PPM1A (PP2CA)

Protein phosphatase 1A (PPM1A / PP2CA) is an enzyme belonging to the PP2C family of Ser / Thr protein phosphatases. Members of PP2C family are negative regulators of cell stress response pathways and the MAP kinases and MAP kinase kinases. It has also been demonstrated to inhibit the activation of p38 and JNK kinase cascades. PPM1A dephosphorylates and promotes nuclear export of TGFβ-activated Smad2/3. Ectopic expression of PPM1A abolishes TGFβ-induced antiproliferative and transcriptional responses, whereas depletion of PPM1A enhances TGFβ signaling in mammalian cells. It has been demonstrated that PPM1A / PP2CA, through dephosphorylation of Smad2/3, plays a critical role in terminating TGFβ signaling. Overexpression of PPM1A is reported to activate the expression of the tumor suppressor gene TP53 / p53, which leads to cell apoptosis.

PPM1A (PP2CA) Related Areas

Enzyme>>Phosphatase & Regulator>>PPM1A/PP2CA

Signal Transduction>>Phosphatase & Regulator>>PPM1A/PP2CA

PPM1A (PP2CA) Alternative Names

PPM1A , PP2CA, PP2C-ALPHA, PP2Calpha, FLJ42306, MGC9201 [Homo sapiens]

Ppm1a, PP2CA, PP2C-alpha, 2310003C21Rik, 2900017D14Rik, AI427932, AU017636, MMPa-2, MPPa-1 [Mus musculus]

Summaries for PPM1A (PP2CA)

Entrez Gene summary for PPM1A (PP2CA):

The protein encoded by PPM1A gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase dephosphorylates, and negatively regulates the activities of, MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses. This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53/p53, which leads to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

OMIM - description for PPM1A (PP2CA):

PPM1A is a serine/threonine protein phosphatase that is essential for regulating cellular stress responses in eukaryotes. For further background information on serine/threonine protein phosphatases.

Wikipedia summary for PPM1A (PP2CA):

Protein phosphatase 1A is an enzyme that in humans is encoded by the PPM1A gene.
The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase dephosphorylates, and negatively regulates the activities of, MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses. This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53/p53, which leads to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants encoding two distinct isoforms have been described.

Human PPM1A (PP2CA) Protein General Information

 

• Protein names: Protein phosphatase 1A
  Short name=PPM1A
• Sequence length: 382 AA.
• Cofactor: Binds 2 magnesium or manganese ions per subunit.
• Sequence similarities: Belongs to the PP2C family.
• Catalytic activity: A phosphoprotein + H₂O = a protein + phosphate.
• Subunit structure: Monomer. Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling. Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling.
• Subcellular location: Nucleus.

General information above from UniProt

Function for PPM1A (PP2CA) Protein

UniProtKB:

PPM1A is enzyme with a broad specificity. PPM1A negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling.

Genatlas:

• PPM1A acts as a negative regulator of cell stress response pathways
• PPM1A negatively regulates the activities of MAP kinases and MAP kinase kinases
• PPM1A inhibits the activation of p38 and JNK kinase cascades induced by environmental stresses
• PPM1A plays an important role in the regulation of receptors and channels
• PPM1A directly dephosphorylates Smad2 and Smad3 to limit their activation which plays a critical role in terminating TGFbeta signaling
• PPM1A is involved in positive regulation of I-kappaB kinase/NF-kappaB cascade
• PPM1A inhibits cell growth
• PPM1A activates the p53 pathway
• PPM1A might contribute to secretory cell function

Homology for human PPM1A (PP2CA)

• ortholog to rattus Ppm1a (99pc)
• ortholog to murine Ppm1a (98.2pc)