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P60484

- PTEN_HUMAN

UniProt

P60484 - PTEN_HUMAN

Protein

Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN

Gene

PTEN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 1 (16 Feb 2004)
      Previous versions | rss
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    Functioni

    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.
    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.

    Catalytic activityi

    Phosphatidylinositol 3,4,5-trisphosphate + H2O = phosphatidylinositol 4,5-bisphosphate + phosphate.
    [a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.
    Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

    Cofactori

    Magnesium.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei124 – 1241Phosphocysteine intermediatePROSITE-ProRule annotation

    GO - Molecular functioni

    1. anaphase-promoting complex binding Source: BHF-UCL
    2. enzyme binding Source: UniProtKB
    3. inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity Source: UniProtKB
    4. lipid binding Source: UniProtKB-KW
    5. magnesium ion binding Source: InterPro
    6. PDZ domain binding Source: UniProtKB
    7. phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity Source: UniProtKB-EC
    8. phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity Source: UniProtKB
    9. phosphatidylinositol-3-phosphatase activity Source: UniProtKB
    10. phosphoprotein phosphatase activity Source: BHF-UCL
    11. protein binding Source: UniProtKB
    12. protein serine/threonine phosphatase activity Source: UniProtKB
    13. protein tyrosine/serine/threonine phosphatase activity Source: InterPro
    14. protein tyrosine phosphatase activity Source: InterPro

    GO - Biological processi

    1. activation of mitotic anaphase-promoting complex activity Source: BHF-UCL
    2. aging Source: Ensembl
    3. angiogenesis Source: Ensembl
    4. apoptotic process Source: UniProtKB
    5. brain morphogenesis Source: BHF-UCL
    6. canonical Wnt signaling pathway Source: BHF-UCL
    7. cardiac muscle tissue development Source: Ensembl
    8. cell migration Source: UniProtKB
    9. cell proliferation Source: UniProtKB
    10. central nervous system development Source: UniProtKB
    11. central nervous system myelin maintenance Source: BHF-UCL
    12. central nervous system neuron axonogenesis Source: BHF-UCL
    13. dendritic spine morphogenesis Source: BHF-UCL
    14. dentate gyrus development Source: BHF-UCL
    15. endothelial cell migration Source: Ensembl
    16. epidermal growth factor receptor signaling pathway Source: Reactome
    17. Fc-epsilon receptor signaling pathway Source: Reactome
    18. fibroblast growth factor receptor signaling pathway Source: Reactome
    19. forebrain morphogenesis Source: BHF-UCL
    20. heart development Source: UniProtKB
    21. innate immune response Source: Reactome
    22. inositol phosphate dephosphorylation Source: UniProtKB
    23. inositol phosphate metabolic process Source: Reactome
    24. learning or memory Source: BHF-UCL
    25. locomotor rhythm Source: BHF-UCL
    26. locomotory behavior Source: BHF-UCL
    27. long term synaptic depression Source: Ensembl
    28. long-term synaptic potentiation Source: Ensembl
    29. male mating behavior Source: Ensembl
    30. maternal behavior Source: Ensembl
    31. memory Source: Ensembl
    32. multicellular organismal response to stress Source: BHF-UCL
    33. negative regulation of apoptotic process Source: Ensembl
    34. negative regulation of axonogenesis Source: BHF-UCL
    35. negative regulation of cell aging Source: Ensembl
    36. negative regulation of cell migration Source: UniProtKB
    37. negative regulation of cell proliferation Source: UniProtKB
    38. negative regulation of cell size Source: BHF-UCL
    39. negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
    40. negative regulation of dendritic spine morphogenesis Source: BHF-UCL
    41. negative regulation of epithelial cell proliferation Source: Ensembl
    42. negative regulation of excitatory postsynaptic membrane potential Source: BHF-UCL
    43. negative regulation of focal adhesion assembly Source: UniProtKB
    44. negative regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
    45. negative regulation of myelination Source: Ensembl
    46. negative regulation of organ growth Source: BHF-UCL
    47. negative regulation of phagocytosis Source: Ensembl
    48. negative regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
    49. negative regulation of protein kinase B signaling Source: UniProtKB
    50. negative regulation of protein phosphorylation Source: BHF-UCL
    51. negative regulation of ribosome biogenesis Source: Ensembl
    52. negative regulation of synaptic vesicle clustering Source: BHF-UCL
    53. neuron-neuron synaptic transmission Source: BHF-UCL
    54. neurotrophin TRK receptor signaling pathway Source: Reactome
    55. peptidyl-tyrosine dephosphorylation Source: GOC
    56. phosphatidylinositol biosynthetic process Source: Reactome
    57. phosphatidylinositol dephosphorylation Source: UniProtKB
    58. phosphatidylinositol-mediated signaling Source: Reactome
    59. phospholipid metabolic process Source: Reactome
    60. platelet-derived growth factor receptor signaling pathway Source: Ensembl
    61. positive regulation of apoptotic process Source: Ensembl
    62. positive regulation of apoptotic signaling pathway Source: Ensembl
    63. positive regulation of cell proliferation Source: BHF-UCL
    64. positive regulation of excitatory postsynaptic membrane potential Source: BHF-UCL
    65. positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: BHF-UCL
    66. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    67. postsynaptic density assembly Source: BHF-UCL
    68. prepulse inhibition Source: BHF-UCL
    69. presynaptic membrane assembly Source: BHF-UCL
    70. prostate gland growth Source: Ensembl
    71. protein dephosphorylation Source: UniProtKB
    72. protein kinase B signaling Source: UniProtKB
    73. protein stabilization Source: BHF-UCL
    74. regulation of B cell apoptotic process Source: Ensembl
    75. regulation of cellular component size Source: BHF-UCL
    76. regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
    77. regulation of myeloid cell apoptotic process Source: Ensembl
    78. regulation of neuron projection development Source: UniProtKB
    79. regulation of protein stability Source: UniProtKB
    80. response to arsenic-containing substance Source: Ensembl
    81. response to ATP Source: Ensembl
    82. response to drug Source: Ensembl
    83. response to estradiol Source: Ensembl
    84. response to ethanol Source: Ensembl
    85. response to glucose Source: Ensembl
    86. response to nutrient Source: Ensembl
    87. response to zinc ion Source: Ensembl
    88. rhythmic synaptic transmission Source: BHF-UCL
    89. small molecule metabolic process Source: Reactome
    90. social behavior Source: BHF-UCL
    91. synapse assembly Source: BHF-UCL
    92. synapse maturation Source: BHF-UCL
    93. T cell receptor signaling pathway Source: Reactome

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Biological processi

    Apoptosis, Lipid metabolism, Neurogenesis

    Keywords - Ligandi

    Lipid-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS10404-MONOMER.
    ReactomeiREACT_121025. Synthesis of PIPs at the plasma membrane.
    REACT_12447. Negative regulation of the PI3K/AKT network.
    REACT_12555. Downstream TCR signaling.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_150312. Synthesis of IP3 and IP4 in the cytosol.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinkiP60484.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    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)
    Alternative name(s):
    Mutated in multiple advanced cancers 1
    Phosphatase and tensin homolog
    Gene namesi
    Name:PTEN
    Synonyms:MMAC1, TEP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:9588. PTEN.

