ExPASy logo ExPASy Home page Site Map Search ExPASy Contact us Swiss-Prot
Notice: This page will be replaced with www.uniprot.org. Please send us your feedback!
Search for

UniProtKB/Swiss-Prot entry P60484

[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

Note: most headings are clickable, even if they don't appear as links. They link to the user manual or other documents.
Entry information
Entry name PTEN_HUMAN
Primary accession number P60484
Secondary accession numbers O00633 O02679 Q6ICT7
Integrated into Swiss-Prot on February 16, 2004
Sequence was last modified on February 16, 2004 (Sequence version 1)
Annotations were last modified on    July 22, 2008 (Entry version 63)
Name and origin of the protein
Protein name Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Synonyms EC 3.1.3.67
EC 3.1.3.16
EC 3.1.3.48
Phosphatase and tensin homolog
Mutated in multiple advanced cancers 1
Gene name
Name: PTEN
Synonyms: MMAC1, TEP1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
 NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND INDUCTION.
TISSUE=Epithelium;
PubMed=9187108 [NCBI, ExPASy, EBI, Israel, Japan]
Li D.M., Sun H.;
"TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta.";
Cancer Res. 57:2124-2129(1997).
[2]
 NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS GLIOMA SER-15; GLU-36; ARG-42; TRP-57 AND THR-319 DEL.
DOI=10.1038/ng0497-356; PubMed=9090379 [NCBI, ExPASy, EBI, Israel, Japan]
Steck P.A., Pershouse M.A., Jasser S.A., Lin H., Yung W.K.A., Ligon A.H., Langford L.A., Baumgard M.L., Hattier T., Davis T., Frye C., Hu R., Swedlund B., Teng D.H.-F., Tavtigian S.V.;
"Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.";
Nat. Genet. 15:356-363(1997).
[3]
 NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS GLIOBLASTOMA ARG-129 AND PROSTATE CANCER LEU-134.
DOI=10.1126/science.275.5308.1943; PubMed=9072974 [NCBI, ExPASy, EBI, Israel, Japan]
Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie R., Bigner S.H., Giovanella B.C., Ittmann M., Tycko B., Hibshoosh H., Wigler M.H., Parsons R.;
"PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.";
Science 275:1943-1947(1997).
[4]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1054/bjoc.2000.1211; PubMed=10817502 [NCBI, ExPASy, EBI, Israel, Japan]
Hamilton J.A., Stewart L.M.D., Ajayi L., Gray I.C., Gray N.E., Roberts K.G., Watson G.J., Kaisary A.V., Snary D.;
"The expression profile for the tumour suppressor gene PTEN and associated polymorphic markers.";
Br. J. Cancer 82:1671-1676(2000).
[5]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Wang S., Li J., Liaw D., Bose S., Podsypanina K., Parsons R.;
Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
[6]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Jensen K., de la Bastide M., Parsons R., Parnell L.D., Dedhia N., Gottesman T., Gnoj L., Kaplan N., Lodhi M., Johnson A.F., Shohdy N., Hasegawa A., Haberman K., Huang E.N., Schutz K., Calma C., Granat S., Wigler M.H., McCombie W.R.;
"Genomic sequence of PTEN/MMAC1.";
Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
[7]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).";
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
[8]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-290.
Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N., Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
[9]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Lung;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[10]
 FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS GLIOMA TRP-57; ENDOMETRIAL CANCER TYR-123; GLIOBLASTOMA ARG-129; CD ARG-129; PROSTATE CANCER LEU-134; GLIOBLASTOMA ARG-165; BREAST CANCER PRO-167 AND BZ ARG-170.
DOI=10.1073/pnas.94.17.9052; PubMed=9256433 [NCBI, ExPASy, EBI, Israel, Japan]
Myers M.P., Stolarov J.P., Eng C., Li J., Wang S.I., Wigler M.H., Parsons R., Tonks N.K.;
"P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase.";
Proc. Natl. Acad. Sci. U.S.A. 94:9052-9057(1997).
[11]
 FUNCTION, AND CATALYTIC ACTIVITY.
