PPM1A

Protein phosphatase 1A is an enzyme that in humans is encoded by the PPM1A gene.[5][6]

PPM1A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A6Q, 3FXJ, 3FXK, 3FXL, 3FXM, 3FXO, 4RA2, 4RAF, 4RAG
Identifiers
Aliases	PPM1A, PP2C-ALPHA, PP2CA, PP2Calpha, protein phosphatase, Mg2+/Mn2+ dependent 1A
External IDs	OMIM: 606108 MGI: 99878 HomoloGene: 56428 GeneCards: PPM1A
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q23.1 Start 60,245,752 bp[1] End 60,299,087 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12|12 C3 Start 72,757,455 bp[2] End 72,799,819 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • R-SMAD binding • phosphoprotein phosphatase activity • manganese ion binding • protein serine/threonine phosphatase activity • calmodulin-dependent protein phosphatase activity • signal transducer activity • metal ion binding • catalytic activity • GO:0001948 protein binding • cation binding • hydrolase activity • magnesium ion binding Cellular component • cytoplasm • membrane • nucleoplasm • cell nucleus • cytosol • cell membrane Biological process • cellular response to transforming growth factor beta stimulus • peptidyl-threonine dephosphorylation • negative regulation of SMAD protein complex assembly • protein dephosphorylation • negative regulation of transforming growth factor beta receptor signaling pathway • Wnt signaling pathway • negative regulation of transcription from RNA polymerase II promoter • negative regulation of I-kappaB kinase/NF-kappaB signaling • negative regulation of BMP signaling pathway • positive regulation of protein export from nucleus • positive regulation of Wnt signaling pathway • positive regulation of transcription, DNA-templated • N-terminal protein myristoylation • cell cycle arrest • positive regulation of I-kappaB kinase/NF-kappaB signaling • dephosphorylation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5494	19042
Ensembl	ENSG00000100614	ENSMUSG00000021096
UniProt	P35813	P49443
RefSeq (mRNA)	NM_021003 NM_177951 NM_177952	NM_008910
RefSeq (protein)	NP_066283 NP_808820 NP_808821	NP_032936
Location (UCSC)	Chr 14: 60.25 – 60.3 Mb	Chr 12: 72.76 – 72.8 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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. This phosphatase dephosphorylates, and negatively regulates the activities of, MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses. This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53/p53, which leads to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants encoding two distinct isoforms have been described.[6]

Interactions

PPM1A has been shown to interact with Metabotropic glutamate receptor 3.[7] In 2006, Dr. Feng found that PPM1A can terminate TGF-beta signaling by inactivating Smad3 via dephosphorylation. Smad3 is an essential component of the TGF-beta signalling pathway.

References

1. GRCh38: Ensembl release 89: ENSG00000100614 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021096 - 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.
5. Mann DJ, Campbell DG, McGowan CH, Cohen PT (February 1992). "Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1130 (1): 100–4. doi:10.1016/0167-4781(92)90471-b. PMID 1311954.
6. "Entrez Gene: PPM1A protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform".
7. Flajolet M, Rakhilin S, Wang H, Starkova N, Nuangchamnong N, Nairn AC, Greengard P (December 2003). "Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3". Proceedings of the National Academy of Sciences of the United States of America. 100 (26): 16006–11. Bibcode:2003PNAS..10016006F. doi:10.1073/pnas.2136600100. PMC 307683. PMID 14663150.

Further reading

• Redpath NT, Price NT, Severinov KV, Proud CG (April 1993). "Regulation of elongation factor-2 by multisite phosphorylation". European Journal of Biochemistry. 213 (2): 689–99. doi:10.1111/j.1432-1033.1993.tb17809.x. PMID 8386634.
• Das AK, Helps NR, Cohen PT, Barford D (December 1996). "Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution". The EMBO Journal. 15 (24): 6798–809. doi:10.1002/j.1460-2075.1996.tb01071.x. PMC 452505. PMID 9003755.
• Takekawa M, Maeda T, Saito H (August 1998). "Protein phosphatase 2Calpha inhibits the human stress-responsive p38 and JNK MAPK pathways". The EMBO Journal. 17 (16): 4744–52. doi:10.1093/emboj/17.16.4744. PMC 1170803. PMID 9707433.
• Fjeld CC, Denu JM (July 1999). "Kinetic analysis of human serine/threonine protein phosphatase 2Calpha". The Journal of Biological Chemistry. 274 (29): 20336–43. doi:10.1074/jbc.274.29.20336. PMID 10400656.
• Hishiya A, Ohnishi M, Tamura S, Nakamura F (September 1999). "Protein phosphatase 2C inactivates F-actin binding of human platelet moesin". The Journal of Biological Chemistry. 274 (38): 26705–12. doi:10.1074/jbc.274.38.26705. PMID 10480873.
• Cheng A, Ross KE, Kaldis P, Solomon MJ (November 1999). "Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases". Genes & Development. 13 (22): 2946–57. doi:10.1101/gad.13.22.2946. PMC 317162. PMID 10580002.
• Strovel ET, Wu D, Sussman DJ (January 2000). "Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription". The Journal of Biological Chemistry. 275 (4): 2399–403. doi:10.1074/jbc.275.4.2399. PMID 10644691.
• Lifschitz-Mercer B, Sheinin Y, Ben-Meir D, Bramante-Schreiber L, Leider-Trejo L, Karby S, Smorodinsky NI, Lavi S (July 2001). "Protein phosphatase 2Calpha expression in normal human tissues: an immunohistochemical study". Histochemistry and Cell Biology. 116 (1): 31–9. doi:10.1007/s004180100291. PMID 11479720.
• Srivastava J, Goris J, Dilworth SM, Parker PJ (April 2002). "Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by nucleotides". FEBS Letters. 516 (1–3): 265–9. doi:10.1016/S0014-5793(02)02500-0. PMID 11959144.
• Ofek P, Ben-Meir D, Kariv-Inbal Z, Oren M, Lavi S (April 2003). "Cell cycle regulation and p53 activation by protein phosphatase 2C alpha". The Journal of Biological Chemistry. 278 (16): 14299–305. doi:10.1074/jbc.M211699200. PMID 12514180.
• Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S (May 2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways". Oncogene. 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID 12761501.
• Flajolet M, Rakhilin S, Wang H, Starkova N, Nuangchamnong N, Nairn AC, Greengard P (December 2003). "Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3". Proceedings of the National Academy of Sciences of the United States of America. 100 (26): 16006–11. Bibcode:2003PNAS..10016006F. doi:10.1073/pnas.2136600100. PMC 307683. PMID 14663150.
• Yoshizaki T, Maegawa H, Egawa K, Ugi S, Nishio Y, Imamura T, Kobayashi T, Tamura S, Olefsky JM, Kashiwagi A (May 2004). "Protein phosphatase-2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes". The Journal of Biological Chemistry. 279 (21): 22715–26. doi:10.1074/jbc.M313745200. PMID 15016818.
• Li D, Wang F, Lai M, Chen Y, Zhang JF (February 2005). "A protein phosphatase 2calpha-Ca2+ channel complex for dephosphorylation of neuronal Ca2+ channels phosphorylated by protein kinase C". The Journal of Neuroscience. 25 (8): 1914–23. doi:10.1523/JNEUROSCI.4790-04.2005. PMC 6726054. PMID 15728831.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 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.
• Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y (May 2006). "Shugoshin collaborates with protein phosphatase 2A to protect cohesin". Nature. 441 (7089): 46–52. Bibcode:2006Natur.441...46K. doi:10.1038/nature04663. PMID 16541025.