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Gene Review

PPP1R3A  -  protein phosphatase 1, regulatory subunit 3A

Homo sapiens

Synonyms: GM, PP1G, PPP1R3, Protein phosphatase 1 glycogen-associated regulatory subunit, Protein phosphatase 1 regulatory subunit 3A, ...
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Disease relevance of PPP1R3A


High impact information on PPP1R3A

  • When applying heteroduplex formation analysis and nucleotide sequencing of PP1G-subunit cDNA from 30 insulin resistant white NIDDM patients two cases were identified as heterozygous carriers of an Asp905 --> Tyr substitution [5].
  • Here we report genetic alterations of the PPP1R3 gene located at chromosome 7q31, which encodes regulatory subunit 3 of PP1, in various types of human cancers [4].
  • These findings suggest that PPP1R3 alteration plays a role in the development of human cancers and that PPP1R3 could act as a tumor suppressor gene [4].
  • Disruption of the PPP1R3A gene encoding the glycogen targeting subunit (G(M)/R(GL)) of protein phosphatase 1 (PP1) causes substantial lowering of the glycogen synthase activity and a 10-fold decrease in the glycogen levels in skeletal muscle [1].
  • The human cDNA was isolated from a skeletal muscle cDNA library and was found to encode a 126-kDa protein, which shows 73% amino acid identity to the rabbit PP1 G-subunit [6].

Biological context of PPP1R3A

  • In a large kindred of five individuals with severe insulin resistance, we have identified frameshift/premature stop mutations in PPARGAMMA; and the muscle-specific regulatory subunit of protein phosphatase 1 (PPP1R3A) [7].
  • One variant SSCP profile was detected in the region encoding the COOH-terminal part of the PP1 G-subunit in only one NIDDM patient, and subsequent nucleotide sequencing showed a C to A transversion on one allele at base position 2792 [6].
  • Studies of diabetic and nondiabetic PCOS women of other racial and ethnic backgrounds will be necessary to assess the impact of this and other variants in PPP1R3 upon the phenotype and natural history of women with PCOS [8].
  • The PPP1R3 gene is located on chromosome 7q31, and encodes protein phosphatase 1 (regulatory 3) [2].
  • Somatic mutations and genetic polymorphisms of the PPP1R3 gene in patients with several types of cancers [9].

Anatomical context of PPP1R3A


Associations of PPP1R3A with chemical compounds

  • METHODS: We genotyped the PPP1R3 gene Asp905Tyr polymorphism and a common 3'-untranslated region AT (AU)-rich element (ARE) polymorphism in 101 type 2 diabetic patients and 101 controls by oligonucleotide ligation assay (OLA) and polyacrylamide gel elecrophoresis, respectively [3].
  • A polymorphism (PP1ARE) in the 3'-untranslated region of the gene encoding the glycogen-associated regulatory subunit of type 1 protein phosphatase PPP1R3 is associated with insulin resistance in Pima Indians [11].
  • We have previously identified an Asp905Tyr polymorphism of the glycogen-associated regulatory subunit of the protein phosphatase 1 (PPP1R3) gene which among healthy subjects was associated with decreased insulin stimulated non-oxidative glucose metabolism, i.e. primary glycogen synthesis [10].
  • Overexpression of PPP1R3 did not affect either basal or insulin-stimulated 2-deoxy-D-glucose uptake compared with green fluorescent protein-transduced cells [10].
  • A possible pathogenic polymorphism in the gene for the G subunit of the glycogen-associated regulatory form of protein phosphatase 1 (PP1 G subunit), causing an Asp-to-Tyr substitution at codon 905 (Asp905Tyr), has been reported to be associated with insulin resistance and hypersecretion of insulin in the white population [12].

