ID:PHLA3_HUMAN DESCRIPTION: RecName: Full=Pleckstrin homology-like domain family A member 3; AltName: Full=TDAG51/Ipl homolog 1; 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. SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. TISSUE SPECIFICITY: Widely expressed with lowest expression in liver and spleen. INDUCTION: By p53/TP53; expression is directly activated by TP53. TP53 phosphorylation on 'Ser-15' is required to activate the PHLDA3 promoter. 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. MISCELLANEOUS: PHLDA3 genomic locus is frequently observed in primary lung cancers, suggesting a role in tumor suppression. SIMILARITY: Belongs to the PHLDA3 family. SIMILARITY: Contains 1 PH domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9Y5J5
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006915 apoptotic process GO:0009653 anatomical structure morphogenesis GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:0043065 positive regulation of apoptotic process GO:0051898 negative regulation of protein kinase B signaling