You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP01570
Secondary Accession Numbers
  • 6866
Name Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Synonyms
  1. Mutated in multiple advanced cancers 1
  2. Phosphatase and tensin homolog
Gene Name PTEN
Protein Type Unknown
Biological Properties
General Function Involved in magnesium ion binding
Specific 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.
Pathways
  • Endometrial cancer
  • Focal adhesion
  • Glioma
  • Hepatitis B
  • Inositol phosphate metabolism
  • Joubert syndrome
  • Melanoma
  • mTOR signaling pathway
  • p53 signaling pathway
  • Phosphatidylinositol Phosphate Metabolism
  • Phosphatidylinositol signaling system
  • PI3K-Akt signaling pathway
  • Prostate cancer
  • Small cell lung cancer
  • Tight junction
Reactions
Phosphatidylinositol 3,4,5-trisphosphate + Water → phosphatidylinositol 4,5-bisphosphate + Phosphoric acid details
A phosphoprotein + Water → a protein + Phosphoric acid details
Protein tyrosine phosphate + Water → protein tyrosine + Phosphoric acid details
Phosphatidylinositol-3,4,5-trisphosphate + Water → 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate + Phosphoric acid details
GO Classification
Biological Process
learning or memory
negative regulation of organ growth
phosphatidylinositol biosynthetic process
apoptotic process
positive regulation of cell proliferation
negative regulation of apoptotic process
negative regulation of protein kinase B signaling cascade
negative regulation of excitatory postsynaptic membrane potential
activation of mitotic anaphase-promoting complex activity
central nervous system myelin maintenance
central nervous system neuron axonogenesis
dendritic spine morphogenesis
dentate gyrus development
cell migration
forebrain morphogenesis
locomotor rhythm
long-term synaptic potentiation
male mating behavior
cell proliferation
negative regulation of axonogenesis
negative regulation of cell size
negative regulation of cyclin-dependent protein kinase activity involved in G1/S
negative regulation of dendritic spine morphogenesis
negative regulation of epithelial cell proliferation
negative regulation of focal adhesion assembly
negative regulation of myelination
protein stabilization
negative regulation of phosphatidylinositol 3-kinase cascade
negative regulation of ribosome biogenesis
negative regulation of synaptic vesicle clustering
neuron-neuron synaptic transmission
positive regulation of excitatory postsynaptic membrane potential
positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
postsynaptic density assembly
prepulse inhibition
presynaptic membrane assembly
regulation of B cell apoptotic process
prostate gland growth
regulation of myeloid cell apoptotic process
rhythmic synaptic transmission
synapse maturation
phosphatidylinositol dephosphorylation
maternal behavior
protein kinase B signaling cascade
heart development
social behavior
endothelial cell migration
T cell receptor signaling pathway
angiogenesis
inositol phosphate dephosphorylation
positive regulation of sequence-specific DNA binding transcription factor activity
induction of apoptosis
negative regulation of G1/S transition of mitotic cell cycle
canonical Wnt receptor signaling pathway
cardiac muscle tissue development
negative regulation of cell migration
phosphatidylinositol-mediated signaling
multicellular organismal response to stress
negative regulation of cell proliferation
negative regulation of cell aging
epidermal growth factor receptor signaling pathway
fibroblast growth factor receptor signaling pathway
nerve growth factor receptor signaling pathway
Cellular Component
cytosol
myelin sheath adaxonal region
Schmidt-Lanterman incisure
nucleus
internal side of plasma membrane
PML body
neuron projection
Function
phosphoprotein phosphatase activity
