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Showing Protein Protein phosphatase 1 regulatory subunit 15A (HMDBP14465)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP14465
Secondary Accession Numbers None
Name Protein phosphatase 1 regulatory subunit 15A
Synonyms
  1. Growth arrest and DNA damage-inducible protein GADD34
  2. Myeloid differentiation primary response protein MyD116 homolog
Gene Name PPP1R15A
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Recruits the serine/threonine-protein phosphatase PP1 to dephosphorylate the translation initiation factor eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis initiated by stress-inducible kinases and facilitating recovery of cells from stress. Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1. May promote apoptosis by inducing TP53 phosphorylation on 'Ser-15'.
Pathways
  • Protein processing in endoplasmic reticulum
Reactions Not Available
GO Classification
Biological Process
cell cycle arrest
apoptotic process
positive regulation of phosphoprotein phosphatase activity
response to DNA damage stimulus
negative regulation of protein dephosphorylation
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
negative regulation of phosphoprotein phosphatase activity
negative regulation of PERK-mediated unfolded protein response
positive regulation of endoplasmic reticulum stress-induced eIF2 alpha dephosphorylation
positive regulation of peptidyl-serine dephosphorylation
positive regulation of translational initiation in response to stress
protein localization to endoplasmic reticulum
regulation of translational initiation by eIF2 alpha dephosphorylation
response to endoplasmic reticulum stress
Cellular Component
endoplasmic reticulum membrane
cytosol
cytoplasm
endoplasmic reticulum
mitochondrion
Golgi apparatus
mitochondrial outer membrane
protein phosphatase type 1 complex
membrane
Molecular Function
protein kinase binding
protein phosphatase 1 binding
protein phosphatase regulator activity
protein phosphatase activator activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 674
Molecular Weight 73477.025
Theoretical pI 4.609
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O75807
UniProtKB/Swiss-Prot Entry Name PR15A_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  3. Grishin AV, Azhipa O, Semenov I, Corey SJ: Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10172-7. Epub 2001 Aug 21. [PubMed:11517336 ]
  4. Connor JH, Weiser DC, Li S, Hallenbeck JM, Shenolikar S: Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. Mol Cell Biol. 2001 Oct;21(20):6841-50. [PubMed:11564868 ]
  5. Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J: A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science. 2005 Feb 11;307(5711):935-9. [PubMed:15705855 ]
  6. Adler HT, Chinery R, Wu DY, Kussick SJ, Payne JM, Fornace AJ Jr, Tkachuk DC: Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins. Mol Cell Biol. 1999 Oct;19(10):7050-60. [PubMed:10490642 ]
  7. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163 ]
  8. Hollander MC, Zhan Q, Bae I, Fornace AJ Jr: Mammalian GADD34, an apoptosis- and DNA damage-inducible gene. J Biol Chem. 1997 May 23;272(21):13731-7. doi: 10.1074/jbc.272.21.13731. [PubMed:9153226 ]
  9. Zhan Q, Lord KA, Alamo I Jr, Hollander MC, Carrier F, Ron D, Kohn KW, Hoffman B, Liebermann DA, Fornace AJ Jr: The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth. Mol Cell Biol. 1994 Apr;14(4):2361-71. doi: 10.1128/mcb.14.4.2361-2371.1994. [PubMed:8139541 ]
  10. Wu DY, Tkachuck DC, Roberson RS, Schubach WH: The human SNF5/INI1 protein facilitates the function of the growth arrest and DNA damage-inducible protein (GADD34) and modulates GADD34-bound protein phosphatase-1 activity. J Biol Chem. 2002 Aug 2;277(31):27706-15. doi: 10.1074/jbc.M200955200. Epub 2002 May 16. [PubMed:12016208 ]
  11. Yagi A, Hasegawa Y, Xiao H, Haneda M, Kojima E, Nishikimi A, Hasegawa T, Shimokata K, Isobe K: GADD34 induces p53 phosphorylation and p21/WAF1 transcription. J Cell Biochem. 2003 Dec 15;90(6):1242-9. doi: 10.1002/jcb.10711. [PubMed:14635196 ]
  12. Brush MH, Weiser DC, Shenolikar S: Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Mol Cell Biol. 2003 Feb;23(4):1292-303. doi: 10.1128/MCB.23.4.1292-1303.2003. [PubMed:12556489 ]
  13. Hung WJ, Roberson RS, Taft J, Wu DY: Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions. Mol Cell Biol. 2003 May;23(10):3477-86. doi: 10.1128/MCB.23.10.3477-3486.2003. [PubMed:12724406 ]
  14. Shi W, Sun C, He B, Xiong W, Shi X, Yao D, Cao X: GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. J Cell Biol. 2004 Jan 19;164(2):291-300. doi: 10.1083/jcb.200307151. Epub 2004 Jan 12. [PubMed:14718519 ]
  15. Lee YY, Cevallos RC, Jan E: An upstream open reading frame regulates translation of GADD34 during cellular stresses that induce eIF2alpha phosphorylation. J Biol Chem. 2009 Mar 13;284(11):6661-73. doi: 10.1074/jbc.M806735200. Epub 2009 Jan 8. [PubMed:19131336 ]
  16. Zhou W, Brush MH, Choy MS, Shenolikar S: Association with endoplasmic reticulum promotes proteasomal degradation of GADD34 protein. J Biol Chem. 2011 Jun 17;286(24):21687-96. doi: 10.1074/jbc.M110.212787. Epub 2011 Apr 25. [PubMed:21518769 ]
  17. Zhou W, Jeyaraman K, Yusoff P, Shenolikar S: Phosphorylation at tyrosine 262 promotes GADD34 protein turnover. J Biol Chem. 2013 Nov 15;288(46):33146-55. doi: 10.1074/jbc.M113.504407. Epub 2013 Oct 3. [PubMed:24092754 ]