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 20... See more...

Aliases for PPP1R15A Gene

Aliases for PPP1R15A Gene

  • Protein Phosphatase 1 Regulatory Subunit 15A 2 3 4 5
  • GADD34 2 3 4
  • Myeloid Differentiation Primary Response Protein MyD116 Homolog 3 4
  • Protein Phosphatase 1, Regulatory (Inhibitor) Subunit 15A 2 3
  • Growth Arrest And DNA Damage-Inducible Protein GADD34 3 4
  • Growth Arrest And DNA-Damage-Inducible 34 2 3
  • Protein Phosphatase 1, Regulatory Subunit 15A 2
  • PPP1R15A 5

External Ids for PPP1R15A Gene

Previous GeneCards Identifiers for PPP1R15A Gene

  • GC19P050033
  • GC19P049743
  • GC19P054051
  • GC19P054067
  • GC19P049375
  • GC19P045752

Summaries for PPP1R15A Gene

Entrez Gene Summary for PPP1R15A Gene

  • 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]

CIViC Summary for PPP1R15A Gene

GeneCards Summary for PPP1R15A Gene

PPP1R15A (Protein Phosphatase 1 Regulatory Subunit 15A) is a Protein Coding gene. Diseases associated with PPP1R15A include Malignant Pleural Mesothelioma and Epiphyseal Dysplasia, Multiple, With Early-Onset Diabetes Mellitus. Among its related pathways are Beta-Adrenergic Signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include protein kinase binding. An important paralog of this gene is PPP1R15B.

UniProtKB/Swiss-Prot Summary for PPP1R15A Gene

  • 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'.

Gene Wiki entry for PPP1R15A Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PPP1R15A Gene

Genomics for PPP1R15A Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PPP1R15A Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PPP1R15A on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PPP1R15A

Top Transcription factor binding sites by QIAGEN in the PPP1R15A gene promoter:
  • AP-1
  • ATF-2
  • ATF6
  • c-Jun
  • CREB
  • deltaCREB
  • IRF-1
  • IRF-7A
  • Sp1

Genomic Locations for PPP1R15A Gene

Latest Assembly
chr19:48,872,421-48,876,058
(GRCh38/hg38)
Size:
3,638 bases
Orientation:
Plus strand

Previous Assembly
chr19:49,375,649-49,379,319
(GRCh37/hg19 by Entrez Gene)
Size:
3,671 bases
Orientation:
Plus strand

chr19:49,375,649-49,379,314
(GRCh37/hg19 by Ensembl)
Size:
3,666 bases
Orientation:
Plus strand

Genomic View for PPP1R15A Gene

Genes around PPP1R15A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PPP1R15A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PPP1R15A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PPP1R15A Gene

Proteins for PPP1R15A Gene

  • Protein details for PPP1R15A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O75807-PR15A_HUMAN
    Recommended name:
    Protein phosphatase 1 regulatory subunit 15A
    Protein Accession:
    O75807
    Secondary Accessions:
    • B4DKQ3
    • Q6IA96
    • Q9NVU6

    Protein attributes for PPP1R15A Gene

    Size:
    674 amino acids
    Molecular mass:
    73478 Da
    Quaternary structure:
    • Interacts with PCNA (By similarity). Interacts with LYN and KMT2A/MLL1. Interacts with PP1, PPP1R1A and SMARCB1. Interacts with SMAD7. Interacts with BAG1.
    Miscellaneous:
    • The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.

    Three dimensional structures from OCA and Proteopedia for PPP1R15A Gene

    Alternative splice isoforms for PPP1R15A Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PPP1R15A Gene

Post-translational modifications for PPP1R15A Gene

  • Phosphorylated at multiple Ser/Thr residues. Phosphorylated on tyrosine by LYN; which impairs its antiproliferative activity. Phosphorylation at Tyr-262 enhances proteasomal degradation, this position is dephosphorylated by PTPN2.
  • Polyubiquitinated. Exhibits a rapid proteasomal degradation with a half-life under 1 hour, ubiquitination depends on endoplasmic reticulum association.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PPP1R15A Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for PPP1R15A Gene

Domains & Families for PPP1R15A Gene

Gene Families for PPP1R15A Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted intracellular proteins

Protein Domains for PPP1R15A Gene

Suggested Antigen Peptide Sequences for PPP1R15A Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ51898, highly similar to Homo sapiens protein phosphatase 1, regulatory (inhibitor) subunit 15A (PPP1R15A), mRNA (B4DMT2_HUMAN)
  • Myeloid differentiation primary response protein MyD116 homolog (PR15A_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O75807

