ID PTEN_HUMAN Reviewed; 403 AA. AC P60484; O00633; O02679; Q6ICT7; DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot. DT 16-FEB-2004, sequence version 1. DT 24-MAR-2009, entry version 70. DE RecName: Full=Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN; DE EC=3.1.3.67; DE EC=3.1.3.16; DE EC=3.1.3.48; DE AltName: Full=Phosphatase and tensin homolog; DE AltName: Full=Mutated in multiple advanced cancers 1; GN Name=PTEN; Synonyms=MMAC1, TEP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR RP LOCATION, AND INDUCTION. RC TISSUE=Epithelium; RX MEDLINE=97330649; PubMed=9187108; RA Li D.M., Sun H.; RT "TEP1, encoded by a candidate tumor suppressor locus, is a novel RT protein tyrosine phosphatase regulated by transforming growth factor RT beta."; RL Cancer Res. 57:2124-2129(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS GLIOMA RP SER-15; GLU-36; ARG-42; TRP-57 AND THR-319 DEL. RX MEDLINE=97245711; PubMed=9090379; DOI=10.1038/ng0497-356; RA Steck P.A., Pershouse M.A., Jasser S.A., Lin H., Yung W.K.A., RA Ligon A.H., Langford L.A., Baumgard M.L., Hattier T., Davis T., RA Frye C., Hu R., Swedlund B., Teng D.H.-F., Tavtigian S.V.; RT "Identification of a candidate tumour suppressor gene, MMAC1, at RT chromosome 10q23.3 that is mutated in multiple advanced cancers."; RL Nat. Genet. 15:356-363(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS GLIOBLASTOMA ARG-129 AND RP PROSTATE CANCER LEU-134. RX MEDLINE=97228181; PubMed=9072974; DOI=10.1126/science.275.5308.1943; RA Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., RA Miliaresis C., Rodgers L., McCombie R., Bigner S.H., Giovanella B.C., RA Ittmann M., Tycko B., Hibshoosh H., Wigler M.H., Parsons R.; RT "PTEN, a putative protein tyrosine phosphatase gene mutated in human RT brain, breast, and prostate cancer."; RL Science 275:1943-1947(1997). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10817502; DOI=10.1054/bjoc.2000.1211; RA Hamilton J.A., Stewart L.M.D., Ajayi L., Gray I.C., Gray N.E., RA Roberts K.G., Watson G.J., Kaisary A.V., Snary D.; RT "The expression profile for the tumour suppressor gene PTEN and RT associated polymorphic markers."; RL Br. J. Cancer 82:1671-1676(2000). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Wang S., Li J., Liaw D., Bose S., Podsypanina K., Parsons R.; RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Jensen K., de la Bastide M., Parsons R., Parnell L.D., Dedhia N., RA Gottesman T., Gnoj L., Kaplan N., Lodhi M., Johnson A.F., Shohdy N., RA Hasegawa A., Haberman K., Huang E.N., Schutz K., Calma C., Granat S., RA Wigler M.H., McCombie W.R.; RT "Genomic sequence of PTEN/MMAC1."; RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-290. RG NIEHS SNPs program; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS GLIOMA RP TRP-57; ENDOMETRIAL CANCER TYR-123; GLIOBLASTOMA ARG-129; CD ARG-129; RP PROSTATE CANCER LEU-134; GLIOBLASTOMA ARG-165; BREAST CANCER PRO-167 RP AND BZ ARG-170. RX MEDLINE=97404346; PubMed=9256433; DOI=10.1073/pnas.94.17.9052; RA Myers M.P., Stolarov J.P., Eng C., Li J., Wang S.I., Wigler M.H., RA Parsons R., Tonks N.K.; RT "P-TEN, the tumor suppressor from human chromosome 10q23, is a dual- RT specificity phosphatase."; RL Proc. Natl. Acad. Sci. U.S.A. 94:9052-9057(1997). RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX MEDLINE=98256248; PubMed=9593664; DOI=10.1074/jbc.273.22.13375; RA Maehama T., Dixon J.E.; RT "The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second RT messenger, phosphatidylinositol 3,4,5-trisphosphate."; RL J. Biol. Chem. 273:13375-13378(1998). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-130, AND RP CHARACTERIZATION OF VARIANTS CD SER-124 AND CD GLU-129. RX PubMed=9811831; DOI=10.1073/pnas.95.23.13513; RA Myers M.P., Pass I., Batty I.H., Van der Kaay J., Stolarov J.P., RA Hemmings B.A., Wigler M.H., Downes C.P., Tonks N.K.; RT "The lipid phosphatase activity of PTEN is critical for its tumor RT supressor function."; RL Proc. Natl. Acad. Sci. U.S.A. 95:13513-13518(1998). RN [13] RP FUNCTION, MUTAGENESIS OF ASP-92 AND CYS-124, AND CHARACTERIZATION OF RP VARIANT GLU-129. RX PubMed=9616126; DOI=10.1126/science.280.5369.1614; RA Tamura M., Gu J., Matsumoto K., Aota S., Parsons R., Yamada K.M.; RT "Inhibition of cell migration, spreading, and focal adhesions by tumor RT suppressor PTEN."; RL Science 280:1614-1617(1998). RN [14] RP FUNCTION, DOMAIN, AND CHARACTERIZATION OF VARIANTS THR-319 DEL; RP GLN-345 AND ILE-348. RX PubMed=10468583; DOI=10.1073/pnas.96.18.10182; RA Georgescu M.-M., Kirsch K.H., Akagi T., Shishido T., Hanafusa H.; RT "The tumor-suppressor activity of PTEN is regulated by its carboxyl- RT terminal region."; RL Proc. Natl. Acad. Sci. U.S.A. 96:10182-10187(1999). RN [15] RP INTERACTION WITH DLG1 AND MAST2, AND PHOSPHORYLATION AT THR-401. RX PubMed=10646847; RA Adey N.B., Huang L., Ormonde P.A., Baumgard M.L., Pero R., RA Byreddy D.V., Tavtigian S.V., Bartel P.L.; RT "Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both RT inhibits and stimulates PDZ binding."; RL Cancer Res. 60:35-37(2000). RN [16] RP INTERACTION WITH MAGI3. RX MEDLINE=20347267; PubMed=10748157; DOI=10.1074/jbc.M909741199; RA Wu Y., Dowbenko D., Spencer S., Laura R., Lee J., Gu Q., Lasky L.A.; RT "Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of RT MAGI3, a novel membrane-associated guanylate kinase."; RL J. Biol. Chem. 275:21477-21485(2000). RN [17] RP INTERACTION WITH AIP1. RX MEDLINE=20226087; PubMed=10760291; DOI=10.1073/pnas.97.8.4233; RA Wu X., Hepner K., Castelino-Prabhu S., Do D., Kaye M.B., Yuan X.