Tchem PHLPP1 PH domain leucine-rich repeat-containing protein phosphatase 1

Protein Summary

Description

Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity). This gene encodes a member of the serine/threonine phosphatase family. The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. Increased expression of this gene may also play a role in obesity and type 2 diabetes by interfering with Akt-mediated insulin signaling. [provided by RefSeq, Dec 2011]

Uniprot Accession IDs

• O60346
• A1A4F5
• Q641Q7
• Q6P4C4
• Q6PJI6
• Q86TN6
• Q96FK2
• Q9NUY1

Gene Name

• PHLPP1

Ensembl ID

• ENST00000262719
• ENSP00000262719
• ENSG00000081913

Symbol

• KIAA0606
• PHLPP
• PLEKHE1
• SCOP
• SCOP
• PHLPP
• PPM3A
• PLEKHE1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
pathway	0.93
kinase perturbation	0.88
disease perturbation	0.87
transcription factor binding site profile	0.86
virus perturbation	0.72

Protein Classes

DTO Classes

Protein / Epigenetic Regulator / Reader / Plant Homeodomain / Ph Domain Leucine-rich Repeat-containing Protein Phosphatase 1

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: 156.2   (req: < 5)

Gene RIFs: 54   (req: <= 3)

Antibodies: 157   (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: 156.2   (req: >= 5)

Gene RIFs: 54   (req: > 3)

Antibodies: 157   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 11

Tchem

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

Active Ligands: 3

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

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 (3)

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1 – 3 of 3

CHEMBL3414669

PHLPP1Tchem Enzyme

pKd : 6.16

8-bromo-2-methyl-2-(4-methylpentyl)chroman-6-sulfonamide

PHLPP1Tchem Enzyme

pKd : 6.16

CHEMBL3414686

PHLPP1Tchem Enzyme

pKd : 6.14

Protein-Protein Interactions (124)

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1 – 10 of 124

• See Interactions on String-DB

HAVCR2

Tbio

Novelty:  0.00155885

p_int:  0.999999091

p_ni:  9.09e-7

Data Source:  BioPlex

USP46

Tbio

Family:  Enzyme

Novelty:  0.04594593

p_int:  0.999989802

p_ni:  0.000010186

p_wrong:  1.2e-8

Score:  0.835

Data Source:  BioPlex,STRINGDB

SLC9A3R2

Tbio

Family:  Transporter

Novelty:  0.01401705

p_int:  0.996554616

p_ni:  0.003443909

p_wrong:  0.000001475

Score:  0.337

Data Source:  BioPlex,STRINGDB

EFNB2

Tbio

Novelty:  0.00255095

p_int:  0.994782943

p_ni:  0.005216017

p_wrong:  0.00000104

Score:  0.15

Data Source:  BioPlex,STRINGDB

USP1

Tchem

Family:  Enzyme

Novelty:  0.0092606

p_int:  0.943165926

p_ni:  0.056831754

p_wrong:  0.00000232

Score:  0.606

Data Source:  BioPlex,STRINGDB

RFPL2

Tdark

Novelty:  1.87914964

p_int:  0.911673559

p_ni:  0.076313421

p_wrong:  0.01201302

Score:  0.227

Data Source:  BioPlex,STRINGDB

SKP2

Tbio

Family:  Enzyme

Novelty:  0.00182658

p_int:  0.883000579

p_ni:  0.087267034

p_wrong:  0.029732387

Score:  0.272

Data Source:  BioPlex,STRINGDB

AKT1

Tchem

Family:  Kinase

Novelty:  0.00003185

Score:  0.991

Data Source:  Reactome,STRINGDB

AKT3

Tchem

Family:  Kinase

Novelty:  0.00308931

Score:  0.985

Data Source:  STRINGDB

AKT2

Tchem

Family:  Kinase

Novelty:  0.00167027

Score:  0.976

Data Source:  STRINGDB

Nearest Tclin Targets (2)

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Downstream (2)

1 – 2 of 2

GSK3B

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  1

1: PI3K-Akt signaling pathway

RAF1

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  1

1: PI3K-Akt signaling pathway

Pathways (36)

Reactome (4)

KEGG (1)

PathwayCommons (1)

WikiPathways (30)

Intracellular signaling by second messengers (R-HSA-9006925)

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5

1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Intracellular signaling by second messengers	305 targets	R-HSA-9006925
Reactome	Negative regulation of the PI3K/AKT network	110 targets	R-HSA-199418
Reactome	PIP3 activates AKT signaling	266 targets	R-HSA-1257604
Reactome	Signal Transduction	2704 targets	R-HSA-162582

Name	Explore in Pharos	Explore in Source
Intracellular signaling by second messengers	305 targets	R-HSA-9006925
Negative regulation of the PI3K/AKT network	110 targets	R-HSA-199418
PIP3 activates AKT signaling	266 targets	R-HSA-1257604
Signal Transduction	2704 targets	R-HSA-162582

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (16)

Functions (2)

Components (5)

Processes (9)

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1 – 2 of 2

GO Term	Evidence	Assigned by
protein serine/threonine phosphatase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations ()

No disease associations found

GWAS Traits (3)

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5

1 – 3 of 3

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
platelet crit	EFO_0007985	1	1	1		55.2
inflammatory biomarker measurement	EFO_0004872	1	1	0	46.6	7.6
body mass index	EFO_0004340	1	1	1		7.1

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 3 of 3

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
platelet crit	EFO_0007985	1		55.2
inflammatory biomarker measurement	EFO_0004872	0	46.6	7.6
body mass index	EFO_0004340	1		7.1

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
Acetylation
Alternative splicing
Apoptosis
Cell membrane
Complete proteome
Cytoplasm
Hydrolase
Leucine-rich repeat
Manganese
Membrane

GWAS Trait Find Similar Targets

No Header	No Header
body mass index
inflammatory biomarker measurement
platelet crit

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	PH domain and leucine rich repeat protein phosphatase 1	VGNC:13275	468563
Macaque	PH domain and leucine rich repeat protein phosphatase 1		705882
Mouse	PH domain and leucine rich repeat protein phosphatase 1	MGI:2138327	98432
Rat	PH domain and leucine rich repeat protein phosphatase 1	RGD:621308	59265
Dog	PH domain and leucine rich repeat protein phosphatase 1	VGNC:44504	476179

Species	Name	OMA	EggNOG	Inparanoid
Chimp	PH domain and leucine rich repeat protein phosphatase 1
Macaque	PH domain and leucine rich repeat protein phosphatase 1
Mouse	PH domain and leucine rich repeat protein phosphatase 1
Rat	PH domain and leucine rich repeat protein phosphatase 1
Dog	PH domain and leucine rich repeat protein phosphatase 1

Publication Statistics

PubMed Score 156.20

PubMed score by year

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PubTator Score 109.22

PubTator score by year

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Related Publications

Text Mined References (69)

GeneRif Annotations (54)

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PMID	Year	Title