PPM1A
Description
The PPM1A (protein phosphatase, Mg2+/Mn2+ dependent 1A) is a protein-coding gene located on chromosome 14.
PPM1A (Protein phosphatase 1A) is an enzyme encoded by the PPM1A gene in humans. It belongs to the PP2C family of Ser/Thr protein phosphatases, known for their role in negatively regulating cell stress response pathways. PPM1A dephosphorylates and negatively regulates the activity of MAP kinases and MAP kinase kinases, inhibiting the activation of p38 and JNK kinase cascades triggered by environmental stresses. It can also dephosphorylate cyclin-dependent kinases, suggesting involvement in cell cycle control. Overexpression of PPM1A is associated with the activation of the tumor suppressor gene TP53/p53, leading to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants have been identified, encoding two distinct isoforms. PPM1A interacts with Metabotropic glutamate receptor 3.
PPM1A is an enzyme with broad substrate specificity that negatively regulates TGF-beta signaling by dephosphorylating SMAD2 and SMAD3, leading to their dissociation from SMAD4, nuclear export of the SMADs, and termination of the TGF-beta-mediated signaling pathway. It also dephosphorylates PRKAA1 and PRKAA2. Additionally, PPM1A plays a crucial role in terminating TNF-alpha-mediated NF-kappa-B activation by dephosphorylating and inactivating IKBKB/IKKB.
PPM1A is also known as PP2C-ALPHA, PP2CA, PP2Calpha.
Associated Diseases
- endometrial cancer
- microphthalmia with limb anomalies
- Eiken syndrome
- metaphyseal dysplasia, Braun-Tinschert type
