PTEN_HUMAN
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 03-AUG-2022, entry version 207.
DE RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN;
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:9593664, ECO:0000269|PubMed:9811831};
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), AND VARIANTS GLIOBLASTOMA ARG-129
RP AND 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).
RC TISSUE=Spleen;
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, AND CATALYTIC ACTIVITY.
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 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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 [67]
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 [68]
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 [69]
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 [70]
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 [71]
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 [72]
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 [73]
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 [74]
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: Tumor suppressor. Acts as a dual-specificity protein
CC phosphatase, dephosphorylating tyrosine-, serine- and threonine-
CC phosphorylated proteins. Also acts as a lipid phosphatase, removing the
CC phosphate in the D3 position of the inositol ring from
CC phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-
CC diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-
CC tetrakisphosphate with order of substrate preference in vitro
CC PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4
CC (PubMed:26504226, PubMed:16824732). The lipid phosphatase activity is
CC critical for its tumor suppressor function. Antagonizes the PI3K-
CC AKT/PKB signaling pathway by dephosphorylating phosphoinositides and
CC thereby modulating cell cycle progression and cell survival. The
CC unphosphorylated form cooperates with MAGI2 to suppress AKT1
CC activation. Dephosphorylates tyrosine-phosphorylated focal adhesion
CC kinase and inhibits cell migration and integrin-mediated cell spreading
CC and focal adhesion formation. Plays a role as a key modulator of the
CC AKT-mTOR signaling pathway controlling the tempo of the process of
CC newborn neurons integration during adult neurogenesis, including
CC correct neuron positioning, dendritic development and synapse
CC formation. May be a negative regulator of insulin signaling and glucose
CC metabolism in adipose tissue. The nuclear monoubiquitinated form
CC possesses greater apoptotic potential, whereas the cytoplasmic
CC nonubiquitinated form induces less tumor suppressive ability. In motile
CC cells, suppresses the formation of lateral pseudopods and thereby
CC promotes cell polarization and directed movement.
CC {ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:26504226}.
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.
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:9593664,
CC ECO:0000269|PubMed:9811831};
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 -!- 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 -!- 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 -!- 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 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-inositol-
CC 3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-
CC (1D-myo-inositol-4,5-bisphosphate) + phosphate; Xref=Rhea:RHEA:43560,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83420,
CC ChEBI:CHEBI:83423; Evidence={ECO:0000269|PubMed:16824732};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43561;
CC Evidence={ECO:0000305|PubMed:16824732};
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 -!- 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). {ECO:0000250|UniProtKB:O08586,
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}.
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; 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; O14745: SLC9A3R1; NbExp=7; IntAct=EBI-696162, EBI-349787;
CC P60484; Q15599: SLC9A3R2; NbExp=5; IntAct=EBI-696162, EBI-1149760;
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: Slc9a3r2; 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}. Note=Monoubiquitinated form is
CC nuclear. Nonubiquitinated form is cytoplasmic. Colocalized with PML and
CC USP7 in PML nuclear bodies (PubMed:18716620). XIAP/BIRC4 promotes its
CC nuclear localization (PubMed:19473982). {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.
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. {ECO:0000269|PubMed:10646847,
CC ECO:0000269|PubMed:11035045, ECO:0000269|PubMed:11707428,
CC ECO:0000269|PubMed:12297295, ECO:0000269|PubMed:15951562,
CC ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:18716620,
CC ECO:0000269|PubMed:19345329, ECO:0000269|PubMed:20940307}.
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 -!- 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 a
CC CTG start codon of isoform 1. 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="http://atlasgeneticsoncology.org/Genes/PTENID158.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/pten/";
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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 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 AlphaFoldDB; P60484; -.
DR SMR; P60484; -.
DR BioGRID; 111700; 808.
DR ComplexPortal; CPX-3153; PTEN phosphatase complex.
DR CORUM; P60484; -.
DR DIP; DIP-35019N; -.
DR ELM; P60484; -.
DR IntAct; P60484; 68.
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 CarbonylDB; P60484; -.
DR DEPOD; PTEN; -.
DR iPTMnet; P60484; -.
DR MetOSite; P60484; -.
DR PhosphoSitePlus; P60484; -.
DR BioMuta; PTEN; -.
DR DMDM; 42560209; -.
DR EPD; P60484; -.
DR jPOST; P60484; -.
DR MassIVE; P60484; -.
DR MaxQB; P60484; -.
DR PaxDb; P60484; -.
DR PeptideAtlas; P60484; -.
DR PRIDE; P60484; -.
DR ProteomicsDB; 57209; -. [P60484-1]
DR Antibodypedia; 3420; 1806 antibodies from 53 providers.
DR CPTC; P60484; 8 antibodies.
DR DNASU; 5728; -.
