PTEN - Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN - human protein (Function)
 
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PTEN »  Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN   [ EC 3.1.3.67EC 3.1.3.16EC 3.1.3.48 ]
 
Protein also known as:  Mutated in multiple advanced cancers 1.
Gene name:  PTEN
Entry whose protein(s) existence is based on evidence at protein level
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1 1359 3
GENE REF ISO

Function

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Overview 
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. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement.  
1
  • UniProtKB
GO molecular function 
Anaphase-promoting complex bindingdefinition[GO:0010997]  
1
  • BHF-UCL
Enzyme bindingdefinition[GO:0019899]  
1
  • UniProtKB
Inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activitydefinition[GO:0051717]  
1
  • UniProtKB
Lipid bindingdefinition[GO:0008289]  
1
  • UniProtKB KW
Magnesium ion bindingdefinition[GO:0000287] silver  
1
  • InterPro 2 GO
PDZ domain bindingdefinition[GO:0030165]  
2
  • UniProtKB
Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activitydefinition[GO:0016314]  
2
  • UniProtKB
Phosphatidylinositol-3,4-bisphosphate 3-phosphatase activitydefinition[GO:0051800]  
1
  • UniProtKB
Phosphatidylinositol-3-phosphatase activitydefinition[GO:0004438]  
1
  • UniProtKB
Phosphoprotein phosphatase activitydefinition[GO:0004721]  
1
  • BHF-UCL
Platelet-derived growth factor receptor bindingdefinition[GO:0005161] silver  
1
  • Ortholog Compara
Protein bindingdefinition[GO:0005515]  
14
  • IntAct
  • UniProtKB
Protein kinase bindingdefinition[GO:0019901] silver  
1
  • Ortholog Compara
Protein serine/threonine phosphatase activitydefinition[GO:0004722]  
1
  • UniProtKB
Protein tyrosine phosphatase activitydefinition[GO:0004725]  
1
  • UniProtKB
Protein tyrosine/serine/threonine phosphatase activitydefinition[GO:0008138] silver  
1
  • InterPro 2 GO
GO biological process 
Activation of mitotic anaphase-promoting complex activitydefinition[GO:0007092]  
1
  • BHF-UCL
Agingdefinition[GO:0007568] silver  
1
  • Ortholog Compara
Angiogenesisdefinition[GO:0001525] silver  
1
  • Ortholog Compara
Apoptotic processdefinition[GO:0006915]  
1
  • Ortholog Curator
Brain morphogenesisdefinition[GO:0048854]  
1
  • Ortholog Curator
Canonical Wnt signaling pathwaydefinition[GO:0060070]  
1
  • BHF-UCL
Cardiac muscle tissue developmentdefinition[GO:0048738] silver  
1
  • Ortholog Compara
Cell migrationdefinition[GO:0016477]  
1
  • Ortholog Curator
Cell proliferationdefinition[GO:0008283]  
1
  • UniProtKB
Central nervous system developmentdefinition[GO:0007417]  
1
  • Ortholog Curator
Central nervous system myelin maintenancedefinition[GO:0032286]  
1
  • Ortholog Curator
Central nervous system neuron axonogenesisdefinition[GO:0021955]  
1
  • Ortholog Curator
Dendritic spine morphogenesisdefinition[GO:0060997]  
1
  • Ortholog Curator
Dentate gyrus developmentdefinition[GO:0021542]  
1
  • Ortholog Curator
Endothelial cell migrationdefinition[GO:0043542] silver  
1
  • Ortholog Compara
Forebrain morphogenesisdefinition[GO:0048853]  
1
  • Ortholog Curator
Heart developmentdefinition[GO:0007507]  
1
  • Ortholog Curator
Inositol phosphate dephosphorylationdefinition[GO:0046855]  
1
  • UniProtKB
Learning or memorydefinition[GO:0007611]  
1
  • Ortholog Curator
