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

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: 117.58   (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: 117.58   (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

Active Ligands (3)

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1 – 3 of 3

CHEMBL3414686

PHLPP1Tchem Enzyme

Kd: 6.14

CHEMBL3414688

PHLPP1Tchem Enzyme

Kd: 6.16

CHEMBL3414669

PHLPP1Tchem Enzyme

Kd: 6.16

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

Gene Ontology Terms (16)

Functions (2)

Components (5)

Processes (9)

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10

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

Protein-Protein Interactions (124)

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1 – 10 of 124

• See Interactions on String-DB

HAVCR2

Tbio

Novelty: 0.00217571

p_int: 0.999999091

p_ni: 9.09e-7

Data Source: BioPlex

USP46

Tbio

Family: Enzyme

Novelty: 0.05497502

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: 0.01296563

p_int: 0.996554616

p_ni: 0.003443909

p_wrong: 0.000001475

Score: 0.337

Data Source: BioPlex,STRINGDB

EFNB2

Tbio

Novelty: 0.00309066

p_int: 0.994782943

p_ni: 0.005216017

p_wrong: 0.00000104

Score: 0.15

Data Source: BioPlex,STRINGDB

USP1

Tchem

Family: Enzyme

Novelty: 0.0117431

p_int: 0.943165926

p_ni: 0.056831754

p_wrong: 0.00000232

Score: 0.606

Data Source: BioPlex,STRINGDB

RFPL2

Tdark

Novelty: 6

p_int: 0.911673559

p_ni: 0.076313421

p_wrong: 0.01201302

Score: 0.227

Data Source: BioPlex,STRINGDB

SKP2

Tbio

Family: Enzyme

Novelty: 0.00202287

p_int: 0.883000579

p_ni: 0.087267034

p_wrong: 0.029732387

Score: 0.272

Data Source: BioPlex,STRINGDB

AKT1

Tchem

Family: Kinase

Novelty: 0.0000383

Score: 0.991

Data Source: Reactome,STRINGDB

AKT3

Tchem

Family: Kinase

Novelty: 0.00482543

Score: 0.985

Data Source: STRINGDB

AKT2

Tchem

Family: Kinase

Novelty: 0.00224767

Score: 0.976

Data Source: STRINGDB

Publication Statistics

PubMed Score  117.58

PubMed score by year

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PubTator Score  109.22

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

Acetylation
Alternative splicing
Apoptosis
Cell membrane
Complete proteome
Cytoplasm
Hydrolase
Leucine-rich repeat
Manganese
Membrane

GWAS Trait Find Similar Targets

body mass index
chronic lymphocytic leukemia
heel bone mineral density
inflammatory biomarker measurement
neoplasm of mature B-cells

MGI Phenotype Find Similar Targets

behavior/neurological phenotype