ID PTEN_HUMAN Reviewed; 403 AA. AC P60484; B2R904; F2YHV0; O00633; O02679; Q6ICT7; DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot. DT 16-FEB-2004, sequence version 1. DT 27-MAR-2024, entry version 216. DE RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN {ECO:0000305|PubMed:9256433, ECO:0000305|PubMed:9811831}; DE EC=3.1.3.16 {ECO:0000269|PubMed:9256433}; DE EC=3.1.3.48 {ECO:0000269|PubMed:9187108, ECO:0000269|PubMed:9256433}; DE EC=3.1.3.67 {ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:9811831}; DE AltName: Full=Inositol polyphosphate 3-phosphatase {ECO:0000305|PubMed:11418101, ECO:0000305|PubMed:9593664}; DE EC=3.1.3.- {ECO:0000305|PubMed:11418101, ECO:0000305|PubMed:9593664}; DE AltName: Full=Mutated in multiple advanced cancers 1; DE AltName: Full=Phosphatase and tensin homolog; GN Name=PTEN; Synonyms=MMAC1, TEP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP SUBCELLULAR LOCATION, AND INDUCTION. RC TISSUE=Epithelium; RX PubMed=9187108; RA Li D.M., Sun H.; RT "TEP1, encoded by a candidate tumor suppressor locus, is a novel protein RT tyrosine phosphatase regulated by transforming growth factor beta."; RL Cancer Res. 57:2124-2129(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANTS RP GLIOMA SER-15; GLU-36; ARG-42; TRP-57 AND THR-319 DEL. RX PubMed=9090379; DOI=10.1038/ng0497-356; RA Steck P.A., Pershouse M.A., Jasser S.A., Lin H., Yung W.K.A., Ligon A.H., RA Langford L.A., Baumgard M.L., Hattier T., Davis T., Frye C., Hu R., RA Swedlund B., Teng D.H.-F., Tavtigian S.V.; RT "Identification of a candidate tumour suppressor gene, MMAC1, at chromosome RT 10q23.3 that is mutated in multiple advanced cancers."; RL Nat. Genet. 15:356-363(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLIOBLASTOMA ARG-129, AND RP VARIANT PROSTATE CANCER LEU-134. RX 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 brain, RT 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 associated RT 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 [MRNA] (ISOFORM 3). RA Yang C.-W., Hsu Y.-F.; RT "Homo sapiens phosphatase and tensin homolog mRNA splicing variants."; RL Submitted (JAN-2011) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-290. RG NIEHS SNPs program; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS GLIOMA RP TRP-57; ENDOMETRIAL CANCER TYR-123; GLIOBLASTOMA ARG-129; CWS1 ARG-129; RP PROSTATE CANCER LEU-134; GLIOBLASTOMA ARG-165; BREAST CANCER PRO-167 AND BZ RP ARG-170. RX 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 [14] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-124. RX 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 [15] RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-130, AND CHARACTERIZATION RP OF VARIANTS CWS1 SER-124 AND CWS1 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 suppressor function."; RL Proc. Natl. Acad. Sci. U.S.A. 95:13513-13518(1998). RN [16] 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 [17] RP FUNCTION, DOMAIN, AND CHARACTERIZATION OF VARIANTS THR-319 DEL; GLN-345 AND RP 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 [18] 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., Byreddy D.V., RA 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 [19] RP INTERACTION WITH MAGI3. RX 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 MAGI3, RT a novel membrane-associated guanylate kinase."; RL J. Biol. Chem. 275:21477-21485(2000). RN [20] RP INTERACTION WITH MAGI2. RX 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 [21] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=11418101; DOI=10.1016/s0014-5793(01)02500-5; RA Caffrey J.J., Darden T., Wenk M.R., Shears S.B.; RT "Expanding coincident signaling by PTEN through its inositol 1,3,4,5,6- RT pentakisphosphate 3-phosphatase activity."; RL FEBS Lett. 499:6-10(2001). RN [22] RP PHOSPHORYLATION AT SER-370; SER-380; THR-382; THR-383 AND SER-385. RX PubMed=11035045; DOI=10.1074/jbc.m009134200; RA Torres J., Pulido R.; RT "The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at RT its C terminus. Implications for PTEN stability to proteasome-mediated RT degradation."; RL J. Biol. Chem. 276:993-998(2001). RN [23] RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH MAGI2. RX 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 [24] RP PHOSPHORYLATION AT THR-366; SER-370 AND SER-385. RX 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. 528:145-153(2002). RN [25] RP INTERACTION WITH NOP53, REGION, AND CHARACTERIZATION OF VARIANTS CWS1 RP VAL-341; GLU-343 AND GLN-345. RX PubMed=15355975; DOI=10.1074/jbc.c400377200; RA Okahara F., Ikawa H., Kanaho Y., Maehama T.; RT "Regulation of PTEN phosphorylation and stability by a tumor suppressor RT candidate protein."; RL J. Biol. Chem. 279:45300-45303(2004). RN [26] RP INTERACTION WITH STK11, SUBCELLULAR LOCATION, AND PHOSPHORYLATION BY STK11. RX PubMed=15987703; DOI=10.1093/hmg/ddi225; RA Mehenni H., Lin-Marq N., Buchet-Poyau K., Reymond A., Collart M.A., RA Picard D., Antonarakis S.E.; RT "LKB1 interacts with and phosphorylates PTEN: a functional link between two RT proteins involved in cancer predisposing syndromes."; RL Hum. Mol. Genet. 14:2209-2219(2005). RN [27] 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 serine/threonine RT kinases."; RL J. Biol. Chem. 280:28936-28943(2005). RN [28] RP FUNCTION. RX PubMed=15979280; DOI=10.1016/j.cellsig.2005.05.017; RA Deleu S., Choi K., Pesesse X., Cho J., Sulis M.L., Parsons R., Shears S.B.; RT "Physiological levels of PTEN control the size of the cellular RT Ins(1,3,4,5,6)P(5) pool."; RL Cell. Signal. 18:488-498(2006). RN [29] RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND FUNCTION. RX PubMed=16824732; DOI=10.1016/j.cellsig.2006.05.010; RA Vandeput F., Backers K., Villeret V., Pesesse X., Erneux C.; RT "The influence of anionic lipids on SHIP2 phosphatidylinositol 3,4,5- RT trisphosphate 5-phosphatase activity."; RL Cell. Signal. 18:2193-2199(2006). RN [30] RP INTERACTION WITH NEDD4. RX PubMed=17218260; DOI=10.1016/j.cell.2006.11.039; RA Wang X., Trotman L.C., Koppie T., Alimonti A., Chen Z., Gao Z., Wang J., RA Erdjument-Bromage H., Tempst P., Cordon-Cardo C., Pandolfi P.P., Jiang X.; RT "NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN."; RL Cell 128:129-139(2007). RN [31] RP FUNCTION, INTERACTION WITH USP7, UBIQUITINATION AT LYS-13 AND LYS-289, RP DEUBIQUITINATION BY USP7, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-13 AND RP LYS-289, AND CHARACTERIZATION OF VARIANT CWS1 GLU-289. RX PubMed=18716620; DOI=10.1038/nature07290; RA Song M.S., Salmena L., Carracedo A., Egia A., Lo-Coco F., RA Teruya-Feldstein J., Pandolfi P.P.; RT "The deubiquitinylation and localization of PTEN are regulated by a HAUSP- RT PML network."; RL Nature 455:813-817(2008). RN [32] RP INTERACTION WITH FRK, PHOSPHORYLATION AT TYR-336, AND MUTAGENESIS OF RP TYR-336. RX PubMed=19345329; DOI=10.1016/j.ccr.2009.02.012; RA Yim E.-K., Peng G., Dai H., Hu R., Li K., Lu Y., Mills G.B., RA Meric-Bernstam F., Hennessy B.T., Craven R.J., Lin S.-Y.; RT "Rak functions as a tumor suppressor by regulating PTEN protein stability RT and function."; RL Cancer Cell 15:304-314(2009). RN [33] RP UBIQUITINATION BY XIAP/BIRC4, SUBCELLULAR LOCATION, AND INTERACTION WITH RP XIAP/BIRC4. RX PubMed=19473982; DOI=10.1074/jbc.c109.009522; RA Van Themsche C., Leblanc V., Parent S., Asselin E.; RT "X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN RT ubiquitination, content, and compartmentalization."; RL J. Biol. Chem. 284:20462-20466(2009). RN [34] RP PHOSPHORYLATION AT THR-366 AND SER-370, AND MUTAGENESIS OF THR-366 AND RP SER-370. RX PubMed=20940307; DOI=10.1074/jbc.m110.166462; RA Xu D., Yao Y., Jiang X., Lu L., Dai W.; RT "Regulation of PTEN stability and activity by Plk3."; RL J. Biol. Chem. 285:39935-39942(2010). RN [35] RP INTERACTION WITH NDFIP1 AND NDFIP2. RX PubMed=20534535; DOI=10.1073/pnas.0911714107; RA Mund T., Pelham H.R.; RT "Regulation of PTEN/Akt and MAP kinase signaling pathways by the ubiquitin RT ligase activators Ndfip1 and Ndfip2."; RL Proc. Natl. Acad. Sci. U.S.A. 107:11429-11434(2010). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [37] RP FUNCTION IN CELL MIGRATION. RX PubMed=22279049; DOI=10.1101/gad.177642.111; RA Stohr N., Kohn M., Lederer M., Glass M., Reinke C., Singer R.H., RA Huttelmaier S.; RT "IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling."; RL Genes Dev. 26:176-189(2012). RN [38] RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [39] RP ALTERNATIVE INITIATION (ISOFORM ALPHA), CTG START CODON, FUNCTION (ISOFORM RP ALPHA), AND SUBCELLULAR LOCATION (ISOFORM ALPHA). RX PubMed=23744781; DOI=10.1126/science.1234907; RA Hopkins B.D., Fine B., Steinbach N., Dendy M., Rapp Z., Shaw J., Pappas K., RA Yu J.S., Hodakoski C., Mense S., Klein J., Pegno S., Sulis M.L., RA Goldstein H., Amendolara B., Lei L., Maurer M., Bruce J., Canoll P., RA Hibshoosh H., Parsons R.; RT "A secreted PTEN phosphatase that enters cells to alter signaling and RT survival."; RL Science 341:399-402(2013). RN [40] RP INTERACTION WITH PPP1R16B. RX PubMed=25007873; DOI=10.1152/ajprenal.00070.2014; RA Obeidat M., Li L., Ballermann B.J.; RT "TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in RT human glomerular endothelial cells."; RL Am. J. Physiol. 307:F623-F633(2014). RN [41] RP ALTERNATIVE INITIATION (ISOFORM ALPHA), CTG START CODON, SUBCELLULAR RP LOCATION (ISOFORM ALPHA), AND MUTAGENESIS OF MET-1. RX PubMed=24768297; DOI=10.1016/j.cmet.2014.03.023; RA Liang H., He S., Yang J., Jia X., Wang P., Chen X., Zhang Z., Zou X., RA McNutt M.A., Shen W.H., Yin Y.; RT "PTENalpha, a PTEN isoform translated through alternative initiation, RT regulates mitochondrial function and energy metabolism."; RL Cell Metab. 19:836-848(2014). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-366, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [43] RP INTERACTION WITH NDFIP1, AND SUBCELLULAR LOCATION. RX PubMed=25801959; DOI=10.1093/jmcb/mjv020; RA Howitt J., Low L.H., Putz U., Doan A., Lackovic J., Goh C.P., Gunnersen J., RA Silke J., Tan S.S.; RT "Ndfip1 represses cell proliferation by controlling Pten localization and RT signaling specificity."; RL J. Mol. Cell Biol. 7:119-131(2015). RN [44] RP FUNCTION, INTERACTION WITH TNS3 AND PI3K, PHOSPHORYLATION AT THR-319 AND RP THR-321, AND MUTAGENESIS OF SER-229; THR-232; THR-319 AND THR-321. RX PubMed=26166433; DOI=10.1038/ncomms8721; RA Cao X., Kaneko T., Li J.S., Liu A.D., Voss C., Li S.S.; RT "A phosphorylation switch controls the spatiotemporal activation of Rho RT GTPases in directional cell migration."; RL Nat. Commun. 6:7721-7721(2015). RN [45] RP FUNCTION, AND UBIQUITINATION. RX PubMed=31492966; DOI=10.1007/s00018-019-03280-5; RA Zhang J., Zhang Y.L., Zhao L.W., Pi S.B., Zhang S.Y., Tong C., Fan H.Y.; RT "The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by RT targeting PTEN degradation."; RL Cell. Mol. Life Sci. 77:2181-2197(2020). RN [46] RP FUNCTION, AND ISGYLATION. RX PubMed=37279284; DOI=10.1126/scisignal.abm1756; RA Du X., Sheng J., Chen Y., He S., Yang Y., Huang Y., Fu Y., Lie L., Han Z., RA Zhu B., Liu H., Wen Q., Zhou X., Zhou C., Hu S., Ma L.; RT "The E3 ligase HERC5 promotes antimycobacterial responses in macrophages by RT ISGylating the phosphatase PTEN."; RL Sci. Signal. 16:eabm1756-eabm1756(2023). RN [47] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 8-353 IN COMPLEX WITH RP L(+)-TARTRATE, SUBUNIT, DOMAIN, MUTAGENESIS OF ASP-92; HIS-93; LYS-125; RP LYS-128; THR-167; GLN-171; 263-LYS--ALA-269 AND 327-LYS--ALA-335, AND RP CATALYTIC ACTIVITY. RX PubMed=10555148; DOI=10.1016/s0092-8674(00)81663-3; RA Lee J.-O., Yang H., Georgescu M.-M., Di Cristofano A., Maehama T., Shi Y., RA 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 [48] RP VARIANT CWS1 ASN-137 INS. RX 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., Steck P., RA Ott J., Tavtigian S.V., Peacocke M.; RT "The role of MMAC1 mutations in early-onset breast cancer: causative in RT association with Cowden syndrome and excluded in BRCA1-negative cases."; RL Am. J. Hum. Genet. 61:1036-1043(1997). RN [49] RP VARIANTS CWS1 GLU-343 AND LEU-347. RX 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, Cowden RT disease, and juvenile polyposis."; RL Am. J. Hum. Genet. 61:1254-1260(1997). RN [50] 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., Parsons R.; RT "Somatic mutations of PTEN in glioblastoma multiforme."; RL Cancer Res. 57:4183-4186(1997). RN [51] RP VARIANTS CWS1 ARG-123 AND ARG-124. RX 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., Woods D.G., RA 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 [52] RP VARIANT CWS1 GLU-129. RX PubMed=9140396; DOI=10.1038/ng0597-64; RA Liaw D., Marsh D.J., Li J., Dahia P.L.M., Wang S.I., Zheng Z., Bose S., RA Call K.M., Tsou H.C., Peacocke M., Eng C., Parsons R.; RT "Germline mutations of the PTEN gene in Cowden disease, an inherited breast RT and thyroid cancer syndrome."; RL Nat. Genet. 16:64-67(1997). RN [53] RP VARIANT CWS1 ARG-170. RX 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 [54] 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., Barrett J.C., RA Berchuck A., Futreal P.A.; RT "Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias."; RL Cancer Res. 58:2500-2503(1998). RN [55] RP VARIANT CWS1 GLU-289. RX PubMed=9797362; DOI=10.1016/s0016-5085(98)70078-2; 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 polyps in RT patients with Cowden disease."; RL Gastroenterology 115:1084-1089(1998). RN [56] RP VARIANTS CWS1 HIS-68 AND PRO-112. RX 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 [57] RP VARIANTS CWS1. RX 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., Robinson B.G., RA Weber H.C., Parsons R., Peacocke M., Longy M., Eng C.; RT "Mutation spectrum and genotype-phenotype analyses in Cowden disease and RT Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN RT mutation."; RL Hum. Mol. Genet. 7:507-515(1998). RN [58] RP VARIANT CWS1 TYR-136. RX PubMed=9735393; DOI=10.3892/ijo.13.4.665; 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 kindred."; RL Int. J. Oncol. 13:665-668(1998). RN [59] RP VARIANT CWS1 PRO-70. RX PubMed=9832031; DOI=10.1136/jmg.35.11.881; 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 [60] RP VARIANT CWS1 ARG-35. RX 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 [61] RP VARIANT CWS1 GLN-130. RX 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 polyposis RT of the digestive tract with mutation of the PTEN gene."; RL Am. J. Hum. Genet. 64:308-310(1999). RN [62] RP VARIANT CWS1/LDD PRO-112. RX 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., Root A.W.; RT "Severe Lhermitte-Duclos disease with unique germline mutation of PTEN."; RL Am. J. Med. Genet. 82:290-293(1999). RN [63] RP VARIANTS CWS1 ILE-33 DEL; ARG-123; ARG-124 AND GLU-165. RX PubMed=10234502; DOI=10.1038/sj.ejhg.5200289; RA Nelen M.R., Kremer H., Konings I.B.M., Schoute F., van Essen A.J., Koch R., RA Woods C.G., Fryns J.-P., Hamel B.C.J., Hoefsloot L.H., Peeters E.A.J., RA Padberg G.W.; RT "Novel PTEN mutations in patients with Cowden disease: absence of clear RT genotype-phenotype correlations."; RL Eur. J. Hum. Genet. 7:267-273(1999). RN [64] RP VARIANTS CWS1 ASP-34; HIS-68; TYR-105; VAL-135; ARG-170 AND LEU-246. RX 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., Ahmed S.F., RA Bodurtha J., Crowe C., Curtis M.A., Dasouki M., Dunn T., Feit H., RA Geraghty M.T., Graham J.M. Jr., Hodgson S.V., Hunter A., Korf B.R., RA Manchester D., Miesfeldt S., Murday V.A., Nathanson K.L., Parisi M., RA Pober B., Romano C., Tolmie J.L., Trembath R., Winter R.M., Zackai E.H., RA Zori R.T., Weng L.-P., Dahia P.L.M., Eng C.; RT "PTEN mutation spectrum and genotype-phenotype correlations in Bannayan- RT Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome."; RL Hum. Mol. Genet. 8:1461-1472(1999). RN [65] RP CHARACTERIZATION OF VARIANTS ASN-10; CYS-16; GLU-20; SER-27; ARG-61; RP HIS-68; ARG-112; PRO-121; ARG-129; GLY-130; ILE-133; LEU-134; ARG-165; RP ASN-170; CYS-173; HIS-173; PRO-173; ASN-174; PHE-227; CYS-251; GLN-345; RP GLY-369 AND ILE-401, AND CHARACTERIZATION OF VARIANTS CWS1 TYR-71; TYR-93; RP PHE-105; TYR-107; PRO-112; ARG-124; GLU-129; LEU-130; GLN-130; TYR-136; RP CYS-155; ARG-170; GLU-289; GLY-331; VAL-341; ASN-342; GLU-343 AND LEU-347. RX PubMed=10866302; RA Han S.-Y., Kato H., Kato S., Suzuki T., Shibata H., Ishii S., Shiiba K., RA 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 [66] RP VARIANTS MULTIPLE CANCERS LEU-119 AND LEU-158. RX 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 women RT with multiple cancers."; RL J. Med. Genet. 37:336-341(2000). RN [67] 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 [68] RP CHARACTERIZATION OF VARIANTS CWS1 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 protein RT phosphatase activity and up-regulating p27 via its lipid phosphatase RT activity in a breast cancer model."; RL Hum. Mol. Genet. 10:599-604(2001). RN [69] RP VARIANT 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 macrocephaly, RT ventricular dilatation, and features of VATER association."; RL J. Med. Genet. 38:820-823(2001). RN [70] RP VARIANTS CWS1 ASP-34; GLY-47; HIS-68; TYR-105; VAL-135 AND ARG-170. RX 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 syndromes RT using denaturing high-performance liquid chromatography."; RL Neoplasia 3:236-244(2001). RN [71] RP VARIANT GLM2 GLN-234, AND CHARACTERIZATION OF VARIANT GLM2 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., Taphoorn M.J.B., RA Jansen G.H., van Veelen C.W.M., Burgering B., 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 [72] 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 [73] RP DISCUSSION OF PTEN 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 syndrome."; RL J. Med. Genet. 39:937-940(2002). RN [74] RP VARIANTS MCEPHAS 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., 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 [75] 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., Bill B.R., RA Easterday M.C., Staaf J., Oseth L., Czapansky-Beilman D., Avramopoulos D., RA Thomas G.H., Borg A., Valle D., Schimmenti L.A., Selleck S.B.; RT "Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with RT cognitive and behavioral abnormalities."; RL Am. J. Hum. Genet. 80:938-947(2007). RN [76] 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., Ertem M., RA Deda G., Tutar E., Arsan S., Zhou X.-P., Pilarski R., 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). RN [77] RP VARIANTS MCEPHAS ILE-131 AND ASN-167. RX PubMed=23160955; DOI=10.1126/science.1227764; RA O'Roak B.J., Vives L., Fu W., Egertson J.D., Stanaway I.B., Phelps I.G., RA Carvill G., Kumar A., Lee C., Ankenman K., Munson J., Hiatt J.B., RA Turner E.H., Levy R., O'Day D.R., Krumm N., Coe B.P., Martin B.K., RA Borenstein E., Nickerson D.A., Mefford H.C., Doherty D., Akey J.M., RA Bernier R., Eichler E.E., Shendure J.; RT "Multiplex targeted sequencing identifies recurrently mutated genes in RT autism spectrum disorders."; RL Science 338:1619-1622(2012). RN [78] RP VARIANT MCEPHAS 65-TYR--VAL-403 DEL. RX PubMed=26637798; DOI=10.1016/j.neuron.2015.11.009; RA D'Gama A.M., Pochareddy S., Li M., Jamuar S.S., Reiff R.E., Lam A.T., RA Sestan N., Walsh C.A.; RT "Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates RT Multiple Genetic Mechanisms."; RL Neuron 88:910-917(2015). RN [79] RP VARIANT PROSTATE CANCER GLY-126, CHARACTERIZATION OF VARIANT GLY-126, RP MUTAGENESIS OF ALA-126, AND FUNCTION. RX PubMed=26504226; DOI=10.1073/pnas.1422504112; RA Costa H.A., Leitner M.G., Sos M.L., Mavrantoni A., Rychkova A., RA Johnson J.R., Newton B.W., Yee M.C., De La Vega F.M., Ford J.M., RA Krogan N.J., Shokat K.M., Oliver D., Halaszovich C.R., Bustamante C.D.; RT "Discovery and functional characterization of a neomorphic PTEN mutation."; RL Proc. Natl. Acad. Sci. U.S.A. 112:13976-13981(2015). CC -!