Other interactions of PPP1R3A


Analytical, diagnostic and therapeutic context of PPP1R3A


  1. Disruption of the striated muscle glycogen targeting subunit PPP1R3A of protein phosphatase 1 leads to increased weight gain, fat deposition, and development of insulin resistance. Delibegovic, M., Armstrong, C.G., Dobbie, L., Watt, P.W., Smith, A.J., Cohen, P.T. Diabetes (2003) [Pubmed]
  2. PPP1R3 gene (protein phosphatase 1) alterations in colorectal cancer and its relationship to metastasis. Hayashida, Y., Goi, T., Hirono, Y., Katayama, K., Urano, T., Yamaguchi, A. Oncol. Rep. (2005) [Pubmed]
  3. The association between PPP1R3 gene polymorphisms and type 2 diabetes mellitus. Wang, G., Qian, R., Li, Q., Niu, T., Chen, C., Xu, X. Chin. Med. J. (2001) [Pubmed]
  4. Alterations of the PPP1R3 gene in human cancer. Kohno, T., Takakura, S., Yamada, T., Okamoto, A., Tanaka, T., Yokota, J. Cancer Res. (1999) [Pubmed]
  5. A widespread amino acid polymorphism at codon 905 of the glycogen-associated regulatory subunit of protein phosphatase-1 is associated with insulin resistance and hypersecretion of insulin. Hansen, L., Hansen, T., Vestergaard, H., Bjørbaek, C., Echwald, S.M., Clausen, J.O., Chen, Y.H., Chen, M.X., Cohen, P.T., Pedersen, O. Hum. Mol. Genet. (1995) [Pubmed]
  6. Sequence of the human glycogen-associated regulatory subunit of type 1 protein phosphatase and analysis of its coding region and mRNA level in muscle from patients with NIDDM. Chen, Y.H., Hansen, L., Chen, M.X., Bjørbaek, C., Vestergaard, H., Hansen, T., Cohen, P.T., Pedersen, O. Diabetes (1994) [Pubmed]
  7. Peroxisome proliferator-activated receptor-gamma and insulin action: insights from human genetics. Chatterjee, V.K. Horm. Res. (2003) [Pubmed]
  8. Association of the (AU)AT-rich element polymorphism in PPP1R3 with hormonal and metabolic features of polycystic ovary syndrome. Alcoser, S.Y., Hara, M., Bell, G.I., Ehrmann, D.A. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  9. Somatic mutations and genetic polymorphisms of the PPP1R3 gene in patients with several types of cancers. Takakura, S., Kohno, T., Shimizu, K., Ohwada, S., Okamoto, A., Yokota, J. Oncogene (2000) [Pubmed]
  10. Adenovirus-mediated expression of a naturally occurring Asp905Tyr variant of the glycogen-associated regulatory subunit of protein phosphatase-1 in L6 myotubes. Rasmussen, S.K., Hansen, L., Frevert, E.U., Cohen, P.T., Kahn, B.B., Pedersen, O. Diabetologia (2000) [Pubmed]
  11. Polymorphism in the glycogen-associated regulatory subunit of type 1 protein phosphatase (PPP1R3) gene and insulin sensitivity. Hansen, L., Reneland, R., Berglund, L., Rasmussen, S.K., Hansen, T., Lithell, H., Pedersen, O. Diabetes (2000) [Pubmed]
  12. Asp905Tyr polymorphism of protein phosphatase 1 G subunit gene in hypertension. Shen, G.Q., Ikegami, H., Fujisawa, T., Hamada, Y., Kamide, K., Rakugi, H., Higaki, J., Murakami, H., Shimamoto, K., Ogihara, T. Hypertension (1997) [Pubmed]
  13. Genetic variability in the insulin signalling pathway may contribute to the risk of late onset Alzheimer's disease. Liolitsa, D., Powell, J., Lovestone, S. J. Neurol. Neurosurg. Psychiatr. (2002) [Pubmed]
  14. Identification of skeletal muscle autoantigens by expression library screening using sera from autoimmune rippling muscle disease (ARMD) patients. Watkins, T.C., Zelinka, L.M., Kesic, M., Ansevin, C.F., Walker, G.R. J. Cell. Biochem. (2006) [Pubmed]
  15. Alterations of the PPP1R3 gene in hematological malignancies. Inoue, K., Kohno, T., Takakura, S., Morishita, K., Takita, J., Hayashi, Y., Mizoguchi, H., Yokota, J. Int. J. Oncol. (2000) [Pubmed]
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