protein tyrosine phosphatase activity
ion binding
cation binding
metal ion binding
hydrolase activity, acting on ester bonds
binding
catalytic activity
hydrolase activity
phosphoric ester hydrolase activity
phosphatase activity
magnesium ion binding
protein binding
inositol or phosphatidylinositol phosphatase activity
phosphatidylinositol bisphosphate phosphatase activity
phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
protein domain specific binding
pdz domain binding
phosphatidylinositol trisphosphate phosphatase activity
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
protein tyrosine/serine/threonine phosphatase activity
Molecular Function
protein tyrosine/serine/threonine phosphatase activity
protein serine/threonine phosphatase activity
magnesium ion binding
phosphatidylinositol-3-phosphatase activity
inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
lipid binding
protein tyrosine phosphatase activity
Process
phosphorus metabolic process
phosphate metabolic process
dephosphorylation
protein amino acid dephosphorylation
metabolic process
regulation of cell proliferation
posttranscriptional regulation of gene expression
biological regulation
regulation of biological process
regulation of metabolic process
regulation of macromolecule metabolic process
regulation of gene expression
cellular metabolic process
small molecule metabolic process
alcohol metabolic process
regulation of cellular process
negative regulation of signal transduction
negative regulation of intracellular protein kinase cascade
negative regulation of protein kinase b signaling cascade
polyol metabolic process
regulation of cell adhesion
regulation of cell-substrate adhesion
regulation of cell-matrix adhesion
negative regulation of cell-matrix adhesion
negative regulation of focal adhesion assembly
phosphoinositide dephosphorylation
inositol phosphate dephosphorylation
regulation of protein stability
regulation of locomotion
regulation of cell motility
regulation of cell migration
negative regulation of cell migration
negative regulation of cell proliferation
regulation of cell communication
regulation of signal transduction
organophosphate metabolic process
phospholipid metabolic process
inositol metabolic process
glycerophospholipid metabolic process
phosphoinositide metabolic process
Cellular Location
  1. Nucleus
  2. Nucleus
  3. Cytoplasm
  4. PML body
Gene Properties
Chromosome Location 10
Locus 10q23.3
SNPs PTEN
Gene Sequence
>1212 bp
ATGACAGCCATCATCAAAGAGATCGTTAGCAGAAACAAAAGGAGATATCAAGAGGATGGA
TTCGACTTAGACTTGACCTATATTTATCCAAACATTATTGCTATGGGATTTCCTGCAGAA
AGACTTGAAGGCGTATACAGGAACAATATTGATGATGTAGTAAGGTTTTTGGATTCAAAG
CATAAAAACCATTACAAGATATACAATCTTTGTGCTGAAAGACATTATGACACCGCCAAA
TTTAATTGCAGAGTTGCACAATATCCTTTTGAAGACCATAACCCACCACAGCTAGAACTT
ATCAAACCCTTTTGTGAAGATCTTGACCAATGGCTAAGTGAAGATGACAATCATGTTGCA
GCAATTCACTGTAAAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCATATTTATTA
CATCGGGGCAAATTTTTAAAGGCACAAGAGGCCCTAGATTTCTATGGGGAAGTAAGGACC
AGAGACAAAAAGGGAGTAACTATTCCCAGTCAGAGGCGCTATGTGTATTATTATAGCTAC
CTGTTAAAGAATCATCTGGATTATAGACCAGTGGCACTGTTGTTTCACAAGATGATGTTT
GAAACTATTCCAATGTTCAGTGGCGGAACTTGCAATCCTCAGTTTGTGGTCTGCCAGCTA
AAGGTGAAGATATATTCCTCCAATTCAGGACCCACACGACGGGAAGACAAGTTCATGTAC
TTTGAGTTCCCTCAGCCGTTACCTGTGTGTGGTGATATCAAAGTAGAGTTCTTCCACAAA
CAGAACAAGATGCTAAAAAAGGACAAAATGTTTCACTTTTGGGTAAATACATTCTTCATA
CCAGGACCAGAGGAAACCTCAGAAAAAGTAGAAAATGGAAGTCTATGTGATCAAGAAATC
GATAGCATTTGCAGTATAGAGCGTGCAGATAATGACAAGGAATATCTAGTACTTACTTTA
ACAAAAAATGATCTTGACAAAGCAAATAAAGACAAAGCCAACCGATACTTTTCTCCAAAT
TTTAAGGTGAAGCTGTACTTCACAAAAACAGTAGAGGAGCCGTCAAATCCAGAGGCTAGC
AGTTCAACTTCTGTAACACCAGATGTTAGTGACAATGAACCTGATCATTATAGATATTCT
GACACCACTGACTCTGATCCAGAGAATGAACCTTTTGATGAAGATCAGCATACACAAATT
ACAAAAGTCTGA
Protein Properties
Number of Residues 403
Molecular Weight 47165.92
Theoretical pI 6.371
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSK
HKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVA
AIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY
LLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMY
FEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEI
DSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEAS
SSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P60484
UniProtKB/Swiss-Prot Entry Name PTEN_HUMAN
PDB IDs
GenBank Gene ID U96180
GeneCard ID PTEN
GenAtlas ID PTEN
HGNC ID HGNC:9588
References
General References
  1. 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 TO, 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Mund T, Pelham HR: Regulation of PTEN/Akt and MAP kinase signaling pathways by the ubiquitin ligase activators Ndfip1 and Ndfip2. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11429-34. doi: 10.1073/pnas.0911714107. Epub 2010 Jun 7. [PubMed:20534535 ]
  5. Yim EK, Peng G, Dai H, Hu R, Li K, Lu Y, Mills GB, Meric-Bernstam F, Hennessy BT, Craven RJ, Lin SY: Rak functions as a tumor suppressor by regulating PTEN protein stability and function. Cancer Cell. 2009 Apr 7;15(4):304-14. doi: 10.1016/j.ccr.2009.02.012. [PubMed:19345329 ]
  6. Li DM, Sun H: TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res. 1997 Jun 1;57(11):2124-9. [PubMed:9187108 ]
  7. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997 Apr;15(4):356-62. [PubMed:9090379 ]
  8. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997 Mar 28;275(5308):1943-7. [PubMed:9072974 ]
  9. Hamilton JA, Stewart LM, Ajayi L, Gray IC, Gray NE, Roberts KG, Watson GJ, Kaisary AV, Snary D: The expression profile for the tumour suppressor gene PTEN and associated polymorphic markers. Br J Cancer. 2000 May;82(10):1671-6. [PubMed:10817502 ]
  10. Myers MP, Stolarov JP, Eng C, Li J, Wang SI, Wigler MH, Parsons R, Tonks NK: P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9052-7. [PubMed:9256433 ]
  11. Maehama T, Dixon JE: The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1998 May 29;273(22):13375-8. [PubMed:9593664 ]
  12. Myers MP, Pass I, Batty IH, Van der Kaay J, Stolarov JP, Hemmings BA, Wigler MH, Downes CP, Tonks NK: The lipid phosphatase activity of PTEN is critical for its tumor supressor function. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13513-8. [PubMed:9811831 ]
  13. Tamura M, Gu J, Matsumoto K, Aota S, Parsons R, Yamada KM: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science. 1998 Jun 5;280(5369):1614-7. [PubMed:9616126 ]
  14. Georgescu MM, Kirsch KH, Akagi T, Shishido T, Hanafusa H: The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10182-7. [PubMed:10468583 ]
  15. Adey NB, Huang L, Ormonde PA, Baumgard ML, Pero R, Byreddy DV, Tavtigian SV, Bartel PL: Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding. Cancer Res. 2000 Jan 1;60(1):35-7. [PubMed:10646847 ]
  16. Wu Y, Dowbenko D, Spencer S, Laura R, Lee J, Gu Q, Lasky LA: Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase. J Biol Chem. 2000 Jul 14;275(28):21477-85. [PubMed:10748157 ]
  17. Wu X, Hepner K, Castelino-Prabhu S, Do D, Kaye MB, Yuan XJ, Wood J, Ross C, Sawyers CL, Whang YE: Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4233-8. [PubMed:10760291 ]
  18. Vazquez F, Grossman SR, Takahashi Y, Rokas MV, Nakamura N, Sellers WR: Phosphorylation of the PTEN tail acts as an inhibitory switch by preventing its recruitment into a protein complex. J Biol Chem. 2001 Dec 28;276(52):48627-30. Epub 2001 Nov 13. [PubMed:11707428 ]
  19. Miller SJ, Lou DY, Seldin DC, Lane WS, Neel BG: Direct identification of PTEN phosphorylation sites. FEBS Lett. 2002 Sep 25;528(1-3):145-53. [PubMed:12297295 ]
  20. Valiente M, Andres-Pons A, Gomar B, Torres J, Gil A, Tapparel C, Antonarakis SE, Pulido R: Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases. J Biol Chem. 2005 Aug 12;280(32):28936-43. Epub 2005 Jun 10. [PubMed:15951562 ]