-J., RA Wood J., Ross C., Sawyers C.L., Whang Y.E.; RT "Evidence for regulation of the PTEN tumor suppressor by a membrane- RT localized multi-PDZ domain containing scaffold protein MAGI-2."; RL Proc. Natl. Acad. Sci. U.S.A. 97:4233-4238(2000). RN [18] RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH AIP1. RX MEDLINE=21623681; PubMed=11707428; DOI=10.1074/jbc.C100556200; RA Vazquez F., Grossman S.R., Takahashi Y., Rokas M.V., Nakamura N., RA Sellers W.R.; RT "Phosphorylation of the PTEN tail acts as an inhibitory switch by RT preventing its recruitment into a protein complex."; RL J. Biol. Chem. 276:48627-48630(2001). RN [19] RP PHOSPHORYLATION AT THR-366; SER-370 AND SER-385. RX MEDLINE=22233751; PubMed=12297295; DOI=10.1016/S0014-5793(02)03274-X; RA Miller S., Lou D., Seldin D., Lane W., Neel B.; RT "Direct identification of PTEN phosphorylation sites."; RL FEBS Lett. 528:145-145(2002). RN [20] RP INTERACTION WITH MAGI2, MAGI3, MAST1, MAST2 AND MAST3, MUTAGENESIS OF RP VAL-403, AND PHOSPHORYLATION. RX PubMed=15951562; DOI=10.1074/jbc.M504761200; RA Valiente M., Andres-Pons A., Gomar B., Torres J., Gil A., Tapparel C., RA Antonarakis S.E., Pulido R.; RT "Binding of PTEN to specific PDZ domains contributes to PTEN protein RT stability and phosphorylation by microtubule-associated RT serine/threonine kinases."; RL J. Biol. Chem. 280:28936-28943(2005). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 8-353 IN COMPLEX WITH RP L(+)-TARTRATE, SUBUNIT, DOMAIN, AND MUTAGENESIS OF ASP-92; HIS-93; RP LYS-125; LYS-128; THR-167; GLN-171; 263-LYS--ALA-269 AND RP 327-LYS--ALA-335. RX MEDLINE=20021619; PubMed=10555148; DOI=10.1016/S0092-8674(00)81663-3; RA Lee J.-O., Yang H., Georgescu M.-M., Di Cristofano A., Maehama T., RA Shi Y., Dixon J.E., Pandolfi P., Pavletich N.P.; RT "Crystal structure of the PTEN tumor suppressor: implications for its RT phosphoinositide phosphatase activity and membrane association."; RL Cell 99:323-334(1999). RN [22] RP VARIANT CD ASN-137 INS. RX MEDLINE=98007985; PubMed=9345101; DOI=10.1086/301607; RA Tsou H.C., Teng D.H.-F., Ping X.L., Brancolini V., Davis T., Hu R., RA Xie X.X., Gruener A.C., Schrager C.A., Christiano A.M., Eng C., RA Steck P., Ott J., Tavtigian S.V., Peacocke M.; RT "The role of MMAC1 mutations in early-onset breast cancer: causative RT in association with Cowden syndrome and excluded in BRCA1-negative RT cases."; RL Am. J. Hum. Genet. 61:1036-1043(1997). RN [23] RP VARIANTS CD GLU-343 AND LEU-347. RX MEDLINE=98153621; PubMed=9399897; DOI=10.1086/301639; RA Lynch E.D., Ostermeyer E.A., Lee M.K., Arena J.F., Ji H., Dann J., RA Swisshelm K., Suchard D., MacLeod P.M., Kvinnsland S., Gjertsen B.T., RA Heimdal K., Lubs H., Moeller P., King M.-C.; RT "Inherited mutations in PTEN that are associated with breast cancer, RT cowden disease, and juvenile polyposis."; RL Am. J. Hum. Genet. 61:1254-1260(1997). RN [24] RP VARIANTS GLIOBLASTOMA TYR-107; PRO-121; ARG-129; ARG-165 AND GLN-345. RX PubMed=9331071; RA Wang S.I., Puc J., Li J., Bruce J.N., Cairns P., Sidransky D., RA Parsons R.; RT "Somatic mutations of PTEN in glioblastoma multiforme."; RL Cancer Res. 57:4183-4186(1997). RN [25] RP VARIANTS CD ARG-123 AND ARG-124. RX MEDLINE=97402224; PubMed=9259288; DOI=10.1093/hmg/6.8.1383; RA Nelen M.R., van Staveren W.C.G., Peeters E.A.J., Ben-Hassel M., RA Gorlin R.J., Hamm H., Lindboe C.F., Fryns J.-P., Sijmons R.H., RA Woods D.G., Mariman E.C.M., Padberg G.W., Kremer H.; RT "Germline mutations in the PTEN/MMAC1 gene in patients with Cowden RT disease."; RL Hum. Mol. Genet. 6:1383-1387(1997). RN [26] RP VARIANT CD GLU-129. RX MEDLINE=97285123; PubMed=9140396; DOI=10.1038/ng0597-64; RA Liaw D., Marsh D.J., Li J., Dahia P.L.M., Wang S.I., Zheng Z., RA Bose S., Call K.M., Tsou H.C., Peacocke M., Eng C., Parsons R.; RT "Germline mutations of the PTEN gene in Cowden disease, an inherited RT breast and thyroid cancer syndrome."; RL Nat. Genet. 16:64-67(1997). RN [27] RP VARIANT BZS ARG-170. RX MEDLINE=97385233; PubMed=9241266; DOI=10.1038/ng0897-333; RA Marsh D.J., Dahia P.L.M., Zheng Z., Liaw D., Parsons R., Gorlin R.J., RA Eng C.; RT "Germline mutations in PTEN are present in Bannayan-Zonana syndrome."; RL Nat. Genet. 16:333-334(1997). RN [28] RP VARIANTS ENDOMETRIAL HYPERPLASIA ARG-36; LEU-130; CYS-173; ALA-191 AND RP ILE-348. RX PubMed=9635567; RA Maxwell G.L., Risinger J.I., Gumbs C., Shaw H., Bentley R.C., RA Barrett J.C., Berchuck A., Futreal P.A.; RT "Mutation of the PTEN tumor suppressor gene in endometrial RT hyperplasias."; RL Cancer Res. 58:2500-2503(1998). RN [29] RP VARIANT CD GLU-289. RX MEDLINE=99014194; PubMed=9797362; RA Chi S.-G., Kim H.-J., Park B.-J., Min H.-J., Park J.-H., Kim Y.-W., RA Dong S.-H., Kim B.-H., Lee J.-I., Chang Y.-W., Chang R., Kim W.-K., RA Yang M.-H.; RT "Mutational abrogation of the PTEN/MMAC1 gene in gastrointestinal RT polyps in patients with Cowden disease."; RL Gastroenterology 115:1084-1089(1998). RN [30] RP VARIANTS CD HIS-68 AND PRO-112. RX MEDLINE=98260873; PubMed=9600246; DOI=10.1007/s004390050723; RA Tsou H.C., Ping X.L., Xie X.X., Gruener A.C., Zhang H., Nini R., RA Swisshelm K., Sybert V., Diamond T.M., Sutphen R., Peacocke M.; RT "The genetic basis of Cowden's syndrome: three novel mutations in RT PTEN/MMAC1/TEP1."; RL Hum. Genet. 102:467-473(1998). RN [31] RP VARIANTS CD AND BZS. RX MEDLINE=98133933; PubMed=9467011; DOI=10.1093/hmg/7.3.507; RA Marsh D.J., Coulon V., Lunetta K.L., Rocca-Serra P., Dahia P.L.M., RA Zheng Z., Liaw D., Caron S., Duboue B., Lin A.Y., Richardson A.