    Subcellular locationi

    Cytoplasm. Nucleus. NucleusPML 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.
    Isoform alpha : Secreted 2 Publications
    Note: May be secreted via a classical signal peptide and reenter into cells with the help of a poly-Arg motif.

    GO - Cellular componenti

    1. cell projection Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. cytoplasmic side of plasma membrane Source: UniProtKB
    4. cytosol Source: Reactome
    5. dendritic spine Source: Ensembl
    6. mitochondrion Source: Ensembl
    7. myelin sheath adaxonal region Source: BHF-UCL
    8. neuron projection Source: BHF-UCL
    9. nucleus Source: BHF-UCL
    10. plasma membrane Source: UniProtKB
    11. PML body Source: UniProtKB-SubCell
    12. postsynaptic membrane Source: Ensembl
    13. Schmidt-Lanterman incisure Source: BHF-UCL

    Keywords - Cellular componenti

    Cytoplasm, Nucleus, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Cowden 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.13 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti33 – 331Missing in CWS1. 1 Publication
    VAR_008733
    Natural varianti35 – 351M → R in CWS1. 1 Publication
    VAR_008036
    Natural varianti47 – 471R → G in CWS1. 1 Publication
    VAR_011587
    Natural varianti67 – 671I → R in CWS1.
    VAR_007461
    Natural varianti68 – 681Y → H in CWS1 and BRRS; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes. 3 Publications
    VAR_007462
    Natural varianti70 – 701L → P in CWS1. 1 Publication
    VAR_018102
    Natural varianti71 – 711C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026254
    Natural varianti93 – 931H → Y in CWS1.
    VAR_026255
    Natural varianti112 – 1121L → P in CWS1 and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
    VAR_007807
    Natural varianti123 – 1231H → R in CWS1. 2 Publications
    VAR_007463
    Natural varianti124 – 1241C → R in CWS1. 2 Publications
    VAR_007464
    Natural varianti124 – 1241C → S in CWS1; phosphatase-dead protein with neither lipid nor protein phosphatase activity.
    VAR_018104
    Natural varianti129 – 1291G → E in CWS1; no lipid phosphatase activity but retains protein phosphatase activity; retains ability to inhibit focal adhesion formation. 1 Publication
    VAR_007465
    Natural varianti130 – 1301R → L in CWS1 and endometrial hyperplasia; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
    VAR_007467
    Natural varianti130 – 1301R → Q in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
    VAR_007468
    Natural varianti136 – 1361C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P3. 1 Publication
    VAR_007808
    Natural varianti137 – 1371A → AN in CWS1. 1 Publication
    VAR_008737
    Natural varianti155 – 1551Y → C in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026263
    Natural varianti165 – 1651G → E in CWS1. 1 Publication
    VAR_008739
    Natural varianti165 – 1651G → V in CWS1.
    VAR_008738
    Natural varianti246 – 2461P → L in CWS1 and BRRS. 1 Publication
    VAR_008740
    Natural varianti289 – 2891K → E in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
    VAR_008741
    Natural varianti331 – 3311D → G in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes.
    VAR_026275
    Natural varianti341 – 3411F → V in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026276
    Natural varianti342 – 3421K → N in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4 but PtdIns(3,4,5)P3 phosphatase activity is similar to wild-type.
    VAR_026277
    Natural varianti343 – 3431V → E in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
    VAR_008742
    Natural varianti347 – 3471F → L in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
    VAR_008743
    Lhermitte-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.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti112 – 1121L → P in CWS1 and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
    VAR_007807
    Bannayan-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.4 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti34 – 341A → D in BRRS. 2 Publications
    VAR_008734
    Natural varianti68 – 681Y → H in CWS1 and BRRS; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes. 3 Publications
    VAR_007462
    Natural varianti105 – 1051C → F in BRRS; loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026256
    Natural varianti105 – 1051C → Y in BRRS. 2 Publications
    VAR_008735
    Natural varianti107 – 1071D → Y in BRRS and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
    VAR_026257
    Natural varianti135 – 1351I → V in BRRS. 2 Publications
    VAR_008736
    Natural varianti170 – 1701S → R in BRRS; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4. 3 Publications
    VAR_007470
    Natural varianti246 – 2461P → L in CWS1 and BRRS. 1 Publication
    VAR_008740
    Squamous 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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti121 – 1211A → G in HNSCC. 1 Publication
    VAR_018103
    Endometrial 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.
    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.
    Glioma 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.
    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.
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Prostate 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.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    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).1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti93 – 931H → R in MCEPHAS. 1 Publication
    VAR_032634
    Natural varianti241 – 2411F → S in MCEPHAS. 1 Publication
    VAR_032636
    Natural varianti252 – 2521D → G in MCEPHAS. 1 Publication
    VAR_032637
    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.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1 – 11M → I: Expression is restricted to isoform alpha. 1 Publication
    Mutagenesisi13 – 131K → E: Nuclear. Cytoplasmic; when associated with E-289. Shows less tumor suppressive ability; when associated with E-289. 1 Publication
    Mutagenesisi92 – 921D → A: 700-fold reduction in phosphatase activity towards PtdIns(3,4,5)P3. Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation. 2 Publications
    Mutagenesisi93 – 931H → A: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Modest reduction in phosphatase activity towards PtdIns(3,4)P2. 1 Publication
    Mutagenesisi124 – 1241C → A: Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation. 1 Publication
    Mutagenesisi125 – 1251K → M: Reduced phosphatase activity towards PtdIns(3,4,5)P3, PtdIns(3,4)P2 and PtdIns(3)P. 1 Publication
    Mutagenesisi128 – 1281K → M: 85% reduction in phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication
    Mutagenesisi128 – 1281K → R: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication
    Mutagenesisi130 – 1301R → M: Does not affect the ability to inhibit AKT/PKB activation. 1 Publication
    Mutagenesisi167 – 1671T → A or D: 60% reduction in phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication
    Mutagenesisi171 – 1711Q → A or E: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication
    Mutagenesisi263 – 2697KMLKKDK → AAGAADA: Reduces the growth suppression activity and cells show anchorage-independent growth. Reduces binding to phospholipid membranes in vitro. Phosphatase activity towards PtdIns(3,4,5)P3 is not affected.
    Mutagenesisi289 – 2891K → E: Nuclear. Cytoplasmic; when associated with E-13. Shows less tumor suppressive ability; when associated with E-13. 1 Publication
    Mutagenesisi327 – 3359KANKDKANR → AAGADAANA: Reduces growth suppression activity and promotes anchorage-independent growth. Reduces binding to phospholipid membranes in vitro; phosphatase activity towards PtdIns(3,4,5)P3 is not affected.
    Mutagenesisi336 – 3361Y → F: Significantly lower phosphatase activity, reduced protein stability and decreased growth-inhibitory effect. 1 Publication
    Mutagenesisi366 – 3661T → A: Decreased stability. 1 Publication
    Mutagenesisi370 – 3701S → A: Decreased stability. 1 Publication
    Mutagenesisi401 – 4011T → A: Loss of DLG1-binding. No effect on MAGI2- and MAST2-binding.
    Mutagenesisi402 – 4021K → A: No effect on MAGI2-, MAST2- and DLG1-binding.
    Mutagenesisi402 – 4021K → W: Loss of DLG1-, MAGI2-, MAGI3- and MAST2-binding. Decrease of protein stability.
    Mutagenesisi403 – 4031V → A: Loss of DLG1-, MAGI2-, MAGI3-, MAST1-, MAST2- and MAST3-binding. 1 Publication