Locomotor rhythmdefinition[GO:0045475]  
1
  • Ortholog Curator
Locomotory behaviordefinition[GO:0007626]  
1
  • Ortholog Curator
Long term synaptic depressiondefinition[GO:0060292] silver  
1
  • Ortholog Compara
Long-term synaptic potentiationdefinition[GO:0060291] silver  
1
  • Ortholog Compara
Male mating behaviordefinition[GO:0060179] silver  
1
  • Ortholog Compara
Maternal behaviordefinition[GO:0042711] silver  
1
  • Ortholog Compara
Memorydefinition[GO:0007613] silver  
1
  • Ortholog Compara
Multicellular organismal response to stressdefinition[GO:0033555]  
1
  • Ortholog Curator
Negative regulation of apoptotic processdefinition[GO:0043066] silver  
1
  • Ortholog Compara
Negative regulation of axonogenesisdefinition[GO:0050771]  
1
  • Ortholog Curator
Negative regulation of cell agingdefinition[GO:0090344] silver  
1
  • Ortholog Compara
Negative regulation of cell migrationdefinition[GO:0030336]  
2
  • UniProtKB
Negative regulation of cell proliferationdefinition[GO:0008285]  
3
  • BHF-UCL
  • UniProtKB
Negative regulation of cell sizedefinition[GO:0045792]  
1
  • Ortholog Curator
Negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycledefinition[GO:0031658]  
1
  • BHF-UCL
Negative regulation of dendritic spine morphogenesisdefinition[GO:0061002]  
1
  • Ortholog Curator
Negative regulation of epithelial cell proliferationdefinition[GO:0050680] silver  
1
  • Ortholog Compara
Negative regulation of excitatory postsynaptic membrane potentialdefinition[GO:0090394]  
1
  • Ortholog Curator
Negative regulation of focal adhesion assemblydefinition[GO:0051895]  
1
  • UniProtKB
Negative regulation of G1/S transition of mitotic cell cycledefinition[GO:2000134]  
1
  • BHF-UCL
Negative regulation of myelinationdefinition[GO:0031642] silver  
1
  • Ortholog Compara
Negative regulation of organ growthdefinition[GO:0046621]  
1
  • Ortholog Curator
Negative regulation of phagocytosisdefinition[GO:0050765] silver  
1
  • Ortholog Compara
Negative regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014067]  
1
  • BHF-UCL
Negative regulation of protein kinase B signalingdefinition[GO:0051898]  
1
  • UniProtKB
Negative regulation of protein phosphorylationdefinition[GO:0001933]  
1
  • BHF-UCL
Negative regulation of ribosome biogenesisdefinition[GO:0090071] silver  
1
  • Ortholog Compara
Negative regulation of synaptic vesicle clusteringdefinition[GO:2000808]  
1
  • Ortholog Curator
Neuron-neuron synaptic transmissiondefinition[GO:0007270]  
1
  • Ortholog Curator
Peptidyl-tyrosine dephosphorylationdefinition[GO:0035335]  
3
  • GOC
  • InterPro 2 GO
  • EC 2 GO
Phosphatidylinositol dephosphorylationdefinition[GO:0046856]  
3
  • BHF-UCL
  • UniProtKB
Platelet-derived growth factor receptor signaling pathwaydefinition[GO:0048008] silver  
1
  • Ortholog Compara
Positive regulation of apoptotic signaling pathwaydefinition[GO:2001235] silver  
1
  • Ortholog Compara
Positive regulation of cell proliferationdefinition[GO:0008284]  
1
  • Ortholog Curator
Positive regulation of excitatory postsynaptic membrane potentialdefinition[GO:2000463]  
1
  • Ortholog Curator
Positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic processdefinition[GO:2000060]  
1
  • BHF-UCL
Positive regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051091]  
1
  • BHF-UCL
Postsynaptic density assemblydefinition[GO:0097107]  
1
  • Ortholog Curator
Prepulse inhibitiondefinition[GO:0060134]  
1