-L., RA Bonnetblanc J.-M., Bressieux J.-M., Cabarrot-Moreau A., Chompret A., RA Demange L., Eeles R.A., Yahanda A.M., Fearon E.R., Fricker J.-P., RA Gorlin R.J., Hodgson S.V., Huson S., Lacombe D., Leprat F., Odent S., RA Toulouse C., Olopade O.I., Sobol H., Tishler S., Woods C.G., RA Robinson B.G., Weber H.C., Parsons R., Peacocke M., Longy M., Eng C.; RT "Mutation spectrum and genotype-phenotype analyses in Cowden disease RT and Bannayan-Zonana syndrome, two hamartoma syndromes with germline RT PTEN mutation."; RL Hum. Mol. Genet. 7:507-515(1998). RN [32] RP VARIANT CD TYR-136. RX MEDLINE=98408002; PubMed=9735393; RA Scala S., Bruni P., Lo Muzio L., Mignogna M., Viglietto G., Fusco A.; RT "Novel mutation of the PTEN gene in an Italian Cowden's disease RT kindred."; RL Int. J. Oncol. 13:665-668(1998). RN [33] RP VARIANT CD PRO-70. RX PubMed=9832031; RA Marsh D.J., Dahia P.L.M., Caron S., Kum J.B., Frayling I.M., RA Tomlinson I.P.M., Hughes K.S., Eeles R.A., Hodgson S.V., Murday V.A., RA Houlston R., Eng C.; RT "Germline PTEN mutations in Cowden syndrome-like families."; RL J. Med. Genet. 35:881-885(1998). RN [34] RP VARIANT CD ARG-35. RX MEDLINE=98085858; PubMed=9425889; DOI=10.1038/ng0198-12; RA Olschwang S., Serova-Sinilnikova O.M., Lenoir G.M., Thomas G.; RT "PTEN germ-line mutations in juvenile polyposis coli."; RL Nat. Genet. 18:12-14(1998). RN [35] RP VARIANT CD GLN-130. RX MEDLINE=99115112; PubMed=9915974; DOI=10.1086/302207; RA Kurose K., Araki T., Matsunaka T., Takada Y., Emi M.; RT "Variant manifestation of Cowden disease in Japan: hamartomatous RT polyposis of the digestive tract with mutation of the PTEN gene."; RL Am. J. Hum. Genet. 64:308-310(1999). RN [36] RP VARIANT CD/LDD PRO-112. RX MEDLINE=99158469; PubMed=10051160; RX DOI=10.1002/(SICI)1096-8628(19990212)82:4<290::AID-AJMG3>3.0.CO;2-0; RA Sutphen R., Diamond T.M., Minton S.E., Peacocke M., Tsou H.C., RA Root A.W.; RT "Severe Lhermitte-Duclos disease with unique germline mutation of RT PTEN."; RL Am. J. Med. Genet. 82:290-293(1999). RN [37] RP VARIANTS CD ILE-33 DEL; ARG-123; ARG-124 AND GLU-165. RX MEDLINE=99250761; PubMed=10234502; DOI=10.1038/sj.ejhg.5200289; RA Nelen M.R., Kremer H., Konings I.B.M., Schoute F., van Essen A.J., RA Koch R., Woods C.G., Fryns J.-P., Hamel B.C.J., Hoefsloot L.H., RA Peeters E.A.J., Padberg G.W.; RT "Novel PTEN mutations in patients with Cowden disease: absence of RT clear genotype-phenotype correlations."; RL Eur. J. Hum. Genet. 7:267-273(1999). RN [38] RP VARIANTS BZS ASP-34; HIS-68; TYR-105; VAL-135; ARG-170 AND LEU-246. RX MEDLINE=99330553; PubMed=10400993; DOI=10.1093/hmg/8.8.1461; RA Marsh D.J., Kum J.B., Lunetta K.L., Bennett M.J., Gorlin R.J., RA Ahmed S.F., Bodurtha J., Crowe C., Curtis M.A., Dasouki M., Dunn T., RA Feit H., Geraghty M.T., Graham J.M. Jr., Hodgson S.V., Hunter A., RA Korf B.R., Manchester D., Miesfeldt S., Murday V.A., Nathanson K.L., RA Parisi M., Pober B., Romano C., Tolmie J.L., Trembath R., Winter R.M., RA Zackai E.H., Zori R.T., Weng L.-P., Dahia P.L.M., Eng C.; RT "PTEN mutation spectrum and genotype-phenotype correlations in RT Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden RT syndrome."; RL Hum. Mol. Genet. 8:1461-1472(1999). RN [39] RP CHARACTERIZATION OF VARIANTS ASN-10; CYS-16; GLU-20; SER-27; ARG-61; RP HIS-68; CD TYR-71; CD TYR-93; BZS PHE-105; BZS TYR-107; PRO-112; RP ARG-112; PRO-121; ARG-124; ARG-129; GLU-129; GLY-130; CD LEU-130; RP GLN-130; ILE-133; LEU-134; TYR-136; CYS-155; ARG-165; ASN-170; RP ARG-170; CYS-173; HIS-173; PRO-173; ASN-174; PHE-227; CYS-251; RP GLU-289; GLY-331; VAL-341; ASN-342; GLU-343; GLN-345; LEU-347; GLY-369 RP AND ILE-401. RX PubMed=10866302; RA Han S.-Y., Kato H., Kato S., Suzuki T., Shibata H., Ishii S., RA Shiiba K., Matsuno S., Kanamaru R., Ishioka C.; RT "Functional evaluation of PTEN missense mutations using in vitro RT phosphoinositide phosphatase assay."; RL Cancer Res. 60:3147-3151(2000). RN [40] RP VARIANTS MULTIPLE CANCERS LEU-119 AND LEU-158. RX MEDLINE=20267903; PubMed=10807691; DOI=10.1136/jmg.37.5.336; RA De Vivo I., Gertig D.M., Nagase S., Hankinson S.E., O'Brien R., RA Speizer F.E., Parsons R., Hunter D.J.; RT "Novel germline mutations in the PTEN tumour suppressor gene found in RT women with multiple cancers."; RL J. Med. Genet. 37:336-341(2000). RN [41] RP VARIANTS MALIGNANT MELANOMA ASN-19 AND ILE-217. RX PubMed=10978354; DOI=10.1136/jmg.37.9.653; RA Celebi J.T., Shendrik I., Silvers D.N., Peacocke M.; RT "Identification of PTEN mutations in metastatic melanoma specimens."; RL J. Med. Genet. 37:653-657(2000). RN [42] RP CHARACTERIZATION OF VARIANTS CD SER-124 AND GLU-129. RX PubMed=11230179; DOI=10.1093/hmg/10.6.599; RA Weng L.-P., Brown J.L., Eng C.; RT "PTEN coordinates G1 arrest by down-regulating cyclin D1 via its RT protein phosphatase activity and up-regulating p27 via its lipid RT phosphatase activity in a breast cancer model."; RL Hum. Mol. Genet. 10:599-604(2001). RN [43] RP VARIANT VATER ASP-61. RX PubMed=11748304; DOI=10.1136/jmg.38.12.820; RA Reardon W., Zhou X.-P., Eng C.; RT "A novel germline mutation of the PTEN gene in a patient with RT macrocephaly, ventricular dilatation, and features of VATER RT association."; RL J. Med. Genet. 38:820-823(2001). RN [44] RP VARIANT CD GLY-47, AND VARIANTS BZS ASP-34; HIS-68; TYR-105; VAL-135 RP AND ARG-170. RX MEDLINE=21385665; PubMed=11494117; DOI=10.1038/sj.neo.7900154; RA Marsh D.J., Theodosopoulos G., Howell V., Richardson A.