PHLDA3
Domain
The PH domain binds phosphoinositides with a broad specificity. It competes with the PH domain of AKT1 and directly interferes with AKT1 binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), preventing AKT1 association to membrane lipids and subsequent activation of AKT1 signaling.
Function
p53/TP53-regulated repressor of Akt/AKT1 signaling. Represses AKT1 by preventing AKT1-binding to membrane lipids, thereby inhibiting AKT1 translocation to the cellular membrane and activation. Contributes to p53/TP53-dependent apoptosis by repressing AKT1 activity. Its direct transcription regulation by p53/TP53 may explain how p53/TP53 can negatively regulate AKT1. May act as a tumor suppressor.
Sequence Similarities
Belongs to the PHLDA3 family.
Tissue Specificity
Widely expressed with lowest expression in liver and spleen.
Cellular localization
- Cytoplasm
- Membrane
- Peripheral membrane protein
Alternative names
TIH1, PHLDA3, Pleckstrin homology-like domain family A member 3, TDAG51/Ipl homolog 1