- FUNCTION: Dual-specificity protein phosphatase, dephosphorylating CC tyrosine-, serine- and threonine-phosphorylated proteins CC (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a CC lipid phosphatase, removing the phosphate in the D3 position of the CC inositol ring of PtdIns(3,4,5)P3/phosphatidylinositol 3,4,5- CC trisphosphate, PtdIns(3,4)P2/phosphatidylinositol 3,4-diphosphate and CC PtdIns3P/phosphatidylinositol 3-phosphate with a preference for CC PtdIns(3,4,5)P3 (PubMed:9811831, PubMed:16824732, PubMed:26504226, CC PubMed:9593664). Furthermore, this enzyme can also act as a cytosolic CC inositol 3-phosphatase acting on Ins(1,3,4,5,6)P5/inositol 1,3,4,5,6 CC pentakisphosphate and possibly Ins(1,3,4,5)P4/1D-myo-inositol 1,3,4,5- CC tetrakisphosphate (PubMed:11418101, PubMed:15979280). Antagonizes the CC PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides CC and thereby modulating cell cycle progression and cell survival CC (PubMed:31492966, PubMed:37279284). The unphosphorylated form CC cooperates with MAGI2 to suppress AKT1 activation (PubMed:11707428). In CC motile cells, suppresses the formation of lateral pseudopods and CC thereby promotes cell polarization and directed movement CC (PubMed:22279049). Dephosphorylates tyrosine-phosphorylated focal CC adhesion kinase and inhibits cell migration and integrin-mediated cell CC spreading and focal adhesion formation (PubMed:22279049). Required for CC growth factor-induced epithelial cell migration; growth factor CC stimulation induces PTEN phosphorylation which changes its binding CC preference from the p85 regulatory subunit of the PI3K kinase complex CC to DLC1 and results in translocation of the PTEN-DLC1 complex to the CC posterior of migrating cells to promote RHOA activation CC (PubMed:26166433). Meanwhile, TNS3 switches binding preference from CC DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge CC of migrating cells to activate RAC1 activation (PubMed:26166433). Plays CC a role as a key modulator of the AKT-mTOR signaling pathway controlling CC the tempo of the process of newborn neurons integration during adult CC neurogenesis, including correct neuron positioning, dendritic CC development and synapse formation (By similarity). Involved in the CC regulation of synaptic function in excitatory hippocampal synapses. CC Recruited to the postsynaptic membrane upon NMDA receptor activation, CC is required for the modulation of synaptic activity during plasticity. CC Enhancement of lipid phosphatase activity is able to drive depression CC of AMPA receptor-mediated synaptic responses, activity required for CC NMDA receptor-dependent long-term depression (LTD) (By similarity). May CC be a negative regulator of insulin signaling and glucose metabolism in CC adipose tissue. The nuclear monoubiquitinated form possesses greater CC apoptotic potential, whereas the cytoplasmic nonubiquitinated form CC induces less tumor suppressive ability (PubMed:10468583, CC PubMed:18716620). {ECO:0000250|UniProtKB:O08586, CC ECO:0000250|UniProtKB:O54857, ECO:0000269|PubMed:10468583, CC ECO:0000269|PubMed:11418101, ECO:0000269|PubMed:11707428, CC ECO:0000269|PubMed:15979280, ECO:0000269|PubMed:16824732, CC ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:22279049, CC ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26504226, CC ECO:0000269|PubMed:31492966, ECO:0000269|PubMed:37279284, CC ECO:0000269|PubMed:9187108, ECO:0000269|PubMed:9256433, CC ECO:0000269|PubMed:9593664, ECO:0000269|PubMed:9616126, CC ECO:0000269|PubMed:9811831}. CC -!- FUNCTION: [Isoform alpha]: Functional kinase, like isoform 1 it CC antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in CC mitochondrial energetic metabolism by promoting COX activity and ATP CC production, via collaboration with isoform 1 in increasing protein CC levels of PINK1. {ECO:0000269|PubMed:23744781}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5- CC trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- CC inositol-4,5-bisphosphate) + phosphate; Xref=Rhea:RHEA:25017, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57836, CC ChEBI:CHEBI:58456; EC=3.1.3.67; CC Evidence={ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:9811831}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25018; CC Evidence={ECO:0000305|PubMed:16824732}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83421; EC=3.1.3.16; CC Evidence={ECO:0000269|PubMed:9256433}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20630; CC Evidence={ECO:0000305|PubMed:9256433}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:61977; EC=3.1.3.16; CC Evidence={ECO:0000269|PubMed:9256433}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005; CC Evidence={ECO:0000305|PubMed:9256433}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000269|PubMed:9187108, CC ECO:0000269|PubMed:9256433}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10685; CC Evidence={ECO:0000305|PubMed:9256433}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5- CC trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- CC inositol-4,5-bisphosphate) + phosphate; Xref=Rhea:RHEA:43552, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83416, CC ChEBI:CHEBI:83419; Evidence={ECO:0000269|PubMed:16824732, CC ECO:0000269|PubMed:9593664}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43553; CC Evidence={ECO:0000305|PubMed:16824732}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo- CC inositol-3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero- CC 3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphate; CC Xref=Rhea:RHEA:43560, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83420, ChEBI:CHEBI:83423; CC Evidence={ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:9593664}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43561; CC Evidence={ECO:0000305|PubMed:16824732}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + H2O = 1D-myo- CC inositol 1,4,5,6-tetrakisphosphate + phosphate; Xref=Rhea:RHEA:77143, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57627, CC ChEBI:CHEBI:57733; Evidence={ECO:0000269|PubMed:11418101}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77144; CC Evidence={ECO:0000269|PubMed:11418101}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo- CC inositol 1,4,5-trisphosphate + phosphate; Xref=Rhea:RHEA:77155, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57895, CC ChEBI:CHEBI:203600; Evidence={ECO:0000269|PubMed:9593664}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77156; CC Evidence={ECO:0000305|PubMed:9593664}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- ACTIVITY REGULATION: Enzymatic activity is enhanced in the presence of CC phosphatidylserine. {ECO:0000269|PubMed:16824732}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=26 uM for PtdIns(3,4,5)P3 {ECO:0000269|PubMed:11418101}; CC KM=11.5 uM for 1D-myo-inositol 1,3,4-trisphosphate CC {ECO:0000269|PubMed:11418101}; CC KM=4.6 uM for 1D-myo-inositol 1,3,4,5-tetrakisphosphate CC {ECO:0000269|PubMed:11418101}; CC KM=7.1 uM for 1D-myo-inositol 1,3,4,5,6-pentakisphosphate CC {ECO:0000269|PubMed:11418101}; CC Vmax=60 nmol/min/mg enzyme with PtdIns(3,4,5)P3 as substrate CC {ECO:0000269|PubMed:11418101}; CC Vmax=24 nmol/min/mg enzyme with 1D-myo-inositol 1,3,4-trisphosphate CC as substrate {ECO:0000269|PubMed:11418101}; CC Vmax=112 nmol/min/mg enzyme with 1D-myo-inositol CC 1,3,4,5-tetrakisphosphate as substrate {ECO:0000269|PubMed:11418101}; CC Vmax=67 nmol/min/mg enzyme with 1D-myo-inositol CC 1,3,4,5,6-pentakisphosphate as substrate CC {ECO:0000269|PubMed:11418101}; CC -!- SUBUNIT: Monomer. The unphosphorylated form interacts with the second CC PDZ domain of MAGI2 and with DLG1 and MAST2 in vitro (PubMed:10646847, CC PubMed:10760291, PubMed:11707428). Interacts with MAGI2, MAGI3, MAST1 CC and MAST3, but neither with MAST4 nor with DLG5; interaction with MAGI2 CC increases protein stability (PubMed:10748157, PubMed:15951562). CC Interacts with NEDD4 (PubMed:17218260). Interacts with NDFIP1 and CC NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes CC PTEN ubiquitination (PubMed:25801959, PubMed:20534535). Interacts (via CC C2 domain) with FRK (PubMed:19345329). Interacts with USP7; the CC interaction is direct (PubMed:18716620). Interacts with ROCK1 (By CC similarity). Interacts with XIAP/BIRC4 (PubMed:19473982). Interacts CC with STK11; the interaction phosphorylates PTEN (PubMed:15987703). CC Interacts with PPP1R16B (PubMed:25007873). Interacts with NOP53; CC regulates PTEN phosphorylation and increases its stability CC (PubMed:15355975). Interacts (via PDZ domain-binding motif) with DLG4; CC the interaction is induced by NMDA and is required for PTEN location at CC postsynaptic density (By similarity). Interacts with the regulatory p85 CC subunit of the PI3K kinase complex and with Rho GTPase-activating CC protein DLC1; in resting cells, interacts (via C2 tensin-type domain) CC with p85 but, following growth factor stimulation, PTEN is CC phosphorylated which leads to weakened interaction with p85 and CC enhanced interaction (via C2 tensin-type domain) with DLC1 while p85 CC interaction with TNS3 increases (PubMed:26166433). CC {ECO:0000250|UniProtKB:O08586, ECO:0000250|UniProtKB:O54857, CC ECO:0000269|PubMed:10555148, ECO:0000269|PubMed:10646847, CC ECO:0000269|PubMed:10748157, ECO:0000269|PubMed:10760291, CC ECO:0000269|PubMed:11707428, ECO:0000269|PubMed:15355975, CC ECO:0000269|PubMed:15951562, ECO:0000269|PubMed:15987703, CC ECO:0000269|PubMed:17218260, ECO:0000269|PubMed:18716620, CC ECO:0000269|PubMed:19345329, ECO:0000269|PubMed:19473982, CC ECO:0000269|PubMed:20534535, ECO:0000269|PubMed:25007873, CC ECO:0000269|PubMed:25801959, ECO:0000269|PubMed:26166433}. CC -!