Aliases for PTEN Gene
- Phosphatase And Tensin Homolog 2 3 4 5
- Mutated In Multiple Advanced Cancers 1 2 3 4
- MMAC1 3 4
- TEP1 3 4
- Phosphatidylinositol 3,4,5-Trisphosphate 3-Phosphatase And Dual-Specificity Protein Phosphatase PTEN 3
- Phosphatidylinositol-3,4,5-Trisphosphate 3-Phosphatase And Dual-Specificity Protein Phosphatase PTEN 3
- MMAC1 Phosphatase And Tensin Homolog Deleted On Chromosome 10 3
- Mitochondrial Phosphatase And Tensin Protein Alpha 3
- Phosphatase And Tensin-Like Protein 3
- Mitochondrial PTENalpha 3
- EC 220.127.116.11 4
External Ids for PTEN Gene
Previous HGNC Symbols for PTEN Gene
Previous GeneCards Identifiers for PTEN Gene
This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]
PTEN is a multi-functional tumor suppressor that is very commonly lost in human cancer. Observed in prostate cancer, glioblastoma, endometrial, lung and breast cancer to varying degrees. Up to 70% of prostate cancer patients have been observed to have loss of expression of the gene. It is a part of the PI3K/AKT/mTOR pathway and mTOR inhibitors have been relatively ineffective in treating patients with PTEN loss. New appoaches using microRNAs are currently being investigated.
GeneCards Summary for PTEN Gene
PTEN (Phosphatase And Tensin Homolog) is a Protein Coding gene. Diseases associated with PTEN include Bannayan-Riley-Ruvalcaba Syndrome and Cowden Syndrome 1. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and NFAT and Cardiac Hypertrophy. Gene Ontology (GO) annotations related to this gene include protein kinase binding and magnesium ion binding. An important paralog of this gene is TPTE2.
UniProtKB/Swiss-Prot for PTEN Gene
Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4 (PubMed:26504226). The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement.
Isoform alpha: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1.