UniProtKB/Swiss-Prot:

PR15A_HUMAN :
  • Belongs to the PPP1R15 family.
Family:
  • Belongs to the PPP1R15 family.
genes like me logo Genes that share domains with PPP1R15A: view

Function for PPP1R15A Gene

Molecular function for PPP1R15A Gene

UniProtKB/Swiss-Prot 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'.
UniProtKB/Swiss-Prot Induction:
Specifically produced in response to stress: in absence of stress, some upstream open reading frame (uORF) of this transcript is translated, thereby preventing its translation (PubMed:19131336). By methyl methanesulfonate and ionizing irradiation (PubMed:9153226). By IL24/interleukin-24 in melanoma cells; which induces apoptosis (PubMed:10490642, PubMed:12114539).

Phenotypes From GWAS Catalog for PPP1R15A Gene

Gene Ontology (GO) - Molecular Function for PPP1R15A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 11564868
GO:0008157 protein phosphatase 1 binding IPI 12556489
GO:0019888 protein phosphatase regulator activity IC 11564868
GO:0019901 protein kinase binding IPI 11517336
GO:0072542 protein phosphatase activator activity IC 21518769
genes like me logo Genes that share ontologies with PPP1R15A: view
genes like me logo Genes that share phenotypes with PPP1R15A: view

Animal Models for PPP1R15A Gene

MGI Knock Outs for PPP1R15A:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PPP1R15A

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PPP1R15A Gene

Localization for PPP1R15A Gene

Subcellular locations from UniProtKB/Swiss-Prot for PPP1R15A Gene

Endoplasmic reticulum membrane. Peripheral membrane protein. Cytoplasmic side. Mitochondrion outer membrane. Peripheral membrane protein. Cytoplasmic side. Note=Associates with membranes via an N-terminal amphipathic intramembrane region. {ECO:0000269 PubMed:21518769}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PPP1R15A gene
Compartment Confidence
endoplasmic reticulum 5
cytosol 5
mitochondrion 4
golgi apparatus 4
plasma membrane 2
extracellular 2
cytoskeleton 2
nucleus 2
lysosome 2
peroxisome 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for PPP1R15A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000164 protein phosphatase type 1 complex IDA 11564868
GO:0005737 cytoplasm IDA 21518769
GO:0005739 mitochondrion IDA 21518769
GO:0005741 mitochondrial outer membrane IEA --
GO:0005783 endoplasmic reticulum IDA 12556489
genes like me logo Genes that share ontologies with PPP1R15A: view

Pathways & Interactions for PPP1R15A Gene

PathCards logo

SuperPathways for PPP1R15A Gene

SuperPathway Contained pathways
1 Activation of cAMP-Dependent PKA
.77
.77
.71
.56
2 Beta-Adrenergic Signaling
.37
.37
.37
.36
3 TGF-beta receptor signaling activates SMADs
4 Protein processing in endoplasmic reticulum
5 GPCR Pathway
.58
genes like me logo Genes that share pathways with PPP1R15A: view

Pathways by source for PPP1R15A Gene

1 KEGG pathway for PPP1R15A Gene
14 Qiagen pathways for PPP1R15A Gene
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Beta-Adrenergic Signaling
  • Breast Cancer Regulation by Stathmin1
  • cAMP Pathway

SIGNOR curated interactions for PPP1R15A Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for PPP1R15A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006417 regulation of translation IEA --
GO:0006915 apoptotic process TAS 9153226
GO:0006974 cellular response to DNA damage stimulus TAS 9153226
GO:0007050 cell cycle arrest TAS 9153226
GO:0032058 positive regulation of translational initiation in response to stress IC 12556489
genes like me logo Genes that share ontologies with PPP1R15A: view

Drugs & Compounds for PPP1R15A Gene

(10) Drugs for PPP1R15A Gene - From: ApexBio and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Sephin1 Pharma Selective PPP1R15A inhibitor 0

(4) Additional Compounds for PPP1R15A Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(1) ApexBio Compounds for PPP1R15A Gene

Compound Action Cas Number
Sephin1 Selective PPP1R15A inhibitor 13098-73-2
genes like me logo Genes that share compounds with PPP1R15A: view

Drug products for research

Transcripts for PPP1R15A Gene

mRNA/cDNA for PPP1R15A Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PPP1R15A

Alternative Splicing Database (ASD) splice patterns (SP) for PPP1R15A Gene

No ASD Table

Relevant External Links for PPP1R15A Gene

GeneLoc Exon Structure for
PPP1R15A

Expression for PPP1R15A Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PPP1R15A Gene

mRNA differential expression in normal tissues according to GTEx for PPP1R15A Gene

This gene is overexpressed in Whole Blood (x5.3).

