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FLASH GENE
Symbol PPM1A contributors: mct - updated : 30-05-2013
HGNC name protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform
HGNC id 9275
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a catalytic domain
  • secondary structure
  • a catalytic domain composed of a central beta sandwich that binds 2 manganese ions, which is surrounded by alpha helices
  • mono polymer monomer
    HOMOLOGY
    interspecies ortholog to rattus Ppm1a (99pc)
    ortholog to murine Ppm1a (98.2pc)
    Homologene
    FAMILY
  • PP2C family of Ser/Thr protein phosphatases
  • metal-dependent serine/threonine protein phosphatase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • acting as a negative regulator of cell stress response pathways
  • negatively regulating the activities of MAP kinases and MAP kinase kinases
  • inhibiting the activation of p38 and JNK kinase cascades induced by environmental stresses
  • playing an important role in the regulation of receptors and channels
  • directly dephosphorylating Smad2 and Smad3 to limit their activation which plays a critical role in terminating TGFbeta signaling
  • involved in positive regulation of I-kappaB kinase/NF-kappaB cascade
  • inhibiting cell growth
  • activating the p53 pathway
  • might contribute to secretory cell function
  • PPM1A and PPM1B play an important role in the termination of TNF-mediated NF-kappaB activation through dephosphorylating and inactivating IKBKB
  • phosphatase which dephosphorylates and inactivates a broad range of substrates, including TGFB1, MAP kinases, MAPK14 and JNK kinase cascades, and is involved in tumor suppression
  • plays a critical role in the regulation of normal placentation by inhibiting trophoblast migration and invasion
  • critical role of PPM1A in maximizing exporter activity of RANBP3 for efficient termination of canonical TGFB1 signalling
  • plays a role in the differentiation and survival processes of nerve cells
  • might have an important role in oocyte maturation
  • represses HIV-1 gene expression by inhibiting CDK9 T-loop phosphorylation, thus reducing the amount of active CDK9 available for recruitment to the viral LTR
  • N-myristoylation of PPM1A and PPM1B plays a key role in recognition of their physiological substrates in cells
  • CELLULAR PROCESS cell cycle, progression
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text
  • involved in cell cycle control
  • PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Mg2+ (2 ions per subunit)
  • Mn2+ (2 ions per subunit)
  • protein
  • GRM3 (C terminal cytoplasmic tail)
  • PPM1A and PPM1B, are IKBKB phosphatases
  • regulates the nuclear export of SMAD2/3 through targeting nuclear exporter RANBP3
  • directly interacted with and dephosphorylated RANBP3 at Ser 58
  • cell & other
    REGULATION
    Other N-myristoylated and this modification is essential for its ability to dephosphorylate the alpha subunit of AMPK in cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in hydatidiform moles compared with that during normal pregnancy
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS