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{{Infobox_gene}}
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'''Protein phosphatase 1A''' is an [[enzyme]] that in humans is encoded by the ''PPM1A'' [[gene]].<ref name="pmid1311954">{{cite journal |vauthors=Mann DJ, Campbell DG, McGowan CH, Cohen PT | title = Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences | journal = Biochim Biophys Acta | volume = 1130 | issue = 1 | pages = 100–4 |date=Apr 1992 | pmid = 1311954 | pmc =  | doi =  10.1016/0167-4781(92)90471-b}}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PPM1A protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5494| accessdate = }}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = PBB_Protein_PPM1A_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1a6q.
| PDB = {{PDB2|1a6q}}
| Name = Protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform
| HGNCid = 9275
| Symbol = PPM1A
| AltSymbols =; MGC9201; PP2C-ALPHA; PP2CA
| OMIM = 606108
| ECnumber = 
| Homologene = 56428
| MGIid = 99878
| GeneAtlas_image1 = PBB_GE_PPM1A_203966_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_PPM1A_210407_at_tn.png
| Function = {{GNF_GO|id=GO:0000287 |text = magnesium ion binding}} {{GNF_GO|id=GO:0004871 |text = signal transducer activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0015071 |text = protein phosphatase type 2C activity}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}} {{GNF_GO|id=GO:0030145 |text = manganese ion binding}}
| Component = {{GNF_GO|id=GO:0008287 |text = protein serine/threonine phosphatase complex}}
| Process = {{GNF_GO|id=GO:0006470 |text = protein amino acid dephosphorylation}} {{GNF_GO|id=GO:0043123 |text = positive regulation of I-kappaB kinase/NF-kappaB cascade}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5494
    | Hs_Ensembl = ENSG00000100614
    | Hs_RefseqProtein = NP_066283
    | Hs_RefseqmRNA = NM_021003
    | Hs_GenLoc_db =   
    | Hs_GenLoc_chr = 14
    | Hs_GenLoc_start = 59782223
    | Hs_GenLoc_end = 59829813
    | Hs_Uniprot = P35813
    | Mm_EntrezGene = 19042
    | Mm_Ensembl = ENSMUSG00000021096
    | Mm_RefseqmRNA = NM_008910
    | Mm_RefseqProtein = NP_032936
    | Mm_GenLoc_db =   
    | Mm_GenLoc_chr = 12
    | Mm_GenLoc_start = 73702516
    | Mm_GenLoc_end = 73713402
    | Mm_Uniprot = Q8R4T7
  }}
}}
'''Protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform''', also known as '''PPM1A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PPM1A protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5494| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
{{PBB_Summary
| section_title =  
| section_title =  
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: PPM1A protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5494| accessdate = }}</ref>
| summary_text = 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.<ref name="entrez" />
}}
}}
==Interactions==
PPM1A has been shown to [[Protein-protein interaction|interact]] with [[Metabotropic glutamate receptor 3]].<ref name=pmid14663150>{{cite journal |last=Flajolet |first=Marc |authorlink= |author2=Rakhilin Sergey |author3=Wang Hong |author4=Starkova Natalia |author5=Nuangchamnong Nina |author6=Nairn Angus C |author7=Greengard Paul  |date=Dec 2003 |title=Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3 |journal=[[PNAS|Proc. Natl. Acad. Sci. U.S.A.]] |volume=100 |issue=26 |pages=16006–11 |publisher= |location = United States| issn = 0027-8424| pmid = 14663150 |doi = 10.1073/pnas.2136600100 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |pmc=307683 }}</ref>
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==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=Mann DJ, Campbell DG, McGowan CH, Cohen PT |title=Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences. |journal=Biochim. Biophys. Acta |volume=1130 |issue= 1 |pages= 100-4 |year= 1992 |pmid= 1311954 |doi=  }}
*{{cite journal  |vauthors=Redpath NT, Price NT, Severinov KV, Proud CG |title=Regulation of elongation factor-2 by multisite phosphorylation. |journal=Eur. J. Biochem. |volume=213 |issue= 2 |pages= 689–99 |year= 1993 |pmid= 8386634 |doi=10.1111/j.1432-1033.1993.tb17809.x }}
*{{cite journal  | author=Redpath NT, Price NT, Severinov KV, Proud CG |title=Regulation of elongation factor-2 by multisite phosphorylation. |journal=Eur. J. Biochem. |volume=213 |issue= 2 |pages= 689-99 |year= 1993 |pmid= 8386634 |doi=  }}
*{{cite journal  |vauthors=Das AK, Helps NR, Cohen PT, Barford D |title=Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution. |journal=EMBO J. |volume=15 |issue= 24 |pages= 6798–809 |year= 1997 |pmid= 9003755 |doi= | pmc=452505 }}
*{{cite journal  | author=Das AK, Helps NR, Cohen PT, Barford D |title=Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution. |journal=EMBO J. |volume=15 |issue= 24 |pages= 6798-809 |year= 1997 |pmid= 9003755 |doi=  }}
*{{cite journal  |vauthors=Takekawa M, Maeda T, Saito H |title=Protein phosphatase 2Calpha inhibits the human stress-responsive p38 and JNK MAPK pathways. |journal=EMBO J. |volume=17 |issue= 16 |pages= 4744–52 |year= 1998 |pmid= 9707433 |doi= 10.1093/emboj/17.16.4744 | pmc=1170803 }}
*{{cite journal  | author=Takekawa M, Maeda T, Saito H |title=Protein phosphatase 2Calpha inhibits the human stress-responsive p38 and JNK MAPK pathways. |journal=EMBO J. |volume=17 |issue= 16 |pages= 4744-52 |year= 1998 |pmid= 9707433 |doi= 10.1093/emboj/17.16.4744 }}
*{{cite journal  |vauthors=Fjeld CC, Denu JM |title=Kinetic analysis of human serine/threonine protein phosphatase 2Calpha. |journal=J. Biol. Chem. |volume=274 |issue= 29 |pages= 20336–43 |year= 1999 |pmid= 10400656 |doi=10.1074/jbc.274.29.20336  }}
*{{cite journal  | author=Fjeld CC, Denu JM |title=Kinetic analysis of human serine/threonine protein phosphatase 2Calpha. |journal=J. Biol. Chem. |volume=274 |issue= 29 |pages= 20336-43 |year= 1999 |pmid= 10400656 |doi= }}
*{{cite journal  |vauthors=Hishiya A, Ohnishi M, Tamura S, Nakamura F |title=Protein phosphatase 2C inactivates F-actin binding of human platelet moesin. |journal=J. Biol. Chem. |volume=274 |issue= 38 |pages= 26705–12 |year= 1999 |pmid= 10480873 |doi=10.1074/jbc.274.38.26705  }}
*{{cite journal  | author=Hishiya A, Ohnishi M, Tamura S, Nakamura F |title=Protein phosphatase 2C inactivates F-actin binding of human platelet moesin. |journal=J. Biol. Chem. |volume=274 |issue= 38 |pages= 26705-12 |year= 1999 |pmid= 10480873 |doi=  }}
*{{cite journal  |vauthors=Cheng A, Ross KE, Kaldis P, Solomon MJ |title=Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases. |journal=Genes Dev. |volume=13 |issue= 22 |pages= 2946–57 |year= 2000 |pmid= 10580002 |doi=10.1101/gad.13.22.2946  | pmc=317162 }}
*{{cite journal  | author=Cheng A, Ross KE, Kaldis P, Solomon MJ |title=Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases. |journal=Genes Dev. |volume=13 |issue= 22 |pages= 2946-57 |year= 2000 |pmid= 10580002 |doi= }}
*{{cite journal  |vauthors=Strovel ET, Wu D, Sussman DJ |title=Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription. |journal=J. Biol. Chem. |volume=275 |issue= 4 |pages= 2399–403 |year= 2000 |pmid= 10644691 |doi=10.1074/jbc.275.4.2399  }}
*{{cite journal | author=Strovel ET, Wu D, Sussman DJ |title=Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription. |journal=J. Biol. Chem. |volume=275 |issue= 4 |pages= 2399-403 |year= 2000 |pmid= 10644691 |doi= }}
*{{cite journal   |vauthors=Lifschitz-Mercer B, Sheinin Y, Ben-Meir D, etal |title=Protein phosphatase 2Calpha expression in normal human tissues: an immunohistochemical study. |journal=Histochem. Cell Biol. |volume=116 |issue= 1 |pages= 31–9 |year= 2001 |pmid= 11479720 |doi= 10.1007/s004180100291 }}
*{{cite journal  | author=Lifschitz-Mercer B, Sheinin Y, Ben-Meir D, ''et al.'' |title=Protein phosphatase 2Calpha expression in normal human tissues: an immunohistochemical study. |journal=Histochem. Cell Biol. |volume=116 |issue= 1 |pages= 31-9 |year= 2001 |pmid= 11479720 |doi= }}
*{{cite journal  |vauthors=Srivastava J, Goris J, Dilworth SM, Parker PJ |title=Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by nucleotides. |journal=FEBS Lett. |volume=516 |issue= 1-3 |pages= 265–9 |year= 2002 |pmid= 11959144 |doi=10.1016/S0014-5793(02)02500-0  }}
*{{cite journal | author=Srivastava J, Goris J, Dilworth SM, Parker PJ |title=Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by nucleotides. |journal=FEBS Lett. |volume=516 |issue= 1-3 |pages= 265-9 |year= 2002 |pmid= 11959144 |doi= }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal   |vauthors=Ofek P, Ben-Meir D, Kariv-Inbal Z, etal |title=Cell cycle regulation and p53 activation by protein phosphatase 2C alpha. |journal=J. Biol. Chem. |volume=278 |issue= 16 |pages= 14299–305 |year= 2003 |pmid= 12514180 |doi= 10.1074/jbc.M211699200 }}
