PP2C and PP5 have all been implicated in the dephosphorylation of tau PubMed:26631930

Appears in Networks:

p(HGNC:PPP2CA) increases bp(GO:autophagy) View Subject | View Object

Protein phosphatase 2A agonists are reported to activate autophagy by affecting AMPK and mTORC1 signaling pathways (Magnaudeix et al. 2013) PubMed:29626319

Appears in Networks:

p(HGNC:PPP2CA) association complex(GO:microtubule) View Subject | View Object

ABaC binds directly to MTs through a site that encompasses its catalytic subunit and is distinct from its binding site for tau, and ABaC and tau bind to different domains on MTs. PubMed:10464280

Appears in Networks:

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

ABaC binds directly to MTs through a site that encompasses its catalytic subunit and is distinct from its binding site for tau, and ABaC and tau bind to different domains on MTs. PubMed:10464280

Appears in Networks:

p(HGNC:PPP2CA) isA complex(SCOMP:"PP2A Complex") View Subject | View Object

Appears in Networks:

p(HGNC:PPP2CA) hasVariant p(HGNC:PPP2CA, pmod(Me)) View Subject | View Object

Appears in Networks:

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

Appears in Networks:

act(p(HGNC:PPP2CA)) directlyDecreases p(HGNC:GSK3B, pmod(Ph, Ser, 9)) View Subject | View Object

These findings suggest a scenario in which MC-LR-mediated demethylation of PP2Ac is associated with GSK-3β phosphorylation at Ser9 and contributes to dissociation of Bα from PP2Ac, which would result in Bα degradation and disruption of PP2A/Bα-tau interactions, thus promoting tau hyperphosphorylation and paired helical filaments-tau accumulation and, consequently, axonal degeneration and cell death. PubMed:29228318

Appears in Networks:

act(p(HGNC:PPP2CA)) negativeCorrelation p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Here we show that resveratrol treatment directly interferes with the MID1-α4-PP2A degradation complex by reducing MID1 protein expression in vitro and in vivo. This leads to an increase of microtubule-associated PP2A activity and a time- and dose-dependent dephosphorylation of Tau. Interestingly, we further show that MID1 expression is elevated in AD tissue. PubMed:29062069

Appears in Networks:

act(p(HGNC:PPP2CA)) positiveCorrelation act(p(HGNC:PIN1)) View Subject | View Object

Pin1 is indicated to facilitate Tau dephosphorylation via PP2A by binding to the phospho-Thr-231-Pro or phospho-Thr-212-Pro site PubMed:19401603

Appears in Networks:

act(p(HGNC:PPP2CA)) directlyDecreases p(HGNC:MAPT, pmod(Ph, Thr, 231)) View Subject | View Object

Pin1 is indicated to facilitate Tau dephosphorylation via PP2A by binding to the phospho-Thr-231-Pro or phospho-Thr-212-Pro site PubMed:19401603

Appears in Networks:

act(p(HGNC:PPP2CA)) directlyDecreases p(HGNC:MAPT, pmod(Ph, Thr, 212)) View Subject | View Object

Pin1 is indicated to facilitate Tau dephosphorylation via PP2A by binding to the phospho-Thr-231-Pro or phospho-Thr-212-Pro site PubMed:19401603

Appears in Networks:

p(HGNC:PPP2CA) association a(MESH:"Cell Membrane") View Subject | View Object

The isoform C α is predominantly expressed in the plasma membrane and C β in the cytoplasm and nucleus. PubMed:23454242

Appears in Networks:

p(HGNC:PPP2CA) hasVariant p(HGNC:PPP2CA, var("?")) View Subject | View Object

Appears in Networks:

p(HGNC:PPP2CA) increases complex(p(HGNC:PPP2CA), p(INTERPRO:"HEAT repeat")) View Subject | View Object

Structures of the PP2A core enzyme reveal that the catalytic subunit recognizes one end of the scaffold subunit through interactions with the conserved ridge of HEAT repeats 11–15 PubMed:19277525

Appears in Networks:

p(HGNC:PPP2CA) increases complex(GO:"protein phosphatase type 2A complex") View Subject | View Object

Previous studies suggested that carboxy-methylation of the catalytic subunit played an important role in the assembly of heterotrimeric PP2A holoenzymes in cells PubMed:19277525

Appears in Networks:

p(HGNC:PPP2CA) hasVariant p(HGNC:PPP2CA, pmod(HBP:nitration, Tyr)) View Subject | View Object

Appears in Networks:

p(HGNC:PPP2CA) hasVariant p(HGNC:PPP2CA, pmod(Ph, Tyr, 307)) View Subject | View Object

Appears in Networks:

p(HGNC:PPP2CA) hasVariant p(HGNC:PPP2CA, pmod(Ub)) View Subject | View Object

Appears in Networks:

p(HGNC:PPP2CA) hasVariant p(HGNC:PPP2CA, var("p.Leu309Ala")) View Subject | View Object

Appears in Networks:

p(HGNC:PPP2CA) association act(complex(GO:"protein phosphatase type 2A complex")) View Subject | View Object

Deficits in PP2A activity are in line with the reported down-regulation of PP2A catalytic C subunit at the gene (Loring et al.,2001), mRNA (Vogelsberg-Ragaglia et al.,2001) and protein (Sontag et al.,2004b) expression levels in AD. PubMed:24653673

Appears in Networks:

p(HGNC:PPP2CA) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Deficits in PP2A activity are in line with the reported down-regulation of PP2A catalytic C subunit at the gene (Loring et al.,2001), mRNA (Vogelsberg-Ragaglia et al.,2001) and protein (Sontag et al.,2004b) expression levels in AD. PubMed:24653673

Appears in Networks:

deg(p(HGNC:PPP2CA)) positiveCorrelation p(HGNC:IGBP1, frag("?")) View Subject | View Object

Lastly, increased calpain-mediated cleavage of alpha4, which critically modulates PP2A stability, could be responsible for increased degradation of PP2A catalytic subunit in AD (Watkins et al., 2012). PubMed:24653673

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:PPP2CA) decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Knock-down of PP2A catalytic subunit (Kins et al.,2001) or PP2A B’δ (or PPP2R5D) regulatory subunit (Louis et al.,2011), and expression of the methylation-site L309A C subunit mutant (Schild et al.,2006) all induce AD-like tau phosphorylation in transgenic mice PubMed:24653673

Appears in Networks:

p(HGNC:PPP2CA) directlyDecreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Dephosphorylation of tau is achieved mainly by protein phosphatase (PP)2A, PP2B (calcineurin), and PP-1 (92). PubMed:29191965

Appears in Networks:

p(HGNC:PPP2CA) directlyDecreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Among them, PP2A is the main phosphatase:it accounts for ~70% of the human brain tau phosphatase activity, and its activity is reduced in the AD brain (by ~20% and ~40% in the grey and white matter, respectively) PubMed:26631930

Appears in Networks:

act(p(HGNC:PPP2CA)) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Among them, PP2A is the main phosphatase:it accounts for ~70% of the human brain tau phosphatase activity, and its activity is reduced in the AD brain (by ~20% and ~40% in the grey and white matter, respectively) PubMed:26631930

Appears in Networks:

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.