  • Ortholog Curator
Presynaptic membrane assemblydefinition[GO:0097105]  
1
  • Ortholog Curator
Prostate gland growthdefinition[GO:0060736] silver  
1
  • Ortholog Compara
Protein dephosphorylationdefinition[GO:0006470]  
2
  • UniProtKB
Protein kinase B signalingdefinition[GO:0043491]  
1
  • Ortholog Curator
Protein stabilizationdefinition[GO:0050821]  
1
  • BHF-UCL
Regulation of B cell apoptotic processdefinition[GO:0002902] silver  
1
  • Ortholog Compara
Regulation of cellular component sizedefinition[GO:0032535]  
1
  • Ortholog Curator
Regulation of cyclin-dependent protein serine/threonine kinase activitydefinition[GO:0000079]  
1
  • UniProtKB
Regulation of myeloid cell apoptotic processdefinition[GO:0033032] silver  
1
  • Ortholog Compara
Regulation of neuron projection developmentdefinition[GO:0010975]  
1
  • Ortholog Curator
Regulation of protein stabilitydefinition[GO:0031647]  
1
  • UniProtKB
Response to arsenic-containing substancedefinition[GO:0046685] silver  
1
  • Ortholog Compara
Response to ATPdefinition[GO:0033198] silver  
1
  • Ortholog Compara
Response to drugdefinition[GO:0042493] silver  
1
  • Ortholog Compara
Response to estradioldefinition[GO:0032355] silver  
1
  • Ortholog Compara
Response to ethanoldefinition[GO:0045471] silver  
1
  • Ortholog Compara
Response to glucosedefinition[GO:0009749] silver  
1
  • Ortholog Compara
Response to nutrientdefinition[GO:0007584] silver  
1
  • Ortholog Compara
Response to zinc iondefinition[GO:0010043] silver  
1
  • Ortholog Compara
Rhythmic synaptic transmissiondefinition[GO:0060024]  
1
  • Ortholog Curator
Social behaviordefinition[GO:0035176]  
1
  • Ortholog Curator
Synapse assemblydefinition[GO:0007416]  
1
  • Ortholog Curator
Synapse maturationdefinition[GO:0060074]  
1
  • Ortholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 3.1.3.67: Phosphatidylinositol 3,4,5-trisphosphate + H(2)O phosphatidylinositol 4,5-bisphosphate + phosphate.  
1
  • UniProtKB
EC 3.1.3.16: [a protein]-serine/threonine phosphate + H(2)O [a protein]-serine/threonine + phosphate.  
1
  • UniProtKB
EC 3.1.3.48: Protein tyrosine phosphate + H(2)O protein tyrosine + phosphate.  
1
  • UniProtKB
It requires the following cofactor
 Mg(2+)  
1
  • UniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Endometrial cancer  hsa05213+5728  
Focal adhesion  hsa04510+5728  
Glioma  hsa05214+5728  
Inositol phosphate metabolism  hsa00562+5728  
Melanoma  hsa05218+5728  
p53 signaling pathway  hsa04115+5728  
Pathways in cancer  hsa05200+5728  
Phosphatidylinositol signaling system  hsa04070+5728  
Prostate cancer  hsa05215+5728  
Small cell lung cancer  hsa05222+5728  
Tight junction  hsa04530+5728  
According to Reactome, this protein belongs to the following pathways:
Constitutive PI3K/AKT Signaling in Cancer  REACT_147727  
Downstream TCR signaling  REACT_12555  
Negative regulation of the PI3K/AKT network  REACT_12447  
PIP3 activates AKT signaling  REACT_75829  
Synthesis of IP3 and IP4 in the cytosol  REACT_150312  
Synthesis of PIPs at the plasma membrane  REACT_121025  
 
More information is available from:
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Lipid metabolism  definition   [KW-0443]
Neurogenesis  definition   [KW-0524]
Molecular function 
Hydrolase  definition   [KW-0378]
Protein phosphatase  definition   [KW-0904]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: PTEN_(gene)
GenomeRNAi: 5728
PRO: PR:P60484