- INTERACTION: CC P60484; P35226: BMI1; NbExp=7; IntAct=EBI-696162, EBI-2341576; CC P60484; P30260: CDC27; NbExp=7; IntAct=EBI-696162, EBI-994813; CC P60484; Q9P0U4: CXXC1; NbExp=2; IntAct=EBI-696162, EBI-949911; CC P60484; Q16643: DBN1; NbExp=5; IntAct=EBI-696162, EBI-351394; CC P60484; P42685: FRK; NbExp=7; IntAct=EBI-696162, EBI-1383583; CC P60484; O60307: MAST3; NbExp=3; IntAct=EBI-696162, EBI-311420; CC P60484; Q9Y6Q9: NCOA3; NbExp=2; IntAct=EBI-696162, EBI-81196; CC P60484; P46934: NEDD4; NbExp=4; IntAct=EBI-696162, EBI-726944; CC P60484; O14745: NHERF1; NbExp=7; IntAct=EBI-696162, EBI-349787; CC P60484; Q15599: NHERF2; NbExp=5; IntAct=EBI-696162, EBI-1149760; CC P60484; P09619: PDGFRB; NbExp=3; IntAct=EBI-696162, EBI-641237; CC P60484; Q9NRD5: PICK1; NbExp=2; IntAct=EBI-696162, EBI-79165; CC P60484; P62136: PPP1CA; NbExp=2; IntAct=EBI-696162, EBI-357253; CC P60484; Q06830: PRDX1; NbExp=7; IntAct=EBI-696162, EBI-353193; CC P60484; P60484: PTEN; NbExp=9; IntAct=EBI-696162, EBI-696162; CC P60484; O43791: SPOP; NbExp=4; IntAct=EBI-696162, EBI-743549; CC P60484; Q62696: Dlg1; Xeno; NbExp=2; IntAct=EBI-696162, EBI-389325; CC P60484; O88382: Magi2; Xeno; NbExp=3; IntAct=EBI-696162, EBI-696179; CC P60484; Q9JK71: Magi3; Xeno; NbExp=3; IntAct=EBI-696162, EBI-696226; CC P60484; Q9R1L5: Mast1; Xeno; NbExp=3; IntAct=EBI-696162, EBI-491771; CC P60484; Q60592: Mast2; Xeno; NbExp=4; IntAct=EBI-696162, EBI-493888; CC P60484; Q9JHL1: Nherf2; Xeno; NbExp=2; IntAct=EBI-696162, EBI-538451; CC P60484-1; Q19T08: ECSCR; NbExp=4; IntAct=EBI-15722967, EBI-15778214; CC P60484-1; Q5T2D3: OTUD3; NbExp=9; IntAct=EBI-15722967, EBI-16170539; CC P60484-1; P60484-1: PTEN; NbExp=3; IntAct=EBI-15722967, EBI-15722967; CC P60484-1; Q93009: USP7; NbExp=5; IntAct=EBI-15722967, EBI-302474; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15987703, CC ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:19473982, CC ECO:0000269|PubMed:25801959, ECO:0000269|PubMed:9187108}. Nucleus CC {ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:18716620, CC ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:25801959}. Nucleus, PML CC body {ECO:0000269|PubMed:18716620}. Cell projection, dendritic spine CC {ECO:0000250|UniProtKB:O54857}. Postsynaptic density CC {ECO:0000250|UniProtKB:O54857}. Note=Monoubiquitinated form is nuclear. CC Nonubiquitinated form is cytoplasmic. Colocalized with PML and USP7 in CC PML nuclear bodies (PubMed:18716620). XIAP/BIRC4 promotes its nuclear CC localization (PubMed:19473982). Associares with the postsynaptic CC density in response to NMDAR activation (By similarity). CC {ECO:0000250|UniProtKB:O54857, ECO:0000269|PubMed:18716620, CC ECO:0000269|PubMed:19473982}. CC -!- SUBCELLULAR LOCATION: [Isoform alpha]: Secreted CC {ECO:0000269|PubMed:23744781, ECO:0000269|PubMed:24768297}. Note=May be CC secreted via a classical signal peptide and reenter into cells with the CC help of a poly-Arg motif. {ECO:0000269|PubMed:23744781, CC ECO:0000269|PubMed:24768297}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=3; CC Name=1; Synonyms=55kDa; CC IsoId=P60484-1; Sequence=Displayed; CC Name=alpha; Synonyms=70kDa, PTEN-long; CC IsoId=P60484-2; Sequence=VSP_055420; CC Name=3; CC IsoId=P60484-3; Sequence=VSP_055421, VSP_055422, VSP_055423; CC -!- TISSUE SPECIFICITY: Expressed at a relatively high level in all adult CC tissues, including heart, brain, placenta, lung, liver, muscle, kidney CC and pancreas. {ECO:0000269|PubMed:9090379}. CC -!- INDUCTION: Down-regulated by TGFB1. {ECO:0000269|PubMed:9187108}. 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. {ECO:0000269|PubMed:10468583, CC ECO:0000269|PubMed:10555148}. CC -!- PTM: Constitutively phosphorylated by CK2 under normal conditions. CC Phosphorylated in vitro by MAST1, MAST2, MAST3 and STK11. CC Phosphorylation results in an inhibited activity towards PIP3. CC Phosphorylation can both inhibit or promote PDZ-binding. CC Phosphorylation at Tyr-336 by FRK/PTK5 protects this protein from CC ubiquitin-mediated degradation probably by inhibiting its binding to CC NEDD4. Phosphorylation by ROCK1 is essential for its stability and CC activity. Phosphorylation by PLK3 promotes its stability and prevents CC its degradation by the proteasome. Phosphorylated on Thr-319 and Thr- CC 321 in the C2-type tensin domain following EGF stimulation which CC changes its binding preference from the p85 regulatory subunit of the CC PI3K kinase complex to DLC1 (PubMed:26166433). CC {ECO:0000269|PubMed:10646847, ECO:0000269|PubMed:11035045, CC ECO:0000269|PubMed:11707428, ECO:0000269|PubMed:12297295, CC ECO:0000269|PubMed:15951562, ECO:0000269|PubMed:15987703, CC ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:19345329, CC ECO:0000269|PubMed:20940307, ECO:0000269|PubMed:26166433}. CC -!- PTM: Monoubiquitinated; monoubiquitination is increased in presence of CC retinoic acid. Deubiquitinated by USP7; leading to its nuclear CC exclusion. Monoubiquitination of one of either Lys-13 and Lys-289 amino CC acid is sufficient to modulate PTEN compartmentalization. Ubiquitinated CC by XIAP/BIRC4. {ECO:0000269|PubMed:18716620, CC ECO:0000269|PubMed:19473982}. CC -!- PTM: Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, CC leading to its degradation. {ECO:0000269|PubMed:31492966}. CC -!- PTM: ISGylated. ISGylation promotes PTEN degradation. CC {ECO:0000269|PubMed:37279284}. CC -!- DISEASE: Cowden syndrome 1 (CWS1) [MIM:158350]: An autosomal dominant CC hamartomatous polyposis syndrome with age-related penetrance. Cowden CC syndrome is characterized by hamartomatous lesions affecting CC derivatives of ectodermal, mesodermal and endodermal layers, CC macrocephaly, facial trichilemmomas (benign tumors of the hair follicle CC infundibulum), acral keratoses, papillomatous papules, and elevated CC risk for development of several types of malignancy, particularly CC breast carcinoma in women and thyroid carcinoma in both men and women. CC Colon cancer and renal cell carcinoma have also been reported. CC Hamartomas can be found in virtually every organ, but most commonly in CC the skin, gastrointestinal tract, breast and thyroid. CC {ECO:0000269|PubMed:10051160, ECO:0000269|PubMed:10234502, CC ECO:0000269|PubMed:10400993, ECO:0000269|PubMed:10866302, CC ECO:0000269|PubMed:11230179, ECO:0000269|PubMed:11494117, CC ECO:0000269|PubMed:15355975, ECO:0000269|PubMed:18716620, CC ECO:0000269|PubMed:9140396, ECO:0000269|PubMed:9241266, CC ECO:0000269|PubMed:9259288, ECO:0000269|PubMed:9345101, CC ECO:0000269|PubMed:9399897, ECO:0000269|PubMed:9425889, CC ECO:0000269|PubMed:9467011, ECO:0000269|PubMed:9600246, CC ECO:0000269|PubMed:9735393, ECO:0000269|PubMed:9797362, CC ECO:0000269|PubMed:9811831, ECO:0000269|PubMed:9832031, CC ECO:0000269|PubMed:9915974}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Lhermitte-Duclos disease (LDD) [MIM:158350]: A rare disease CC characterized by the occurrence of a slowly enlarging mass within the CC cerebellar cortex corresponding histologically to a cerebellar CC hamartoma. It manifests, most commonly in the third and fourth decades CC of life, with increased intracranial pressure, headache, nausea, CC cerebellar dysfunction, occlusive hydrocephalus, ataxia, visual CC disturbances and other cranial nerve palsies. Various associated CC abnormalities may be present such as megalencephaly, microgyria, CC hydromyelia, polydactyly, partial gigantism, macroglossia. LDD is part CC of the PTEN hamartoma tumor syndromes spectrum that also includes CC Cowden syndrome. Note=The disease is caused by variants affecting the CC gene represented in this entry. CC -!- DISEASE: Squamous cell carcinoma of the head and neck (HNSCC) CC [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. CC The hallmark of cutaneous SCC is malignant transformation of normal CC epidermal keratinocytes. {ECO:0000269|PubMed:11801303}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of CC endometrium, the mucous lining of the uterus. Most endometrial cancers CC are adenocarcinomas, cancers that begin in cells that make and release CC mucus and other fluids. Note=Disease susceptibility is associated with CC variants affecting the gene represented in this entry. CC -!- DISEASE: Note=PTEN mutations are found in a subset of patients with CC Proteus syndrome, a genetically heterogeneous condition. The molecular CC diagnosis of PTEN mutation positive cases classifies Proteus syndrome CC patients as part of the PTEN hamartoma syndrome spectrum. As such, CC patients surviving the early years of Proteus syndrome are likely at a CC greater risk of developing malignancies. CC -!- DISEASE: Glioma 2 (GLM2) [MIM:613028]: Gliomas are benign or malignant CC central nervous system neoplasms derived from glial cells. They CC comprise astrocytomas and glioblastoma multiforme that are derived from CC astrocytes, oligodendrogliomas derived from oligodendrocytes and CC ependymomas derived from ependymocytes. {ECO:0000269|PubMed:12085208}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- DISEASE: Prostate cancer (PC) [MIM:176807]: A malignancy originating in CC tissues of the prostate. Most prostate cancers are adenocarcinomas that CC develop in the acini of the prostatic ducts. Other rare histopathologic CC types of prostate cancer that occur in approximately 5% of patients CC include small cell carcinoma, mucinous carcinoma, prostatic ductal CC carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal CC cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell CC carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:26504226, CC ECO:0000269|PubMed:9072974}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- DISEASE: Macrocephaly/autism syndrome (MCEPHAS) [MIM:605309]: Patients CC have autism spectrum disorders and macrocephaly, with head CC circumferences ranging from +2.5 to +8 SD for age and sex (average head CC circumference +4.0 SD). {ECO:0000269|PubMed:15805158, CC ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:26637798}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Note=A microdeletion of chromosome 10q23 involving BMPR1A and CC PTEN is a cause of chromosome 10q23 deletion syndrome, which shows CC overlapping features of the following three disorders: Bannayan-Zonana CC syndrome, Cowden disease and juvenile polyposis syndrome. CC -!