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NameProtein phosphatase 1 regulatory subunit 15A
Synonyms
  • GADD34
  • Growth arrest and DNA damage-inducible protein GADD34
  • Myeloid differentiation primary response protein MyD116 homolog
Gene NamePPP1R15A
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009122|Protein phosphatase 1 regulatory subunit 15A
MAPGQAPHQATPWRDAHPFFLLSPVMGLLSRAWSRLRGLGPLEPWLVEAVKGAALVEAGL
EGEARTPLAIPHTPWGRRPEEEAEDSGGPGEDRETLGLKTSSSLPEAWGLLDDDDGMYGE
REATSVPRGQGSQFADGQRAPLSPSLLIRTLQGSDKNPGEEKAEEEGVAEEEGVNKFSYP
PSHRECCPAVEEEDDEEAVKKEAHRTSTSALSPGSKPSTWVSCPGEEENQATEDKRTERS
KGARKTSVSPRSSGSDPRSWEYRSGEASEEKEEKAHKETGKGEAAPGPQSSAPAQRPQLK
SWWCQPSDEEEGEVKALGAAEKDGEAECPPCIPPPSAFLKAWVYWPGEDTEEEEDEEEDE
DSDSGSDEEEGEAEASSSTPATGVFLKSWVYQPGEDTEEEEDEDSDTGSAEDEREAETSA
STPPASAFLKAWVYRPGEDTEEEEDEDVDSEDKEDDSEAALGEAESDPHPSHPDQRAHFR
GWGYRPGKETEEEEAAEDWGEAEPCPFRVAIYVPGEKPPPPWAPPRLPLRLQRRLKRPET
PTHDPDPETPLKARKVRFSEKVTVHFLAVWAGPAQAARQGPWEQLARDRSRFARRITQAQ
EELSPCLTPAARARAWARLRNPPLAPIPALTQTLPSSSVPSSPVQTTPLSQAVATPSRSS
AAAAAALDLSGRRG
Number of residues674
Molecular Weight73477.025
Theoretical pINot Available
GO Classification
Functions
  • protein phosphatase 1 binding
  • protein kinase binding
  • protein phosphatase type 1 activator activity
  • protein phosphatase type 1 regulator activity
Processes
  • negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
  • apoptotic process
  • positive regulation of peptidyl-serine phosphorylation
  • negative regulation of protein dephosphorylation
  • negative regulation of PERK-mediated unfolded protein response
  • positive regulation of phosphoprotein phosphatase activity
  • endoplasmic reticulum unfolded protein response
  • negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation
  • transforming growth factor beta receptor signaling pathway
  • positive regulation of endoplasmic reticulum stress-induced eIF2 alpha dephosphorylation
  • positive regulation of gene expression
  • positive regulation of translational initiation in response to stress
  • response to endoplasmic reticulum stress
  • protein localization to endoplasmic reticulum
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
  • regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation
  • positive regulation of transcription from RNA polymerase I promoter
  • regulation of translational initiation by eIF2 alpha dephosphorylation
  • peptidyl-serine dephosphorylation
  • cell cycle arrest
  • negative regulation of transforming growth factor beta receptor signaling pathway
  • negative regulation of phosphoprotein phosphatase activity
  • cellular response to DNA damage stimulus
  • positive regulation of peptidyl-serine dephosphorylation
Components
  • cytoplasm
  • mitochondrion
  • membrane
  • endoplasmic reticulum
  • endoplasmic reticulum membrane
  • mitochondrial outer membrane
  • Golgi apparatus
  • cytosol
  • protein phosphatase type 1 complex
General FunctionProtein phosphatase type 1 regulator activity