Protein differential expression in normal tissues from HIPED for PPP1R15A Gene

This gene is overexpressed in Retina (41.0) and Testis (16.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PPP1R15A Gene



Protein tissue co-expression partners for PPP1R15A Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PPP1R15A

SOURCE GeneReport for Unigene cluster for PPP1R15A Gene:

Hs.631593

Evidence on tissue expression from TISSUES for PPP1R15A Gene

  • Nervous system(4.9)
  • Blood(4.6)
  • Lung(4)
  • Skin(3.2)
  • Pancreas(3.1)
  • Muscle(3.1)
  • Bone marrow(3)
  • Liver(2.9)
  • Heart(2.9)
  • Intestine(2.8)
  • Kidney(2.7)
  • Adrenal gland(2.4)
  • Spleen(2.3)
  • Lymph node(2.3)
  • Stomach(2.2)
  • Thyroid gland(2.1)
  • Eye(2.1)
genes like me logo Genes that share expression patterns with PPP1R15A: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for PPP1R15A Gene

Orthologs for PPP1R15A Gene

This gene was present in the common ancestor of chordates.

Orthologs for PPP1R15A Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PPP1R15A 29 30
  • 99.06 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PPP1R15A 29 30
  • 74.81 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Ppp1r15a 29 16 30
  • 66.77 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia PPP1R15A 30
  • 59 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia PPP1R15A 30
  • 36 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii ppp1r15a 30
  • 24 (a)
OneToOne
Species where no ortholog for PPP1R15A was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for PPP1R15A Gene

ENSEMBL:
Gene Tree for PPP1R15A (if available)
TreeFam:
Gene Tree for PPP1R15A (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PPP1R15A: view image
Alliance of Genome Resources:
Additional Orthologs for PPP1R15A

Paralogs for PPP1R15A Gene

Paralogs for PPP1R15A Gene

genes like me logo Genes that share paralogs with PPP1R15A: view

Variants for PPP1R15A Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PPP1R15A Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
rs141370460 Benign: not provided 48,875,607(+) C/T
NM_014330.3(PPP1R15A):c.1666-7C>T
INTRON
rs77377218 Benign: not provided 48,873,785(+) G/A
NM_014330.3(PPP1R15A):c.552G>A (p.Arg184=)
SYNONYMOUS
rs1050166 -- p.Ala381Val
rs11541192 -- p.Gly312Ser
rs2270946 -- p.Arg594Cys

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for PPP1R15A Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for PPP1R15A Gene

Variant ID Type Subtype PubMed ID
nsv470148 CNV gain 18288195
nsv833855 CNV loss 17160897
nsv833856 CNV loss 17160897
nsv9739 CNV gain+loss 18304495

Variation tolerance for PPP1R15A Gene

Residual Variation Intolerance Score: 97.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 17.66; 98.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PPP1R15A Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PPP1R15A
Leiden Open Variation Database (LOVD)
PPP1R15A

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PPP1R15A Gene

Disorders for PPP1R15A Gene

MalaCards: The human disease database

(6) MalaCards diseases for PPP1R15A Gene - From: COP and GCD

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for PPP1R15A

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with PPP1R15A: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PPP1R15A Gene

Publications for PPP1R15A Gene

  1. Mammalian GADD34, an apoptosis- and DNA damage-inducible gene. (PMID: 9153226) Hollander MC … Fornace AJ (The Journal of biological chemistry 1997) 2 3 4 22
  2. An upstream open reading frame regulates translation of GADD34 during cellular stresses that induce eIF2alpha phosphorylation. (PMID: 19131336) Lee YY … Jan E (The Journal of biological chemistry 2009) 3 4 22
  3. GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. (PMID: 14718519) Shi W … Cao X (The Journal of cell biology 2004) 3 4 22
  4. Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions. (PMID: 12724406) Hung WJ … Wu DY (Molecular and cellular biology 2003) 3 4 22
  5. 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. (PMID: 12556489) Brush MH … Shenolikar S (Molecular and cellular biology 2003) 3 4 22

Products for PPP1R15A Gene

Sources for PPP1R15A Gene