T3DB: Protein phosphatase 1 regulatory subunit 15A

Name	Protein phosphatase 1 regulatory subunit 15A
Synonyms	GADD34 Growth arrest and DNA damage-inducible protein GADD34 Myeloid differentiation primary response protein MyD116 homolog
Gene Name	PPP1R15A
Organism	Human
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 residues	674
Molecular Weight	73477.025
Theoretical pI	Not Available
GO Classification	Functions protein phosphatase 1 binding protein kinase binding protein phosphatase type 1 activator activity protein phosphatase type 1 regulator activity Processes positive regulation of peptidyl-serine dephosphorylation cellular response to DNA damage stimulus 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 Components protein phosphatase type 1 complex cytosol cytoplasm mitochondrion membrane endoplasmic reticulum endoplasmic reticulum membrane mitochondrial outer membrane Golgi apparatus
General Function	Protein phosphatase type 1 regulator activity
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'.
Pfam Domain Function	PP1c_bdg (PF10488 )
Transmembrane Regions	Not Available
GenBank Protein ID	Not Available
UniProtKB ID	O75807
UniProtKB Entry Name	PR15A_HUMAN
Cellular Location	Endoplasmic 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 ID	Not Available
GeneCard ID	Not Available
GenAtlas ID	Not Available
HGNC ID	HGNC:14375
Chromosome Location	19
Locus	Not Available
References	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. 9153226 Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039 Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334 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 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 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 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. 11564868 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. Epub 2002 May 16. 12016208 Sarkar D, Su ZZ, Lebedeva IV, Sauane M, Gopalkrishnan RV, Valerie K, Dent P, Fisher PB: mda-7 (IL-24) Mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK. Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10054-9. Epub 2002 Jul 11. 12114539 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. 14635196 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 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 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. Epub 2004 Jan 12. 14718519 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. 15705855 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 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