    Keywords - Diseasei

    Disease mutation, Tumor suppressor

    Organism-specific databases

    MIMi137800. phenotype.
    153480. phenotype.
    158350. phenotype.
    176807. phenotype.
    275355. phenotype.
    276950. phenotype.
    605309. phenotype.
    608089. phenotype.
    612242. phenotype.
    613028. phenotype.
    Orphaneti109. Bannayan-Riley-Ruvalcaba syndrome.
    201. Cowden syndrome.
    145. Hereditary breast and ovarian cancer syndrome.
    79076. Juvenile polyposis of infancy.
    65285. Lhermitte-Duclos disease.
    210548. Macrocephaly-autism syndrome.
    744. Proteus syndrome.
    2969. Proteus-like syndrome.
    137608. Segmental outgrowth - lipomatosis - arteriovenous malformation - epidermal nevus.
    67037. Squamous cell carcinoma of head and neck.
    PharmGKBiPA33942.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 403402Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENPRO_0000215904Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylthreonine1 Publication
    Cross-linki13 – 13Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki289 – 289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei336 – 3361Phosphotyrosine; by FRK1 Publication
    Modified residuei366 – 3661Phosphothreonine; by GSK3-beta and PLK32 Publications
    Modified residuei370 – 3701Phosphoserine; by CK2 and PLK33 Publications
    Modified residuei380 – 3801Phosphoserine; by ROCK1 and CK21 Publication
    Modified residuei382 – 3821Phosphothreonine; by ROCK1 and CK21 Publication
    Modified residuei383 – 3831Phosphothreonine; by ROCK1 and CK21 Publication
    Modified residuei385 – 3851Phosphoserine; by CK22 Publications
    Modified residuei401 – 4011Phosphothreonine1 Publication

    Post-translational modificationi

    Constitutively phosphorylated by CK2 under normal conditions. Phosphorylated in vitro by MAST1, MAST2, MAST3 and STK11. 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.9 Publications
    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/BIRC4.2 Publications

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP60484.
    PaxDbiP60484.
    PRIDEiP60484.

    PTM databases

    PhosphoSiteiP60484.

    Miscellaneous databases

    PMAP-CutDBP60484.

    Expressioni

    Tissue specificityi

    Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas.1 Publication

    Inductioni

    Down-regulated by TGFB1.1 Publication

    Gene expression databases

    ArrayExpressiP60484.
    BgeeiP60484.
    CleanExiHS_PTEN.
    HS_TEP1.
    GenevestigatoriP60484.

    Organism-specific databases

    HPAiCAB004076.
    HPA031335.

    Interactioni

    Subunit structurei

    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. Interacts with STK11; the interaction phosphorylates PTEN.By similarity12 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    BMI1P352263EBI-696162,EBI-2341576
    CDC27P302607EBI-696162,EBI-994813
    DBN1Q166435EBI-696162,EBI-351394
    Dlg1Q626962EBI-696162,EBI-389325From a different organism.
    FRKP426857EBI-696162,EBI-1383583
    Magi2O883823EBI-696162,EBI-696179From a different organism.
    Magi3Q9JK713EBI-696162,EBI-696226From a different organism.
    Mast1Q9R1L53EBI-696162,EBI-491771From a different organism.
    Mast2Q605924EBI-696162,EBI-493888From a different organism.
    MAST3O603073EBI-696162,EBI-311420
    NCOA3Q9Y6Q92EBI-696162,EBI-81196
    NEDD4P469344EBI-696162,EBI-726944
    PDGFRBP096193EBI-696162,EBI-641237
    PPP1CAP621362EBI-696162,EBI-357253
    PRDX1Q068307EBI-696162,EBI-353193
    SLC9A3R1O147455EBI-696162,EBI-349787
    SLC9A3R2Q155995EBI-696162,EBI-1149760
    Slc9a3r2Q9JHL12EBI-696162,EBI-538451From a different organism.

    Protein-protein interaction databases

    BioGridi111700. 90 interactions.
    DIPiDIP-35019N.
    IntActiP60484. 38 interactions.
    MINTiMINT-127351.
    STRINGi9606.ENSP00000361021.

    Structurei

    Secondary structure

    1
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni19 – 224
    Beta strandi23 – 297
    Beta strandi32 – 354
    Beta strandi39 – 413
    Helixi50 – 6011
    Beta strandi61 – 633
    Beta strandi65 – 739
    Beta strandi85 – 906
    Helixi98 – 1003
    Helixi101 – 11212
    Turni113 – 1153
    Beta strandi118 – 1236
    Beta strandi125 – 1284
    Helixi129 – 14113
    Helixi148 – 15912
    Beta strandi161 – 1633
    Helixi169 – 18416
    Beta strandi192 – 20211
    Beta strandi213 – 2197
    Beta strandi222 – 2265
    Beta strandi232 – 2354
    Beta strandi238 – 25922
    Beta strandi268 – 2769
    Helixi277 – 2793
    Beta strandi315 – 3217
    Helixi322 – 3243
    Helixi328 – 3303
    Beta strandi335 – 3373
    Beta strandi342 – 3498
    Beta strandi395 – 4039

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1D5RX-ray2.10A8-353[»]
    2KYLNMR-B391-403[»]
    4O1VX-ray2.00B354-368[»]
    ProteinModelPortaliP60484.
    SMRiP60484. Positions 14-351.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP60484.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini14 – 185172Phosphatase tensin-typePROSITE-ProRule annotationAdd
    BLAST
    Domaini190 – 350161C2 tensin-typePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni401 – 4033PDZ domain-binding

    Domaini

    The C2 domain binds phospholipid membranes in vitro in a Ca2+-independent manner; this binding is important for its tumor suppressor function.2 Publications

    Sequence similaritiesi

    Contains 1 C2 tensin-type domain.PROSITE-ProRule annotation
    Contains 1 phosphatase tensin-type domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG2453.
    HOGENOMiHOG000008008.
    HOVERGENiHBG000239.
    InParanoidiP60484.
    KOiK01110.
    OMAiKEYLILT.
    OrthoDBiEOG7R2BJ5.
    PhylomeDBiP60484.
    TreeFamiTF324513.

