PPP1R15A

PPP1R15A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4XPN
Identifiers
Aliases	PPP1R15A , GADD34, protein phosphatase 1 regulatory subunit 15A
External IDs	OMIM: 611048; MGI: 1927072; HomoloGene: 8639; GeneCards: PPP1R15A; OMA:PPP1R15A - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19q13.33 Start 48,872,421 bp [1] End 48,876,058 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7|7 B3 Start 45,172,340 bp [2] End 45,175,692 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastric mucosa monocyte vena cava sural nerve upper lobe of left lung granulocyte skin of abdomen gallbladder ascending aorta olfactory zone of nasal mucosa Top expressed in fetal liver hematopoietic progenitor cell tibiofemoral joint decidua granulocyte muscle of thigh islet of Langerhans saccule spleen lip human fetus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding protein kinase binding protein phosphatase 1 binding protein phosphatase activator activity protein phosphatase regulator activity Cellular component Golgi apparatus endoplasmic reticulum membrane membrane mitochondrial outer membrane protein phosphatase type 1 complex endoplasmic reticulum mitochondrion cytosol cytoplasm Biological process negative regulation of protein dephosphorylation cellular response to DNA damage stimulus positive regulation of endoplasmic reticulum stress-induced eIF2 alpha dephosphorylation positive regulation of translational initiation in response to stress positive regulation of phosphoprotein phosphatase activity intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress negative regulation of phosphoprotein phosphatase activity protein localization to endoplasmic reticulum regulation of translational initiation by eIF2 alpha dephosphorylation negative regulation of PERK-mediated unfolded protein response regulation of translation apoptotic process response to endoplasmic reticulum stress positive regulation of peptidyl-serine dephosphorylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23645 17872 Ensembl ENSG00000087074 ENSMUSG00000040435 UniProt O75807 P17564 RefSeq (mRNA) NM_014330 NM_008654 RefSeq (protein) NP_055145 NP_032680 Location (UCSC) Chr 19: 48.87 – 48.88 Mb Chr 7: 45.17 – 45.18 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Protein phosphatase 1 regulatory subunit 15A, also known as growth arrest and DNA damage-inducible protein (GADD34), is a protein that in humans is encoded by the PPP1R15A gene. ^{[5] [6] [7]}

The Gadd34/MyD116 gene was originally discovered as a member in a set of gadd and MyD mammalian genes encoding acidic proteins that synergistically suppress cell growth. ^[8] Later on it has been characterized as a gene playing a role in ER stress-induced cell death, being a target of ATF4 that plays a role in ER-mediated cell death via promoting protein dephosphorylation of eIF2α and reversing translational inhibition. ^[9]

Function

This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The induction of this gene by ionizing radiation occurs in certain cell lines regardless of p53 status, and its protein response is correlated with apoptosis following ionizing radiation. ^[7]

Interactions

PPP1R15A has been shown to interact with:

• BAG1 ^[10]
• LYN, ^[11]
• MLL, ^[12]
• PPP1CA, ^{[10] [13] [14]}
• PPP1CB, ^{[13] [14]}
• PPP1CC, ^{[13] [14]}
• SMARCB1, ^{[12] [13]} and
• TSN. ^[15]

References

1. GRCh38: Ensembl release 89: ENSG00000087074 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040435 – 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. Hollander MC, Zhan Q, Bae I, Fornace AJ Jr (Jul 1997). "Mammalian GADD34, an apoptosis- and DNA damage-inducible gene". J Biol Chem. 272 (21): 13731–7. doi: 10.1074/jbc.272.21.13731 . PMID   9153226.
6. Korabiowska M, Betke H, Kellner S, Stachura J, Schauer A (Jan 1998). "Differential expression of growth arrest, DNA damage genes and tumour suppressor gene p53 in naevi and malignant melanomas". Anticancer Res. 17 (5A): 3697–700. PMID   9413226.
7. "Entrez Gene: PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A".
8. Zhan Q, Lord KA, Alamo I, Hollander MC, Carrier F, Ron D, Kohn KW, Hoffman B, Liebermann DA, Fornace AJ (April 1994). "The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth". Mol. Cell. Biol. 14 (4): 2361–71. doi:10.1128/mcb.14.4.2361. PMC   358603 . PMID   8139541.
9. Sano R, Reed JC (July 2013). "ER stress-induced cell death mechanisms". Biochim. Biophys. Acta. 1833 (12): 3460–70. doi:10.1016/j.bbamcr.2013.06.028. PMC   3834229 . PMID   23850759.
10. Hung WJ, Roberson RS, Taft J, Wu DY (2003). "Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions". Mol. Cell. Biol. 23 (10): 3477–86. doi:10.1128/MCB.23.10.3477-3486.2003. PMC   164759 . PMID   12724406.
11. Grishin AV, Azhipa O, Semenov I, Corey SJ (2001). "Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10172–7. Bibcode:2001PNAS...9810172G. doi: 10.1073/pnas.191130798 . PMC   56934 . PMID   11517336.
12. Adler HT, Chinery R, Wu DY, Kussick SJ, Payne JM, Fornace AJ, Tkachuk DC (1999). "Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins". Mol. Cell. Biol. 19 (10): 7050–60. doi:10.1128/mcb.19.10.7050. PMC   84700 . PMID   10490642.
13. Wu DY, Tkachuck DC, Roberson RS, Schubach WH (2002). "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. 277 (31): 27706–15. doi: 10.1074/jbc.M200955200 . PMID   12016208.
14. Connor JH, Weiser DC, Li S, Hallenbeck JM, Shenolikar S (2001). "Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1". Mol. Cell. Biol. 21 (20): 6841–50. doi:10.1128/MCB.21.20.6841-6850.2001. PMC   99861 . PMID   11564868.
15. Hasegawa T, Isobe K (1999). "Evidence for the interaction between Translin and GADD34 in mammalian cells". Biochim. Biophys. Acta. 1428 (2–3): 161–8. doi:10.1016/s0304-4165(99)00060-4. PMID   10434033.