DR Ensembl; ENST00000371953.8; ENSP00000361021.3; ENSG00000171862.12. [P60484-1]
DR Ensembl; ENST00000688308.1; ENSP00000508752.1; ENSG00000171862.12. [P60484-1]
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 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 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; HARTMNG; -.
DR OrthoDB; 639380at2759; -.
DR PhylomeDB; P60484; -.
DR TreeFam; TF324513; -.
DR BioCyc; MetaCyc:HS10404-MON; -.
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; 66 hits in 1058 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 189 other tissues.
DR ExpressionAtlas; P60484; baseline and differential.
DR Genevisible; P60484; HS.
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: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:0043220; C:Schmidt-Lanterman incisure; ISS:BHF-UCL.
DR GO; GO:0045202; C:synapse; IEA:GOC.
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: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:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB.
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-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
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:0030534; P:adult behavior; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl.
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:0048738; P:cardiac muscle tissue development; IEA:Ensembl.
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:0071456; P:cellular response to hypoxia; IEA:Ensembl.
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:0016311; P:dephosphorylation; IBA:GO_Central.
DR GO; GO:0043542; P:endothelial cell migration; IEA:Ensembl.
DR GO; GO:0048853; P:forebrain morphogenesis; ISS:BHF-UCL.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IDA:UniProtKB.
DR GO; GO:0007611; P:learning or memory; ISS:BHF-UCL.
DR GO; GO:0045475; P:locomotor rhythm; ISS:BHF-UCL.
DR GO; GO:0007626; P:locomotory behavior; ISS:BHF-UCL.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0060179; P:male mating behavior; IEA:Ensembl.
DR GO; GO:0042711; P:maternal behavior; IEA:Ensembl.
DR GO; GO:0033555; P:multicellular organismal response to stress; ISS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0048681; P:negative regulation of axon regeneration; IEA:Ensembl.
DR GO; GO:0050771; P:negative regulation of axonogenesis; ISS:BHF-UCL.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; IEA:Ensembl.
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:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; 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:0031642; P:negative regulation of myelination; IEA:Ensembl.
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:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; TAS:BHF-UCL.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0090071; P:negative regulation of ribosome biogenesis; IEA:Ensembl.
DR GO; GO:2000808; P:negative regulation of synaptic vesicle clustering; ISS:BHF-UCL.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IEA:Ensembl.
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:0014065; P:phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
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:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISS:BHF-UCL.
DR GO; GO:1903984; P:positive regulation of TRAIL-activated apoptotic signaling pathway; IMP: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:0060736; P:prostate gland growth; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:BHF-UCL.
DR GO; GO:0002902; P:regulation of B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0032535; P:regulation of cellular component size; ISS:BHF-UCL.
DR GO; GO:0060341; P:regulation of cellular localization; IEA:Ensembl.
DR GO; GO:2000109; P:regulation of macrophage apoptotic process; IEA:Ensembl.
DR GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; IEA:Ensembl.
DR GO; GO:0060024; P:rhythmic synaptic transmission; ISS:BHF-UCL.
DR GO; GO:0035176; P:social behavior; ISS:BHF-UCL.
DR GO; GO:0007416; P:synapse assembly; ISS:BHF-UCL.
DR GO; GO:0060074; P:synapse maturation; ISS:BHF-UCL.
DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl.
DR CDD; cd14509; PTP_PTEN; 1.
DR Gene3D; 3.90.190.10; -; 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; 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 Pfam; PF10409; PTEN_C2; 1.
DR PIRSF; PIRSF038025; PTEN; 1.
DR SMART; SM01326; PTEN_C2; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS51182; C2_TENSIN; 1.
DR PROSITE; PS51181; PPASE_TENSIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation; Alternative splicing;
KW Apoptosis; Autism spectrum disorder; Cytoplasm; Disease variant; Hydrolase;
KW Isopeptide bond; Lipid metabolism; Lipid-binding; Neurogenesis; Nucleus;
KW Phosphoprotein; Protein phosphatase; Reference proteome; Secreted;
KW 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 REGION 401..403
FT /note="PDZ domain-binding"
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 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 (foun in a patient with macrocephaly,
FT ventriculomegaly, vertebral anomalies, anal atresia,
FT congenital cardiac disease, tracheoesophageal fistula,
FT renal anomalies, radial dysplasia and other limb defects;
FT unknown pathological 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; the patient also suffered from
FT benign meningioma; 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: Expression is restricted to isoform alpha."
FT /evidence="ECO:0000269|PubMed:24768297"
FT MUTAGEN 13
FT /note="K->E: Nuclear. Cytoplasmic; when associated with E-
FT 289. Shows less tumor suppressive ability; when associated
FT 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 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 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 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 MAST2-
FT 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