-L., Benn D.E., RA Proos A.L., Eng C., Robinson B.G.; RT "Rapid mutation scanning of genes associated with familial cancer RT syndromes using denaturing high-performance liquid chromatography."; RL Neoplasia 3:236-244(2001). RN [45] RP CHARACTERIZATION OF VARIANT OLIGODENDROGLIOMA GLN-234. RX PubMed=12085208; DOI=10.1038/sj.bjc.6600206; RA Staal F.J.T., van der Luijt R.B., Baert M.R.M., van Drunen J., RA van Bakel H., Peters E., de Valk I., van Amstel H.K.P., RA Taphoorn M.J.B., Jansen G.H., van Veelen C.W.M., Burgering B., RA Staal G.E.J.; RT "A novel germline mutation of PTEN associated with brain tumours of RT multiple lineages."; RL Br. J. Cancer 86:1586-1591(2002). RN [46] RP VARIANT HNSCC GLY-121. RX PubMed=11801303; DOI=10.1016/S0165-4608(01)00509-X; RA Poetsch M., Lorenz G., Kleist B.; RT "Detection of new PTEN/MMAC1 mutations in head and neck squamous cell RT carcinomas with loss of chromosome 10."; RL Cancer Genet. Cytogenet. 132:20-24(2002). RN [47] RP INVOLVEMENT IN PROTEUS SYNDROME. RX PubMed=12471211; DOI=10.1136/jmg.39.12.937; RA Smith J.M., Kirk E.P.E., Theodosopoulos G., Marshall G.M., Walker J., RA Rogers M., Field M., Brereton J.J., Marsh D.J.; RT "Germline mutation of the tumour suppressor PTEN in Proteus RT syndrome."; RL J. Med. Genet. 39:937-940(2002). RN [48] RP VARIANTS MACROCEPHALY/AUTISM SYNDROME ARG-93; SER-241 AND GLY-252. RX PubMed=15805158; DOI=10.1136/jmg.2004.024646; RA Butler M.G., Dasouki M.J., Zhou X.-P., Talebizadeh Z., Brown M., RA Takahashi T.N., Miles J.H., Wang C.H., Stratton R., Pilarski R., RA Eng C.; RT "Subset of individuals with autism spectrum disorders and extreme RT macrocephaly associated with germline PTEN tumour suppressor gene RT mutations."; RL J. Med. Genet. 42:318-321(2005). RN [49] RP INVOLVEMENT IN CHROMOSOME 10Q23 DELETION SYNDROME. RX PubMed=17436248; DOI=10.1086/513607; RA Balciuniene J., Feng N., Iyadurai K., Hirsch B., Charnas L., RA Bill B.R., Easterday M.C., Staaf J., Oseth L., Czapansky-Beilman D., RA Avramopoulos D., Thomas G.H., Borg A., Valle D., Schimmenti L.A., RA Selleck S.B.; RT "Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated RT with cognitive and behavioral abnormalities."; RL Am. J. Hum. Genet. 80:938-947(2007). RN [50] RP VARIANT VAL-132. RX PubMed=16752378; DOI=10.1002/ajmg.a.31273; RA Tekin M., Hismi B.O., Fitoz S., Yalcinkaya F., Ekim M., Kansu A., RA Ertem M., Deda G., Tutar E., Arsan S., Zhou X.-P., Pilarski R., RA Eng C., Akar N.; RT "A germline PTEN mutation with manifestations of prenatal onset and RT verrucous epidermal nevus."; RL Am. J. Med. Genet. A 140:1472-1475(2006). CC -!- FUNCTION: Tumor suppressor. Acts as a dual-specificity protein CC phosphatase, dephosphorylating tyrosine-, serine- and threonine- CC phosphorylated proteins. Also acts as a lipid phosphatase, CC removing the phosphate in the D3 position of the inositol ring CC from phosphatidylinositol 3,4,5-trisphosphate, CC phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3- CC phosphate and inositol 1,3,4,5-tetrakisphosphate with order of CC substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > CC PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is CC critical for its tumor suppressor function. Antagonizes the PI3K- CC AKT/PKB signaling pathway by dephosphorylating phosphoinositides CC and thereby modulating cell cycle progression and cell survival. CC The unphosphorylated form cooperates with AIP1 to suppress AKT1 CC activation. Dephosphorylates tyrosine-phosphorylated focal CC adhesion kinase and inhibits cell migration and integrin-mediated CC cell spreading and focal adhesion formation. May be a negative CC regulator of insulin signaling and glucose metabolism in adipose CC tissue. CC -!- CATALYTIC ACTIVITY: Phosphatidylinositol 3,4,5-trisphosphate + CC H(2)O = phosphatidylinositol 4,5-bisphosphate + phosphate. CC -!- CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein + CC phosphate. CC -!- CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein CC tyrosine + phosphate. CC -!- COFACTOR: Magnesium. CC -!- SUBUNIT: Monomer. The unphosphorylated form interacts with the CC second PDZ domain of AIP1 and with DLG1 and MAST2 in vitro. CC Interacts with MAGI2, MAGI3, MAST1 and MAST3, but neither with CC MAST4 nor with DLG5. Interaction with MAGI2 increases protein CC stability. CC -!- INTERACTION: CC P49452:Cenpc1 (xeno); NbExp=1; IntAct=EBI-696162, EBI-1186252; CC Q62696:Dlg1 (xeno); NbExp=1; IntAct=EBI-696162, EBI-389325; CC P11021:HSPA5; NbExp=1; IntAct=EBI-696162, EBI-354921; CC O88382:Magi2 (xeno); NbExp=2; IntAct=EBI-696162, EBI-696179; CC Q9JK71:Magi3 (xeno); NbExp=1; IntAct=EBI-696162, EBI-696226; CC Q9R1L5:Mast1 (xeno); NbExp=2; IntAct=EBI-696162, EBI-491771; CC Q60592:Mast2 (xeno); NbExp=2; IntAct=EBI-696162, EBI-493888; CC O60307:MAST3; NbExp=2; IntAct=EBI-696162, EBI-311420; CC P62136:PPP1CA; NbExp=2; IntAct=EBI-696162, EBI-357253; CC O08586:Pten (xeno); NbExp=1; IntAct=EBI-696162, EBI-1186266; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- TISSUE SPECIFICITY: Expressed at a relatively high level in all CC adult tissues, including heart, brain, placenta, lung, liver, CC muscle, kidney and pancreas. CC -!- INDUCTION: Down-regulated by transforming growth factor beta (TGF- CC beta). CC -!- DOMAIN: The C2 domain binds phospholipid membranes in vitro in a CC Ca(2+)-independent manner; this binding is important for its tumor CC suppressor function. CC -!