*{{cite journal | author=Ofek P, Ben-Meir D, Kariv-Inbal Z, ''et al.'' |title=Cell cycle regulation and p53 activation by protein phosphatase 2C alpha. |journal=J. Biol. Chem. |volume=278 |issue= 16 |pages= 14299-305 |year= 2003 |pmid= 12514180 |doi= 10.1074/jbc.M211699200 }}
*{{cite journal   |vauthors=Matsuda A, Suzuki Y, Honda G, etal |title=Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. |journal=Oncogene |volume=22 |issue= 21 |pages= 3307–18 |year= 2003 |pmid= 12761501 |doi= 10.1038/sj.onc.1206406 }}
*{{cite journal | author=Matsuda A, Suzuki Y, Honda G, ''et al.'' |title=Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. |journal=Oncogene |volume=22 |issue= 21 |pages= 3307-18 |year= 2003 |pmid= 12761501 |doi= 10.1038/sj.onc.1206406 }}
*{{cite journal   |vauthors=Flajolet M, Rakhilin S, Wang H, etal |title=Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=100 |issue= 26 |pages= 16006–11 |year= 2004 |pmid= 14663150 |doi= 10.1073/pnas.2136600100  | pmc=307683 }}
*{{cite journal | author=Flajolet M, Rakhilin S, Wang H, ''et al.'' |title=Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=100 |issue= 26 |pages= 16006-11 |year= 2004 |pmid= 14663150 |doi= 10.1073/pnas.2136600100 }}
*{{cite journal   |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal   |vauthors=Yoshizaki T, Maegawa H, Egawa K, etal |title=Protein phosphatase-2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. |journal=J. Biol. Chem. |volume=279 |issue= 21 |pages= 22715–26 |year= 2004 |pmid= 15016818 |doi= 10.1074/jbc.M313745200 }}
*{{cite journal | author=Yoshizaki T, Maegawa H, Egawa K, ''et al.'' |title=Protein phosphatase-2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. |journal=J. Biol. Chem. |volume=279 |issue= 21 |pages= 22715-26 |year= 2004 |pmid= 15016818 |doi= 10.1074/jbc.M313745200 }}
*{{cite journal   |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal   |vauthors=Li D, Wang F, Lai M, etal |title=A protein phosphatase 2calpha-Ca2+ channel complex for dephosphorylation of neuronal Ca2+ channels phosphorylated by protein kinase C. |journal=J. Neurosci. |volume=25 |issue= 8 |pages= 1914–23 |year= 2005 |pmid= 15728831 |doi= 10.1523/JNEUROSCI.4790-04.2005 }}
*{{cite journal | author=Li D, Wang F, Lai M, ''et al.'' |title=A protein phosphatase 2calpha-Ca2+ channel complex for dephosphorylation of neuronal Ca2+ channels phosphorylated by protein kinase C. |journal=J. Neurosci. |volume=25 |issue= 8 |pages= 1914-23 |year= 2005 |pmid= 15728831 |doi= 10.1523/JNEUROSCI.4790-04.2005 }}
*{{cite journal   |vauthors=Rual JF, Venkatesan K, Hao T, etal |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
*{{cite journal | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
*{{cite journal   |vauthors=Kitajima TS, Sakuno T, Ishiguro K, etal |title=Shugoshin collaborates with protein phosphatase 2A to protect cohesin. |journal=Nature |volume=441 |issue= 7089 |pages= 46–52 |year= 2006 |pmid= 16541025 |doi= 10.1038/nature04663 }}
*{{cite journal | author=Kitajima TS, Sakuno T, Ishiguro K, ''et al.'' |title=Shugoshin collaborates with protein phosphatase 2A to protect cohesin. |journal=Nature |volume=441 |issue= 7089 |pages= 46-52 |year= 2006 |pmid= 16541025 |doi= 10.1038/nature04663 }}
}}
}}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=5494}}
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Revision as of 18:32, 7 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Protein phosphatase 1A is an enzyme that in humans is encoded by the PPM1A gene.[1][2]

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.[2]

Interactions

PPM1A has been shown to interact with Metabotropic glutamate receptor 3.[3] 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. ↑ Mann DJ, Campbell DG, McGowan CH, Cohen PT (Apr 1992). "Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences". Biochim Biophys Acta. 1130 (1): 100–4. doi:10.1016/0167-4781(92)90471-b. PMID 1311954.
  2. ↑ 2.0 2.1 "Entrez Gene: PPM1A protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform".
  3. ↑ Flajolet, Marc; Rakhilin Sergey; Wang Hong; Starkova Natalia; Nuangchamnong Nina; Nairn Angus C; Greengard Paul (Dec 2003). "Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3". Proc. Natl. Acad. Sci. U.S.A. United States. 100 (26): 16006–11. doi:10.1073/pnas.2136600100. ISSN 0027-8424. PMC 307683. PMID 14663150.

Further reading



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