    Family and domain databases

    Gene3Di3.90.190.10. 1 hit.
    InterProiIPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN.
    IPR000008. C2_dom.
    IPR000340. Dual-sp_phosphatase_cat-dom.
    IPR029021. Prot-tyrosine_phosphatase-like.
    IPR014020. Tensin_C2-dom.
    IPR029023. Tensin_lipid_phosphatase_dom.
    IPR016130. Tyr_Pase_AS.
    [Graphical view]
    PfamiPF00782. DSPc. 1 hit.
    PF10409. PTEN_C2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF038025. PTEN. 1 hit.
    SUPFAMiSSF49562. SSF49562. 1 hit.
    SSF52799. SSF52799. 1 hit.
    PROSITEiPS51182. C2_TENSIN. 1 hit.
    PS51181. PPASE_TENSIN. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. Align

    Isoform 1 (identifier: P60484-1) [UniParc]FASTAAdd to Basket

    Also known as: 55kDa

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI    50
    DDVVRFLDSK HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL 100
    IKPFCEDLDQ WLSEDDNHVA AIHCKAGKGR TGVMICAYLL HRGKFLKAQE 150
    ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY LLKNHLDYRP VALLFHKMMF 200
    ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY FEFPQPLPVC 250
    GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI 300
    DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT 350
    VEEPSNPEAS SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHTQI 400
    TKV 403
    Length:403
    Mass (Da):47,166
    Last modified:February 16, 2004 - v1
    Checksum:i75F97C3DD6802BA9
    GO
    Isoform alpha (identifier: P60484-2) [UniParc]FASTAAdd to Basket

    Also known as: 70kDa, PTEN-long

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MERGGEAAAA...FFFSHRLPDM

    Note: Produced by alternative initiation at a CTG start codon of isoform 1. May contain a signal peptide at positions 1-21.

    Show »
    Length:576
    Mass (Da):64,882
    Checksum:iE0A3C5E42AEC150D
    GO
    Isoform 3 (identifier: P60484-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         55-70: RFLDSKHKNHYKIYNL → S
         165-190: GVTIPSQRRYVYYYSYLLKNHLDYRP → ADPTGGIPDKGIIVIGDGSSMDVIAP
         191-403: Missing.

    Show »
    Length:175
    Mass (Da):19,796
    Checksum:iEB3BBB17D7302085
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti10 – 101S → N Retains phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes.
    VAR_026248
    Natural varianti15 – 151R → S in glioma. 1 Publication
    VAR_007457
    Natural varianti16 – 161Y → C Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains the ability to bind phospholipid membranes.
    VAR_026249
    Natural varianti19 – 191D → N in malignant melanoma; somatic mutation. 1 Publication
    VAR_018100
    Natural varianti20 – 201G → E Reduced phosphatase activity towards Ins(1,3,4,5)P4; retains phosphatase activity towards PtdIns(3,4,5)P3.
    VAR_026250
    Natural varianti27 – 271Y → S Loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026251
    Natural varianti33 – 331Missing in CWS1. 1 Publication
    VAR_008733
    Natural varianti34 – 341A → D in BRRS. 2 Publications
    VAR_008734
    Natural varianti35 – 351M → R in CWS1. 1 Publication
    VAR_008036
    Natural varianti36 – 361G → E in glioma. 1 Publication
    VAR_007458
    Natural varianti36 – 361G → R in endometrial hyperplasia. 1 Publication
    VAR_026252
    Natural varianti42 – 421L → R in glioma; retains phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes. 1 Publication
    VAR_007459
    Natural varianti47 – 471R → G in CWS1. 1 Publication
    VAR_011587
    Natural varianti57 – 571L → W in glioma; loss of protein phosphatase activity. 1 Publication
    VAR_007460
    Natural varianti61 – 611H → D in VATER. 1 Publication
    VAR_018101
    Natural varianti61 – 611H → R Loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026253
    Natural varianti67 – 671I → R in CWS1.
    VAR_007461
    Natural varianti68 – 681Y → H in CWS1 and BRRS; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes. 3 Publications
    VAR_007462
    Natural varianti70 – 701L → P in CWS1. 1 Publication
    VAR_018102
    Natural varianti71 – 711C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026254
    Natural varianti93 – 931H → R in MCEPHAS. 1 Publication
    VAR_032634
    Natural varianti93 – 931H → Y in CWS1.
    VAR_026255
    Natural varianti105 – 1051C → F in BRRS; loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026256
    Natural varianti105 – 1051C → Y in BRRS. 2 Publications
    VAR_008735
    Natural varianti107 – 1071D → Y in BRRS and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
    VAR_026257
    Natural varianti112 – 1121L → P in CWS1 and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
    VAR_007807
    Natural varianti112 – 1121L → R Loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026258
    Natural varianti119 – 1191V → L in multiple cancers. 1 Publication
    VAR_011588
    Natural varianti121 – 1211A → G in HNSCC. 1 Publication
    VAR_018103
    Natural varianti121 – 1211A → P in glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
    VAR_026259
    Natural varianti123 – 1231H → R in CWS1. 2 Publications
    VAR_007463
    Natural varianti123 – 1231H → Y in endometrial cancer; loss of protein phosphatase activity.
    VAR_026260
    Natural varianti124 – 1241C → R in CWS1. 2 Publications
    VAR_007464
    Natural varianti124 – 1241C → S in CWS1; phosphatase-dead protein with neither lipid nor protein phosphatase activity.
    VAR_018104
    Natural varianti129 – 1291G → E in CWS1; no lipid phosphatase activity but retains protein phosphatase activity; retains ability to inhibit focal adhesion formation. 1 Publication
    VAR_007465
    Natural varianti129 – 1291G → R in glioblastoma; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
    VAR_007466
    Natural varianti130 – 1301R → G Loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3.
    VAR_026261
    Natural varianti130 – 1301R → L in CWS1 and endometrial hyperplasia; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
    VAR_007467
    Natural varianti130 – 1301R → Q in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
    VAR_007468
    Natural varianti132 – 1321G → V in one patient with clinical findings suggesting hamartoma tumor syndrome. 1 Publication
    VAR_032635
    Natural varianti133 – 1331V → I Loss of phosphatase activity towards Ins(1,3,4,5)P3.
    VAR_026262
    Natural varianti134 – 1341M → L in prostate cancer; no effect on protein phosphatase activity; reduced phosphatase activity towards Ins(1,3,4,5)P3 but retains PtdIns(3,4,5)P3 phosphatase activity. 1 Publication
    VAR_007469
    Natural varianti135 – 1351I → V in BRRS. 2 Publications
    VAR_008736
    Natural varianti136 – 1361C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P3. 1 Publication
    VAR_007808
    Natural varianti137 – 1371A → AN in CWS1. 1 Publication
    VAR_008737
    Natural varianti155 – 1551Y → C in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026263
    Natural varianti158 – 1581V → L in multiple cancers. 1 Publication
    VAR_011589
    Natural varianti165 – 1651G → E in CWS1. 1 Publication
    VAR_008739
    Natural varianti165 – 1651G → R in glioblastoma; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
    VAR_026264
    Natural varianti165 – 1651G → V in CWS1.
    VAR_008738
    Natural varianti167 – 1671T → P in breast cancer; severely reduced protein phosphatase activity.
    VAR_026265
    Natural varianti170 – 1701S → N Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes.
    VAR_026266
    Natural varianti170 – 1701S → R in BRRS; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4. 3 Publications
    VAR_007470
    Natural varianti173 – 1731R → C in endometrial hyperplasia; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains ability to bind phospholipid membranes. 1 Publication
    VAR_026267
    Natural varianti173 – 1731R → H Loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026268
    Natural varianti173 – 1731R → P Loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026269
    Natural varianti174 – 1741Y → N Loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026270
    Natural varianti191 – 1911V → A in endometrial hyperplasia. 1 Publication
    VAR_026271
    Natural varianti217 – 2171V → I in malignant melanoma; somatic mutation. 1 Publication
    VAR_018105
    Natural varianti227 – 2271S → F Reduced phosphatase activity towards Ins(1,3,4,5)P4 but retains PtdIns(3,4,5)P3 phosphatase activity.
    VAR_026272
    Natural varianti234 – 2341R → Q in a patient with glioma and meningioma; not capable of inducing apoptosis; induced increased cell proliferation; led to high constitutive AKT1 activation which could not be increased further by stimulation with insulin.
    VAR_018106
    Natural varianti241 – 2411F → S in MCEPHAS. 1 Publication
    VAR_032636
    Natural varianti246 – 2461P → L in CWS1 and BRRS. 1 Publication
    VAR_008740
    Natural varianti251 – 2511G → C Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes.
    VAR_026273
    Natural varianti252 – 2521D → G in MCEPHAS. 1 Publication
    VAR_032637
    Natural varianti289 – 2891K → E in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
    VAR_008741
    Natural varianti290 – 2901V → L.1 Publication
    Corresponds to variant rs35600253 [ dbSNP | Ensembl ].
    VAR_025167
    Natural varianti319 – 3191Missing in glioma; reduced tumor suppressor activity; fails to inactivate AKT/PKB. 1 Publication
    VAR_026274
    Natural varianti331 – 3311D → G in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes.
    VAR_026275
    Natural varianti341 – 3411F → V in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4.
    VAR_026276
    Natural varianti342 – 3421K → N in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4 but PtdIns(3,4,5)P3 phosphatase activity is similar to wild-type.
    VAR_026277
    Natural varianti343 – 3431V → E in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
    VAR_008742
    Natural varianti345 – 3451L → Q in glioblastoma; reduced tumor suppressor activity; loss of phosphatase activity towards Ins(1,3,4,5)P4; reduced ability to inactivate AKT/PKB; retains ability to bind phospholipid membranes. 1 Publication
    VAR_026278
    Natural varianti347 – 3471F → L in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
    VAR_008743
    Natural varianti348 – 3481T → I in endometrial hyperplasia; reduced phosphatase activity towards PtdIns(3,4,5)P3; mildly reduced tumor suppressor activity; reduced ability to inactivate AKT/PKB. 1 Publication
    VAR_026279
    Natural varianti369 – 3691V → G Retains Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 phosphatase activity; retains ability to bind phospholipid membranes.
    VAR_026280
    Natural varianti401 – 4011T → I Retains Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 phosphatase activity; retains ability to bind phospholipid membranes.
    VAR_026281