- PTM: Phosphorylated in vitro by MAST1, MAST2 and MAST3. CC Phosphorylation results in an inhibited activity towards PIP3. CC Phosphorylation can both inhibit or promote PDZ-binding. CC -!- DISEASE: Mutations of PTEN are found in a large number of cancers. CC -!- DISEASE: Defects in PTEN are a cause of Cowden disease (CD) CC [MIM:158350]; also known as Cowden syndrome (CS). CD is an CC autosomal dominant cancer predisposition syndrome associated with CC elevated risk for tumors of the breast, thyroid and skin. The CC predominant phenotype for CD is multiple hamartoma syndrome, in CC many organ systems including the breast (70% of CD patients), CC thyroid (40-60%), skin, CNS (40%), gastrointestinal tract. CC Affected individuals are at an increased risk of both breast and CC thyroid cancers. Trichilemmomas (benign tumors of the hair CC follicle infundibulum), and mucocutaneous papillomatosis (99%) are CC hallmarks of CD. CC -!- DISEASE: Defects in PTEN are the cause of Lhermitte-Duclos disease CC (LDD) [MIM:158350]; also known as cerebelloparenchymal disorder CC VI. LDD is characterized by dysplastic gangliocytoma of the CC cerebellum which often results in cerebellar signs and seizures. CC LDD and CD seem to be the same entity, and are considered as CC hamartoma-neoplasia syndromes. CC -!- DISEASE: Defects in PTEN are a cause of Bannayan-Zonana syndrome CC (BZS) [MIM:153480]; also known as Ruvalcaba-Riley-Smith or CC Bannayan-Riley-Ruvalcaba syndrome (BRRS). In BZS there seems not CC to be an increased risk of malignancy. It has a partial clinical CC overlap with CD. BZS is characterized by the classic triad of CC macrocephaly, lipomatosis and pigmented macules of the gland CC penis. CC -!- DISEASE: Defects in PTEN are a cause of squamous cell carcinoma of CC the head and neck (HNSCC) [MIM:275355]. CC -!- DISEASE: Defects in PTEN are a cause of susceptibility to CC endometrial cancer [MIM:608089]. CC -!- DISEASE: Defects in PTEN are a cause of Proteus syndrome CC [MIM:176920]. Proteus syndrome is a hamartomatous disorder CC characterized by overgrowth of multiple tissues, connective tissue CC and epidermal naevi, and vascular malformations. These CC presentations are usually apparent at birth or soon after and CC continue to develop as the patient ages. It is named after the CC Greek god Proteus who, legend has it, could change his shape at CC will to avoid capture. Tumors, mostly benign but some malignant, CC have also been reported in Proteus syndrome, generally presenting CC by the age of 20 years and including papillary adenocarcinoma of CC the testis, meningioma, and cystadenoma of the ovaries. CC -!- DISEASE: Defects in PTEN are a cause of oligodendroglioma CC [MIM:137800]; also called oligodendroblastoma or familial glioma CC of brain. Oligodendroglioma is a usually benign neoplasm derived CC from and composed of oligodendrogliocytes in varying stages of CC differentiation. The majority are seen in adults in the white CC matter of the brain. CC -!- DISEASE: Defects in PTEN are a cause of VACTERL association with CC hydrocephalus [MIM:276950]; which includes also VATER association CC with hydrocephalus. VACTERL is an acronym for vertebral anomalies, CC anal atresia, congenital cardiac disease, tracheoesophageal CC fistula, renal anomalies, radial dysplasia, and other limb CC defects. CC -!- DISEASE: Defects in PTEN are involved in prostate cancer CC [MIM:176807]. CC -!- DISEASE: Defects in PTEN are a cause of macrocephaly/autism CC syndrome [MIM:605309]. Patients have autism spectrum disorders and CC macrocephaly, with head circumferences ranging from +2.5 to +8 SD CC for age and sex (average head circumference +4.0 SD). CC -!- DISEASE: A microdeletion of chromosome 10q23 involving PTEN and CC BMPR1A is a cause of chromosome 10q23 deletion syndrome CC [MIM:612242]. This syndrome shows overlapping features of the CC following three disorders: Bannayan-Zonana syndrome, Cowden CC disease and juvenile polyposis syndrome. CC -!- SIMILARITY: Contains 1 C2 tensin-type domain. CC -!- SIMILARITY: Contains 1 phosphatase tensin-type domain. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/PTENID158.html"; CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=PTEN"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/pten/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U96180; AAB66902.1; -; mRNA. DR EMBL; U92436; AAC51182.1; -; mRNA. DR EMBL; U93051; AAC51183.1; -; mRNA. DR EMBL; AF143315; AAD38372.1; -; Genomic_DNA. DR EMBL; AF143312; AAD38372.1; JOINED; Genomic_DNA. DR EMBL; AF143313; AAD38372.1; JOINED; Genomic_DNA. DR EMBL; AF143314; AAD38372.1; JOINED; Genomic_DNA. DR EMBL; AF000734; AAC08699.1; -; Genomic_DNA. DR EMBL; AF000726; AAC08699.1; JOINED; Genomic_DNA. DR EMBL; AF000727; AAC08699.1; JOINED; Genomic_DNA. DR EMBL; AF000728; AAC08699.1; JOINED; Genomic_DNA. DR EMBL; AF000729; AAC08699.1; JOINED; Genomic_DNA. DR EMBL; AF000730; AAC08699.1; JOINED; Genomic_DNA. DR EMBL; AF000731; AAC08699.1; JOINED; Genomic_DNA. DR EMBL; AF000732; AAC08699.1; JOINED; Genomic_DNA. DR EMBL; AF000733; AAC08699.1; JOINED; Genomic_DNA. DR EMBL; AF067844; AAD13528.1; -; Unassigned_DNA. DR EMBL; CR450306; CAG29302.1; -; mRNA. DR EMBL; DQ073384; AAY57327.1; -; Genomic_DNA. DR EMBL; BC005821; AAH05821.1; -; mRNA. DR IPI; IPI00012587; -. DR RefSeq; NP_000305.3; -. DR UniGene; Hs.500466; -. DR PDB; 1D5R; X-ray; 2.10 A; A=8-353. DR PDBsum; 1D5R; -. DR IntAct; P60484; 16. DR PhosphoSite; P60484; -. DR