ID:PTEN_HUMAN DESCRIPTION: RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN; EC=3.1.3.16; EC=3.1.3.48; EC=3.1.3.67; AltName: Full=Mutated in multiple advanced cancers 1; AltName: Full=Phosphatase and tensin homolog; FUNCTION: 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. 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. CATALYTIC ACTIVITY: Phosphatidylinositol 3,4,5-trisphosphate + H(2)O = phosphatidylinositol 4,5-bisphosphate + phosphate. CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein + phosphate. CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. COFACTOR: Magnesium. SUBUNIT: Monomer. The unphosphorylated form interacts with the second PDZ domain of AIP1 and with DLG1 and MAST2 in vitro. Interacts with MAGI2, MAGI3, MAST1 and MAST3, but neither with MAST4 nor with DLG5. Interaction with MAGI2 increases protein stability. Interacts with NEDD4. Interacts with NDFIP1 and NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes PTEN ubiquitination. Interacts (via C2 domain) with FRK. Interacts with USP7; the interaction is direct. Interacts with ROCK1 (By similarity). Interacts with XIAP/BIRC4. INTERACTION: P30260:CDC27; NbExp=7; IntAct=EBI-696162, EBI-994813; Q62696:Dlg1 (xeno); NbExp=2; IntAct=EBI-696162, EBI-389325; P42685:FRK; NbExp=7; IntAct=EBI-696162, EBI-1383583; O88382:Magi2 (xeno); NbExp=3; IntAct=EBI-696162, EBI-696179; Q9JK71:Magi3 (xeno); NbExp=3; IntAct=EBI-696162, EBI-696226; Q9R1L5:Mast1 (xeno); NbExp=3; IntAct=EBI-696162, EBI-491771; Q60592:Mast2 (xeno); NbExp=4; IntAct=EBI-696162, EBI-493888; O60307:MAST3; NbExp=3; IntAct=EBI-696162, EBI-311420; P46934:NEDD4; NbExp=4; IntAct=EBI-696162, EBI-726944; P62136:PPP1CA; NbExp=2; IntAct=EBI-696162, EBI-357253; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus, PML body. Note=Monoubiquitinated form is nuclear. Nonubiquitinated form is cytoplasmic. Colocalized with PML and USP7 in PML nuclear bodies. XIAP/BIRC4 promotes its nuclear localization. TISSUE SPECIFICITY: Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas. INDUCTION: Down-regulated by TGFB1. DOMAIN: The C2 domain binds phospholipid membranes in vitro in a Ca(2+)-independent manner; this binding is important for its tumor suppressor function. PTM: Phosphorylated in vitro by MAST1, MAST2 and MAST3. Phosphorylation results in an inhibited activity towards PIP3. Phosphorylation can both inhibit or promote PDZ-binding. Phosphorylation at Tyr-336 by FRK/PTK5 protects this protein from ubiquitin-mediated degradation probably by inhibiting its binding to NEDD4. Phosphorylation by ROCK1 is essential for its stability and activity. Phosphorylation by PLK3 promotes its stability and prevents its degradation by the proteasome. PTM: Monoubiquitinated; monoubiquitination is increased in presence of retinoic acid. Deubiquitinated by USP7; leading to its nuclear exclusion. Monoubiquitination of one of either Lys-13 and Lys-289 amino acid is sufficient to modulate PTEN compartmentalization. Ubiquitinated by XIAP/BIRC4. DISEASE: Defects in PTEN are a cause of Cowden disease (CD) [MIM:158350]; also known as Cowden syndrome (CS). CD is an autosomal dominant cancer predisposition syndrome associated with elevated risk for tumors of the breast, thyroid and skin. The predominant phenotype for CD is multiple hamartoma syndrome, in many organ systems including the breast (70% of CD patients), thyroid (40-60%), skin, CNS (40%), gastrointestinal tract. Affected individuals are at an increased risk of both breast and thyroid cancers. Trichilemmomas (benign tumors of the hair follicle infundibulum), and mucocutaneous papillomatosis (99%) are hallmarks of CD. DISEASE: Defects in PTEN are the cause of Lhermitte-Duclos disease (LDD) [MIM:158350]; also known as cerebelloparenchymal disorder VI. LDD is characterized by dysplastic gangliocytoma of the cerebellum which often results in cerebellar signs and seizures. LDD and CD seem to be the same entity, and are considered as hamartoma-neoplasia syndromes. DISEASE: Defects in PTEN are a cause of Bannayan-Zonana syndrome (BZS) [MIM:153480]; also known as Ruvalcaba-Myhre-Smith syndrome (RMSS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS). In BZS there seems not to be an increased risk of malignancy. It has a partial clinical overlap with CD. BZS is characterized by the classic triad of macrocephaly, lipomatosis and pigmented macules of the gland penis. DISEASE: Defects in PTEN are a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:275355]; also known as squamous cell carcinoma of the head and neck. DISEASE: Defects in PTEN are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:608089]. DISEASE: Note=PTEN mutations are found in a subset of patients with Proteus syndrome, a genetically heterogeneous condition. The molecular diagnosis of PTEN mutation positive cases classifies Proteus syndrome patients as part of the PTEN hamartoma syndrome spectrum. As such, patients surviving the early years of Proteus syndrome are likely at a greater risk of developing malignancies. DISEASE: Defects in PTEN are a cause of susceptibility to glioma type 2 (GLM2) [MIM:613028]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. DISEASE: Defects in PTEN are a cause of VACTERL association with hydrocephalus (VACTERL-H) [MIM:276950]. VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects. DISEASE: Defects in PTEN may be a cause of susceptibility to prostate cancer (PC) [MIM:176807]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. DISEASE: Defects in PTEN are a cause of macrocephaly/autism syndrome (MCEPHAS) [MIM:605309]. Patients have autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference +4.0 SD). DISEASE: Note=A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome. SIMILARITY: Contains 1 C2 tensin-type domain. SIMILARITY: Contains 1 phosphatase tensin-type domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PTENID158.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PTEN"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/pten/";