- MISCELLANEOUS: [Isoform alpha]: Produced by alternative initiation at CC an upstream CTG start codon. May contain a signal peptide at positions CC 1-21. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the PTEN phosphatase protein family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/158/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; -; Genomic_DNA. DR EMBL; JF268690; ADZ48535.1; -; mRNA. DR EMBL; CR450306; CAG29302.1; -; mRNA. DR EMBL; AK313581; BAG36351.1; -; mRNA. DR EMBL; DQ073384; AAY57327.1; -; Genomic_DNA. DR EMBL; CH471066; EAW50174.1; -; Genomic_DNA. DR EMBL; BC005821; AAH05821.1; -; mRNA. DR CCDS; CCDS31238.1; -. [P60484-1] DR RefSeq; NP_000305.3; NM_000314.6. [P60484-1] DR RefSeq; NP_001291646.2; NM_001304717.2. DR RefSeq; NP_001291647.1; NM_001304718.1. DR PDB; 1D5R; X-ray; 2.10 A; A=8-353. DR PDB; 2KYL; NMR; -; B=391-403. DR PDB; 4O1V; X-ray; 2.00 A; B=354-368. DR PDB; 5BUG; X-ray; 2.40 A; A/B/C/D=14-351. DR PDB; 5BZX; X-ray; 2.50 A; A/B/C/D=14-351. DR PDB; 5BZZ; X-ray; 2.20 A; A/B/C/D=14-351. DR PDB; 7JTX; X-ray; 3.23 A; A=7-395. DR PDB; 7JUK; X-ray; 3.15 A; A=7-353, A=378-390. DR PDB; 7JUL; X-ray; 2.53 A; A=7-353, A=378-390. DR PDB; 7JVX; X-ray; 3.20 A; A=1-403. DR PDB; 7PC7; X-ray; 2.10 A; E/F=394-403. DR PDBsum; 1D5R; -. DR PDBsum; 2KYL; -. DR PDBsum; 4O1V; -. DR PDBsum; 5BUG; -. DR PDBsum; 5BZX; -. DR PDBsum; 5BZZ; -. DR PDBsum; 7JTX; -. DR PDBsum; 7JUK; -. DR PDBsum; 7JUL; -. DR PDBsum; 7JVX; -. DR PDBsum; 7PC7; -. DR AlphaFoldDB; P60484; -. DR SMR; P60484; -. DR BioGRID; 111700; 845. DR ComplexPortal; CPX-3153; PTEN phosphatase complex. DR CORUM; P60484; -. DR DIP; DIP-35019N; -. DR ELM; P60484; -. DR IntAct; P60484; 82. DR MINT; P60484; -. DR STRING; 9606.ENSP00000361021; -. DR BindingDB; P60484; -. DR ChEMBL; CHEMBL2052032; -. DR DrugBank; DB04327; Phosphatidylethanolamine. DR GuidetoPHARMACOLOGY; 2497; -. DR SwissLipids; SLP:000000849; -. DR TCDB; 1.A.51.2.4; the voltage-gated proton channel (vpc) family. DR CarbonylDB; P60484; -. DR DEPOD; PTEN; -. DR GlyGen; P60484; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P60484; -. DR MetOSite; P60484; -. DR PhosphoSitePlus; P60484; -. DR BioMuta; PTEN; -. DR DMDM; 42560209; -. DR CPTAC; CPTAC-5746; -. DR CPTAC; CPTAC-5747; -. DR CPTAC; CPTAC-5748; -. DR CPTAC; non-CPTAC-5426; -. DR CPTAC; non-CPTAC-5429; -. DR CPTAC; non-CPTAC-5430; -. DR CPTAC; non-CPTAC-5566; -. DR CPTAC; non-CPTAC-5567; -. DR EPD; P60484; -. DR jPOST; P60484; -. DR MassIVE; P60484; -. DR MaxQB; P60484; -. DR PaxDb; 9606-ENSP00000361021; -. DR PeptideAtlas; P60484; -. DR ProteomicsDB; 57209; -. [P60484-1] DR Pumba; P60484; -. DR Antibodypedia; 3420; 2149 antibodies from 53 providers. DR CPTC; P60484; 8 antibodies. DR DNASU; 5728; -. DR Ensembl; ENST00000371953.8; ENSP00000361021.3; ENSG00000171862.15. [P60484-1] DR Ensembl; ENST00000644628.2; ENSP00000494918.2; ENSG00000284792.2. [P60484-1] DR Ensembl; ENST00000688308.1; ENSP00000508752.1; ENSG00000171862.15. [P60484-1] DR Ensembl; ENST00000710385.1; ENSP00000518242.1; ENSG00000284792.2. [P60484-1] DR Ensembl; ENST00000710387.1; ENSP00000518244.1; ENSG00000284792.2. [P60484-2] DR GeneID; 5728; -. DR KEGG; hsa:5728; -. DR MANE-Select; ENST00000371953.8; ENSP00000361021.3; NM_000314.8; NP_000305.3. DR UCSC; uc001kfb.4; human. [P60484-1] DR AGR; HGNC:9588; -. DR CTD; 5728; -. DR DisGeNET; 5728; -. DR GeneCards; PTEN; -. DR GeneReviews; PTEN; -. DR HGNC; HGNC:9588; PTEN. DR HPA; ENSG00000171862; Low tissue specificity. DR MalaCards; PTEN; -. DR MIM; 137800; phenotype. DR MIM; 158350; phenotype. DR MIM; 176807; phenotype. DR MIM; 275355; phenotype. DR MIM; 601728; gene. DR MIM; 605309; phenotype. DR MIM; 608089; phenotype. DR MIM; 612242; phenotype. DR MIM; 613028; phenotype. DR neXtProt; NX_P60484; -. DR OpenTargets; ENSG00000171862; -. DR Orphanet; 397596; Activated PI3K-delta syndrome. DR Orphanet; 109; Bannayan-Riley-Ruvalcaba syndrome. DR Orphanet; 101070; Bilateral frontoparietal polymicrogyria. DR Orphanet; 201; Cowden syndrome. DR Orphanet; 145; Hereditary breast and/or ovarian cancer syndrome. DR Orphanet; 79076; Juvenile polyposis of infancy. DR Orphanet; 65285; Lhermitte-Duclos disease. DR Orphanet; 210548; Macrocephaly-intellectual disability-autism syndrome. DR Orphanet; 744; Proteus syndrome. DR Orphanet; 2969; Proteus-like syndrome. DR Orphanet; 137608; Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome. DR Orphanet; 500481; Squamous cell carcinoma of salivary glands. DR Orphanet; 494547; Squamous cell carcinoma of the hypopharynx. DR Orphanet; 494550; Squamous cell carcinoma of the larynx. DR Orphanet; 502366; Squamous cell carcinoma of the lip. DR Orphanet; 500464; Squamous cell carcinoma of the nasal cavity and paranasal sinuses. DR Orphanet; 502363; Squamous cell carcinoma of the oral cavity. DR Orphanet; 500478; Squamous cell carcinoma of the oropharynx. DR PharmGKB; PA33942; -. DR VEuPathDB; HostDB:ENSG00000171862; -. DR eggNOG; KOG2283; Eukaryota. DR GeneTree; ENSGT00940000154335; -. DR HOGENOM; CLU_020105_5_2_1; -. DR InParanoid; P60484; -. DR OMA; FWLNTYF; -. DR OrthoDB; 5477362at2759; -. DR PhylomeDB; P60484; -. DR TreeFam; TF324513; -. DR BioCyc; MetaCyc:HS10404-MONOMER; -. DR BRENDA; 3.1.3.16; 2681. DR BRENDA; 3.1.3.67; 2681. DR PathwayCommons; P60484; -. DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane. DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol. DR Reactome; R-HSA-199418; Negative regulation of the PI3K/AKT network. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. DR Reactome; R-HSA-5674404; PTEN Loss of Function in Cancer. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases. DR Reactome; R-HSA-8943723; Regulation of PTEN mRNA translation. DR Reactome; R-HSA-8948747; Regulation of PTEN localization. DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity. DR Reactome; R-HSA-8986944; Transcriptional Regulation by MECP2. DR SignaLink; P60484; -. DR SIGNOR; P60484; -. DR BioGRID-ORCS; 5728; 85 hits in 1159 CRISPR screens. DR ChiTaRS; PTEN; human. DR EvolutionaryTrace; P60484; -. DR GeneWiki; PTEN_(gene); -. DR GenomeRNAi; 5728; -. DR Pharos; P60484; Tchem. DR PRO; PR:P60484; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; P60484; Protein. DR Bgee; ENSG00000171862; Expressed in sperm and 191 other cell types or tissues. DR ExpressionAtlas; P60484; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IMP:UniProtKB. DR GO; GO:0042995; C:cell projection; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0035749; C:myelin sheath adaxonal region; ISS:BHF-UCL. DR GO; GO:0043005; C:neuron projection; ISS:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0043220; C:Schmidt-Lanterman incisure; ISS:BHF-UCL. DR GO; GO:0010997; F:anaphase-promoting complex binding; IPI:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0030351; F:inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity; IDA:UniProtKB. DR GO; GO:0051717; F:inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity; IDA:UniProtKB. DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW. DR GO; GO:0140678; F:molecular function inhibitor activity; IMP:DisProt. DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB. DR GO; GO:0052866; F:phosphatidylinositol phosphate phosphatase activity; IDA:UniProt. DR GO; GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity; IDA:UniProtKB. DR GO; GO:0051800; F:phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity; IDA:UniProtKB. DR GO; GO:0004438; F:phosphatidylinositol-3-phosphate phosphatase activity; IDA:UniProtKB. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:BHF-UCL. 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:1990381; F:ubiquitin-specific protease binding; IPI:MGI. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0048854; P:brain morphogenesis; ISS:BHF-UCL. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:BHF-UCL. DR GO; GO:0016477; P:cell migration; ISS:UniProtKB. DR GO; GO:0048870; P:cell motility; IBA:GO_Central. DR GO; GO:0071257; P:cellular response to electrical stimulus; IMP:BHF-UCL. DR GO; GO:0007417; P:central nervous system development; ISS:UniProtKB. DR GO; GO:0032286; P:central nervous system myelin maintenance; ISS:BHF-UCL. DR GO; GO:0021955; P:central nervous system neuron axonogenesis; ISS:BHF-UCL. DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:BHF-UCL. DR GO; GO:0021542; P:dentate gyrus development; ISS:BHF-UCL. DR GO; GO:0048853; P:forebrain morphogenesis; ISS:BHF-UCL. DR GO; GO:0007507; P:heart development; ISS:UniProtKB. DR GO; GO:0007611; P:learning or memory; ISS:BHF-UCL. DR GO; GO:0051179; P:localization; IDA:DisProt. DR GO; GO:0045475; P:locomotor rhythm; ISS:BHF-UCL. DR GO; GO:0007626; P:locomotory behavior; ISS:BHF-UCL. DR GO; GO:0033555; P:multicellular organismal response to stress; ISS:BHF-UCL. DR GO; GO:0050771; P:negative regulation of axonogenesis; ISS:BHF-UCL. DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IDA:UniProtKB. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0045792; P:negative regulation of cell size; ISS:BHF-UCL. DR GO; GO:2000773; P:negative regulation of cellular senescence; ISS:BHF-UCL. DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL. DR GO; GO:0061002; P:negative regulation of dendritic spine morphogenesis; ISS:BHF-UCL. DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IMP:BHF-UCL. DR GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; ISS:BHF-UCL. DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; IMP:UniProtKB. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IDA:BHF-UCL. DR GO; GO:0051548; P:negative regulation of keratinocyte migration; IMP:BHF-UCL. DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:ARUK-UCL. DR GO; GO:0046621; P:negative regulation of organ growth; ISS:BHF-UCL. DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; IMP:UniProtKB. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProt. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:BHF-UCL. DR GO; GO:2000808; P:negative regulation of synaptic vesicle clustering; ISS:BHF-UCL. DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL. DR GO; GO:1903690; P:negative regulation of wound healing, spreading of epidermal cells; IMP:BHF-UCL. DR GO; GO:0007270; P:neuron-neuron synaptic transmission; ISS:BHF-UCL. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome. DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:BHF-UCL. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:BHF-UCL. DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISS:BHF-UCL. DR GO; GO:1904668; P:positive regulation of ubiquitin protein ligase activity; IDA:BHF-UCL. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IDA:BHF-UCL. DR GO; GO:0097107; P:postsynaptic density assembly; ISS:BHF-UCL. DR GO; GO:0060134; P:prepulse inhibition; ISS:BHF-UCL. DR GO; GO:0097105; P:presynaptic membrane assembly; ISS:BHF-UCL. DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB. DR GO; GO:0050821; P:protein stabilization; IDA:BHF-UCL. DR GO; GO:0032535; P:regulation of cellular component size; ISS:BHF-UCL. DR GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB. DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central. DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB. DR GO; GO:0060024; P:rhythmic synaptic transmission; ISS:BHF-UCL. DR GO; GO:0035176; P:social behavior; ISS:BHF-UCL. DR GO; GO:0007056; P:spindle assembly involved in female meiosis; IDA:UniProt. DR GO; GO:0007416; P:synapse assembly; ISS:BHF-UCL. DR GO; GO:0060074; P:synapse maturation; ISS:BHF-UCL. DR CDD; cd14509; PTP_PTEN; 1. DR Gene3D; 2.60.40.1110; -; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR InterPro; IPR017361; Bifunc_PIno_P3_Pase/Pase_PTEN. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR000242; PTP_cat. DR InterPro; IPR045101; PTP_PTEN. DR InterPro; IPR014020; Tensin_C2-dom. DR InterPro; IPR029023; Tensin_phosphatase. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR003595; Tyr_Pase_cat. DR InterPro; IPR000387; Tyr_Pase_dom. DR PANTHER; PTHR12305; PHOSPHATASE WITH HOMOLOGY TO TENSIN; 1. DR PANTHER; PTHR12305:SF81; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE 3-PHOSPHATASE AND DUAL-SPECIFICITY PROTEIN PHOSPHATASE PTEN; 1. DR Pfam; PF10409; PTEN_C2; 1. DR Pfam; PF00102; Y_phosphatase; 1. DR PIRSF; PIRSF038025; PTEN; 1. DR SMART; SM01326; PTEN_C2; 1. DR SMART; SM00404; PTPc_motif; 1. DR SMART; SM01301; PTPlike_phytase; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR PROSITE; PS51182; C2_TENSIN; 1. DR PROSITE; PS51181; PPASE_TENSIN; 1. DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1. DR Genevisible; P60484; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative initiation; Alternative splicing; KW Apoptosis; Autism spectrum disorder; Cell projection; Cytoplasm; KW Disease variant; Hydrolase; Isopeptide bond; Lipid metabolism; KW Lipid-binding; Neurogenesis; Nucleus; Phosphoprotein; Protein phosphatase; KW Reference proteome; Secreted; Synapse; Tumor suppressor; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..403 FT /note="Phosphatidylinositol 3,4,5-trisphosphate 3- FT phosphatase and dual-specificity protein phosphatase PTEN" FT /id="PRO_0000215904" FT DOMAIN 14..185 FT /note="Phosphatase tensin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590" FT DOMAIN 190..350 FT /note="C2 tensin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00589" FT REGION 338..348 FT /note="Required for interaction with NOP53" FT /evidence="ECO:0000269|PubMed:15355975" FT REGION 352..403 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 401..403 FT /note="PDZ domain-binding" FT /evidence="ECO:0000250|UniProtKB:O08586" FT COMPBIAS 353..370 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 371..385 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 124 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 294 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08586" FT MOD_RES 319 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26166433" FT MOD_RES 321 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26166433" FT MOD_RES 336 FT /note="Phosphotyrosine; by FRK" FT /evidence="ECO:0000269|PubMed:19345329" FT MOD_RES 366 FT /note="Phosphothreonine; by GSK3-beta and PLK3" FT /evidence="ECO:0000269|PubMed:12297295, FT ECO:0000269|PubMed:20940307, ECO:0007744|PubMed:24275569" FT MOD_RES 370 FT /note="Phosphoserine; by CK2 and PLK3" FT /evidence="ECO:0000269|PubMed:11035045, FT ECO:0000269|PubMed:12297295, ECO:0000269|PubMed:20940307" FT MOD_RES 380 FT /note="Phosphoserine; by ROCK1 and CK2" FT /evidence="ECO:0000269|PubMed:11035045" FT MOD_RES 382 FT /note="Phosphothreonine; by ROCK1 and CK2" FT /evidence="ECO:0000269|PubMed:11035045" FT MOD_RES 383 FT /note="Phosphothreonine; by ROCK1 and CK2" FT /evidence="ECO:0000269|PubMed:11035045" FT MOD_RES 385 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:11035045, FT ECO:0000269|PubMed:12297295" FT MOD_RES 401 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:10646847" FT CROSSLNK 13 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18716620" FT CROSSLNK 289 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18716620" FT VAR_SEQ 1 FT /note="M -> MERGGEAAAAAAAAAAAPGRGSESPVTISRAGNAGELVSPLLLPPTR FT RRRRRHIQGPGPVLNLPSAAAAPPVARAPEAAGGGSRSEDYSSSPHSAAAAARPLAAEE FT KQAQSLQPSSSRRSSHYPAAVQSQAAAERGASATAKSRAISILQKKPRHQQLLPSLSSF FT FFSHRLPDM (in isoform alpha)" FT /evidence="ECO:0000305" FT /id="VSP_055420" FT VAR_SEQ 55..70 FT /note="RFLDSKHKNHYKIYNL -> S (in isoform 3)" FT /evidence="ECO:0000303|Ref.7" FT /id="VSP_055421" FT VAR_SEQ 165..190 FT /note="GVTIPSQRRYVYYYSYLLKNHLDYRP -> ADPTGGIPDKGIIVIGDGSSMD FT VIAP (in isoform 3)" FT /evidence="ECO:0000303|Ref.7" FT /id="VSP_055422" FT VAR_SEQ 191..403 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.7" FT /id="VSP_055423" FT VARIANT 10 FT /note="S -> N (retains phosphatase activity towards FT Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to FT bind phospholipid membranes)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026248" FT VARIANT 15 FT /note="R -> S (in glioma; dbSNP:rs1064794096)" FT /evidence="ECO:0000269|PubMed:9090379" FT /id="VAR_007457" FT VARIANT 16 FT /note="Y -> C (loss of phosphatase activity towards FT Ins(1,3,4,5)P4; retains the ability to bind phospholipid FT membranes)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026249" FT VARIANT 19 FT /note="D -> N (in malignant melanoma; somatic mutation; FT dbSNP:rs121909233)" FT /evidence="ECO:0000269|PubMed:10978354" FT /id="VAR_018100" FT VARIANT 20 FT /note="G -> E (reduced phosphatase activity towards FT Ins(1,3,4,5)P4; retains phosphatase activity towards FT PtdIns(3,4,5)P3; dbSNP:rs1064795967)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026250" FT VARIANT 27 FT /note="Y -> S (loss of phosphatase activity towards FT Ins(1,3,4,5)P4; dbSNP:rs886041877)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026251" FT VARIANT 33 FT /note="Missing (in CWS1; dbSNP:rs1554893765)" FT /evidence="ECO:0000269|PubMed:10234502" FT /id="VAR_008733" FT VARIANT 34 FT /note="A -> D (in CWS1)" FT /evidence="ECO:0000269|PubMed:10400993, FT ECO:0000269|PubMed:11494117" FT /id="VAR_008734" FT VARIANT 35 FT /note="M -> R (in CWS1; dbSNP:rs121909225)" FT /evidence="ECO:0000269|PubMed:9425889" FT /id="VAR_008036" FT VARIANT 36 FT /note="G -> E (in glioma; dbSNP:rs1554893792)" FT /evidence="ECO:0000269|PubMed:9090379" FT /id="VAR_007458" FT VARIANT 36 FT /note="G -> R (in endometrial hyperplasia; FT dbSNP:rs786204854)" FT /evidence="ECO:0000269|PubMed:9635567" FT /id="VAR_026252" FT VARIANT 42 FT /note="L -> R (in glioma; retains phosphatase activity FT towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the FT ability to bind phospholipid membranes)" FT /evidence="ECO:0000269|PubMed:9090379" FT /id="VAR_007459" FT VARIANT 47 FT /note="R -> G (in CWS1; dbSNP:rs786204855)" FT /evidence="ECO:0000269|PubMed:11494117" FT /id="VAR_011587" FT VARIANT 57 FT /note="L -> W (in glioma; loss of protein phosphatase FT activity; dbSNP:rs786202398)" FT /evidence="ECO:0000269|PubMed:9090379, FT ECO:0000269|PubMed:9256433" FT /id="VAR_007460" FT VARIANT 61 FT /note="H -> D (found in a patient with congenital cardiac FT disease, macrocephaly, ventriculomegaly, skeletal defects, FT anal atresia, tracheoesophageal fistula, renal anomalies; FT uncertain significance; dbSNP:rs121909236)" FT /evidence="ECO:0000269|PubMed:11748304" FT /id="VAR_018101" FT VARIANT 61 FT /note="H -> R (loss of phosphatase activity towards FT Ins(1,3,4,5)P4; dbSNP:rs398123316)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026253" FT VARIANT 65..403 FT /note="Missing (in MCEPHAS)" FT /evidence="ECO:0000269|PubMed:26637798" FT /id="VAR_078705" FT VARIANT 67 FT /note="I -> R (in CWS1)" FT /id="VAR_007461" FT VARIANT 68 FT /note="Y -> H (in CWS1; loss of phosphatase activity FT towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the FT ability to bind phospholipid membranes; dbSNP:rs398123317)" FT /evidence="ECO:0000269|PubMed:10400993, FT ECO:0000269|PubMed:10866302, ECO:0000269|PubMed:11494117, FT ECO:0000269|PubMed:9600246" FT /id="VAR_007462" FT VARIANT 70 FT /note="L -> P (in CWS1; dbSNP:rs121909226)" FT /evidence="ECO:0000269|PubMed:9832031" FT /id="VAR_018102" FT VARIANT 71 FT /note="C -> Y (in CWS1; loss of phosphatase activity FT towards Ins(1,3,4,5)P4)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026254" FT VARIANT 93 FT /note="H -> R (in