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: 185.67   (req: < 5)

Gene RIFs: 68   (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: 185.67   (req: >= 5)

Gene RIFs: 68   (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