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NamePhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Synonyms
  • 3.1.3.16
  • MMAC1
  • Mutated in multiple advanced cancers 1
  • Phosphatase and tensin homolog
  • TEP1
Gene NamePTEN
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009278|Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSK
HKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVA
AIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY
LLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMY
FEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEI
DSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEAS
SSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV
Number of residues403
Molecular Weight47165.92
Theoretical pINot Available
GO Classification
Functions
  • phosphoprotein phosphatase activity
  • identical protein binding
  • protein tyrosine phosphatase activity
  • magnesium ion binding
  • anaphase-promoting complex binding
  • enzyme binding
  • protein tyrosine/serine/threonine phosphatase activity
  • inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
  • protein serine/threonine phosphatase activity
  • phosphatidylinositol-3-phosphatase activity
  • phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
  • phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
  • PDZ domain binding
  • lipid binding
Processes
  • regulation of myeloid cell apoptotic process
  • canonical Wnt signaling pathway
  • long term synaptic depression
  • learning or memory
  • postsynaptic density assembly
  • regulation of neuron projection development
  • Fc-epsilon receptor signaling pathway
  • regulation of B cell apoptotic process
  • maternal behavior
  • long-term synaptic potentiation
  • regulation of cellular component size
  • brain morphogenesis
  • negative regulation of G1/S transition of mitotic cell cycle
  • positive regulation of sequence-specific DNA binding transcription factor activity
  • social behavior
  • negative regulation of focal adhesion assembly
  • presynaptic membrane assembly
  • response to estradiol
  • prostate gland growth
  • negative regulation of excitatory postsynaptic potential
  • protein stabilization
  • phosphatidylinositol-mediated signaling
  • prepulse inhibition
  • regulation of axon regeneration
  • apoptotic process
  • phosphatidylinositol biosynthetic process
  • positive regulation of ERK1 and ERK2 cascade
  • multicellular organismal response to stress
  • synapse maturation
  • fibroblast growth factor receptor signaling pathway
  • response to ATP
  • negative regulation of phosphatidylinositol 3-kinase signaling
  • cell proliferation
  • cellular response to hypoxia
  • negative regulation of organ growth
  • heart development
  • response to glucose
  • central nervous system neuron axonogenesis
  • memory
  • negative regulation of epithelial cell proliferation
  • negative regulation of cell aging
  • negative regulation of apoptotic process
  • response to arsenic-containing substance
  • forebrain morphogenesis
  • negative regulation of protein kinase B signaling
  • gene expression
  • negative regulation of cell migration
  • male mating behavior
  • activation of APC-Cdc20 complex activity
  • negative regulation of cell proliferation
  • regulation of synaptic transmission, GABAergic
  • small molecule metabolic process
  • response to nutrient
  • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
  • neurotrophin TRK receptor signaling pathway
  • positive regulation of cell proliferation
  • cardiac muscle tissue development
  • negative regulation of cell size
  • transcription initiation from RNA polymerase II promoter
  • phospholipid metabolic process
  • regulation of protein stability
  • locomotory behavior
  • endothelial cell migration
  • neuron-neuron synaptic transmission
  • response to ethanol
  • negative regulation of myelination
  • adult behavior
  • central nervous system myelin maintenance
  • negative regulation of axonogenesis
  • response to zinc ion
  • negative regulation of phagocytosis
  • central nervous system development
  • negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
  • locomotor rhythm
  • cell migration
  • T cell receptor signaling pathway
  • negative regulation of protein phosphorylation
  • rhythmic synaptic transmission
  • negative regulation of dendritic spine morphogenesis
  • phosphatidylinositol dephosphorylation
  • epidermal growth factor receptor signaling pathway
  • protein dephosphorylation
  • peptidyl-tyrosine dephosphorylation
  • inositol phosphate dephosphorylation
  • response to drug
  • protein kinase B signaling
  • synapse assembly
  • negative regulation of ribosome biogenesis
  • dendritic spine morphogenesis
  • innate immune response
  • aging
  • inositol phosphate metabolic process
  • angiogenesis
  • positive regulation of excitatory postsynaptic potential
  • negative regulation of synaptic vesicle clustering
  • regulation of cyclin-dependent protein serine/threonine kinase activity
  • platelet-derived growth factor receptor signaling pathway
  • positive regulation of apoptotic signaling pathway
  • dentate gyrus development
Components
  • plasma membrane
  • PML body
  • cell projection
  • dendritic spine
  • myelin sheath adaxonal region
  • cytoplasmic side of plasma membrane
  • Schmidt-Lanterman incisure
  • cytoplasm
  • cytosol
  • mitochondrion
  • neuron projection
  • nucleoplasm
  • extracellular region
  • postsynaptic membrane
  • apical plasma membrane
  • nucleus
General FunctionProtein tyrosine/serine/threonine phosphatase activity
Specific FunctionTumor 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP60484
UniProtKB Entry NamePTEN_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0021732|Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)
ATGACAGCCATCATCAAAGAGATCGTTAGCAGAAACAAAAGGAGATATCAAGAGGATGGA
TTCGACTTAGACTTGACCTATATTTATCCAAACATTATTGCTATGGGATTTCCTGCAGAA
AGACTTGAAGGCGTATACAGGAACAATATTGATGATGTAGTAAGGTTTTTGGATTCAAAG
CATAAAAACCATTACAAGATATACAATCTTTGTGCTGAAAGACATTATGACACCGCCAAA
TTTAATTGCAGAGTTGCACAATATCCTTTTGAAGACCATAACCCACCACAGCTAGAACTT
ATCAAACCCTTTTGTGAAGATCTTGACCAATGGCTAAGTGAAGATGACAATCATGTTGCA
GCAATTCACTGTAAAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCATATTTATTA
