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
Gene location (Human)
Chr.	Chromosome 17 (human)
End	60,666,280 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	85,237,892 bp
RNA expression pattern
	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
	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
	8493
	53892
	ENSG00000170836
	ENSMUSG00000020525
	O15297
	Q9QZ67
	NM_003620
	NM_016910
	NP_003611
	NP_058606
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated August 19, 2024

Protein phosphatase 1D is an enzyme that in humans is encoded by the PPM1D gene.^[5]^[6]

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.^[6] Pathogenic variants in exons 5-6 in the PPM1D gene can cause the neurodevelopmental disorder known as Jansen-de Vries Syndrome (JdVS)^[7].

Interactions

PPM1D has been shown to interact with CDC5L.^[8]

Related Research Articles

p53, also known as Tumor protein P53, cellular tumor antigen p53, or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins are crucial in vertebrates, where they prevent cancer formation. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence TP53 is classified as a tumor suppressor gene.

<i>PTEN</i> (gene) Tumor suppressor gene

Phosphatase and tensin homolog (PTEN) is a phosphatase in humans and is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers, specifically glioblastoma, lung cancer, breast cancer, and prostate cancer. Genes corresponding to PTEN (orthologs) have been identified in most mammals for which complete genome data are available.

<span class="mw-page-title-main">Transcription factor Jun</span> Mammalian protein found in Homo sapiens

Transcription factor Jun is a protein that in humans is encoded by the JUN gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the JUN gene. c-jun was the first oncogenic transcription factor discovered. The proto-oncogene c-Jun is the cellular homolog of the viral oncoprotein v-jun. The viral homolog v-jun was discovered in avian sarcoma virus 17 and was named for ju-nana, the Japanese word for 17. The human JUN encodes a protein that is highly similar to the viral protein, which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies.

CHEK2 is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been linked to a wide range of cancers.

Jun dimerization protein 2 (JUNDM2) is a protein that in humans is encoded by the JDP2 gene. The Jun dimerization protein is a member of the AP-1 family of transcription factors.

<span class="mw-page-title-main">TOP2A</span> Protein-coding gene in the species Homo sapiens

DNA topoisomerase IIα is a human enzyme encoded by the TOP2A gene.

Metastasis-associated protein MTA1 is a protein that in humans is encoded by the MTA1 gene. MTA1 is the founding member of the MTA family of genes. MTA1 is primarily localized in the nucleus but also found to be distributed in the extra-nuclear compartments. MTA1 is a component of several chromatin remodeling complexes including the nucleosome remodeling and deacetylation complex (NuRD). MTA1 regulates gene expression by functioning as a coregulator to integrate DNA-interacting factors to gene activity. MTA1 participates in physiological functions in the normal and cancer cells. MTA1 is one of the most upregulated proteins in human cancer and associates with cancer progression, aggressive phenotypes, and poor prognosis of cancer patients.

Protein NDRG1 is a protein that in humans is encoded by the NDRG1 gene.

Apoptosis-stimulating of p53 protein 2 (ASPP2) also known as Bcl2-binding protein (Bbp) and tumor suppressor p53-binding protein 2 (p53BP2) is a protein that in humans is encoded by the TP53BP2 gene. Multiple transcript variants encoding different isoforms have been found for this gene.

Protein phosphatase 1 regulatory subunit 15A, also known as growth arrest and DNA damage-inducible protein (GADD34), is a protein that in humans is encoded by the PPP1R15A gene.

40S ribosomal protein S16' is a protein that in humans is encoded by the RPS16 gene.

Dual specificity protein phosphatase 3 is an enzyme that in humans is encoded by the DUSP3 gene.

Serine/threonine-protein kinase VRK1 is an enzyme that in humans is encoded by the VRK1 gene.

Serine/threonine-protein kinase PLK2 is an enzyme that in humans is encoded by the PLK2 gene.

Receptor-type tyrosine-protein phosphatase gamma is an enzyme that in humans is encoded by the PTPRG gene.

Tyrosine-protein phosphatase non-receptor type 9 is an enzyme that in humans is encoded by the PTPN9 gene.

60S ribosomal protein L13 is a protein that in humans is encoded by the RPL13 gene.

Dual specificity protein phosphatase 16 is an enzyme that in humans is encoded by the DUSP16 gene.

Protein CIP2A also known as cancerous inhibitor of PP2A (CIP2A) is a protein that in humans is encoded by the KIAA1524 gene.

Etoposide-induced protein 2.4 homolog is a protein that in humans is encoded by the EI24 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000170836 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020525 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Fiscella M, Zhang H, Fan S, Sakaguchi K, Shen S, Mercer WE, Vande Woude GF, O'Connor PM, Appella E (July 1997). "Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner". Proc Natl Acad Sci U S A. 94 (12): 6048–53. Bibcode:1997PNAS...94.6048F. doi: 10.1073/pnas.94.12.6048 . PMC 20998 . PMID 9177166.
1 2 "Entrez Gene: PPM1D protein phosphatase 1D magnesium-dependent, delta isoform".
↑ Wojcik, Monica H; Srivastava, Siddharth; Agrawal, Pankaj B; Balci, Tugce B; Callewaert, Bert; Calvo, Pier Luigi; Carli, Diana; Caudle, Michelle; Colaiacovo, Samantha; Cross, Laura; Demetriou, Kalliope; Drazba, Katy; Dutra-Clarke, Marina; Edwards, Matthew; Genetti, Casie A (July 2023). "Jansen-DeVries Syndrome: Expansion of the PPM1D Clinical and Phenotypic Spectrum in 34 Families". American journal of medical genetics. Part A. 191 (7): 1900–1910. doi:10.1002/ajmg.a.63226. ISSN 1552-4825. PMID 37183572.
↑ Ajuh, P; Kuster B; Panov K; Zomerdijk J C; Mann M; Lamond A I (December 2000). "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. ISSN 0261-4189. PMC 305846 . PMID 11101529.

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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000170836 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020525 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9177166-5] Fiscella M, Zhang H, Fan S, Sakaguchi K, Shen S, Mercer WE, Vande Woude GF, O'Connor PM, Appella E (July 1997). "Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner". Proc Natl Acad Sci U S A. 94 (12): 6048–53. Bibcode:1997PNAS...94.6048F. doi: 10.1073/pnas.94.12.6048 . PMC 20998 . PMID 9177166.

[entrez-6] 1 2 "Entrez Gene: PPM1D protein phosphatase 1D magnesium-dependent, delta isoform".

[7] Wojcik, Monica H; Srivastava, Siddharth; Agrawal, Pankaj B; Balci, Tugce B; Callewaert, Bert; Calvo, Pier Luigi; Carli, Diana; Caudle, Michelle; Colaiacovo, Samantha; Cross, Laura; Demetriou, Kalliope; Drazba, Katy; Dutra-Clarke, Marina; Edwards, Matthew; Genetti, Casie A (July 2023). "Jansen-DeVries Syndrome: Expansion of the PPM1D Clinical and Phenotypic Spectrum in 34 Families". American journal of medical genetics. Part A. 191 (7): 1900–1910. doi:10.1002/ajmg.a.63226. ISSN 1552-4825. PMID 37183572.

[pmid11101529-8] Ajuh, P; Kuster B; Panov K; Zomerdijk J C; Mann M; Lamond A I (December 2000). "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. ISSN 0261-4189. PMC 305846 . PMID 11101529.

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PPM1D

Contents

Interactions

Related Research Articles

References

Further reading