PPP1R15A protein phosphatase 1 regulatory subunit 15A [Homo sapiens (human)] - Gene

Summary

Official Symbol: PPP1R15Aprovided by HGNC
Official Full Name: protein phosphatase 1 regulatory subunit 15Aprovided by HGNC
Primary source: HGNC:HGNC:14375
See related: Ensembl:ENSG00000087074 MIM:611048; AllianceGenome:HGNC:14375
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GADD34
Summary: 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. [provided by RefSeq, Jul 2008]
Expression: Broad expression in bone marrow (RPKM 214.4), gall bladder (RPKM 51.1) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.33

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (48872421..48876058)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (51867284..51870921)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (49375678..49379315)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Protein phosphatase 1 regulatory subunit 15 A promotes translation initiation and induces G2M phase arrest during cuproptosis in cancers.
Title: Protein phosphatase 1 regulatory subunit 15 A promotes translation initiation and induces G2M phase arrest during cuproptosis in cancers.
The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP).
Title: The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP).
Enterovirus 71 Activates GADD34 via Precursor 3CD to Promote IRES-Mediated Viral Translation.
Title: Enterovirus 71 Activates GADD34 via Precursor 3CD to Promote IRES-Mediated Viral Translation.
Substrate recognition determinants of human eIF2alpha phosphatases.
Title: Substrate recognition determinants of human eIF2α phosphatases.
Sensitization of the UPR by loss of PPP1R15A promotes fibrosis and senescence in IPF.
Title: Sensitization of the UPR by loss of PPP1R15A promotes fibrosis and senescence in IPF.
Higher-order phosphatase-substrate contacts terminate the integrated stress response.
Title: Higher-order phosphatase-substrate contacts terminate the integrated stress response.
GADD34 plays an essential role in autophagy by tuning translation during starvation, thus enabling lysosomal biogenesis and a sustained autophagic flux. Hence, the TFEB-GADD34 axis integrates the mTORC1 and ISR pathways in response to starvation.
Title: GADD34 is a modulator of autophagy during starvation.
these findings suggest that GADD34 inhibits TRAIL-induced HCC cell apoptosis through TRAF6- and ERK-mediated stabilization of MCL-1.
Title: The regulatory protein GADD34 inhibits TRAIL-induced apoptosis via TRAF6/ERK-dependent stabilization of myeloid cell leukemia 1 in liver cancer cells.
The results highlighted a novel role for the GADD34/PP1alpha complex in coordinating the dephosphorylation and reactivation of eIF2alpha and SIRT1 to determine cell fate following oxidative stress.
Title: Oxidative stress promotes SIRT1 recruitment to the GADD34/PP1α complex to activate its deacetylase function.
Depletion of HES1 increased cell death in response to endoplasmic reticulum stress in mouse and human cells, in a manner that depended on the pro-apoptotic gene growth arrest and DNA damage-inducible protein GADD34.
Title: Hairy and enhancer of split 1 (HES1) protects cells from endoplasmic reticulum stress-induced apoptosis through repression of GADD34.

Submit: New GeneRIF Correction See all GeneRIFs (46)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH71420 (e-PCR)
- UniSTS:33075

RH81092 (e-PCR)
- UniSTS:92765

STS-R32980 (e-PCR)
- UniSTS:62928

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase 1 binding	IDA Inferred from Direct Assay more info	PubMed
enables protein phosphatase 1 binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase activator activity	IC Inferred by Curator more info	PubMed
enables protein phosphatase regulator activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein phosphatase regulator activity	IC Inferred by Curator more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	TAS Traceable Author Statement more info	PubMed
involved_in apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of PERK-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of protein dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of endoplasmic reticulum stress-induced eIF2 alpha dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of endoplasmic reticulum stress-induced eIF2 alpha dephosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of peptidyl-serine dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phosphoprotein phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of translational initiation in response to stress	IC Inferred by Curator more info	PubMed
involved_in protein localization to endoplasmic reticulum	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell cycle	TAS Traceable Author Statement more info	PubMed
involved_in regulation of translational initiation by eIF2 alpha dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in response to endoplasmic reticulum stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	NAS Non-traceable Author Statement more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial outer membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
part_of protein phosphatase type 1 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of protein phosphatase type 1 complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: protein phosphatase 1 regulatory subunit 15A

Names: growth arrest and DNA damage-inducible protein GADD34; growth arrest and DNA-damage-inducible 34; myeloid differentiation primary response protein MyD116 homolog; protein phosphatase 1, regulatory (inhibitor) subunit 15A

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.