CATCGGGGCAAATTTTTAAAGGCACAAGAGGCCCTAGATTTCTATGGGGAAGTAAGGACC
AGAGACAAAAAGGGAGTAACTATTCCCAGTCAGAGGCGCTATGTGTATTATTATAGCTAC
CTGTTAAAGAATCATCTGGATTATAGACCAGTGGCACTGTTGTTTCACAAGATGATGTTT
GAAACTATTCCAATGTTCAGTGGCGGAACTTGCAATCCTCAGTTTGTGGTCTGCCAGCTA
AAGGTGAAGATATATTCCTCCAATTCAGGACCCACACGACGGGAAGACAAGTTCATGTAC
TTTGAGTTCCCTCAGCCGTTACCTGTGTGTGGTGATATCAAAGTAGAGTTCTTCCACAAA
CAGAACAAGATGCTAAAAAAGGACAAAATGTTTCACTTTTGGGTAAATACATTCTTCATA
CCAGGACCAGAGGAAACCTCAGAAAAAGTAGAAAATGGAAGTCTATGTGATCAAGAAATC
GATAGCATTTGCAGTATAGAGCGTGCAGATAATGACAAGGAATATCTAGTACTTACTTTA
ACAAAAAATGATCTTGACAAAGCAAATAAAGACAAAGCCAACCGATACTTTTCTCCAAAT
TTTAAGGTGAAGCTGTACTTCACAAAAACAGTAGAGGAGCCGTCAAATCCAGAGGCTAGC
AGTTCAACTTCTGTAACACCAGATGTTAGTGACAATGAACCTGATCATTATAGATATTCT
GACACCACTGACTCTGATCCAGAGAATGAACCTTTTGATGAAGATCAGCATACACAAATT
ACAAAAGTCTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:9588
Chromosome Location10
LocusNot Available
References
  1. 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. 9187108
  2. 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. 9090379
  3. 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. 9072974
  4. 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. 10817502
  5. 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. 14702039
  6. 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. 15489334
  7. 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. 9256433
  8. 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. 9593664
  9. 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. 9811831
  10. 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. 9616126
  11. 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. 10468583
  12. 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. 10646847
  13. 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. 10748157
  14. 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. 10760291
  15. Torres J, Pulido R: The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. J Biol Chem. 2001 Jan 12;276(2):993-8. 11035045
  16. 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. 11707428
  17. 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. 12297295
  18. Mehenni H, Lin-Marq N, Buchet-Poyau K, Reymond A, Collart MA, Picard D, Antonarakis SE: LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes. Hum Mol Genet. 2005 Aug 1;14(15):2209-19. Epub 2005 Jun 29. 15987703
  19. 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. 15951562
  20. 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. 17218260
  21. 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. 18716620
  22. 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. 19345329
  23. Van Themsche C, Leblanc V, Parent S, Asselin E: X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization. J Biol Chem. 2009 Jul 31;284(31):20462-6. doi: 10.1074/jbc.C109.009522. Epub 2009 May 27. 19473982
  24. Xu D, Yao Y, Jiang X, Lu L, Dai W: Regulation of PTEN stability and activity by Plk3. J Biol Chem. 2010 Dec 17;285(51):39935-42. doi: 10.1074/jbc.M110.166462. Epub 2010 Oct 12. 20940307
  25. 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. 20534535
  26. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  27. Stohr N, Kohn M, Lederer M, Glass M, Reinke C, Singer RH, Huttelmaier S: IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling. Genes Dev. 2012 Jan 15;26(2):176-89. doi: 10.1101/gad.177642.111. 22279049
  28. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. 22814378
  29. Hopkins BD, Fine B, Steinbach N, Dendy M, Rapp Z, Shaw J, Pappas K, Yu JS, Hodakoski C, Mense S, Klein J, Pegno S, Sulis ML, Goldstein H, Amendolara B, Lei L, Maurer M, Bruce J, Canoll P, Hibshoosh H, Parsons R: A secreted PTEN phosphatase that enters cells to alter signaling and survival. Science. 2013 Jul 26;341(6144):399-402. doi: 10.1126/science.1234907. Epub 2013 Jun 6. 23744781
  30. Liang H, He S, Yang J, Jia X, Wang P, Chen X, Zhang Z, Zou X, McNutt MA, Shen WH, Yin Y: PTENalpha, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism. Cell Metab. 2014 May 6;19(5):836-48. doi: 10.1016/j.cmet.2014.03.023. Epub 2014 Apr 24. 24768297
  31. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  32. 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. 10555148
  33. 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. 9345101
  34. 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. 9399897
  35. 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. 9331071
  36. 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. 9259288
  37. 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. 9140396
  38. 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. 9241266
  39. 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. 9635567
  40. 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. 9797362
  41. 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. 9600246
  42. 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. 9467011
  43. 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. 9735393
  44. 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. 9832031
  45. 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. 9425889
  46. 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. 9915974
  47. 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. 10051160
  48. 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. 10234502
  49. 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. 10400993
  50. 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. 10866302
  51. 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. 10807691
  52. 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. 10978354
  53. 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. 11230179
  54. 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. 11748304
  55. 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. 11494117
  56. 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. 12085208
  57. 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. 11801303
  58. 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. 12471211
  59. 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. 15805158
  60. 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. 17436248
  61. 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. 16752378