DOI=10.1074/jbc.273.22.13375; PubMed=9593664 [NCBI, ExPASy, EBI, Israel, Japan]
Maehama T., Dixon J.E.;
"The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.";
J. Biol. Chem. 273:13375-13378(1998).
[12]
 FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-130, AND CHARACTERIZATION OF VARIANTS CD SER-124 AND CD GLU-129.
DOI=10.1073/pnas.95.23.13513; PubMed=9811831 [NCBI, ExPASy, EBI, Israel, Japan]
Myers M.P., Pass I., Batty I.H., Van der Kaay J., Stolarov J.P., Hemmings B.A., Wigler M.H., Downes C.P., Tonks N.K.;
"The lipid phosphatase activity of PTEN is critical for its tumor supressor function.";
Proc. Natl. Acad. Sci. U.S.A. 95:13513-13518(1998).
[13]
 FUNCTION, MUTAGENESIS OF ASP-92 AND CYS-124, AND CHARACTERIZATION OF VARIANT GLU-129.
DOI=10.1126/science.280.5369.1614; PubMed=9616126 [NCBI, ExPASy, EBI, Israel, Japan]
Tamura M., Gu J., Matsumoto K., Aota S., Parsons R., Yamada K.M.;
"Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN.";
Science 280:1614-1617(1998).
[14]
 FUNCTION, DOMAIN, AND CHARACTERIZATION OF VARIANTS THR-319 DEL; GLN-345 AND ILE-348.
DOI=10.1073/pnas.96.18.10182; PubMed=10468583 [NCBI, ExPASy, EBI, Israel, Japan]
Georgescu M.-M., Kirsch K.H., Akagi T., Shishido T., Hanafusa H.;
"The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region.";
Proc. Natl. Acad. Sci. U.S.A. 96:10182-10187(1999).
[15]
 INTERACTION WITH DLG1 AND MAST2, AND PHOSPHORYLATION AT THR-401.
PubMed=10646847 [NCBI, ExPASy, EBI, Israel, Japan]
Adey N.B., Huang L., Ormonde P.A., Baumgard M.L., Pero R., Byreddy D.V., Tavtigian S.V., Bartel P.L.;
"Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding.";
Cancer Res. 60:35-37(2000).
[16]
 INTERACTION WITH MAGI3.
DOI=10.1074/jbc.M909741199; PubMed=10748157 [NCBI, ExPASy, EBI, Israel, Japan]
Wu Y., Dowbenko D., Spencer S., Laura R., Lee J., Gu Q., Lasky L.A.;
"Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase.";
J. Biol. Chem. 275:21477-21485(2000).
[17]
 INTERACTION WITH AIP1.
DOI=10.1073/pnas.97.8.4233; PubMed=10760291 [NCBI, ExPASy, EBI, Israel, Japan]
Wu X., Hepner K., Castelino-Prabhu S., Do D., Kaye M.B., Yuan X.-J., Wood J., Ross C., Sawyers C.L., Whang Y.E.;
"Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2.";
Proc. Natl. Acad. Sci. U.S.A. 97:4233-4238(2000).
[18]
 FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH AIP1.
DOI=10.1074/jbc.C100556200; PubMed=11707428 [NCBI, ExPASy, EBI, Israel, Japan]
Vazquez F., Grossman S.R., Takahashi Y., Rokas M.V., Nakamura N., Sellers W.R.;
"Phosphorylation of the PTEN tail acts as an inhibitory switch by preventing its recruitment into a protein complex.";
J. Biol. Chem. 276:48627-48630(2001).
[19]
 PHOSPHORYLATION AT THR-366; SER-370 AND SER-385.
DOI=10.1016/S0014-5793(02)03274-X; PubMed=12297295 [NCBI, ExPASy, EBI, Israel, Japan]
Miller S., Lou D., Seldin D., Lane W., Neel B.;
"Direct identification of PTEN phosphorylation sites.";
FEBS Lett. 528:145-145(2002).
[20]
 X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 8-353 IN COMPLEX WITH L(+)-TARTRATE, SUBUNIT, DOMAIN, AND MUTAGENESIS OF ASP-92; HIS-93; LYS-125; LYS-128; THR-167; GLN-171; 263-LYS--ALA-269 AND 327-LYS--ALA-335.