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 P60484
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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:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity GO:0001525 angiogenesis GO:0001933 negative regulation of protein phosphorylation GO:0002902 regulation of B cell apoptotic process GO:0006470 protein dephosphorylation GO:0006629 lipid metabolic process GO:0006661 phosphatidylinositol biosynthetic process GO:0006915 apoptotic process GO:0007270 neuron-neuron synaptic transmission GO:0007399 nervous system development GO:0007416 synapse assembly GO:0007417 central nervous system development GO:0007507 heart development GO:0007568 aging GO:0007584 response to nutrient GO:0007611 learning or memory GO:0007613 memory GO:0007626 locomotory behavior GO:0008283 cell proliferation GO:0008284 positive regulation of cell proliferation GO:0008285 negative regulation of cell proliferation GO:0009749 response to glucose GO:0010033 response to organic substance GO:0010035 response to inorganic substance GO:0010043 response to zinc ion GO:0010628 positive regulation of gene expression GO:0010666 positive regulation of cardiac muscle cell apoptotic process GO:0010719 negative regulation of epithelial to mesenchymal transition GO:0010975 regulation of neuron projection development GO:0014067 negative regulation of phosphatidylinositol 3-kinase signaling GO:0014070 response to organic cyclic compound GO:0014823 response to activity GO:0016311 dephosphorylation GO:0016477 cell migration GO:0016579 protein deubiquitination GO:0021542 dentate gyrus development GO:0021955 central nervous system neuron axonogenesis GO:0030336 negative regulation of cell migration GO:0030534 adult behavior GO:0031175 neuron projection development GO:0031642 negative regulation of myelination GO:0031647 regulation of protein stability GO:0031658 negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle GO:0032228 regulation of synaptic transmission, GABAergic GO:0032286 central nervous system myelin maintenance GO:0032355 response to estradiol GO:0032535 regulation of cellular component size GO:0032869 cellular response to insulin stimulus GO:0033032 regulation of myeloid cell apoptotic process GO:0033198 response to ATP GO:0033555 multicellular organismal response to stress GO:0035176 social behavior GO:0035335 peptidyl-tyrosine dephosphorylation GO:0036294 cellular response to decreased oxygen levels GO:0042493 response to drug GO:0042711 maternal behavior GO:0043065 positive regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0043491 protein kinase B signaling GO:0043542 endothelial cell migration GO:0043647 inositol phosphate metabolic process GO:0044320 cellular response to leptin stimulus GO:0045471 response to ethanol GO:0045475 locomotor rhythm GO:0045666 positive regulation of neuron differentiation GO:0045792 negative regulation of cell size GO:0046621 negative regulation of organ growth GO:0046685 response to arsenic-containing substance GO:0046855 inositol phosphate dephosphorylation GO:0046856 phosphatidylinositol dephosphorylation GO:0048008 platelet-derived growth factor receptor signaling pathway GO:0048679 regulation of axon regeneration GO:0048681 negative regulation of axon regeneration GO:0048738 cardiac muscle tissue development GO:0048853 forebrain morphogenesis GO:0048854 brain morphogenesis GO:0050680 negative regulation of epithelial cell proliferation GO:0050765 negative regulation of phagocytosis GO:0050771 negative regulation of axonogenesis GO:0050821 protein stabilization GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051548 negative regulation of keratinocyte migration GO:0051726 regulation of cell cycle GO:0051895 negative regulation of focal adhesion assembly GO:0051898 negative regulation of protein kinase B signaling GO:0060024 rhythmic synaptic transmission GO:0060044 negative regulation of cardiac muscle cell proliferation GO:0060070 canonical Wnt signaling pathway GO:0060074 synapse maturation GO:0060134 prepulse inhibition GO:0060179 male mating behavior GO:0060291 long-term synaptic potentiation GO:0060292 long term synaptic depression GO:0060341 regulation of cellular localization GO:0060736 prostate gland growth GO:0060997 dendritic spine morphogenesis GO:0061002 negative regulation of dendritic spine morphogenesis GO:0070373 negative regulation of ERK1 and ERK2 cascade GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0071257 cellular response to electrical stimulus GO:0071361 cellular response to ethanol GO:0071456 cellular response to hypoxia GO:0090071 negative regulation of ribosome biogenesis GO:0090344 negative regulation of cell aging GO:0090394 negative regulation of excitatory postsynaptic potential GO:0097105 presynaptic membrane assembly GO:0097107 postsynaptic density assembly GO:1901017 negative regulation of potassium ion transmembrane transporter activity GO:1903690 negative regulation of wound healing, spreading of epidermal cells GO:1903984 positive regulation of TRAIL-activated apoptotic signaling pathway GO:1904668 positive regulation of ubiquitin protein ligase activity GO:1904706 negative regulation of vascular smooth muscle cell proliferation GO:1990090 cellular response to nerve growth factor stimulus GO:1990314 cellular response to insulin-like growth factor stimulus GO:2000060 positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:2000134 negative regulation of G1/S transition of mitotic cell cycle GO:2000272 negative regulation of receptor activity GO:2000463 positive regulation of excitatory postsynaptic potential GO:2000808 negative regulation of synaptic vesicle clustering GO:2001235 positive regulation of apoptotic signaling pathway
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Common Gene Haplotype Alleles 