  21. Wang X, Trotman LC, Koppie T, Alimonti A, Chen Z, Gao Z, Wang J, Erdjument-Bromage H, Tempst P, Cordon-Cardo C, Pandolfi PP, Jiang X: NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell. 2007 Jan 12;128(1):129-39. [PubMed:17218260 ]
  22. Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J, Pandolfi PP: The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature. 2008 Oct 9;455(7214):813-7. doi: 10.1038/nature07290. Epub 2008 Aug 20. [PubMed:18716620 ]
  23. Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich NP: Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell. 1999 Oct 29;99(3):323-34. [PubMed:10555148 ]
  24. Tsou HC, Teng DH, Ping XL, Brancolini V, Davis T, Hu R, Xie XX, Gruener AC, Schrager CA, Christiano AM, Eng C, Steck P, Ott J, Tavtigian SV, Peacocke M: The role of MMAC1 mutations in early-onset breast cancer: causative in association with Cowden syndrome and excluded in BRCA1-negative cases. Am J Hum Genet. 1997 Nov;61(5):1036-43. [PubMed:9345101 ]
  25. Lynch ED, Ostermeyer EA, Lee MK, Arena JF, Ji H, Dann J, Swisshelm K, Suchard D, MacLeod PM, Kvinnsland S, Gjertsen BT, Heimdal K, Lubs H, Moller P, King MC: Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis. Am J Hum Genet. 1997 Dec;61(6):1254-60. [PubMed:9399897 ]
  26. Wang SI, Puc J, Li J, Bruce JN, Cairns P, Sidransky D, Parsons R: Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res. 1997 Oct 1;57(19):4183-6. [PubMed:9331071 ]
  27. Nelen MR, van Staveren WC, Peeters EA, Hassel MB, Gorlin RJ, Hamm H, Lindboe CF, Fryns JP, Sijmons RH, Woods DG, Mariman EC, Padberg GW, Kremer H: Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Hum Mol Genet. 1997 Aug;6(8):1383-7. [PubMed:9259288 ]
  28. Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, Bose S, Call KM, Tsou HC, Peacocke M, Eng C, Parsons R: Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet. 1997 May;16(1):64-7. [PubMed:9140396 ]
  29. Marsh DJ, Dahia PL, Zheng Z, Liaw D, Parsons R, Gorlin RJ, Eng C: Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Nat Genet. 1997 Aug;16(4):333-4. [PubMed:9241266 ]
  30. Maxwell GL, Risinger JI, Gumbs C, Shaw H, Bentley RC, Barrett JC, Berchuck A, Futreal PA: Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias. Cancer Res. 1998 Jun 15;58(12):2500-3. [PubMed:9635567 ]
  31. Chi SG, Kim HJ, Park BJ, Min HJ, Park JH, Kim YW, Dong SH, Kim BH, Lee JI, Chang YW, Chang R, Kim WK, Yang MH: Mutational abrogation of the PTEN/MMAC1 gene in gastrointestinal polyps in patients with Cowden disease. Gastroenterology. 1998 Nov;115(5):1084-9. [PubMed:9797362 ]
  32. Tsou HC, Ping XL, Xie XX, Gruener AC, Zhang H, Nini R, Swisshelm K, Sybert V, Diamond TM, Sutphen R, Peacocke M: The genetic basis of Cowden's syndrome: three novel mutations in PTEN/MMAC1/TEP1. Hum Genet. 1998 Apr;102(4):467-73. [PubMed:9600246 ]
  33. Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, Liaw D, Caron S, Duboue B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, Huson S, Lacombe D, Eng C, et al.: Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet. 1998 Mar;7(3):507-15. [PubMed:9467011 ]
  34. Scala S, Bruni P, Lo Muzio L, Mignogna M, Viglietto G, Fusco A: Novel mutation of the PTEN gene in an Italian Cowden's disease kindred. Int J Oncol. 1998 Oct;13(4):665-8. [PubMed:9735393 ]
  35. Marsh DJ, Dahia PL, Caron S, Kum JB, Frayling IM, Tomlinson IP, Hughes KS, Eeles RA, Hodgson SV, Murday VA, Houlston R, Eng C: Germline PTEN mutations in Cowden syndrome-like families. J Med Genet. 1998 Nov;35(11):881-5. [PubMed:9832031 ]
  36. Olschwang S, Serova-Sinilnikova OM, Lenoir GM, Thomas G: PTEN germ-line mutations in juvenile polyposis coli. Nat Genet. 1998 Jan;18(1):12-4. [PubMed:9425889 ]