PRIDE; P60484; -. DR Ensembl; ENSG00000171862; Homo sapiens. DR GeneID; 5728; -. DR KEGG; hsa:5728; -. DR GeneCards; GC10P089613; -. DR H-InvDB; HIX0009010; -. DR H-InvDB; HIX0025699; -. DR HGNC; HGNC:9588; PTEN. DR HPA; CAB004076; -. DR MIM; 137800; phenotype. DR MIM; 153480; phenotype. DR MIM; 158350; phenotype. DR MIM; 176807; phenotype. DR MIM; 176920; phenotype. DR MIM; 275355; phenotype. DR MIM; 276950; phenotype. DR MIM; 601728; gene. DR MIM; 605309; phenotype. DR MIM; 608089; phenotype. DR MIM; 612242; phenotype. DR Orphanet; 94; Astrocytoma. DR Orphanet; 109; Bannayan-Riley-Ruvalcaba syndrome. DR Orphanet; 145; Breast cancer, familial. DR Orphanet; 201; Cowden syndrome. DR Orphanet; 79076; Juvenile polyposis of infancy. DR Orphanet; 65285; Lhermitte-Duclos disease. DR Orphanet; 2495; Meningioma. DR Orphanet; 46484; Oligodendroglioma. DR Orphanet; 1331; Prostate cancer, familial. DR Orphanet; 744; Proteus syndrome. DR Orphanet; 2969; Proteus-like syndrome - mental retardation - eye defects. DR Orphanet; 67037; Squamous cell carcinoma of head and neck. DR Orphanet; 3412; VACTERL with hydrocephalus. DR PharmGKB; PA33942; -. DR HOGENOM; P60484; -. DR HOVERGEN; P60484; -. DR BRENDA; 3.1.3.16; 247. DR BRENDA; 3.1.3.48; 247. DR BRENDA; 3.1.3.67; 247. DR Pathway_Interaction_DB; bcr_5pathway; BCR signaling pathway. DR Pathway_Interaction_DB; kitpathway; Signaling events mediated by Stem cell factor receptor (c-Kit). DR Pathway_Interaction_DB; met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met). DR Pathway_Interaction_DB; mtor_4pathway; mTOR signaling pathway. DR Pathway_Interaction_DB; pdgfrbpathway; PDGFR-beta signaling pathway. DR Pathway_Interaction_DB; pi3kcipathway; Class I PI3K signaling events. DR Pathway_Interaction_DB; tcrpathway; TCR signaling in naive CD4+ T cells. DR Reactome; REACT_11061; Signalling by NGF. DR Reactome; REACT_6900; Signaling in Immune system. DR NextBio; 22282; -. DR ArrayExpress; P60484; -. DR Bgee; P60484; -. DR CleanEx; HS_PTEN; -. DR CleanEx; HS_TEP1; -. DR GermOnline; ENSG00000171862; Homo sapiens. DR GO; GO:0005829; C:cytosol; EXP:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0051717; F:inositol-1,3,4,5-tetrakisphosphate 3-phosph...; IDA:UniProtKB. DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB. DR GO; GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-...; IDA:UniProtKB. DR GO; GO:0051800; F:phosphatidylinositol-3,4-bisphosphate 3-pho...; IDA:UniProtKB. DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IDA:UniProtKB. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB. DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphata...; IEA:InterPro. DR GO; GO:0007417; P:central nervous system development; ISS:UniProtKB. DR GO; GO:0006917; P:induction of apoptosis; ISS:UniProtKB. DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IDA:UniProtKB. DR GO; GO:0045786; P:negative regulation of cell cycle; IEA:UniProtKB-KW. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB. DR GO; GO:0051895; P:negative regulation of focal adhesion forma...; IMP:UniProtKB. DR GO; GO:0051898; P:negative regulation of protein kinase B sig...; IMP:UniProtKB. DR GO; GO:0046856; P:phosphoinositide dephosphorylation; IDA:UniProtKB. DR GO; GO:0006470; P:protein amino acid dephosphorylation; IDA:UniProtKB. DR GO; GO:0000079; P:regulation of cyclin-dependent protein kina...; TAS:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB. DR InterPro; IPR017361; Bifunc_PIno_P3_Pase/Pase_PTEN. DR InterPro; IPR014020; C2_tensin-type. DR InterPro; IPR014019; Phosphatase_tensin-typ. DR InterPro; IPR000340; Tyr_Pase_dual_specific. DR Pfam; PF00782; DSPc; 1. DR Pfam; PF10409; PTEN_C2; 1. DR PIRSF; PIRSF038025; PTEN; 1. DR PROSITE; PS51182; C2_TENSIN; 1. DR PROSITE; PS51181; PPASE_TENSIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Anti-oncogene; Cell cycle; Cytoplasm; Disease mutation; KW Hydrolase; Lipid metabolism; Lipid-binding; Phosphoprotein; KW Polymorphism; Protein phosphatase. FT CHAIN 1 403 Phosphatidylinositol-3,4,5-trisphosphate FT 3-phosphatase and dual-specificity FT protein phosphatase PTEN. FT /FTId=PRO_0000215904. FT DOMAIN 14 185 Phosphatase tensin-type. FT DOMAIN 190 350 C2 tensin-type. FT REGION 401 403 PDZ domain-binding. FT ACT_SITE 124 124 Phosphocysteine intermediate (Potential). FT MOD_RES 366 366 Phosphothreonine. FT MOD_RES 370 370 Phosphoserine; by CK2. FT MOD_RES 385 385 Phosphoserine; by CK2. FT MOD_RES 401 401 Phosphothreonine. FT VARIANT 10 10 S -> N (retains phosphatase activity FT towards Ins(1,3,4,5)P4 and FT PtdIns(3,4,5)P3; retains the ability to FT bind phospholipid membranes). FT /FTId=VAR_026248. FT VARIANT 15 15 R -> S (in glioma). FT /FTId=VAR_007457. FT VARIANT 16 16 Y -> C (loss of phosphatase activity FT towards Ins(1,3,4,5)P4; retains the FT ability to bind phospholipid membranes). FT /FTId=VAR_026249. FT VARIANT 19 19 D -> N (in malignant melanoma; somatic FT mutation). FT /FTId=VAR_018100. FT VARIANT 20 20 G -> E (reduced phosphatase activity FT towards Ins(1,3,4,5)P4; retains FT phosphatase activity towards FT PtdIns(3,4,5)P3). FT /FTId=VAR_026250. FT VARIANT 27 27 Y -> S (loss of phosphatase activity FT towards Ins(1,3,4,5)P4). FT /FTId=VAR_026251. FT VARIANT 33 33 Missing (in CD). FT /FTId=VAR_008733. FT VARIANT 34 34 A -> D (in BZS). FT /FTId=VAR_008734. FT VARIANT 35 35 M -> R (in CD). FT /FTId=VAR_008036. FT VARIANT 36 36 G -> E (in glioma). FT /FTId=VAR_007458. FT VARIANT 36 36 G -> R (in endometrial hyperplasia). FT /FTId=VAR_026252. FT VARIANT 42 42 L -> R (in glioma; retains phosphatase FT activity towards Ins(1,3,4,5)P4 and FT PtdIns(3,4,5)P3; retains the ability to FT bind phospholipid membranes). FT /FTId=VAR_007459. FT VARIANT 47 47 R -> G (in CD). FT /FTId=VAR_011587. FT VARIANT 57 57 L -> W (in glioma; loss of protein FT phosphatase activity). FT /FTId=VAR_007460. FT VARIANT 61 61 H -> D (in VATER). FT /FTId=VAR_018101. FT VARIANT 61 61 H -> R (loss of phosphatase activity FT towards Ins(1,3,4,5)P4). FT /FTId=VAR_026253. FT VARIANT 67 67 I -> R (in CD). FT /FTId=VAR_007461. FT VARIANT 68 68 Y -> H (in CD and BZS; loss of FT phosphatase activity towards FT Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; FT retains the ability to bind phospholipid FT membranes). FT /FTId=VAR_007462. FT VARIANT 70 70 L -> P (in CD). FT /FTId=VAR_018102. FT VARIANT 71 71 C -> Y (in CD; loss of phosphatase FT activity towards Ins(1,3,4,5)P4). FT /FTId=VAR_026254. FT VARIANT 93 93 H -> R (in macrocephaly/autism syndrome). FT /FTId=VAR_032634. FT VARIANT 93 93 H -> Y (in CD). FT /FTId=VAR_026255. FT VARIANT 105 105 C -> F (in BZS; loss of phosphatase FT activity towards Ins(1,3,4,5)P4). FT /FTId=VAR_026256. FT VARIANT 105 105 C -> Y (in BZS). FT /FTId=VAR_008735. FT VARIANT 107 107 D -> Y (in BZS and glioblastoma; loss of FT phosphatase activity towards FT Ins(1,3,4,5)P4). FT /FTId=VAR_026257. FT VARIANT 112 112 L -> P (in CD and LDD; loss of FT phosphatase activity towards FT Ins(1,3,4,5)P4). FT /FTId=VAR_007807. FT VARIANT 112 112 L -> R (loss of phosphatase activity FT towards Ins(1,3,4,5)P4). FT /FTId=VAR_026258. FT VARIANT 119 119 V -> L (in multiple cancers). FT /FTId=VAR_011588. FT VARIANT 121 121 A -> G (in HNSCC). FT /FTId=VAR_018103. FT VARIANT 121 121 A -> P (in glioblastoma; loss of FT phosphatase activity towards FT Ins(1,3,4,5)P4). FT /FTId=VAR_026259. FT VARIANT 123 123 H -> R (in CD). FT /FTId=VAR_007463. FT VARIANT 123 123 H -> Y (in endometrial cancer; loss of FT protein phosphatase activity). FT /FTId=VAR_026260. FT VARIANT 124 124 C -> R (in CD). FT /FTId=VAR_007464. FT VARIANT 124 124 C -> S (in CD; phosphatase-dead protein FT with neither lipid nor protein FT phosphatase activity). FT /FTId=VAR_018104. FT VARIANT 129 129 G -> E (in CD; no lipid phosphatase FT activity but retains protein phosphatase FT activity; retains ability to inhibit FT focal adhesion formation). FT /FTId=VAR_007465. FT VARIANT 129 129 G -> R (in glioblastoma; severely reduced FT protein phosphatase activity; loss of FT phosphatase activity towards FT Ins(1,3,4,5)P4). FT /FTId=VAR_007466. FT VARIANT 130 130 R -> G (loss of phosphatase activity FT towards Ins(1,3,4,5)P4 and FT PtdIns(3,4,5)P3). FT /FTId=VAR_026261. FT VARIANT 130 130 R -> L (in CD and endometrial FT hyperplasia; loss of phosphatase activity FT towards Ins(1,3,4,5)P4; retains ability FT to bind phospholipid membranes). FT /FTId=VAR_007467. FT VARIANT 130 130 R -> Q (in CD; loss of phosphatase FT activity towards Ins(1,3,4,5)P4; retains FT ability to bind phospholipid membranes). FT /FTId=VAR_007468. FT VARIANT 132 132 G -> V (in one patient with clinical FT findings suggesting hamartoma tumor FT syndrome). FT /FTId=VAR_032635. FT VARIANT 133 133 V -> I (loss of phosphatase activity FT towards Ins(1,3,4,5)P3). FT /FTId=VAR_026262. FT VARIANT 134 134 M -> L (in prostate cancer; no effect on FT protein phosphatase activity; reduced FT phosphatase activity towards FT Ins(1,3,4,5)P3 but retains FT PtdIns(3,4,5)P3 phosphatase activity). FT /FTId=VAR_007469. FT VARIANT 135 135 I -> V (in BZS). FT /FTId=VAR_008736. FT VARIANT 136 136 C -> Y (in CD; loss of phosphatase FT activity towards Ins(1,3,4,5)P3). FT /FTId=VAR_007808. FT VARIANT 137 137 A -> AN (in CD). FT /FTId=VAR_008737. FT VARIANT 155 155 Y -> C (in CD; loss of phosphatase FT activity towards Ins(1,3,4,5)P4). FT /FTId=VAR_026263. FT VARIANT 158 158 V -> L (in multiple cancers). FT /FTId=VAR_011589. FT VARIANT 165 165 G -> E (in CD). FT /FTId=VAR_008739. FT VARIANT 165 165 G -> R (in glioblastoma; severely reduced FT protein phosphatase activity; loss of FT phosphatase activity towards FT Ins(1,3,4,5)P4; retains ability to bind FT phospholipid membranes). FT /FTId=VAR_026264. FT VARIANT 165 165 G -> V (in CD). FT /FTId=VAR_008738. FT VARIANT 167 167 T -> P (in breast cancer; severely FT reduced protein phosphatase activity). FT /FTId=VAR_026265. FT VARIANT 170 170 S -> N (loss of phosphatase activity FT towards Ins(1,3,4,5)P4; retains ability FT to bind phospholipid membranes). FT /FTId=VAR_026266. FT VARIANT 170 170 S -> R (in BZS; severely reduced protein FT phosphatase activity; loss of phosphatase FT activity towards Ins(1,3,4,5)P4). FT /FTId=VAR_007470. FT VARIANT 173 173 R -> C (in endometrial hyperplasia; loss FT of phosphatase activity towards FT Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; FT retains ability to bind phospholipid FT membranes). FT /FTId=VAR_026267. FT VARIANT 173 173 R -> H (loss of phosphatase activity FT towards Ins(1,3,4,5)P4). FT /FTId=VAR_026268. FT VARIANT 173 173 R -> P (loss of phosphatase activity FT towards Ins(1,3,4,5)P4). FT /FTId=VAR_026269. FT VARIANT 174 174 Y -> N (loss of phosphatase activity FT towards Ins(1,3,4,5)P4). FT /FTId=VAR_026270. FT VARIANT 191 191 V -> A (in endometrial hyperplasia). FT /FTId=VAR_026271. FT VARIANT 217 217 V -> I (in malignant melanoma; somatic FT mutation). FT /FTId=VAR_018105. FT VARIANT 227 227 S -> F (reduced phosphatase activity