DOI=10.1016/S0092-8674(00)81663-3; PubMed=10555148 [NCBI, ExPASy, EBI, Israel, Japan]
Lee J.-O., Yang H., Georgescu M.-M., Di Cristofano A., Maehama T., Shi Y., Dixon J.E., Pandolfi P., Pavletich N.P.;
"Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.";
Cell 99:323-334(1999).
[21]
 VARIANT CD ASN-137 INS.
DOI=10.1086/301607; PubMed=9345101 [NCBI, ExPASy, EBI, Israel, Japan]
Tsou H.C., Teng D.H.-F., Ping X.L., Brancolini V., Davis T., Hu R., Xie X.X., Gruener A.C., Schrager C.A., Christiano A.M., Eng C., Steck P., Ott J., Tavtigian S.V., Peacocke M.;
"The role of MMAC1 mutations in early-onset breast cancer: causative in association with Cowden syndrome and excluded in BRCA1-negative cases.";
Am. J. Hum. Genet. 61:1036-1043(1997).
[22]
 VARIANTS CD GLU-343 AND LEU-347.
DOI=10.1086/301639; PubMed=9399897 [NCBI, ExPASy, EBI, Israel, Japan]
Lynch E.D., Ostermeyer E.A., Lee M.K., Arena J.F., Ji H., Dann J., Swisshelm K., Suchard D., MacLeod P.M., Kvinnsland S., Gjertsen B.T., Heimdal K., Lubs H., Moeller P., King M.-C.;
"Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis.";
Am. J. Hum. Genet. 61:1254-1260(1997).
[23]
 VARIANTS GLIOBLASTOMA TYR-107; PRO-121; ARG-129; ARG-165 AND GLN-345.
PubMed=9331071 [NCBI, ExPASy, EBI, Israel, Japan]
Wang S.I., Puc J., Li J., Bruce J.N., Cairns P., Sidransky D., Parsons R.;
"Somatic mutations of PTEN in glioblastoma multiforme.";
Cancer Res. 57:4183-4186(1997).
[24]
 VARIANTS CD ARG-123 AND ARG-124.
DOI=10.1093/hmg/6.8.1383; PubMed=9259288 [NCBI, ExPASy, EBI, Israel, Japan]
Nelen M.R., van Staveren W.C.G., Peeters E.A.J., Ben-Hassel M., Gorlin R.J., Hamm H., Lindboe C.F., Fryns J.-P., Sijmons R.H., Woods D.G., Mariman E.C.M., Padberg G.W., Kremer H.;
"Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease.";
Hum. Mol. Genet. 6:1383-1387(1997).
[25]
 VARIANT CD GLU-129.
DOI=10.1038/ng0597-64; PubMed=9140396 [NCBI, ExPASy, EBI, Israel, Japan]
Liaw D., Marsh D.J., Li J., Dahia P.L.M., Wang S.I., Zheng Z., Bose S., Call K.M., Tsou H.C., Peacocke M., Eng C., Parsons R.;
"Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome.";
Nat. Genet. 16:64-67(1997).
[26]
 VARIANT BZS ARG-170.
DOI=10.1038/ng0897-333; PubMed=9241266 [NCBI, ExPASy, EBI, Israel, Japan]
Marsh D.J., Dahia P.L.M., Zheng Z., Liaw D., Parsons R., Gorlin R.J., Eng C.;
"Germline mutations in PTEN are present in Bannayan-Zonana syndrome.";
Nat. Genet. 16:333-334(1997).
[27]
 VARIANTS ENDOMETRIAL HYPERPLASIA ARG-36; LEU-130; CYS-173; ALA-191 AND ILE-348.
PubMed=9635567 [NCBI, ExPASy, EBI, Israel, Japan]
Maxwell G.L., Risinger J.I., Gumbs C., Shaw H., Bentley R.C., Barrett J.C., Berchuck A., Futreal P.A.;
"Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias.";
Cancer Res. 58:2500-2503(1998).
[28]
 VARIANT CD GLU-289.
PubMed=9797362 [NCBI, ExPASy, EBI, Israel, Japan]
Chi S.-G., Kim H.-J., Park B.-J., Min H.-J., Park J.-H., Kim Y.-W., Dong S.-H., Kim B.-H., Lee J.-I., Chang Y.-W., Chang R., Kim W.-K., Yang M.-H.;
"Mutational abrogation of the PTEN/MMAC1 gene in gastrointestinal polyps in patients with Cowden disease.";
Gastroenterology 115:1084-1089(1998).