  37. Kurose K, Araki T, Matsunaka T, Takada Y, Emi M: Variant manifestation of Cowden disease in Japan: hamartomatous polyposis of the digestive tract with mutation of the PTEN gene. Am J Hum Genet. 1999 Jan;64(1):308-10. [PubMed:9915974 ]
  38. Sutphen R, Diamond TM, Minton SE, Peacocke M, Tsou HC, Root AW: Severe Lhermitte-Duclos disease with unique germline mutation of PTEN. Am J Med Genet. 1999 Feb 12;82(4):290-3. [PubMed:10051160 ]
  39. Nelen MR, Kremer H, Konings IB, Schoute F, van Essen AJ, Koch R, Woods CG, Fryns JP, Hamel B, Hoefsloot LH, Peeters EA, Padberg GW: Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. Eur J Hum Genet. 1999 Apr;7(3):267-73. [PubMed:10234502 ]
  40. Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, Bodurtha J, Crowe C, Curtis MA, Dasouki M, Dunn T, Feit H, Geraghty MT, Graham JM Jr, Hodgson SV, Hunter A, Korf BR, Manchester D, Miesfeldt S, Murday VA, Nathanson KL, Parisi M, Pober B, Romano C, Eng C, et al.: PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Hum Mol Genet. 1999 Aug;8(8):1461-72. [PubMed:10400993 ]
  41. Han SY, Kato H, Kato S, Suzuki T, Shibata H, Ishii S, Shiiba K, Matsuno S, Kanamaru R, Ishioka C: Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay. Cancer Res. 2000 Jun 15;60(12):3147-51. [PubMed:10866302 ]
  42. De Vivo I, Gertig DM, Nagase S, Hankinson SE, O'Brien R, Speizer FE, Parsons R, Hunter DJ: Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers. J Med Genet. 2000 May;37(5):336-41. [PubMed:10807691 ]
  43. Celebi JT, Shendrik I, Silvers DN, Peacocke M: Identification of PTEN mutations in metastatic melanoma specimens. J Med Genet. 2000 Sep;37(9):653-7. [PubMed:10978354 ]
  44. Weng LP, Brown JL, Eng C: PTEN coordinates G(1) 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. Hum Mol Genet. 2001 Mar 15;10(6):599-604. [PubMed:11230179 ]
  45. Reardon W, Zhou XP, Eng C: A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association. J Med Genet. 2001 Dec;38(12):820-3. [PubMed:11748304 ]
  46. Marsh DJ, Theodosopoulos G, Howell V, Richardson AL, Benn DE, Proos AL, Eng C, Robinson BG: Rapid mutation scanning of genes associated with familial cancer syndromes using denaturing high-performance liquid chromatography. Neoplasia. 2001 May-Jun;3(3):236-44. [PubMed:11494117 ]
  47. Staal FJ, van der Luijt RB, Baert MR, van Drunen J, van Bakel H, Peters E, de Valk I, van Amstel HK, Taphoorn MJ, Jansen GH, van Veelen CW, Burgering B, Staal GE: A novel germline mutation of PTEN associated with brain tumours of multiple lineages. Br J Cancer. 2002 May 20;86(10):1586-91. [PubMed:12085208 ]
  48. Poetsch M, Lorenz G, Kleist B: Detection of new PTEN/MMAC1 mutations in head and neck squamous cell carcinomas with loss of chromosome 10. Cancer Genet Cytogenet. 2002 Jan 1;132(1):20-4. [PubMed:11801303 ]
  49. Smith JM, Kirk EP, Theodosopoulos G, Marshall GM, Walker J, Rogers M, Field M, Brereton JJ, Marsh DJ: Germline mutation of the tumour suppressor PTEN in Proteus syndrome. J Med Genet. 2002 Dec;39(12):937-40. [PubMed:12471211 ]
  50. Butler MG, Dasouki MJ, Zhou XP, Talebizadeh Z, Brown M, Takahashi TN, Miles JH, Wang CH, Stratton R, Pilarski R, Eng C: Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet. 2005 Apr;42(4):318-21. [PubMed:15805158 ]
  51. Balciuniene J, Feng N, Iyadurai K, Hirsch B, Charnas L, Bill BR, Easterday MC, Staaf J, Oseth L, Czapansky-Beilman D, Avramopoulos D, Thomas GH, Borg A, Valle D, Schimmenti LA, Selleck SB: Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with cognitive and behavioral abnormalities. Am J Hum Genet. 2007 May;80(5):938-47. Epub 2007 Mar 20. [PubMed:17436248 ]
  52. Tekin M, Hismi BO, Fitoz S, Yalcinkaya F, Ekim M, Kansu A, Ertem M, Deda G, Tutar E, Arsan S, Zhou XP, Pilarski R, Eng C, Akar N: A germline PTEN mutation with manifestations of prenatal onset and verrucous epidermal nevus. Am J Med Genet A. 2006 Jul 1;140(13):1472-5. [PubMed:16752378 ]