Protein found in humans
PPP1R15A |
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Available structures |
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PDB | Ortholog search: PDBe RCSB |
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Identifiers |
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Aliases | PPP1R15A, GADD34, protein phosphatase 1 regulatory subunit 15A |
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External IDs | OMIM: 611048; MGI: 1927072; HomoloGene: 8639; GeneCards: PPP1R15A; OMA:PPP1R15A - orthologs |
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Gene location (Human) |
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![Chromosome 19 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/5/54/Ideogram_human_chromosome_19.svg/300px-Ideogram_human_chromosome_19.svg.png) | Chr. | Chromosome 19 (human)[1] |
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| Band | 19q13.33 | Start | 48,872,421 bp[1] |
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End | 48,876,058 bp[1] |
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Gene location (Mouse) |
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![Chromosome 7 (mouse)](//upload.wikimedia.org/wikipedia/commons/thumb/e/e4/Ideogram_house_mouse_chromosome_7.svg/260px-Ideogram_house_mouse_chromosome_7.svg.png) | Chr. | Chromosome 7 (mouse)[2] |
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| Band | 7|7 B3 | Start | 45,172,340 bp[2] |
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End | 45,175,692 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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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
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| Top expressed in | - fetal liver hematopoietic progenitor cell
- tibiofemoral joint
- decidua
- granulocyte
- muscle of thigh
- islet of Langerhans
- saccule
- spleen
- lip
- human fetus
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| More reference expression data |
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BioGPS | ![](//upload.wikimedia.org/wikipedia/commons/thumb/9/97/PBB_GE_PPP1R15A_37028_at_fs.png/250px-PBB_GE_PPP1R15A_37028_at_fs.png)
![](//upload.wikimedia.org/wikipedia/commons/thumb/c/ca/PBB_GE_PPP1R15A_202014_at_fs.png/250px-PBB_GE_PPP1R15A_202014_at_fs.png) | More reference expression data |
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Gene ontology |
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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 |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (protein) | | |
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Location (UCSC) | Chr 19: 48.87 – 48.88 Mb | Chr 7: 45.17 – 45.18 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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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:
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. 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.