Specific FunctionRecruits 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'.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDO75807
UniProtKB Entry NamePR15A_HUMAN
Cellular LocationEndoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0020851|Protein phosphatase 1 regulatory subunit 15A (PPP1R15A)
ATGGCCCCAGGCCAAGCACCCCATCAGGCTACCCCGTGGAGGGATGCCCACCCTTTCTTC
CTCCTGTCCCCAGTGATGGGCCTCCTCAGCCGCGCCTGGAGCCGCCTGAGGGGCCTGGGA
CCTCTAGAGCCCTGGCTGGTGGAAGCAGTAAAAGGAGCAGCTCTGGTAGAAGCTGGCCTG
GAGGGAGAAGCTAGGACTCCTCTGGCAATCCCCCATACCCCTTGGGGCAGACGCCCTGAA
GAGGAGGCTGAAGACAGTGGAGGCCCTGGAGAGGACAGAGAAACACTGGGGCTGAAAACC
AGCAGTTCCCTTCCTGAAGCCTGGGGACTTTTGGATGATGATGATGGCATGTATGGTGAG
CGAGAGGCAACCAGTGTCCCTAGAGGGCAGGGAAGTCAATTTGCAGATGGCCAGCGTGCT
CCCCTGTCTCCCAGCCTTCTGATAAGGACACTGCAAGGTTCTGATAAGAACCCAGGGGAG
GAGAAAGCCGAGGAAGAGGGAGTTGCTGAAGAGGAGGGAGTTAACAAGTTCTCTTATCCA
CCATCACACCGGGAGTGTTGTCCAGCCGTGGAGGAGGAGGACGATGAAGAAGCTGTAAAG
AAAGAAGCTCACAGAACCTCTACTTCTGCCTTGTCTCCAGGATCCAAGCCCAGCACTTGG
GTGTCTTGCCCAGGGGAGGAAGAGAATCAAGCCACGGAGGATAAAAGAACAGAAAGAAGT
AAAGGAGCCAGGAAGACCTCCGTGTCCCCCCGATCTTCAGGCTCCGACCCCAGGTCCTGG
GAGTATCGTTCAGGAGAGGCGTCCGAGGAGAAGGAGGAAAAGGCACACAAAGAAACTGGG
AAAGGAGAAGCTGCCCCAGGGCCGCAATCCTCAGCCCCAGCCCAGAGGCCCCAGCTCAAG
TCCTGGTGGTGCCAACCCAGTGATGAAGAGGAGGGTGAGGTCAAGGCTTTGGGGGCAGCT
GAGAAGGATGGAGAAGCTGAGTGTCCTCCCTGCATCCCCCCACCAAGTGCCTTCCTGAAG
GCCTGGGTGTATTGGCCAGGAGAGGACACAGAGGAAGAGGAAGATGAGGAAGAAGATGAG
GACAGTGACTCTGGATCAGATGAGGAAGAGGGAGAAGCTGAGGCTTCCTCTTCCACTCCT
GCTACAGGTGTCTTCTTGAAGTCCTGGGTCTATCAGCCAGGAGAGGACACAGAGGAGGAG
GAAGATGAGGACAGTGATACAGGATCAGCCGAGGATGAAAGAGAAGCTGAGACTTCTGCT
TCCACACCCCCTGCAAGTGCTTTCTTGAAGGCCTGGGTGTATCGGCCAGGAGAGGACACG
GAGGAGGAGGAAGATGAGGATGTGGATAGTGAGGATAAGGAAGATGATTCAGAAGCAGCC
TTGGGAGAAGCTGAGTCAGACCCACATCCCTCCCACCCGGACCAGAGGGCCCACTTCAGG
GGCTGGGGATATCGACCTGGAAAAGAGACAGAGGAAGAGGAAGCTGCTGAGGACTGGGGA
GAAGCTGAGCCCTGCCCCTTCCGAGTGGCCATCTATGTACCTGGAGAGAAGCCACCGCCT
CCCTGGGCTCCTCCTAGGCTGCCCCTCCGACTGCAAAGGCGGCTCAAGCGCCCAGAAACC
CCTACTCATGATCCGGACCCTGAGACTCCCCTAAAGGCCAGAAAGGTGCGCTTCTCCGAG
AAGGTCACTGTCCATTTCCTGGCTGTCTGGGCAGGGCCGGCCCAGGCCGCCCGCCAGGGC
CCCTGGGAGCAGCTTGCTCGGGATCGCAGCCGCTTCGCACGCCGCATCACCCAGGCCCAG
GAGGAGCTGAGCCCCTGCCTCACCCCTGCTGCCCGGGCCAGAGCCTGGGCACGCCTCAGG
AACCCACCTTTAGCCCCCATCCCTGCCCTCACCCAGACCTTGCCTTCCTCCTCTGTCCCT
TCGTCCCCAGTCCAGACCACGCCCTTGAGCCAAGCTGTGGCCACACCTTCCCGCTCGTCT
GCTGCTGCAGCGGCTGCCCTGGACCTCAGTGGGAGGCGTGGCTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:14375
Chromosome Location19
LocusNot Available
References
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  4. 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. 8139541
  5. 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. 10490642
  6. 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. 11517336
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  11. 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. 12556489
  12. 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. 12724406
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  15. 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. 21518769
  16. 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. 24092754