Gene content    
PTEN ( by HUGO)
Phosphatase And Tensin Homolog
Tumor suppressor gene
Phosphatase And Tensin Homolog
Mutated In Multiple Advanced Cancers 1
MMAC1
BZS
MHAM
TEP1
CWS1
GLM2
10q23del
DEC
PTEN1
MMAC1 Phosphatase And Tensin Homolog Deleted On Chromosome 10
Phosphatase And Tensin-Like Protein
Phosphatidylinositol 3
4
5-Trisphosphate 3-Phosphatase And Dual-Specificity Protein Phosphatase PTEN
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
NCBI: 10q23.3    Ensembl: 10q23.31
PTEN_HUMANSize: 403 amino acidsMass: 47166 Da

  • 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 2 PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for PTEN: 1D5R (3D) [IMAGE] 2KYL (3D) [IMAGE]
  • Tissue specificity: Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas [IMAGE] Pathway & Disease-focused RT2 Profiler PCR Arrays including PTEN (see all 23): Parkinson's Disease in human mouse
  • 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. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement Catalytic activity: Phosphatidylinositol 3,4,5-trisphosphate + H(2)O = phosphatidylinositol 4,5-bisphosphate + phosphate Catalytic activity: [a protein]-serine/threonine phosphate + H(2)O = [a protein]-serine/threonine + phosphate
                          
    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 Catalytic activity: Phosphatidylinositol 3,4,5-trisphosphate + H(2)O = phosphatidylinositol 4,5-bisphosphate + phosphate Catalytic activity: [a protein]-serine/threonine phosphate + H(2)O = [a protein]-serine/threonine + phosphate Catalytic activity: Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate
  • Catalytic activity:
    Phosphatidylinositol 3,4,5-trisphosphate + H(2)O = phosphatidylinositol 4,5-bisphosphate + phosphate
                          
    [a protein]-serine/threonine phosphate + H(2)O = [a protein]-serine/threonine + phosphate
                          
    Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate
  • Similarity:
    Contains 1 C2 tensin-type domain
                          
    Contains 1 phosphatase tensin-type domain [IMAGE]
  • Protein Domain/Family    
    Source ID Domain Name Type
    InterProIPR000008C2_domC2Domain
    IPR000340Dual-sp_phosphatase_cat-domDual specificity protein phosphataseDomain
    BlocksIPB000340Dual specificity protein phosphataseDual specificity protein phosphatase

    Gene Ontology    
    Type Term Evidence Source Pub
    Biological Process cell proliferation TAS GOA 10918569
    inositol phosphate dephosphorylation IDA GOA 9593664
    negative regulation of cell migration IMP GOA 17880912
    negative regulation of cell proliferation IMP GOA 10468583
    negative regulation of cell proliferation IDA GOA 19057511
    negative regulation of focal adhesion assembly IMP GOA 9616126
    negative regulation of phosphatidylinositol 3-kinase signaling TAS GOA 18082964
    negative regulation of protein kinase B signaling IMP GOA 10760291
    peptidyl-tyrosine dephosphorylation IDA GOA 9256433
    phosphatidylinositol dephosphorylation IDA GOA 9593664
    protein dephosphorylation TAS GOA 9367992
    protein dephosphorylation IDA GOA 9256433
    regulation of cyclin-dependent protein serine/threonine kinase activity TAS GOA 10918569
    regulation of protein stability IMP GOA 10866658
    Cellular Component cell projection IDA GOA 10760291
    cytoplasm TAS GOA 9367992
    cytoplasmic side of plasma membrane IDA GOA 10940933
    plasma membrane IDA GOA 10760291
    Molecular Function enzyme binding IPI GOA 16845383
    inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity IDA GOA 9593664
    PDZ domain binding IPI GOA 10646847
    phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity IDA GOA 9593664
    phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity IDA GOA 9811831
    phosphatidylinositol-3-phosphatase activity IDA GOA 9811831
    protein binding IPI GOA 15951562
    protein serine/threonine phosphatase activity IDA GOA 9256433
    protein tyrosine phosphatase activity IDA GOA 9256433

    Disorder & Mutation    
    Source Disease
    SWISS-PROTGlioma 2 (GLM2) [MIM:613028]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
    SWISS-PROTVACTERL 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. Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTProstate cancer (PC) [MIM:176807]: 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. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
    SWISS-PROTMacrocephaly/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). Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTEndometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
    SWISS-PROTNote=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
    SWISS-PROTSquamous cell carcinoma of the head and neck (HNSCC) [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTBannayan-Riley-Ruvalcaba syndrome (BRRS) [MIM:153480]: A rare hamartomatous disorder characterized by macrocephaly and multiple hemangiomas as well as subcutaneous and visceral lipomas. It belongs to the family of hamartomatous polyposis syndromes that includes Peutz Jeghers syndrome, juvenile polyposis, and Cowden syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTLhermitte-Duclos disease (LDD) [MIM:158350]: A rare disease characterized by the occurrence of a slowly enlarging mass within the cerebellar cortex corresponding histologically to a cerebellar hamartoma. It manifests, most commonly in the third and fourth decades of life, with increased intracranial pressure, headache, nausea, cerebellar dysfunction, occlusive hydrocephalus, ataxia, visual disturbances and other cranial nerve palsies. Various associated abnormalities may be present such as megalencephaly, microgyria, hydromyelia, polydactyly, partial gigantism, macroglossia. LDD is part of the PTEN hamartoma tumor syndromes spectrum that also includes Cowden syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTCowden syndrome 1 (CWS1) [MIM:158350]: An autosomal dominant hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. Note=The disease is caused by mutations affecting the gene represented in this entry

    PTEN cross reference    
    PubMed OMIM Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene