Tchem PPP1R15A Protein phosphatase 1 regulatory subunit 15A

Protein Summary

Description

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'. 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]

Uniprot Accession IDs

• O75807
• B4DKQ3
• Q6IA96
• Q9NVU6

Gene Name

• PPP1R15A

Ensembl ID

• ENST00000200453
• ENSP00000200453
• ENSG00000087074

Symbol

• GADD34
• GADD34

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
small molecule perturbation	0.95
biological process	0.91
transcription factor binding site profile	0.88
virus perturbation	0.88
gene perturbation	0.87

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 205.12   (req: < 5)

Gene RIFs: 37   (req: <= 3)

Antibodies: 255   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 205.12   (req: >= 5)

Gene RIFs: 37   (req: > 3)

Antibodies: 255   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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GENEVA

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GlyGen

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ARCHS4

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Approved Drugs (0)

No approved drugs found

Active Ligands (1)

Explore Active Ligands

1 – 1 of 1

Raphin 1

PPP1R15ATchem Enzyme

pIC50 : 7.48

Protein-Protein Interactions (147)

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1 – 10 of 147

• See Interactions on String-DB

PLEKHA1

Tbio

Novelty:  0.03634462

p_int:  0.999997674

p_ni:  0.000002323

p_wrong:  3e-9

Score:  0.309

Data Source:  BioPlex,STRINGDB

MINK1

Tchem

Family:  Kinase

Novelty:  0.00505208

p_int:  0.999945172

p_ni:  0.000054782

p_wrong:  4.6e-8

Score:  0.374

Data Source:  BioPlex,STRINGDB

ZNF92

Tbio

Family:  TF

Novelty:  0.05724663

p_int:  0.966354822

p_ni:  0.033581644

p_wrong:  0.000063534

Score:  0.189

Data Source:  BioPlex,STRINGDB

POP4

Tbio

Family:  Enzyme

Novelty:  0.01072287

p_int:  0.959835715

p_ni:  0.040164277

p_wrong:  8e-9

Score:  0.183

Data Source:  BioPlex,STRINGDB

MUM1

Tbio

Family:  Epigenetic

Novelty:  0.11597088

p_int:  0.903895162

p_ni:  0.001691073

p_wrong:  0.094413765

Score:  0.269

Data Source:  BioPlex,STRINGDB

BBX

Tbio

Family:  TF

Novelty:  0.02157387

p_int:  0.86113603

p_ni:  0.138863951

p_wrong:  1.9e-8

Score:  0.188

Data Source:  BioPlex,STRINGDB

ATF4

Tbio

Family:  TF

Novelty:  0.00253408

Score:  0.989

Data Source:  STRINGDB

PPP1CC

Tchem

Family:  Enzyme

Novelty:  0.00465946

Score:  0.979

Data Source:  Reactome,STRINGDB

PPP1CA

Tchem

Family:  Enzyme

Novelty:  0.00354658

Score:  0.977

Data Source:  Reactome,STRINGDB

SMAD7

Tbio

Family:  TF

Novelty:  0.00116343

Score:  0.974

Data Source:  Reactome,STRINGDB

Nearest Tclin Targets (1)

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Downstream (1)

1 – 1 of 1

BCL2

Tclin

Family:  Other

KEGG Distance:  4

Common Pathways:  1

1: Protein processing in endoplasmic reticulum

Pathways (25)

Reactome (5)

KEGG (1)

PathwayCommons (3)

WikiPathways (16)

Downregulation of TGF-beta receptor signaling (R-HSA-2173788)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Downregulation of TGF-beta receptor signaling	26 targets	R-HSA-2173788
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by TGF-beta Receptor Complex	73 targets	R-HSA-170834
Reactome	Signaling by TGF-beta family members	102 targets	R-HSA-9006936
Reactome	TGF-beta receptor signaling activates SMADs	32 targets	R-HSA-2173789

Name	Explore in Pharos	Explore in Source
Downregulation of TGF-beta receptor signaling	26 targets	R-HSA-2173788
Signal Transduction	2704 targets	R-HSA-162582
Signaling by TGF-beta Receptor Complex	73 targets	R-HSA-170834
Signaling by TGF-beta family members	102 targets	R-HSA-9006936
TGF-beta receptor signaling activates SMADs	32 targets	R-HSA-2173789

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (27)

Functions (4)

Components (9)

Processes (14)

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1 – 4 of 4

GO Term	Evidence	Assigned by
protein phosphatase 1 binding	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
protein kinase binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein phosphatase regulator activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
protein phosphatase activator activity	Inferred by Curator (IC)	ParkinsonsUK-UCL

Disease Associations ()

No disease associations found

GWAS Traits (12)

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1 – 5 of 12

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
reticulocyte measurement	EFO_0010700	3	5	6		96.1
red blood cell distribution width	EFO_0005192	4	3	5		95.1
reticulocyte count	EFO_0007986	6	4	12		94.4
eosinophil count	EFO_0004842	3	1	3		70.9
mean corpuscular hemoglobin concentration	EFO_0004528	1	1	1		64.4

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
reticulocyte measurement	EFO_0010700	6		96.1
red blood cell distribution width	EFO_0005192	5		95.1
reticulocyte count	EFO_0007986	12		94.4
eosinophil count	EFO_0004842	3		70.9
mean corpuscular hemoglobin concentration	EFO_0004528	1		64.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Apoptosis
Complete proteome
Endoplasmic reticulum
Membrane
Mitochondrion
Mitochondrion outer membrane
Phosphoprotein
Polymorphism

GWAS Trait Find Similar Targets

No Header	No Header
eosinophil count
eosinophil percentage of leukocytes
leukocyte count
lymphocyte count
mean corpuscular hemoglobin concentration
neutrophil percentage of granulocytes
platelet crit
red blood cell distribution width
reticulocyte count
reticulocyte measurement

MGI Phenotype Find Similar Targets

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cellular phenotype
hematopoietic system phenotype
immune system phenotype

IDG Resources

No IDG generated resources found

Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	protein phosphatase 1 regulatory subunit 15A	VGNC:12063	456191
Macaque	protein phosphatase 1 regulatory subunit 15A		718350
Mouse	protein phosphatase 1, regulatory (inhibitor) subunit 15A	MGI:1927072	17872
Rat	protein phosphatase 1, regulatory subunit 15A	RGD:621526	171071
Dog	protein phosphatase 1 regulatory subunit 15A	VGNC:53754	476419

Species	Name	OMA	EggNOG	Inparanoid
Chimp	protein phosphatase 1 regulatory subunit 15A
Macaque	protein phosphatase 1 regulatory subunit 15A
Mouse	protein phosphatase 1, regulatory (inhibitor) subunit 15A
Rat	protein phosphatase 1, regulatory subunit 15A
Dog	protein phosphatase 1 regulatory subunit 15A

Publication Statistics

PubMed Score 205.12

PubMed score by year

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PubTator Score 98.48

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Related Publications

Text Mined References (58)

GeneRif Annotations (37)

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PMID	Year	Title