MCEPHAS; dbSNP:rs121909238)" FT /evidence="ECO:0000269|PubMed:15805158" FT /id="VAR_032634" FT VARIANT 93 FT /note="H -> Y (in CWS1; dbSNP:rs786204927)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026255" FT VARIANT 105 FT /note="C -> F (in CWS1; loss of phosphatase activity FT towards Ins(1,3,4,5)P4)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026256" FT VARIANT 105 FT /note="C -> Y (in CWS1; dbSNP:rs587782343)" FT /evidence="ECO:0000269|PubMed:10400993, FT ECO:0000269|PubMed:11494117" FT /id="VAR_008735" FT VARIANT 107 FT /note="D -> Y (in CWS1 and glioblastoma; loss of FT phosphatase activity towards Ins(1,3,4,5)P4; FT dbSNP:rs57374291)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:9331071" FT /id="VAR_026257" FT VARIANT 112 FT /note="L -> P (in CWS1 and LDD; loss of phosphatase FT activity towards Ins(1,3,4,5)P4; dbSNP:rs121909230)" FT /evidence="ECO:0000269|PubMed:10051160, FT ECO:0000269|PubMed:10866302, ECO:0000269|PubMed:9600246" FT /id="VAR_007807" FT VARIANT 112 FT /note="L -> R (loss of phosphatase activity towards FT Ins(1,3,4,5)P4)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026258" FT VARIANT 119 FT /note="V -> L (in multiple cancers; dbSNP:rs139767111)" FT /evidence="ECO:0000269|PubMed:10807691" FT /id="VAR_011588" FT VARIANT 121 FT /note="A -> G (in HNSCC; dbSNP:rs121909237)" FT /evidence="ECO:0000269|PubMed:11801303" FT /id="VAR_018103" FT VARIANT 121 FT /note="A -> P (in glioblastoma; loss of phosphatase FT activity towards Ins(1,3,4,5)P4)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:9331071" FT /id="VAR_026259" FT VARIANT 123 FT /note="H -> R (in CWS1; dbSNP:rs121909222)" FT /evidence="ECO:0000269|PubMed:10234502, FT ECO:0000269|PubMed:9259288" FT /id="VAR_007463" FT VARIANT 123 FT /note="H -> Y (in endometrial cancer; loss of protein FT phosphatase activity; dbSNP:rs786204931)" FT /evidence="ECO:0000269|PubMed:9256433" FT /id="VAR_026260" FT VARIANT 124 FT /note="C -> R (in CWS1; dbSNP:rs121909223)" FT /evidence="ECO:0000269|PubMed:10234502, FT ECO:0000269|PubMed:10866302, ECO:0000269|PubMed:9259288" FT /id="VAR_007464" FT VARIANT 124 FT /note="C -> S (in CWS1; phosphatase-dead protein with FT neither lipid nor protein phosphatase activity; FT dbSNP:rs121909223)" FT /evidence="ECO:0000269|PubMed:11230179, FT ECO:0000269|PubMed:9811831" FT /id="VAR_018104" FT VARIANT 126 FT /note="A -> G (in a patient with prostate cancer; reduced FT phosphatase activity towards PtdIns(3,4,5); shifts its FT activity from phosphatidylinositol phosphate 3-phosphatase FT to phosphatidylinositol phosphate 5-phosphatase; disrupts FT PI3K/ATK signaling; reduced cell migration)" FT /evidence="ECO:0000269|PubMed:26504226" FT /id="VAR_076551" FT VARIANT 129 FT /note="G -> E (in CWS1; no lipid phosphatase activity but FT retains protein phosphatase activity; retains ability to FT inhibit focal adhesion formation; dbSNP:rs121909218)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:11230179, ECO:0000269|PubMed:9140396, FT ECO:0000269|PubMed:9616126, ECO:0000269|PubMed:9811831" FT /id="VAR_007465" FT VARIANT 129 FT /note="G -> R (in glioblastoma; severely reduced protein FT phosphatase activity; loss of phosphatase activity towards FT Ins(1,3,4,5)P4; dbSNP:rs786204929)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:9072974, ECO:0000269|PubMed:9256433, FT ECO:0000269|PubMed:9331071" FT /id="VAR_007466" FT VARIANT 130 FT /note="R -> G (loss of phosphatase activity towards FT Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; dbSNP:rs121909224)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026261" FT VARIANT 130 FT /note="R -> L (in CWS1 and endometrial hyperplasia; loss of FT phosphatase activity towards Ins(1,3,4,5)P4; retains FT ability to bind phospholipid membranes; dbSNP:rs121909229)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:9635567" FT /id="VAR_007467" FT VARIANT 130 FT /note="R -> Q (in CWS1; loss of phosphatase activity FT towards Ins(1,3,4,5)P4; retains ability to bind FT phospholipid membranes; dbSNP:rs121909229)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:9915974" FT /id="VAR_007468" FT VARIANT 131 FT /note="T -> I (in MCEPHAS; dbSNP:rs397514560)" FT /evidence="ECO:0000269|PubMed:23160955" FT /id="VAR_076762" FT VARIANT 132 FT /note="G -> V (in one patient with clinical findings FT suggesting hamartoma tumor syndrome; dbSNP:rs121909241)" FT /evidence="ECO:0000269|PubMed:16752378" FT /id="VAR_032635" FT VARIANT 133 FT /note="V -> I (loss of phosphatase activity towards FT Ins(1,3,4,5)P3)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026262" FT VARIANT 134 FT /note="M -> L (in prostate cancer; no effect on protein FT phosphatase activity; reduced phosphatase activity towards FT Ins(1,3,4,5)P3 but retains PtdIns(3,4,5)P3 phosphatase FT activity)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:9072974, ECO:0000269|PubMed:9256433" FT /id="VAR_007469" FT VARIANT 135 FT /note="I -> V (in CWS1; dbSNP:rs587782360)" FT /evidence="ECO:0000269|PubMed:10400993, FT ECO:0000269|PubMed:11494117" FT /id="VAR_008736" FT VARIANT 136 FT /note="C -> Y (in CWS1; loss of phosphatase activity FT towards Ins(1,3,4,5)P3; dbSNP:rs786204859)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:9735393" FT /id="VAR_007808" FT VARIANT 137 FT /note="A -> AN (in CWS1)" FT /evidence="ECO:0000269|PubMed:9345101" FT /id="VAR_008737" FT VARIANT 155 FT /note="Y -> C (in CWS1; loss of phosphatase activity FT towards Ins(1,3,4,5)P4; dbSNP:rs1060500126)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026263" FT VARIANT 158 FT /note="V -> L (in multiple cancers)" FT /evidence="ECO:0000269|PubMed:10807691" FT /id="VAR_011589" FT VARIANT 165 FT /note="G -> E (in CWS1)" FT /evidence="ECO:0000269|PubMed:10234502" FT /id="VAR_008739" FT VARIANT 165 FT /note="G -> R (in glioblastoma; severely reduced protein FT phosphatase activity; loss of phosphatase activity towards FT Ins(1,3,4,5)P4; retains ability to bind phospholipid FT membranes; dbSNP:rs587782603)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:9256433, ECO:0000269|PubMed:9331071" FT /id="VAR_026264" FT VARIANT 165 FT /note="G -> V (in CWS1; dbSNP:rs786204863)" FT /id="VAR_008738" FT VARIANT 167 FT /note="T -> N (in MCEPHAS; dbSNP:rs397514559)" FT /evidence="ECO:0000269|PubMed:23160955" FT /id="VAR_076763" FT VARIANT 167 FT /note="T -> P (in breast cancer; severely reduced protein FT phosphatase activity)" FT /evidence="ECO:0000269|PubMed:9256433" FT /id="VAR_026265" FT VARIANT 170 FT /note="S -> N (loss of phosphatase activity towards FT Ins(1,3,4,5)P4; retains ability to bind phospholipid FT membranes)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026266" FT VARIANT 170 FT /note="S -> R (in CWS1; severely reduced protein FT phosphatase activity; loss of phosphatase activity towards FT Ins(1,3,4,5)P4; dbSNP:rs121909221)" FT /evidence="ECO:0000269|PubMed:10400993, FT ECO:0000269|PubMed:10866302, ECO:0000269|PubMed:11494117, FT ECO:0000269|PubMed:9241266, ECO:0000269|PubMed:9256433" FT /id="VAR_007470" FT VARIANT 173 FT /note="R -> C (in endometrial hyperplasia; loss of FT phosphatase activity towards Ins(1,3,4,5)P4 and FT PtdIns(3,4,5)P3; retains ability to bind phospholipid FT membranes; dbSNP:rs121913293)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:9635567" FT /id="VAR_026267" FT VARIANT 173 FT /note="R -> H (loss of phosphatase activity towards FT Ins(1,3,4,5)P4; dbSNP:rs121913294)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026268" FT VARIANT 173 FT /note="R -> P (loss of phosphatase activity towards FT Ins(1,3,4,5)P4; dbSNP:rs121913294)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026269" FT VARIANT 174 FT /note="Y -> N (loss of phosphatase activity towards FT Ins(1,3,4,5)P4; dbSNP:rs587782316)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026270" FT VARIANT 191 FT /note="V -> A (in endometrial hyperplasia)" FT /evidence="ECO:0000269|PubMed:9635567" FT /id="VAR_026271" FT VARIANT 217 FT /note="V -> I (in malignant melanoma; somatic mutation; FT dbSNP:rs121909234)" FT /evidence="ECO:0000269|PubMed:10978354" FT /id="VAR_018105" FT VARIANT 227 FT /note="S -> F (reduced phosphatase activity towards FT Ins(1,3,4,5)P4; retains PtdIns(3,4,5)P3 phosphatase FT activity; dbSNP:rs905615413)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026272" FT VARIANT 234 FT /note="R -> Q (in GLM2; not capable of inducing apoptosis; FT induced increased cell proliferation; led to high FT constitutive AKT1 activation which could not be increased FT further by stimulation with insulin; dbSNP:rs121909235)" FT /evidence="ECO:0000269|PubMed:12085208" FT /id="VAR_018106" FT VARIANT 241 FT /note="F -> S (in MCEPHAS; dbSNP:rs121909240)" FT /evidence="ECO:0000269|PubMed:15805158" FT /id="VAR_032636" FT VARIANT 246 FT /note="P -> L (in CWS1; dbSNP:rs587782350)" FT /evidence="ECO:0000269|PubMed:10400993" FT /id="VAR_008740" FT VARIANT 251 FT /note="G -> C (loss of phosphatase activity towards FT Ins(1,3,4,5)P4; retains ability to bind phospholipid FT membranes)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026273" FT VARIANT 252 FT /note="D -> G (in MCEPHAS; dbSNP:rs121909239)" FT /evidence="ECO:0000269|PubMed:15805158" FT /id="VAR_032637" FT VARIANT 289 FT /note="K -> E (in CWS1; reduced phosphatase activity FT towards Ins(1,3,4,5)P4; retains ability to bind FT phospholipid membranes; predominantly nuclear; FT dbSNP:rs562015640)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:9797362" FT /id="VAR_008741" FT VARIANT 290 FT /note="V -> L (in dbSNP:rs35600253)" FT /evidence="ECO:0000269|Ref.10" FT /id="VAR_025167" FT VARIANT 319 FT /note="Missing (in glioma; reduced tumor suppressor FT activity; fails to inactivate AKT/PKB)" FT /evidence="ECO:0000269|PubMed:10468583, FT ECO:0000269|PubMed:9090379" FT /id="VAR_026274" FT VARIANT 331 FT /note="D -> G (in CWS1; reduced phosphatase activity FT towards