Summary

Name PHLPP1
Full Name PH domain leucine-rich repeat-containing protein phosphatase 1
Synonyms Pleckstrin homology domain-containing family E member 1, PH domain-containing family E member 1, Suprachiasmatic nucleus circadian oscillatory protein, hSCOP | KIAA0606, PHLPP, PLEKHE1, SCOP
Primary ID O60346
Links - -
Type protein
Relations 16
Function 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).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates img/direct_inhibition.png phosphorylation PHLPP1 0.36
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation RAF1 0.277
Publications: 1 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png dephosphorylation AKT3 0.636
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation AKT1 0.752
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation AKT1 0.752
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation AKT 0.752
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation AKT2 0.607
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png dephosphorylation PRKCA 0.254
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png dephosphorylation PRKCB 0.347
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png dephosphorylation PRKCB 0.347
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png dephosphorylation STK4 0.303
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation RPS6KB1 0.594
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png dephosphorylation AKT2 0.607
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation AKT2 0.607
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding STK4 0.303
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation AKT 0.752
Publications: 1 Organism: Homo Sapiens