PPM1D

Protein phosphatase 1D is an enzyme that in humans is encoded by the PPM1D gene.

PPM1D
Identifiers
Aliases	PPM1D, PP2C-DELTA, WIP1, protein phosphatase, Mg2+/Mn2+ dependent 1D, IDDGIP, JDVS, WIP1 protein, human, PPM1D protein, human
External IDs	OMIM: 605100; MGI: 1858214; HomoloGene: 31185; GeneCards: PPM1D; OMA:PPM1D - orthologs
Gene location (Human) Chr. Chromosome 17 (human) Band 17q23.2 Start 60,600,193 bp End 60,666,280 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 C|11 51.34 cM Start 85,202,070 bp End 85,237,892 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte amniotic fluid ventricular zone gonad placenta ganglionic eminence mucosa of sigmoid colon jejunal mucosa germinal epithelium Achilles tendon Top expressed in seminiferous tubule spermatid genital tubercle fetal liver hematopoietic progenitor cell tail of embryo spermatocyte zygote lobe of cerebellum medial ganglionic eminence cerebellar vermis More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein serine/threonine phosphatase activity protein binding catalytic activity phosphoprotein phosphatase activity hydrolase activity metal ion binding cation binding mitogen-activated protein kinase binding protein serine/threonine kinase activity Cellular component nucleoplasm nucleus cytoplasm cytosol Biological process cellular response to starvation cell cycle response to radiation protein dephosphorylation G2/M transition of mitotic cell cycle response to bacterium peptidyl-threonine dephosphorylation negative regulation of cell population proliferation DNA methylation transcription initiation from RNA polymerase II promoter protein phosphorylation negative regulation of gene expression, epigenetic DNA damage response, signal transduction by p53 class mediator Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8493 53892 Ensembl ENSG00000170836 ENSMUSG00000020525 UniProt O15297 Q9QZ67 RefSeq (mRNA) NM_003620 NM_016910 RefSeq (protein) NP_003611 NP_058606 Location (UCSC) Chr 17: 60.6 – 60.67 Mb Chr 11: 85.2 – 85.24 Mb PubMed search
Wikidata
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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. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase (MAPK/p38) through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development. Pathogenic variants in exons 5-6 in the PPM1D gene can cause the neurodevelopmental disorder known as Jansen-de Vries Syndrome (JdVS).

Interactions

PPM1D has been shown to interact with CDC5L.

Further reading

• Adams MD, Kerlavage AR, Fleischmann RD, et al. (1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature. 377 (6547 Suppl): 3–174. PMID 7566098.
• Hirano K, Ito M, Hartshorne DJ (1995). "Interaction of the ribosomal protein, L5, with protein phosphatase type 1". J. Biol. Chem. 270 (34): 19786–90. doi:10.1074/jbc.270.34.19786. PMID 7649987.
• Takekawa M, Adachi M, Nakahata A, et al. (2001). "p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation". EMBO J. 19 (23): 6517–26. doi:10.1093/emboj/19.23.6517. PMC 305857. PMID 11101524.
• Ajuh P, Kuster B, Panov K, et al. (2001). "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". EMBO J. 19 (23): 6569–81. doi:10.1093/emboj/19.23.6569. PMC 305846. PMID 11101529.
• Choi J, Nannenga B, Demidov ON, et al. (2002). "Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control". Mol. Cell. Biol. 22 (4): 1094–105. doi:10.1128/MCB.22.4.1094-1105.2002. PMC 134641. PMID 11809801.
• Li J, Yang Y, Peng Y, et al. (2002). "Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23". Nat. Genet. 31 (2): 133–4. doi:10.1038/ng888. PMID 12021784. S2CID 5750250.
• Bulavin DV, Demidov ON, Saito S, et al. (2002). "Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity". Nat. Genet. 31 (2): 210–5. doi:10.1038/ng894. PMID 12021785. S2CID 30048056.
• Morimoto H, Okamura H, Haneji T (2002). "Interaction of protein phosphatase 1 delta with nucleolin in human osteoblastic cells". J. Histochem. Cytochem. 50 (9): 1187–93. doi:10.1177/002215540205000905. PMID 12185196.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Imabayashi H, Mori T, Gojo S, et al. (2003). "Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis". Exp. Cell Res. 288 (1): 35–50. doi:10.1016/S0014-4827(03)00130-7. PMID 12878157.
• Bernards R (2004). "Wip-ing out cancer". Nat. Genet. 36 (4): 319–20. doi:10.1038/ng0404-319. PMID 15054481.
• Lu X, Bocangel D, Nannenga B, et al. (2004). "The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair". Mol. Cell. 15 (4): 621–34. doi:10.1016/j.molcel.2004.08.007. PMID 15327777.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Yamaguchi H, Minopoli G, Demidov ON, et al. (2005). "Substrate specificity of the human protein phosphatase 2Cdelta, Wip1". Biochemistry. 44 (14): 5285–94. doi:10.1021/bi0476634. PMID 15807522.
• Lu X, Nannenga B, Donehower LA (2005). "PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints". Genes Dev. 19 (10): 1162–74. doi:10.1101/gad.1291305. PMC 1132003. PMID 15870257.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Rauta J, Alarmo EL, Kauraniemi P, et al. (2006). "The serine-threonine protein phosphatase PPM1D is frequently activated through amplification in aggressive primary breast tumours". Breast Cancer Res. Treat. 95 (3): 257–63. doi:10.1007/s10549-005-9017-7. PMID 16254685. S2CID 9693018.
• Fujimoto H, Onishi N, Kato N, et al. (2006). "Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase". Cell Death Differ. 13 (7): 1170–80. doi:10.1038/sj.cdd.4401801. PMID 16311512.
• Mendrzyk F, Radlwimmer B, Joos S, et al. (2006). "Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma". J. Clin. Oncol. 23 (34): 8853–62. doi:10.1200/JCO.2005.02.8589. PMID 16314645.