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Hasegawa T, Isobe K (1999). "Evidence for the interaction between Translin and GADD34 in mammalian cells". Biochim. Biophys. Acta. 1428 (2–3): 161–8. doi:10.1016/s0304-4165(99)00060-4. PMID   10434033.
• Adler HT, Chinery R, Wu DY, et al. (2000). "Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins". Mol. Cell. Biol. 19 (10): 7050–60. doi:10.1128/mcb.19.10.7050. PMC   84700 . PMID   10490642.
• Hasegawa T, Yagi A, Isobe K (2000). "Interaction between GADD34 and kinesin superfamily, KIF3A". Biochem. Biophys. Res. Commun. 267 (2): 593–6. doi:10.1006/bbrc.1999.1991. PMID   10631107.
• Hasegawa T, Xiao H, Hamajima F, Isobe K (2001). "Interaction between DNA-damage protein GADD34 and a new member of the Hsp40 family of heat shock proteins that is induced by a DNA-damaging reagent". Biochem. J. 352 (3): 795–800. doi:10.1042/0264-6021:3520795. PMC   1221519 . PMID   11104688.
• Grishin AV, Azhipa O, Semenov I, Corey SJ (2001). "Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10172–7. Bibcode:2001PNAS...9810172G. doi: 10.1073/pnas.191130798 . PMC   56934 . PMID   11517336.
• Connor JH, Weiser DC, Li S, et al. (2001). "Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1". Mol. Cell. Biol. 21 (20): 6841–50. doi:10.1128/MCB.21.20.6841-6850.2001. PMC   99861 . PMID   11564868.
• Wu DY, Tkachuck DC, Roberson RS, Schubach WH (2002). "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. 277 (31): 27706–15. doi: 10.1074/jbc.M200955200 . PMID   12016208.
• Korabiowska M, Cordon-Cardo C, Betke H, et al. (2003). "GADD153 is an independent prognostic factor in melanoma: immunohistochemical and molecular genetic analysis". Histol. Histopathol. 17 (3): 805–11. PMID   12168790.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Brush MH, Weiser DC, Shenolikar S (2003). "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. 23 (4): 1292–303. doi:10.1128/MCB.23.4.1292-1303.2003. PMC   141149 . PMID   12556489.
• Hung WJ, Roberson RS, Taft J, Wu DY (2003). "Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions". Mol. Cell. Biol. 23 (10): 3477–86. doi:10.1128/MCB.23.10.3477-3486.2003. PMC   164759 . PMID   12724406.
• Hollander MC, Poola-Kella S, Fornace AJ (2003). "Gadd34 functional domains involved in growth suppression and apoptosis". Oncogene. 22 (25): 3827–32. doi:10.1038/sj.onc.1206567. PMID   12813455. S2CID   27555253.
• Powolny A, Takahashi K, Hopkins RG, Loo G (2004). "Induction of GADD gene expression by phenethylisothiocyanate in human colon adenocarcinoma cells" (PDF). J. Cell. Biochem. 90 (6): 1128–39. doi:10.1002/jcb.10733. PMID   14635187. S2CID   33081723.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Shi W, Sun C, He B, et al. (2004). "GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor". J. Cell Biol. 164 (2): 291–300. doi:10.1083/jcb.200307151. PMC   2172339 . PMID   14718519.
• Colland F, Jacq X, Trouplin V, et al. (2004). "Functional proteomics mapping of a human signaling pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC   442148 . PMID   15231748.