FT towards Ins(1,3,4,5)P4 but retains FT PtdIns(3,4,5)P3 phosphatase activity). FT /FTId=VAR_026272. FT VARIANT 234 234 R -> Q (in oligodendroglioma; not capable FT of inducing apoptosis; induced increased FT cell proliferation; led to high FT constitutive AKT1 activation which could FT not be increased further by stimulation FT with insulin). FT /FTId=VAR_018106. FT VARIANT 241 241 F -> S (in macrocephaly/autism syndrome). FT /FTId=VAR_032636. FT VARIANT 246 246 P -> L (in CD and BZS). FT /FTId=VAR_008740. FT VARIANT 251 251 G -> C (loss of phosphatase activity FT towards Ins(1,3,4,5)P4; retains ability FT to bind phospholipid membranes). FT /FTId=VAR_026273. FT VARIANT 252 252 D -> G (in macrocephaly/autism syndrome). FT /FTId=VAR_032637. FT VARIANT 289 289 K -> E (in CD; reduced phosphatase FT activity towards Ins(1,3,4,5)P4; retains FT ability to bind phospholipid membranes). FT /FTId=VAR_008741. FT VARIANT 290 290 V -> L (in dbSNP:rs35600253). FT /FTId=VAR_025167. FT VARIANT 319 319 Missing (in glioma; reduced tumor FT suppressor activity; fails to inactivate FT AKT/PKB). FT /FTId=VAR_026274. FT VARIANT 331 331 D -> G (in CD; reduced phosphatase FT activity towards Ins(1,3,4,5)P4; retains FT ability to bind phospholipid membranes). FT /FTId=VAR_026275. FT VARIANT 341 341 F -> V (in CD; loss of phosphatase FT activity towards Ins(1,3,4,5)P4). FT /FTId=VAR_026276. FT VARIANT 342 342 K -> N (in CD; reduced phosphatase FT activity towards Ins(1,3,4,5)P4 but FT PtdIns(3,4,5)P3 phosphatase activity is FT similar to wild-type). FT /FTId=VAR_026277. FT VARIANT 343 343 V -> E (in CD; loss of phosphatase FT activity towards Ins(1,3,4,5)P4). FT /FTId=VAR_008742. FT VARIANT 345 345 L -> Q (in glioblastoma; reduced tumor FT suppressor activity; loss of phosphatase FT activity towards Ins(1,3,4,5)P4; reduced FT ability to inactivate AKT/PKB; retains FT ability to bind phospholipid membranes). FT /FTId=VAR_026278. FT VARIANT 347 347 F -> L (in CD; reduced phosphatase FT activity towards Ins(1,3,4,5)P4). FT /FTId=VAR_008743. FT VARIANT 348 348 T -> I (in endometrial hyperplasia; FT reduced phosphatase activity towards FT PtdIns(3,4,5)P3; mildly reduced tumor FT suppressor activity; reduced ability to FT inactivate AKT/PKB). FT /FTId=VAR_026279. FT VARIANT 369 369 V -> G (retains Ins(1,3,4,5)P4 and FT PtdIns(3,4,5)P3 phosphatase activity; FT retains ability to bind phospholipid FT membranes). FT /FTId=VAR_026280. FT VARIANT 401 401 T -> I (retains Ins(1,3,4,5)P4 and FT PtdIns(3,4,5)P3 phosphatase activity; FT retains ability to bind phospholipid FT membranes). FT /FTId=VAR_026281. FT MUTAGEN 92 92 D->A: 700-fold reduction in phosphatase FT activity towards PtdIns(3,4,5)P3. Loss of FT protein phosphatase activity. Unable to FT inhibit focal adhesion formation. FT MUTAGEN 93 93 H->A: 75% reduction in phosphatase FT activity towards PtdIns(3,4,5)P3. Modest FT reduction in phosphatase activity towards FT PtsIns(3,4)P2. FT MUTAGEN 124 124 C->A: Loss of protein phosphatase FT activity. Unable to inhibit focal FT adhesion formation. FT MUTAGEN 125 125 K->M: Reduced phosphatase activity FT towards PtdIns(3,4,5)P3, PtsIns(3,4)P2 FT and PtdIns(3)P. FT MUTAGEN 128 128 K->M: 85% reduction in phosphatase FT activity towards PtdIns(3,4,5)P3. FT MUTAGEN 128 128 K->R: Does not reduce phosphatase FT activity towards PtdIns(3,4,5)P3. FT MUTAGEN 130 130 R->M: Does not affect the ability to FT inhibit AKT/PKB activation. FT MUTAGEN 167 167 T->A,D: 60% reduction in phosphatase FT activity towards PtdIns(3,4,5)P3. FT MUTAGEN 171 171 Q->A,E: 75% reduction in phosphatase FT activity towards PtdIns(3,4,5)P3. FT MUTAGEN 263 269 KMLKKDK->AAGAADA: Reduces the growth FT suppression activity and cells show FT anchorage-independent growth. Reduces FT binding to phospholipid membranes in FT vitro. Phosphatase activity towards FT PtdIns(3,4,5)P3 is not affected. FT MUTAGEN 327 335 KANKDKANR->AAGADAANA: Reduces the growth FT suppression activity and cells show FT anchorage-independent growth. Reduces FT binding to phospholipid membranes in FT vitro; phosphatase activity towards FT PtdIns(3,4,5)P3 is not affected. FT MUTAGEN 401 401 T->A: Loss of DLG1-binding. No effect on FT MAGI2- and MAST2-binding. FT MUTAGEN 402 402 K->A: No effect on MAGI2-, MAST2- and FT DLG1-binding. FT MUTAGEN 402 402 K->W: Loss of DLG1-, MAGI2-, MAGI3- and FT MAST2-binding. Decrease of protein FT stability. FT MUTAGEN 403 403 V->A: Loss of DLG1-, MAGI2-, MAGI3-, FT MAST1-, MAST2- and MAST3-binding. FT TURN 19 22 FT STRAND 23 29 FT STRAND 32 35 FT STRAND 39 41 FT HELIX 50 60 FT STRAND 61 63 FT STRAND 65 73 FT STRAND 85 90 FT HELIX 98 100 FT HELIX 101 112 FT TURN 113 115 FT STRAND 118 123 FT STRAND 125 128 FT HELIX 129 141 FT HELIX 148 159 FT STRAND 161 163 FT HELIX 169 184 FT STRAND 192 202 FT STRAND 213 219 FT STRAND 222 226 FT STRAND 232 235 FT STRAND 238 259 FT STRAND 268 276 FT HELIX 277 279 FT STRAND 315 321 FT HELIX 322 324 FT HELIX 328 330 FT STRAND 335 337 FT STRAND 342 349 SQ SEQUENCE 403 AA; 47166 MW; 75F97C3DD6802BA9 CRC64; MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI DDVVRFLDSK HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL IKPFCEDLDQ WLSEDDNHVA AIHCKAGKGR TGVMICAYLL HRGKFLKAQE ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY LLKNHLDYRP VALLFHKMMF ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY FEFPQPLPVC GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT VEEPSNPEAS SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHTQI TKV //