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MERGGEAAAAAAAAAAAPGR GSESPVTISRAGNAGELVSP LLLPPTRRRRRRHIQGPGPV LNLPSAAAAPPVARAPEAAG GGSRSEDYSSSPHSAAAAAR PLAAEEKQAQSLQPSSSRRS SHYPAAVQSQAAAERGASAT AKSRAISILQKKPRHQQLLP SLSSFFFSHRLPDM in isoform alpha. CuratedVSP_055420
    Alternative sequencei55 – 7016RFLDS…KIYNL → S in isoform 3. 1 PublicationVSP_055421Add
    BLAST
    Alternative sequencei165 – 19026GVTIP…LDYRP → ADPTGGIPDKGIIVIGDGSS MDVIAP in isoform 3. 1 PublicationVSP_055422Add
    BLAST
    Alternative sequencei191 – 403213Missing in isoform 3. 1 PublicationVSP_055423Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U96180 mRNA. Translation: AAB66902.1.
    U92436 mRNA. Translation: AAC51182.1.
    U93051 mRNA. Translation: AAC51183.1.
    AF143315
    , AF143312, AF143313, AF143314 Genomic DNA. Translation: AAD38372.1.
    AF000734
    , AF000726, AF000727, AF000728, AF000729, AF000730, AF000731, AF000732, AF000733 Genomic DNA. Translation: AAC08699.1.
    AF067844 Genomic DNA. Translation: AAD13528.1.
    JF268690 mRNA. Translation: ADZ48535.1.
    CR450306 mRNA. Translation: CAG29302.1.
    AK313581 mRNA. Translation: BAG36351.1.
    DQ073384 Genomic DNA. Translation: AAY57327.1.
    CH471066 Genomic DNA. Translation: EAW50174.1.
    BC005821 mRNA. Translation: AAH05821.1.
    CCDSiCCDS31238.1.
    RefSeqiNP_000305.3. NM_000314.4.
    UniGeneiHs.500466.

    Genome annotation databases

    EnsembliENST00000371953; ENSP00000361021; ENSG00000171862. [P60484-1]
    GeneIDi5728.
    KEGGihsa:5728.
    UCSCiuc001kfb.3. human.

    Polymorphism databases

    DMDMi42560209.

    Keywords - Coding sequence diversityi

    Alternative initiation, Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U96180 mRNA. Translation: AAB66902.1 .
    U92436 mRNA. Translation: AAC51182.1 .
    U93051 mRNA. Translation: AAC51183.1 .
    AF143315
    , AF143312 , AF143313 , AF143314 Genomic DNA. Translation: AAD38372.1 .
    AF000734
    , AF000726 , AF000727 , AF000728 , AF000729 , AF000730 , AF000731 , AF000732 , AF000733 Genomic DNA. Translation: AAC08699.1 .
    AF067844 Genomic DNA. Translation: AAD13528.1 .
    JF268690 mRNA. Translation: ADZ48535.1 .
    CR450306 mRNA. Translation: CAG29302.1 .
    AK313581 mRNA. Translation: BAG36351.1 .
    DQ073384 Genomic DNA. Translation: AAY57327.1 .
    CH471066 Genomic DNA. Translation: EAW50174.1 .
    BC005821 mRNA. Translation: AAH05821.1 .
    CCDSi CCDS31238.1.
    RefSeqi NP_000305.3. NM_000314.4.
    UniGenei Hs.500466.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1D5R X-ray 2.10 A 8-353 [» ]
    2KYL NMR - B 391-403 [» ]
    4O1V X-ray 2.00 B 354-368 [» ]
    ProteinModelPortali P60484.
    SMRi P60484. Positions 14-351.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111700. 90 interactions.
    DIPi DIP-35019N.
    IntActi P60484. 38 interactions.
    MINTi MINT-127351.
    STRINGi 9606.ENSP00000361021.

