Tchem PPM1A Protein phosphatase 1A

Protein Summary

Description

Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB. The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase dephosphorylates, and negatively regulates the activities of, MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses. This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53/p53, which leads to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P35813
• B5BU11
• J3KNM0
• O75551

Gene Name

• PPM1A

Ensembl ID

• ENST00000325642
• ENSP00000327255
• ENSG00000100614
• ENST00000325658
• ENSP00000314850
• ENST00000395076
• ENSP00000378514

Symbol

• PPPM1A
• PP2CA
• PP2Calpha
• PP2C-ALPHA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	1
transcription factor perturbation	0.98
biological process	0.96
virus perturbation	0.96
microRNA	0.91

Protein Classes

PANTHER Classes

Protein / Hydrolase / Phosphatase / Protein Phosphatase / Protein Phosphatase 1a

Protein / Enzyme Modulator / Kinase Modulator / Kinase Inhibitor / Protein Phosphatase 1a

DTO Classes

Protein / Enzyme / Hydrolase / Phosphatase / Protein Phosphatase / Protein Phosphatase 1a

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: 83.86   (req: < 5)

Gene RIFs: 30   (req: <= 3)

Antibodies: 414   (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: 83.86   (req: >= 5)

Gene RIFs: 30   (req: > 3)

Antibodies: 414   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 21

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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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (1)

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1 – 1 of 1

CHEMBL444092

PPM1ATchem Enzyme

pIC50 : 11

Protein-Protein Interactions (110)

Explore Interacting Targets

1 – 10 of 110

• See Interactions on String-DB

PPM1B

Tchem

Family:  Enzyme

Novelty:  0.02370446

p_int:  0.999999759

p_ni:  2.41e-7

Score:  0.719

Data Source:  BioPlex,STRINGDB

INPPL1

Tchem

Family:  Enzyme

Novelty:  0.00634126

p_int:  0.999994066

p_ni:  0.000005934

Score:  0.176

Data Source:  BioPlex,STRINGDB

HAO2

Tchem

Family:  Enzyme

Novelty:  0.03029536

p_int:  0.999959923

p_ni:  0.000040077

Score:  0.176

Data Source:  BioPlex,STRINGDB

CERKL

Tbio

Family:  Enzyme

Novelty:  0.04190552

p_int:  0.999958076

p_ni:  0.000041924

Score:  0.527

Data Source:  BioPlex,STRINGDB

RNASE13

Tbio

Family:  Enzyme

Novelty:  0.05907604

p_int:  0.999741087

p_ni:  0.000258913

Score:  0.169

Data Source:  BioPlex,STRINGDB

PLA2G2D

Tchem

Family:  Enzyme

Novelty:  0.01212618

p_int:  0.999345693

p_ni:  0.0006543

p_wrong:  8e-9

Data Source:  BioPlex

PRSS22

Tdark

Family:  Enzyme

Novelty:  0.38206974

p_int:  0.998435309

p_ni:  0.001564691

Score:  0.297

Data Source:  BioPlex,STRINGDB

IL20

Tbio

Novelty:  0.78184288

p_int:  0.998006335

p_ni:  0.001924359

p_wrong:  0.000069306

Data Source:  BioPlex

GDF3

Tbio

Novelty:  0.02003647

p_int:  0.996357878

p_ni:  0.003642122

Score:  0.303

Data Source:  BioPlex,STRINGDB

TECPR2

Tbio

Novelty:  0.11606334

p_int:  0.996212983

p_ni:  0.003787016

Score:  0.187

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (2)

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Downstream (2)

1 – 2 of 2

MAP2K1

Tclin

Family:  Kinase

KEGG Distance:  4

Common Pathways:  1

1: MAPK signaling pathway

MAP2K2

Tclin

Family:  Kinase

KEGG Distance:  4

Common Pathways:  1

1: MAPK signaling pathway

Pathways (87)

Reactome (10)

KEGG (1)

PathwayCommons (3)

WikiPathways (73)

Downregulation of SMAD2/3:SMAD4 transcriptional activity (R-HSA-2173795)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Downregulation of SMAD2/3:SMAD4 transcriptional activity	23 targets	R-HSA-2173795
Reactome	Energy dependent regulation of mTOR by LKB1-AMPK	28 targets	R-HSA-380972
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436
Reactome	RNA Polymerase II Transcription	1314 targets	R-HSA-73857

Name	Explore in Pharos	Explore in Source
Downregulation of SMAD2/3:SMAD4 transcriptional activity	23 targets	R-HSA-2173795
Energy dependent regulation of mTOR by LKB1-AMPK	28 targets	R-HSA-380972
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436
RNA Polymerase II Transcription	1314 targets	R-HSA-73857

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (26)

Functions (5)

Components (5)

Processes (16)

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GO Term	Evidence	Assigned by
calmodulin-dependent protein phosphatase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine phosphatase activity	Inferred from Direct Assay (IDA)	UniProtKB
R-SMAD binding	Inferred from Physical Interaction (IPI)	UniProtKB
magnesium ion binding	Inferred from Electronic Annotation (IEA)	InterPro
manganese ion binding	Inferred from Electronic Annotation (IEA)	InterPro

Disease Associations ()

No disease associations found

GWAS Traits (13)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
cup-to-disc ratio measurement	EFO_0006939	4	4	5		93.7
optic disc size measurement	EFO_0004832	2	2	2		82.7
optic cup area measurement	EFO_0006940	2	2	3		79.8
hair color	EFO_0003924	1	1	0	1.1	55.2
refractive error measurement	EFO_0007814	3	2	2	6.5	46.4

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
cup-to-disc ratio measurement	EFO_0006939	5		93.7
optic disc size measurement	EFO_0004832	2		82.7
optic cup area measurement	EFO_0006940	3		79.8
hair color	EFO_0003924	0	1.1	55.2
refractive error measurement	EFO_0007814	2	6.5	46.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Complete proteome
Cytoplasm
Hydrolase
Lipoprotein
Magnesium
Manganese
Membrane
Metal-binding

GWAS Trait Find Similar Targets

No Header	No Header
age at onset
appendicular lean mass
BMI-adjusted hip circumference
cup-to-disc ratio measurement
diastolic blood pressure
hair color
hair colour measurement
Myopia
open-angle glaucoma
optic cup area measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype

IDG Resources

No IDG generated resources found

Orthologs (16)

1 – 5 of 16

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	protein phosphatase, Mg2+/Mn2+ dependent 1A	VGNC:8292	452950
Macaque	protein phosphatase, Mg2+/Mn2+ dependent 1A		702987
Mouse	protein phosphatase 1A, magnesium dependent, alpha isoform	MGI:99878	19042
Rat	protein phosphatase, Mg2+/Mn2+ dependent, 1A	RGD:3373	24666
Dog	protein phosphatase, Mg2+/Mn2+ dependent 1A	VGNC:44862	480344

Species	Name	OMA	EggNOG	Inparanoid
Chimp	protein phosphatase, Mg2+/Mn2+ dependent 1A
Macaque	protein phosphatase, Mg2+/Mn2+ dependent 1A
Mouse	protein phosphatase 1A, magnesium dependent, alpha isoform
Rat	protein phosphatase, Mg2+/Mn2+ dependent, 1A
Dog	protein phosphatase, Mg2+/Mn2+ dependent 1A

Publication Statistics

PubMed Score 83.86

PubMed score by year

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PubTator Score 68.07

PubTator score by year

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Related Publications

Text Mined References (57)

GeneRif Annotations (30)

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PMID	Year	Title