PPM1A

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 distinct isoforms have been described. [provided by RefSeq]

Full Name

protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform

Function

Enzyme with a broad specificity. 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. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.

Biological Process

Cellular response to transforming growth factor beta stimulusIEA:Ensembl
DephosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
N-terminal protein myristoylationISS:UniProtKB
Negative regulation of BMP signaling pathwayIEA:Ensembl
Negative regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of NIK/NF-kappaB signalingManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of SMAD protein complex assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of transcription by RNA polymerase IITAS:Reactome
Negative regulation of transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Peptidyl-threonine dephosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentHMP:UniProtKB
Positive regulation of protein export from nucleusIEA:Ensembl
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:BHF-UCL
Protein dephosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Protein export from nucleusIEA:Ensembl
Regulation of cell cycleTAS:Reactome

Cellular Location

Nucleus
Cytoplasm, cytosol
Membrane
Weakly associates at the membrane and N-myristoylation mediates the membrane localization.

PTM

N-myristoylation is essential for the recognition of its substrates for dephosphorylation.