[29]
 VARIANTS CD HIS-68 AND PRO-112.
DOI=10.1007/s004390050723; PubMed=9600246 [NCBI, ExPASy, EBI, Israel, Japan]
Tsou H.C., Ping X.L., Xie X.X., Gruener A.C., Zhang H., Nini R., Swisshelm K., Sybert V., Diamond T.M., Sutphen R., Peacocke M.;
"The genetic basis of Cowden's syndrome: three novel mutations in PTEN/MMAC1/TEP1.";
Hum. Genet. 102:467-473(1998).
[30]
 VARIANTS CD AND BZS.
DOI=10.1093/hmg/7.3.507; PubMed=9467011 [NCBI, ExPASy, EBI, Israel, Japan]
Marsh D.J., Coulon V., Lunetta K.L., Rocca-Serra P., Dahia P.L.M., Zheng Z., Liaw D., Caron S., Duboue B., Lin A.Y., Richardson A.-L., Bonnetblanc J.-M., Bressieux J.-M., Cabarrot-Moreau A., Chompret A., Demange L., Eeles R.A., Yahanda A.M., Fearon E.R., Fricker J.-P., Gorlin R.J., Hodgson S.V., Huson S., Lacombe D., Leprat F., Odent S., Toulouse C., Olopade O.I., Sobol H., Tishler S., Woods C.G., Robinson B.G., Weber H.C., Parsons R., Peacocke M., Longy M., Eng C.;
"Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.";
Hum. Mol. Genet. 7:507-515(1998).
[31]
 VARIANT CD TYR-136.
PubMed=9735393 [NCBI, ExPASy, EBI, Israel, Japan]
Scala S., Bruni P., Lo Muzio L., Mignogna M., Viglietto G., Fusco A.;
"Novel mutation of the PTEN gene in an Italian Cowden's disease kindred.";
Int. J. Oncol. 13:665-668(1998).
[32]
 VARIANT CD PRO-70.
PubMed=9832031 [NCBI, ExPASy, EBI, Israel, Japan]
Marsh D.J., Dahia P.L.M., Caron S., Kum J.B., Frayling I.M., Tomlinson I.P.M., Hughes K.S., Eeles R.A., Hodgson S.V., Murday V.A., Houlston R., Eng C.;
"Germline PTEN mutations in Cowden syndrome-like families.";
J. Med. Genet. 35:881-885(1998).
[33]
 VARIANT CD ARG-35.
DOI=10.1038/ng0198-12; PubMed=9425889 [NCBI, ExPASy, EBI, Israel, Japan]
Olschwang S., Serova-Sinilnikova O.M., Lenoir G.M., Thomas G.;
"PTEN germ-line mutations in juvenile polyposis coli.";
Nat. Genet. 18:12-14(1998).
[34]
 VARIANT CD GLN-130.
DOI=10.1086/302207; PubMed=9915974 [NCBI, ExPASy, EBI, Israel, Japan]
Kurose K., Araki T., Matsunaka T., Takada Y., Emi M.;
"Variant manifestation of Cowden disease in Japan: hamartomatous polyposis of the digestive tract with mutation of the PTEN gene.";
Am. J. Hum. Genet. 64:308-310(1999).
[35]
 VARIANT CD/LDD PRO-112.
DOI=10.1002/(SICI)1096-8628(19990212)82:4<290::AID-AJMG3>3.0.CO;2-0; PubMed=10051160 [NCBI, ExPASy, EBI, Israel, Japan]
Sutphen R., Diamond T.M., Minton S.E., Peacocke M., Tsou H.C., Root A.W.;
"Severe Lhermitte-Duclos disease with unique germline mutation of PTEN.";
Am. J. Med. Genet. 82:290-293(1999).
[36]
 VARIANTS CD ILE-33 DEL; ARG-123; ARG-124 AND GLU-165.
DOI=10.1038/sj.ejhg.5200289; PubMed=10234502 [NCBI, ExPASy, EBI, Israel, Japan]
Nelen M.R., Kremer H., Konings I.B.M., Schoute F., van Essen A.J., Koch R., Woods C.G., Fryns J.-P., Hamel B.C.J., Hoefsloot L.H., Peeters E.A.J., Padberg G.W.;
"Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations.";
Eur. J. Hum. Genet. 7:267-273(1999).
[37]
 VARIANTS BZS ASP-34; HIS-68; TYR-105; VAL-135; ARG-170 AND LEU-246.
DOI=10.1093/hmg/8.8.1461; PubMed=10400993 [NCBI, ExPASy, EBI, Israel, Japan]
Marsh D.J., Kum J.B., Lunetta K.L., Bennett M.J., Gorlin R.J., Ahmed S.F., Bodurtha J., Crowe C., Curtis M.A., Dasouki M., Dunn T., Feit H., Geraghty M.T., Graham J.M. Jr., Hodgson S.V., Hunter A., Korf B.R., Manchester D., Miesfeldt S., Murday V.A., Nathanson K.L., Parisi M., Pober B., Romano C., Tolmie J.L., Trembath R., Winter R.M., Zackai E.H., Zori R.T., Weng L.-P., Dahia P.L.M., Eng C.;
"PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome.";
Hum. Mol. Genet. 8:1461-1472(1999).
[38]
 CHARACTERIZATION OF VARIANTS ASN-10; CYS-16; GLU-20; SER-27; ARG-61; HIS-68; CD TYR-71; CD TYR-93; BZS PHE-105; BZS TYR-107; PRO-112; ARG-112; PRO-121; ARG-124; ARG-129; GLU-129; GLY-130; CD LEU-130; GLN-130; ILE-133; LEU-134; TYR-136; CYS-155; ARG-165; ASN-170; ARG-170; CYS-173; HIS-173; PRO-173; ASN-174; PHE-227; CYS-251; GLU-289; GLY-331; VAL-341; ASN-342; GLU-343; GLN-345; LEU-347; GLY-369 AND ILE-401.
PubMed=10866302 [NCBI, ExPASy, EBI, Israel, Japan]
Han S.-Y., Kato H., Kato S., Suzuki T., Shibata H., Ishii S., Shiiba K., Matsuno S., Kanamaru R., Ishioka C.;
"Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay.";
Cancer Res. 60:3147-3151(2000).
[39]
 VARIANTS MULTIPLE CANCERS LEU-119 AND LEU-158.
DOI=10.1136/jmg.37.5.336; PubMed=10807691 [NCBI, ExPASy, EBI, Israel, Japan]
De Vivo I., Gertig D.M., Nagase S., Hankinson S.E., O'Brien R., Speizer F.E., Parsons R., Hunter D.J.;
"Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers.";
J. Med. Genet. 37:336-341(2000).
[40]
 VARIANTS MALIGNANT MELANOMA ASN-19 AND ILE-217.
DOI=10.1136/jmg.37.9.653; PubMed=10978354 [NCBI, ExPASy, EBI, Israel, Japan]
Celebi J.T., Shendrik I., Silvers D.N., Peacocke M.;
"Identification of PTEN mutations in metastatic melanoma specimens.";
J. Med. Genet. 37:653-657(2000).
[41]
 CHARACTERIZATION OF VARIANTS CD SER-124 AND GLU-129.
DOI=10.1093/hmg/10.6.599; PubMed=11230179 [NCBI, ExPASy, EBI, Israel, Japan]
Weng L.-P., Brown J.L., Eng C.;
"PTEN coordinates G1 arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model.";
Hum. Mol. Genet. 10:599-604(2001).
[42]
 VARIANT VATER ASP-61.
DOI=10.1136/jmg.38.12.820; PubMed=11748304 [NCBI, ExPASy, EBI, Israel, Japan]
Reardon W., Zhou X.-P., Eng C.;
"A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association.";
J. Med. Genet. 38:820-823(2001).
[43]
 VARIANT CD GLY-47, AND VARIANTS BZS ASP-34; HIS-68; TYR-105; VAL-135 AND ARG-170.
DOI=10.1038/sj.neo.7900154; PubMed=11494117 [NCBI, ExPASy, EBI, Israel, Japan]
Marsh D.J., Theodosopoulos G., Howell V., Richardson A.-L., Benn D.E., Proos A.L., Eng C., Robinson B.G.;
"Rapid mutation scanning of genes associated with familial cancer syndromes using denaturing high-performance liquid chromatography.";
Neoplasia 3:236-244(2001).
[44]
 CHARACTERIZATION OF VARIANT OLIGODENDROGLIOMA GLN-234.
DOI=10.1038/sj.bjc.6600206; PubMed=12085208 [NCBI, ExPASy, EBI, Israel, Japan]
Staal F.J.T., van der Luijt R.B., Baert M.R.M., van Drunen J., van Bakel H., Peters E., de Valk I., van Amstel H.K.P., Taphoorn M.J.B., Jansen G.H., van Veelen C.W.M., Burgering B., Staal G.E.J.;
"A novel germline mutation of PTEN associated with brain tumours of multiple lineages.";
Br. J. Cancer 86:1586-1591(2002).
[45]
 VARIANT HNSCC GLY-121.
DOI=10.1016/S0165-4608(01)00509-X; PubMed=11801303 [NCBI, ExPASy, EBI, Israel, Japan]
Poetsch M., Lorenz G., Kleist B.;
"Detection of new PTEN/MMAC1 mutations in head and neck squamous cell carcinomas with loss of chromosome 10.";
Cancer Genet. Cytogenet. 132:20-24(2002).
[46]
 INVOLVEMENT IN PROTEUS SYNDROME.
DOI=10.1136/jmg.39.12.937; PubMed=12471211 [NCBI, ExPASy, EBI, Israel, Japan]
Smith J.M., Kirk E.P.E., Theodosopoulos G., Marshall G.M., Walker J., Rogers M., Field M., Brereton J.J., Marsh D.J.;
"Germline mutation of the tumour suppressor PTEN in Proteus syndrome.";
J. Med. Genet. 39:937-940(2002).
[47]
 VARIANTS MACROCEPHALY/AUTISM SYNDROME ARG-93; SER-241 AND GLY-252.
DOI=10.1136/jmg.2004.024646; PubMed=15805158 [NCBI, ExPASy, EBI, Israel, Japan]
Butler M.G., Dasouki M.J., Zhou X.-P., Talebizadeh Z., Brown M., Takahashi T.N., Miles J.H., Wang C.H., Stratton R., Pilarski R., Eng C.;
"Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.";
J. Med. Genet. 42:318-321(2005).
[48]
 VARIANT VAL-132.
DOI=10.1002/ajmg.a.31273; PubMed=16752378 [NCBI, ExPASy, EBI, Israel, Japan]
Tekin M., Hismi B.O., Fitoz S., Yalcinkaya F., Ekim M., Kansu A., Ertem M., Deda G., Tutar E., Arsan S., Zhou X.-P., Pilarski R., Eng C., Akar N.;
"A germline PTEN mutation with manifestations of prenatal onset and verrucous epidermal nevus.";
Am. J. Med. Genet. A 140:1472-1475(2006).
Comments
  • FUNCTION: Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue.
  • CATALYTIC ACTIVITY: Phosphatidylinositol 3,4,5-trisphosphate + H2O = phosphatidylinositol 4,5-bisphosphate + phosphate.
  • CATALYTIC ACTIVITY: A phosphoprotein + H2O = a protein + phosphate.
  • CATALYTIC ACTIVITY: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
  • COFACTOR: Magnesium.
  • SUBUNIT: Monomer. The unphosphorylated form interacts with the second PDZ domain of AIP1 and with DLG1 and MAST2 in vitro. Interacts with MAGI3.