    Chemistry

    ChEMBLi CHEMBL2052032.

    PTM databases

    PhosphoSitei P60484.

    Polymorphism databases

    DMDMi 42560209.

    Proteomic databases

    MaxQBi P60484.
    PaxDbi P60484.
    PRIDEi P60484.

    Protocols and materials databases

    DNASUi 5728.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000371953 ; ENSP00000361021 ; ENSG00000171862 . [P60484-1 ]
    GeneIDi 5728.
    KEGGi hsa:5728.
    UCSCi uc001kfb.3. human.

    Organism-specific databases

    CTDi 5728.
    GeneCardsi GC10P089613.
    GeneReviewsi PTEN.
    HGNCi HGNC:9588. PTEN.
    HPAi CAB004076.
    HPA031335.
    MIMi 137800. phenotype.
    153480. phenotype.
    158350. phenotype.
    176807. phenotype.
    275355. phenotype.
    276950. phenotype.
    601728. gene.
    605309. phenotype.
    608089. phenotype.
    612242. phenotype.
    613028. phenotype.
    neXtProti NX_P60484.
    Orphaneti 109. Bannayan-Riley-Ruvalcaba syndrome.
    201. Cowden syndrome.
    145. Hereditary breast and ovarian cancer syndrome.
    79076. Juvenile polyposis of infancy.
    65285. Lhermitte-Duclos disease.
    210548. Macrocephaly-autism syndrome.
    744. Proteus syndrome.
    2969. Proteus-like syndrome.
    137608. Segmental outgrowth - lipomatosis - arteriovenous malformation - epidermal nevus.
    67037. Squamous cell carcinoma of head and neck.
    PharmGKBi PA33942.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2453.
    HOGENOMi HOG000008008.
    HOVERGENi HBG000239.
    InParanoidi P60484.
    KOi K01110.
    OMAi KEYLILT.
    OrthoDBi EOG7R2BJ5.
    PhylomeDBi P60484.
    TreeFami TF324513.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS10404-MONOMER.
    Reactomei REACT_121025. Synthesis of PIPs at the plasma membrane.
    REACT_12447. Negative regulation of the PI3K/AKT network.
    REACT_12555. Downstream TCR signaling.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_150312. Synthesis of IP3 and IP4 in the cytosol.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinki P60484.

    Miscellaneous databases

    ChiTaRSi PTEN. human.
    EvolutionaryTracei P60484.
    GeneWikii PTEN_(gene).
    GenomeRNAii 5728.
    NextBioi 22282.
    PMAP-CutDB P60484.
    PROi P60484.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P60484.
    Bgeei P60484.
    CleanExi HS_PTEN.
    HS_TEP1.
    Genevestigatori P60484.

