PPM1D

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
Enzyme activity EC # BRENDA ExPASy KEGG MetaCyc 3.1.3.16 ↗ ↗ ↗ ↗
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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Protein phosphatase 1D is an enzyme that in humans is encoded by the PPM1D gene.

Gene

The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases.

Function

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.

Clinical significance

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, Fuldner RA, Bult CJ, Lee NH, et al. (September 1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence". 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". The Journal of Biological Chemistry. 270 (34): 19786–19790. doi:10.1074/jbc.270.34.19786. PMID 7649987.
• Takekawa M, Adachi M, Nakahata A, Nakayama I, Itoh F, Tsukuda H, et al. (December 2000). "p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation". The EMBO Journal. 19 (23): 6517–6526. doi:10.1093/emboj/19.23.6517. PMC 305857. PMID 11101524.
• Choi J, Nannenga B, Demidov ON, Bulavin DV, Cooney A, Brayton C, et al. (February 2002). "Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control". Molecular and Cellular Biology. 22 (4): 1094–1105. doi:10.1128/MCB.22.4.1094-1105.2002. PMC 134641. PMID 11809801.
• Li J, Yang Y, Peng Y, Austin RJ, van Eyndhoven WG, Nguyen KC, et al. (June 2002). "Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23". Nature Genetics. 31 (2): 133–134. doi:10.1038/ng888. PMID 12021784. S2CID 5750250.
• Bulavin DV, Demidov ON, Saito S, Kauraniemi P, Phillips C, Amundson SA, et al. (June 2002). "Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity". Nature Genetics. 31 (2): 210–215. 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". The Journal of Histochemistry and Cytochemistry. 50 (9): 1187–1193. doi:10.1177/002215540205000905. PMID 12185196.
• Imabayashi H, Mori T, Gojo S, Kiyono T, Sugiyama T, Irie R, et al. (August 2003). "Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis". Experimental Cell Research. 288 (1): 35–50. doi:10.1016/S0014-4827(03)00130-7. PMID 12878157.
• Bernards R (April 2004). "Wip-ing out cancer". Nature Genetics. 36 (4): 319–320. doi:10.1038/ng0404-319. PMID 15054481.
• Lu X, Bocangel D, Nannenga B, Yamaguchi H, Appella E, Donehower LA (August 2004). "The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair". Molecular Cell. 15 (4): 621–634. doi:10.1016/j.molcel.2004.08.007. PMID 15327777.
• Yamaguchi H, Minopoli G, Demidov ON, Chatterjee DK, Anderson CW, Durell SR, et al. (April 2005). "Substrate specificity of the human protein phosphatase 2Cdelta, Wip1". Biochemistry. 44 (14): 5285–5294. doi:10.1021/bi0476634. PMID 15807522.
• Lu X, Nannenga B, Donehower LA (2005). "PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints". Genes & Development. 19 (10): 1162–1174. doi:10.1101/gad.1291305. PMC 1132003. PMID 15870257.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Rauta J, Alarmo EL, Kauraniemi P, Karhu R, Kuukasjärvi T, Kallioniemi A (February 2006). "The serine-threonine protein phosphatase PPM1D is frequently activated through amplification in aggressive primary breast tumours". Breast Cancer Research and Treatment. 95 (3): 257–263. doi:10.1007/s10549-005-9017-7. PMID 16254685. S2CID 9693018.
• Fujimoto H, Onishi N, Kato N, Takekawa M, Xu XZ, Kosugi A, et al. (July 2006). "Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase". Cell Death and Differentiation. 13 (7): 1170–1180. doi:10.1038/sj.cdd.4401801. PMID 16311512.
• Mendrzyk F, Radlwimmer B, Joos S, Kokocinski F, Benner A, Stange DE, et al. (December 2005). "Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma". Journal of Clinical Oncology. 23 (34): 8853–8862. doi:10.1200/JCO.2005.02.8589. PMID 16314645.