Ins(1,3,4,5)P4; retains ability to bind FT phospholipid membranes)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026275" FT VARIANT 341 FT /note="F -> V (in CWS1; loss of interaction with NOP53; FT decreased phosphorylation at S-380; decreased stability; FT loss of phosphatase activity towards Ins(1,3,4,5)P4; FT dbSNP:rs1554825652)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:15355975" FT /id="VAR_026276" FT VARIANT 342 FT /note="K -> N (in CWS1; reduced phosphatase activity FT towards Ins(1,3,4,5)P4 but PtdIns(3,4,5)P3 phosphatase FT activity is similar to wild-type; dbSNP:rs398123314)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026277" FT VARIANT 343 FT /note="V -> E (in CWS1; loss of interaction with NOP53; FT decreased phosphorylation at S-380; decreased stability; FT loss of phosphatase activity towards Ins(1,3,4,5)P4)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:15355975, ECO:0000269|PubMed:9399897" FT /id="VAR_008742" FT VARIANT 345 FT /note="L -> Q (in glioblastoma; reduced tumor suppressor FT activity; loss of interaction with NOP53; decreased FT phosphorylation at S-380; decreased stability; loss of FT phosphatase activity towards Ins(1,3,4,5)P4; reduced FT ability to inactivate AKT/PKB; retains ability to bind FT phospholipid membranes)" FT /evidence="ECO:0000269|PubMed:10468583, FT ECO:0000269|PubMed:10866302, ECO:0000269|PubMed:15355975, FT ECO:0000269|PubMed:9331071" FT /id="VAR_026278" FT VARIANT 347 FT /note="F -> L (in CWS1; reduced phosphatase activity FT towards Ins(1,3,4,5)P4)" FT /evidence="ECO:0000269|PubMed:10866302, FT ECO:0000269|PubMed:9399897" FT /id="VAR_008743" FT VARIANT 348 FT /note="T -> I (in endometrial hyperplasia; reduced FT phosphatase activity towards PtdIns(3,4,5)P3; mildly FT reduced tumor suppressor activity; reduced ability to FT inactivate AKT/PKB)" FT /evidence="ECO:0000269|PubMed:10468583, FT ECO:0000269|PubMed:9635567" FT /id="VAR_026279" FT VARIANT 369 FT /note="V -> G (retains Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 FT phosphatase activity; retains ability to bind phospholipid FT membranes)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026280" FT VARIANT 401 FT /note="T -> I (retains Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 FT phosphatase activity; retains ability to bind phospholipid FT membranes)" FT /evidence="ECO:0000269|PubMed:10866302" FT /id="VAR_026281" FT MUTAGEN 1 FT /note="M->I: Prevents expression of isoform 1 and increased FT expression of isoform alpha." FT /evidence="ECO:0000269|PubMed:24768297" FT MUTAGEN 13 FT /note="K->E: Nuclear. Cytoplasmic; when associated with FT E-289. Shows less tumor suppressive ability; when FT associated with E-289." FT /evidence="ECO:0000269|PubMed:18716620" FT MUTAGEN 92 FT /note="D->A: 700-fold reduction in phosphatase activity FT towards PtdIns(3,4,5)P3. Loss of protein phosphatase FT activity. Unable to inhibit focal adhesion formation." FT /evidence="ECO:0000269|PubMed:10555148, FT ECO:0000269|PubMed:9616126" FT MUTAGEN 93 FT /note="H->A: 75% reduction in phosphatase activity towards FT PtdIns(3,4,5)P3. Modest reduction in phosphatase activity FT towards PtdIns(3,4)P2." FT /evidence="ECO:0000269|PubMed:10555148" FT MUTAGEN 124 FT /note="C->A: Loss of protein phosphatase activity. Unable FT to inhibit focal adhesion formation." FT /evidence="ECO:0000269|PubMed:9616126" FT MUTAGEN 124 FT /note="C->S: Loss of FT phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase FT activity." FT /evidence="ECO:0000269|PubMed:9593664" FT MUTAGEN 125 FT /note="K->M: Reduced phosphatase activity towards FT PtdIns(3,4,5)P3, PtdIns(3,4)P2 and PtdIns(3)P." FT /evidence="ECO:0000269|PubMed:10555148" FT MUTAGEN 126 FT /note="A->P: Does not reduce phosphatase activity towards FT PtdIns(3,4,5)P3 and PtdIns(3,4)P2." FT /evidence="ECO:0000269|PubMed:26504226" FT MUTAGEN 126 FT /note="A->S: Does not reduce phosphatase activity towards FT PtdIns(3,4,5)P3 and PtdIns(3,4)P2." FT /evidence="ECO:0000269|PubMed:26504226" FT MUTAGEN 126 FT /note="A->V: Does not reduce phosphatase activity towards FT PtdIns(3,4,5)P3 and PtdIns(3,4)P2." FT /evidence="ECO:0000269|PubMed:26504226" FT MUTAGEN 128 FT /note="K->M: 85% reduction in phosphatase activity towards FT PtdIns(3,4,5)P3." FT /evidence="ECO:0000269|PubMed:10555148" FT MUTAGEN 128 FT /note="K->R: Does not reduce phosphatase activity towards FT PtdIns(3,4,5)P3." FT /evidence="ECO:0000269|PubMed:10555148" FT MUTAGEN 130 FT /note="R->M: Does not affect the ability to inhibit AKT/PKB FT activation." FT /evidence="ECO:0000269|PubMed:9811831" FT MUTAGEN 167 FT /note="T->A,D: 60% reduction in phosphatase activity FT towards PtdIns(3,4,5)P3." FT /evidence="ECO:0000269|PubMed:10555148" FT MUTAGEN 171 FT /note="Q->A,E: 75% reduction in phosphatase activity FT towards PtdIns(3,4,5)P3." FT /evidence="ECO:0000269|PubMed:10555148" FT MUTAGEN 229 FT /note="S->A: No effect on interaction with DLC1 or p85." FT /evidence="ECO:0000269|PubMed:26166433" FT MUTAGEN 232 FT /note="T->A: No effect on interaction with DLC1 or p85." FT /evidence="ECO:0000269|PubMed:26166433" FT MUTAGEN 263..269 FT /note="KMLKKDK->AAGAADA: Reduces the growth suppression FT activity and cells show anchorage-independent growth. FT Reduces binding to phospholipid membranes in vitro. FT Phosphatase activity towards PtdIns(3,4,5)P3 is not FT affected." FT /evidence="ECO:0000269|PubMed:10555148" FT MUTAGEN 289 FT /note="K->E: Cytoplasmic; when associated with E-13. Shows FT less tumor suppressive ability; when associated with E-13." FT /evidence="ECO:0000269|PubMed:18716620" FT MUTAGEN 319 FT /note="T->A: Reduces phosphorylation of the C2 tensin-like FT domain and abolishes interaction with DLC1 following EGF FT stimulation. Abolishes phosphorylation of the C2 FT tensin-like domain; when associated with A-321." FT /evidence="ECO:0000269|PubMed:26166433" FT MUTAGEN 319 FT /note="T->E: Constitutive interaction with DLC1." FT /evidence="ECO:0000269|PubMed:26166433" FT MUTAGEN 319 FT /note="T->Y: Constitutive interaction with DLC1 and FT interaction with p85 following EGF stimulation." FT /evidence="ECO:0000269|PubMed:26166433" FT MUTAGEN 321 FT /note="T->A: Reduces phosphorylation of the C2 tensin-like FT domain and abolishes interaction with DLC1 following EGF FT stimulation. Abolishes phosphorylation of the C2 FT tensin-like domain; when associated with A-319." FT /evidence="ECO:0000269|PubMed:26166433" FT MUTAGEN 321 FT /note="T->E: Constitutive interaction with DLC1." FT /evidence="ECO:0000269|PubMed:26166433" FT MUTAGEN 327..335 FT /note="KANKDKANR->AAGADAANA: Reduces growth suppression FT activity and promotes anchorage-independent growth. Reduces FT binding to phospholipid membranes in vitro; phosphatase FT activity towards PtdIns(3,4,5)P3 is not affected." FT /evidence="ECO:0000269|PubMed:10555148" FT MUTAGEN 336 FT /note="Y->F: Significantly lower phosphatase activity, FT reduced protein stability and decreased growth-inhibitory FT effect." FT /evidence="ECO:0000269|PubMed:19345329" FT MUTAGEN 366 FT /note="T->A: Decreased stability." FT /evidence="ECO:0000269|PubMed:20940307" FT MUTAGEN 370 FT /note="S->A: Decreased stability." FT /evidence="ECO:0000269|PubMed:20940307" FT MUTAGEN 401 FT /note="T->A: Loss of DLG1-binding. No effect on MAGI2- and FT MAST2-binding." FT MUTAGEN 402 FT /note="K->A: No effect on MAGI2-, MAST2- and DLG1-binding." FT MUTAGEN 402 FT /note="K->W: Loss of DLG1-, MAGI2-, MAGI3- and FT MAST2-binding. Decrease of protein stability." FT MUTAGEN 403 FT /note="V->A: Loss of DLG1-, MAGI2-, MAGI3-, MAST1-, FT MAST2- and MAST3-binding." FT /evidence="ECO:0000269|PubMed:15951562" FT HELIX 8..10 FT /evidence="ECO:0007829|PDB:7JUL" FT TURN 19..22 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 23..29 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 32..35 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 39..41 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 44..47 FT /evidence="ECO:0007829|PDB:5BZZ" FT HELIX 50..60 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 61..63 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 65..73 FT /evidence="ECO:0007829|PDB:1D5R" FT HELIX 78..80 FT /evidence="ECO:0007829|PDB:5BZZ" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:5BZZ" FT STRAND 85..90 FT /evidence="ECO:0007829|PDB:1D5R" FT HELIX 98..100 FT /evidence="ECO:0007829|PDB:1D5R" FT HELIX 101..112 FT /evidence="ECO:0007829|PDB:1D5R" FT TURN 113..115 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 118..123 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 125..128 FT /evidence="ECO:0007829|PDB:1D5R" FT HELIX 129..141 FT /evidence="ECO:0007829|PDB:1D5R" FT HELIX 148..159 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 161..163 FT /evidence="ECO:0007829|PDB:1D5R" FT HELIX 169..184 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 192..202 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 206..209 FT /evidence="ECO:0007829|PDB:5BZZ" FT STRAND 213..219 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 222..226 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 232..235 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 238..259 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 262..264 FT /evidence="ECO:0007829|PDB:5BZZ" FT STRAND 268..276 FT /evidence="ECO:0007829|PDB:1D5R" FT HELIX 277..279 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 280..284 FT /evidence="ECO:0007829|PDB:5BZZ" FT STRAND 310..312 FT /evidence="ECO:0007829|PDB:5BZX" FT STRAND 315..321 FT /evidence="ECO:0007829|PDB:1D5R" FT HELIX 322..324 FT /evidence="ECO:0007829|PDB:1D5R" FT HELIX 328..330 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 335..337 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 342..349 FT /evidence="ECO:0007829|PDB:1D5R" FT STRAND 395..403 FT /evidence="ECO:0007829|PDB:2KYL" 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 //