    Family and domain databases

    Gene3Di 3.90.190.10. 1 hit.
    InterProi IPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN.
    IPR000008. C2_dom.
    IPR000340. Dual-sp_phosphatase_cat-dom.
    IPR029021. Prot-tyrosine_phosphatase-like.
    IPR014020. Tensin_C2-dom.
    IPR029023. Tensin_lipid_phosphatase_dom.
    IPR016130. Tyr_Pase_AS.
    [Graphical view ]
    Pfami PF00782. DSPc. 1 hit.
    PF10409. PTEN_C2. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF038025. PTEN. 1 hit.
    SUPFAMi SSF49562. SSF49562. 1 hit.
    SSF52799. SSF52799. 1 hit.
    PROSITEi PS51182. C2_TENSIN. 1 hit.
    PS51181. PPASE_TENSIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta."
      Li D.M., Sun H.
      Cancer Res. 57:2124-2129(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INDUCTION.
      Tissue: Epithelium.
    2. "Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers."
      Steck P.A., Pershouse M.A., Jasser S.A., Lin H., Yung W.K.A., Ligon A.H., Langford L.A., Baumgard M.L., Hattier T., Davis T., Frye C., Hu R., Swedlund B., Teng D.H.-F., Tavtigian S.V.
      Nat. Genet. 15:356-363(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS GLIOMA SER-15; GLU-36; ARG-42; TRP-57 AND THR-319 DEL.
    3. "PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer."
      Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie R., Bigner S.H., Giovanella B.C., Ittmann M., Tycko B., Hibshoosh H., Wigler M.H., Parsons R.
      Science 275:1943-1947(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GLIOBLASTOMA ARG-129 AND PROSTATE CANCER LEU-134.
    4. "The expression profile for the tumour suppressor gene PTEN and associated polymorphic markers."
      Hamilton J.A., Stewart L.M.D., Ajayi L., Gray I.C., Gray N.E., Roberts K.G., Watson G.J., Kaisary A.V., Snary D.
      Br. J. Cancer 82:1671-1676(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. Wang S., Li J., Liaw D., Bose S., Podsypanina K., Parsons R.
      Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    7. "Homo sapiens phosphatase and tensin homolog mRNA splicing variants."
      Yang C.-W., Hsu Y.-F.
      Submitted (JAN-2011) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
    8. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    9. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Spleen.
    10. NIEHS SNPs program
      Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-290.
    11. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    12. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Lung.
    13. "P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase."
      Myers M.P., Stolarov J.P., Eng C., Li J., Wang S.I., Wigler M.H., Parsons R., Tonks N.K.
      Proc. Natl. Acad. Sci. U.S.A. 94:9052-9057(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS GLIOMA TRP-57; ENDOMETRIAL CANCER TYR-123; GLIOBLASTOMA ARG-129; CWS1 ARG-129; PROSTATE CANCER LEU-134; GLIOBLASTOMA ARG-165; BREAST CANCER PRO-167 AND BZ ARG-170.
    14. "The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate."
      Maehama T., Dixon J.E.
      J. Biol. Chem. 273:13375-13378(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY.
    15. Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-130, CHARACTERIZATION OF VARIANTS CWS1 SER-124 AND CWS1 GLU-129.
    16. "Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN."
      Tamura M., Gu J., Matsumoto K., Aota S., Parsons R., Yamada K.M.
      Science 280:1614-1617(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASP-92 AND CYS-124, CHARACTERIZATION OF VARIANT GLU-129.
    17. "The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region."
      Georgescu M.-M., Kirsch K.H., Akagi T., Shishido T., Hanafusa H.
      Proc. Natl. Acad. Sci. U.S.A. 96:10182-10187(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DOMAIN, CHARACTERIZATION OF VARIANTS THR-319 DEL; GLN-345 AND ILE-348.
    18. "Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding."
      Adey N.B., Huang L., Ormonde P.A., Baumgard M.L., Pero R., Byreddy D.V., Tavtigian S.V., Bartel P.L.
      Cancer Res. 60:35-37(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DLG1 AND MAST2, PHOSPHORYLATION AT THR-401.
    19. "Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase."
      Wu Y., Dowbenko D., Spencer S., Laura R., Lee J., Gu Q., Lasky L.A.
      J. Biol. Chem. 275:21477-21485(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAGI3.
    20. "Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2."
      Wu X., Hepner K., Castelino-Prabhu S., Do D., Kaye M.B., Yuan X.-J., Wood J., Ross C., Sawyers C.L., Whang Y.E.
      Proc. Natl. Acad. Sci. U.S.A. 97:4233-4238(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AIP1.
    21. "The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation."
      Torres J., Pulido R.
      J. Biol. Chem. 276:993-998(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-370; SER-380; THR-382; THR-383 AND SER-385.
    22. "Phosphorylation of the PTEN tail acts as an inhibitory switch by preventing its recruitment into a protein complex."
      Vazquez F., Grossman S.R., Takahashi Y., Rokas M.V., Nakamura N., Sellers W.R.
      J. Biol. Chem. 276:48627-48630(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH AIP1.
    23. "Direct identification of PTEN phosphorylation sites."
      Miller S., Lou D., Seldin D., Lane W., Neel B.
      FEBS Lett. 528:145-153(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-366; SER-370 AND SER-385.
    24. "LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes."
      Mehenni H., Lin-Marq N., Buchet-Poyau K., Reymond A., Collart M.A., Picard D., Antonarakis S.E.
      Hum. Mol. Genet. 14:2209-2219(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH STK11, SUBCELLULAR LOCATION, PHOSPHORYLATION BY STK11.
    25. "Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases."
      Valiente M., Andres-Pons A., Gomar B., Torres J., Gil A., Tapparel C., Antonarakis S.E., Pulido R.
      J. Biol. Chem. 280:28936-28943(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAGI2; MAGI3; MAST1; MAST2 AND MAST3, MUTAGENESIS OF VAL-403, PHOSPHORYLATION.
    26. Cited for: INTERACTION WITH NEDD4.
    27. "The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network."
      Song M.S., Salmena L., Carracedo A., Egia A., Lo-Coco F., Teruya-Feldstein J., Pandolfi P.P.
      Nature 455:813-817(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH USP7, UBIQUITINATION AT LYS-13 AND LYS-289, DEUBIQUITINATION BY USP7, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-13 AND LYS-289.
    28. "Rak functions as a tumor suppressor by regulating PTEN protein stability and function."
      Yim E.-K., Peng G., Dai H., Hu R., Li K., Lu Y., Mills G.B., Meric-Bernstam F., Hennessy B.T., Craven R.J., Lin S.-Y.
      Cancer Cell 15:304-314(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FRK, PHOSPHORYLATION AT TYR-336, MUTAGENESIS OF TYR-336.
    29. "X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization."
      Van Themsche C., Leblanc V., Parent S., Asselin E.
      J. Biol. Chem. 284:20462-20466(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION BY XIAP/BIRC4, SUBCELLULAR LOCATION, INTERACTION WITH XIAP/BIRC4.
    30. "Regulation of PTEN stability and activity by Plk3."
      Xu D., Yao Y., Jiang X., Lu L., Dai W.
      J. Biol. Chem. 285:39935-39942(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-366 AND SER-370, MUTAGENESIS OF THR-366 AND SER-370.
    31. "Regulation of PTEN/Akt and MAP kinase signaling pathways by the ubiquitin ligase activators Ndfip1 and Ndfip2."
      Mund T., Pelham H.R.
      Proc. Natl. Acad. Sci. U.S.A. 107:11429-11434(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NDFIP1 AND NDFIP2.
    32. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    33. "IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling."
      Stohr N., Kohn M., Lederer M., Glass M., Reinke C., Singer R.H., Huttelmaier S.
      Genes Dev. 26:176-189(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CELL MIGRATION.
    34. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    35. Cited for: ALTERNATIVE INITIATION (ISOFORM ALPHA), CTG START CODON, FUNCTION (ISOFORM ALPHA), SUBCELLULAR LOCATION (ISOFORM ALPHA).
    36. "PTENalpha, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism."
      Liang H., He S., Yang J., Jia X., Wang P., Chen X., Zhang Z., Zou X., McNutt M.A., Shen W.H., Yin Y.
