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
Gene location (Human)
Chr.	Chromosome 19 (human)
End	48,876,058 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	45,175,692 bp
RNA expression pattern
	Top expressed in
	bone marrow; ; sural nerve; ; gastric mucosa; ; anterior pituitary; ; upper lobe of left lung;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	GO:0001948 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
	23645
	17872
	ENSG00000087074
	ENSMUSG00000040435
	O75807
	P17564
	NM_014330
	NM_008654
	NP_055145
	NP_032680
	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[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000087074 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000040435 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ ^a ^b "Entrez Gene: PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A".
^ 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.
^ 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.
^ ^a ^b 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.
^ 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.
^ ^a ^b 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.
^ ^a ^b ^c ^d 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.
^ ^a ^b ^c 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.
^ 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.
Powolny A, Takahashi K, Hopkins RG, Loo G (2004). "Induction of GADD gene expression by phenethylisothiocyanate in human colon adenocarcinoma cells". 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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000087074 - Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid9153226-5] 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.

[pmid9413226-6] 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.

[entrez-7] "Entrez Gene: PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A".

[pmid8139541-8] 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.

[pmid23850759-9] 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.

[pmid12724406-10] 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.

[pmid11517336-11] 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.

[pmid10490642-12] 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.

[pmid12016208-13] 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.

[pmid11564868-14] 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.

[pmid10434033-15] 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.

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