      Cell Metab. 19:836-848(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE INITIATION (ISOFORM ALPHA), CTG START CODON, SUBCELLULAR LOCATION (ISOFORM ALPHA), MUTAGENESIS OF MET-1.
    37. "Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association."
      Lee J.-O., Yang H., Georgescu M.-M., Di Cristofano A., Maehama T., Shi Y., Dixon J.E., Pandolfi P., Pavletich N.P.
      Cell 99:323-334(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 8-353 IN COMPLEX WITH L(+)-TARTRATE, SUBUNIT, DOMAIN, MUTAGENESIS OF ASP-92; HIS-93; LYS-125; LYS-128; THR-167; GLN-171; 263-LYS--ALA-269 AND 327-LYS--ALA-335.
    38. "The role of MMAC1 mutations in early-onset breast cancer: causative in association with Cowden syndrome and excluded in BRCA1-negative cases."
      Tsou H.C., Teng D.H.-F., Ping X.L., Brancolini V., Davis T., Hu R., Xie X.X., Gruener A.C., Schrager C.A., Christiano A.M., Eng C., Steck P., Ott J., Tavtigian S.V., Peacocke M.
      Am. J. Hum. Genet. 61:1036-1043(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CWS1 ASN-137 INS.
    39. "Inherited mutations in PTEN that are associated with breast cancer, Cowden disease, and juvenile polyposis."
      Lynch E.D., Ostermeyer E.A., Lee M.K., Arena J.F., Ji H., Dann J., Swisshelm K., Suchard D., MacLeod P.M., Kvinnsland S., Gjertsen B.T., Heimdal K., Lubs H., Moeller P., King M.-C.
      Am. J. Hum. Genet. 61:1254-1260(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CWS1 GLU-343 AND LEU-347.
    40. "Somatic mutations of PTEN in glioblastoma multiforme."
      Wang S.I., Puc J., Li J., Bruce J.N., Cairns P., Sidransky D., Parsons R.
      Cancer Res. 57:4183-4186(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS GLIOBLASTOMA TYR-107; PRO-121; ARG-129; ARG-165 AND GLN-345.
    41. Cited for: VARIANTS CWS1 ARG-123 AND ARG-124.
    42. "Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome."
      Liaw D., Marsh D.J., Li J., Dahia P.L.M., Wang S.I., Zheng Z., Bose S., Call K.M., Tsou H.C., Peacocke M., Eng C., Parsons R.
      Nat. Genet. 16:64-67(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CWS1 GLU-129.
    43. "Germline mutations in PTEN are present in Bannayan-Zonana syndrome."
      Marsh D.J., Dahia P.L.M., Zheng Z., Liaw D., Parsons R., Gorlin R.J., Eng C.
      Nat. Genet. 16:333-334(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT BRRS ARG-170.
    44. "Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias."
      Maxwell G.L., Risinger J.I., Gumbs C., Shaw H., Bentley R.C., Barrett J.C., Berchuck A., Futreal P.A.
      Cancer Res. 58:2500-2503(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS ENDOMETRIAL HYPERPLASIA ARG-36; LEU-130; CYS-173; ALA-191 AND ILE-348.
    45. "Mutational abrogation of the PTEN/MMAC1 gene in gastrointestinal polyps in patients with Cowden disease."
      Chi S.-G., Kim H.-J., Park B.-J., Min H.-J., Park J.-H., Kim Y.-W., Dong S.-H., Kim B.-H., Lee J.-I., Chang Y.-W., Chang R., Kim W.-K., Yang M.-H.
      Gastroenterology 115:1084-1089(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CWS1 GLU-289.
    46. "The genetic basis of Cowden's syndrome: three novel mutations in PTEN/MMAC1/TEP1."
      Tsou H.C., Ping X.L., Xie X.X., Gruener A.C., Zhang H., Nini R., Swisshelm K., Sybert V., Diamond T.M., Sutphen R., Peacocke M.
      Hum. Genet. 102:467-473(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CWS1 HIS-68 AND PRO-112.
    47. Cited for: VARIANTS CWS1 AND BRRS.
    48. "Novel mutation of the PTEN gene in an Italian Cowden's disease kindred."
      Scala S., Bruni P., Lo Muzio L., Mignogna M., Viglietto G., Fusco A.
      Int. J. Oncol. 13:665-668(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CWS1 TYR-136.
    49. Cited for: VARIANT CWS1 PRO-70.
    50. Cited for: VARIANT CWS1 ARG-35.
    51. "Variant manifestation of Cowden disease in Japan: hamartomatous polyposis of the digestive tract with mutation of the PTEN gene."
      Kurose K., Araki T., Matsunaka T., Takada Y., Emi M.
      Am. J. Hum. Genet. 64:308-310(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CWS1 GLN-130.
    52. "Severe Lhermitte-Duclos disease with unique germline mutation of PTEN."
      Sutphen R., Diamond T.M., Minton S.E., Peacocke M., Tsou H.C., Root A.W.
      Am. J. Med. Genet. 82:290-293(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CWS1/LDD PRO-112.
    53. "Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations."
      Nelen M.R., Kremer H., Konings I.B.M., Schoute F., van Essen A.J., Koch R., Woods C.G., Fryns J.-P., Hamel B.C.J., Hoefsloot L.H., Peeters E.A.J., Padberg G.W.
      Eur. J. Hum. Genet. 7:267-273(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CWS1 ILE-33 DEL; ARG-123; ARG-124 AND GLU-165.
    54. Cited for: VARIANTS BRRS ASP-34; HIS-68; TYR-105; VAL-135; ARG-170 AND LEU-246.
    55. "Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay."
      Han S.-Y., Kato H., Kato S., Suzuki T., Shibata H., Ishii S., Shiiba K., Matsuno S., Kanamaru R., Ishioka C.
      Cancer Res. 60:3147-3151(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANTS ASN-10; CYS-16; GLU-20; SER-27; ARG-61; HIS-68; CWS1 TYR-71; CWS1 TYR-93; BRRS PHE-105; BRRS TYR-107; PRO-112; ARG-112; PRO-121; ARG-124; ARG-129; GLU-129; GLY-130; CWS1 LEU-130; GLN-130; ILE-133; LEU-134; TYR-136; CYS-155; ARG-165; ASN-170; ARG-170; CYS-173; HIS-173; PRO-173; ASN-174; PHE-227; CYS-251; GLU-289; GLY-331; VAL-341; ASN-342; GLU-343; GLN-345; LEU-347; GLY-369 AND ILE-401.
    56. "Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers."
      De Vivo I., Gertig D.M., Nagase S., Hankinson S.E., O'Brien R., Speizer F.E., Parsons R., Hunter D.J.
      J. Med. Genet. 37:336-341(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MULTIPLE CANCERS LEU-119 AND LEU-158.
    57. "Identification of PTEN mutations in metastatic melanoma specimens."
      Celebi J.T., Shendrik I., Silvers D.N., Peacocke M.
      J. Med. Genet. 37:653-657(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MALIGNANT MELANOMA ASN-19 AND ILE-217.
    58. "PTEN coordinates G1 arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model."
      Weng L.-P., Brown J.L., Eng C.
      Hum. Mol. Genet. 10:599-604(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANTS CWS1 SER-124 AND GLU-129.
    59. "A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association."
      Reardon W., Zhou X.-P., Eng C.
      J. Med. Genet. 38:820-823(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT VATER ASP-61.
    60. "Rapid mutation scanning of genes associated with familial cancer syndromes using denaturing high-performance liquid chromatography."
      Marsh D.J., Theodosopoulos G., Howell V., Richardson A.-L., Benn D.E., Proos A.L., Eng C., Robinson B.G.
      Neoplasia 3:236-244(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CWS1 GLY-47, VARIANTS BRRS ASP-34; HIS-68; TYR-105; VAL-135 AND ARG-170.
    61. Cited for: CHARACTERIZATION OF VARIANT GLN-234.
    62. "Detection of new PTEN/MMAC1 mutations in head and neck squamous cell carcinomas with loss of chromosome 10."
      Poetsch M., Lorenz G., Kleist B.
      Cancer Genet. Cytogenet. 132:20-24(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HNSCC GLY-121.
    63. Cited for: DISCUSSION OF PTEN INVOLVEMENT IN PROTEUS SYNDROME.
    64. "Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations."
      Butler M.G., Dasouki M.J., Zhou X.-P., Talebizadeh Z., Brown M., Takahashi T.N., Miles J.H., Wang C.H., Stratton R., Pilarski R., Eng C.
      J. Med. Genet. 42:318-321(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MCEPHAS ARG-93; SER-241 AND GLY-252.
    65. Cited for: INVOLVEMENT IN CHROMOSOME 10Q23 DELETION SYNDROME.
    66. "A germline PTEN mutation with manifestations of prenatal onset and verrucous epidermal nevus."
      Tekin M., Hismi B.O., Fitoz S., Yalcinkaya F., Ekim M., Kansu A., Ertem M., Deda G., Tutar E., Arsan S., Zhou X.-P., Pilarski R., Eng C., Akar N.
      Am. J. Med. Genet. A 140:1472-1475(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT VAL-132.

    Entry informationi

    Entry nameiPTEN_HUMAN
    AccessioniPrimary (citable) accession number: P60484
    Secondary accession number(s): B2R904
    , F2YHV0, O00633, O02679, Q6ICT7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 16, 2004
    Last sequence update: February 16, 2004
    Last modified: October 1, 2014
    This is version 137 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3