  • INTERACTION:
    P49452:Cenpc1 (xeno); NbExp=1; IntAct=EBI-696162, EBI-1186252;
    Q62696:Dlg1 (xeno); NbExp=1; IntAct=EBI-696162, EBI-389325;
    P11021:HSPA5; NbExp=1; IntAct=EBI-696162, EBI-354921;
    O88382:Magi2 (xeno); NbExp=2; IntAct=EBI-696162, EBI-696179;
    Q9JK71:Magi3 (xeno); NbExp=1; IntAct=EBI-696162, EBI-696226;
    Q9R1L5:Mast1 (xeno); NbExp=2; IntAct=EBI-696162, EBI-491771;
    Q60592:Mast2 (xeno); NbExp=2; IntAct=EBI-696162, EBI-493888;
    O60307:MAST3; NbExp=2; IntAct=EBI-696162, EBI-311420;
    P62136:PPP1CA; NbExp=2; IntAct=EBI-696162, EBI-357253;
    O08586:Pten (xeno); NbExp=1; IntAct=EBI-696162, EBI-1186266;
  • SUBCELLULAR LOCATION: Cytoplasm.
  • TISSUE SPECIFICITY: Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas.
  • INDUCTION: Down-regulated by transforming growth factor beta (TGF-beta).
  • DOMAIN: The C2 domain binds phospholipid membranes in vitro in a Ca(2+)-independent manner; this binding is important for its tumor suppressor function.
  • PTM: Phosphorylation results in an inhibited activity towards PIP3. Phosphorylation can both inhibit and promote PDZ-binding.
  • DISEASE: Mutations of PTEN are found in a large number of cancers.
  • DISEASE: Defects in PTEN are a cause of Cowden disease (CD) [MIM:158350]; also known as Cowden syndrome (CS). CD is an autosomal dominant cancer predisposition syndrome associated with elevated risk for tumors of the breast, thyroid and skin. The predominant phenotype for CD is multiple hamartoma syndrome, in many organ systems including the breast (70% of CD patients), thyroid (40-60%), skin, CNS (40%), gastrointestinal tract. Affected individuals are at an increased risk of both breast and thyroid cancers. Trichilemmomas (benign tumors of the hair follicle infundibulum), and mucocutaneous papillomatosis (99%) are hallmarks of CD.
  • DISEASE: Defects in PTEN are the cause of Lhermitte-Duclos disease (LDD) [MIM:158350]; also known as cerebelloparenchymal disorder VI. LDD is characterized by dysplastic gangliocytoma of the cerebellum which often results in cerebellar signs and seizures. LDD and CD seem to be the same entity, and are considered as hamartoma-neoplasia syndromes.
  • DISEASE: Defects in PTEN are a cause of Bannayan-Zonana syndrome (BZS) [MIM:153480]; also known as Ruvalcaba-Riley-Smith or Bannayan-Riley-Ruvalcaba syndrome (BRRS). In BZS there seems not to be an increased risk of malignancy. It has a partial clinical overlap with CD. BZS is characterized by the classic triad of macrocephaly, lipomatosis and pigmented macules of the gland penis.
  • DISEASE: Defects in PTEN are a cause of squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355].
  • DISEASE: Defects in PTEN are a cause of susceptibility to endometrial cancer [MIM:608089].
  • DISEASE: Defects in PTEN are a cause of Proteus syndrome [MIM:176920]. Proteus syndrome is a hamartomatous disorder characterized by overgrowth of multiple tissues, connective tissue and epidermal naevi, and vascular malformations. These presentations are usually apparent at birth or soon after and continue to develop as the patient ages. It is named after the Greek god Proteus who, legend has it, could change his shape at will to avoid capture. Tumors, mostly benign but some malignant, have also been reported in Proteus syndrome, generally presenting by the age of 20 years and including papillary adenocarcinoma of the testis, meningioma, and cystadenoma of the ovaries.
  • DISEASE: Defects in PTEN are a cause of oligodendroglioma [MIM:137800]; also called oligodendroblastoma or familial glioma of brain. Oligodendroglioma is a usually benign neoplasm derived from and composed of oligodendrogliocytes in varying stages of differentiation. The majority are seen in adults in the white matter of the brain.
  • DISEASE: Defects in PTEN are a cause of VACTERL association with hydrocephalus [MIM:276950]; which includes also VATER association with hydrocephalus. VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects.
  • DISEASE: Defects in PTEN are involved in prostate cancer [MIM:176807].
  • DISEASE: Defects in PTEN are a cause of macrocephaly/autism syndrome [MIM:605309]. Patients have autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference +4.0 SD).
  • SIMILARITY: Contains 1 C2 tensin-type domain.
  • SIMILARITY: Contains 1 phosphatase tensin-type domain.
  • WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PTENID158.html";.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=PTEN";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
U96180; AAB66902.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U92436; AAC51182.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U93051; AAC51183.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF143315; AAD38372.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF143312; AAD38372.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF143313; AAD38372.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF143314; AAD38372.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF000734; AAC08699.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF000726; AAC08699.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF000727; AAC08699.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF000728; AAC08699.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF000729; AAC08699.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF000730; AAC08699.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF000731; AAC08699.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF000732; AAC08699.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF000733; AAC08699.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF067844; AAD13528.1; -; Unassigned_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
CR450306; CAG29302.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ073384; AAY57327.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC005821; AAH05821.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_000305.3; -.
UniGene Hs.500466
3D structure databases
PDB
1D5R; X-ray; 2.10 A; A=8-353.[ExPASy / RCSB / EBI]
PDBsum 1D5R; -.
ModBase P60484.
Protein-protein interaction databases
IntAct P60484; -.
PTM databases
PhosphoSite P60484; -.
Polymorphism databases
NIEHS-SNPs PTEN.
Organism-specific databases
H-InvDB HIX0009010; -.
HIX0025699; -.
HGNC HGNC:9588; PTEN.
GenAtlas PTEN.
HPA CAB004076; -.
MIM 137800; phenotype. [NCBI / EBI]
153480; phenotype. [NCBI / EBI]
158350; phenotype. [NCBI / EBI]
176807; phenotype. [NCBI / EBI]
176920; phenotype. [NCBI / EBI]
275355; phenotype. [NCBI / EBI]
276950; phenotype. [NCBI / EBI]
601728; gene. [NCBI / EBI]
605309; phenotype. [NCBI / EBI]
608089; phenotype. [NCBI / EBI]
Orphanet 94; Astrocytoma.
109; Bannayan-Riley-Ruvalcaba syndrome.
201; Cowden syndrome.
360; Glioblastoma.
65285; Lhermitte-Duclos disease.
2495; Meningioma.
46484; Oligodendroglioma.
1331; Prostate cancer, familial.
744; Proteus syndrome.
67037; Squamous cell carcinoma of head and neck.
3412; VACTERL with hydrocephalus.
PharmGKB PA33942; -.
GeneCards P60484.
Gene expression databases
ArrayExpress P60484; -.
CleanEx HS_PTEN; -.
HS_TEP1; -.
GermOnline ENSG00000171862; Homo sapiens.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0051717; Molecular function: inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity (inferred from direct assay from UniProtKB).
GO:0030165; Molecular function: PDZ domain binding (inferred from physical interaction from UniProtKB).
GO:0016314; Molecular function: phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity (inferred from direct assay from UniProtKB).
GO:0051800; Molecular function: phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity (inferred from direct assay from UniProtKB).
GO:0004438; Molecular function: phosphatidylinositol-3-phosphatase activity (inferred from direct assay from UniProtKB).
GO:0004722; Molecular function: protein serine/threonine phosphatase activity (inferred from direct assay from UniProtKB).
GO:0004725; Molecular function: protein tyrosine phosphatase activity (inferred from direct assay from UniProtKB).
GO:0007417; Biological process: central nervous system development (inferred from sequence or structural similarity from UniProtKB).
GO:0007507; Biological process: heart development (inferred from sequence or structural similarity from UniProtKB).
GO:0006917; Biological process: induction of apoptosis (inferred from sequence or structural similarity from UniProtKB).
GO:0046855; Biological process: inositol phosphate dephosphorylation (inferred from direct assay from UniProtKB).
GO:0030336; Biological process: negative regulation of cell migration (inferred from mutant phenotype from UniProtKB).
GO:0008285; Biological process: negative regulation of cell proliferation (inferred from mutant phenotype from UniProtKB).
GO:0051895; Biological process: negative regulation of focal adhesion formation (inferred from mutant phenotype from UniProtKB).
GO:0051898; Biological process: negative regulation of protein kinase B signaling cascade (inferred from mutant phenotype from UniProtKB).
GO:0046856; Biological process: phosphoinositide dephosphorylation (inferred from direct assay from UniProtKB).
GO:0006470; Biological process: protein amino acid dephosphorylation (inferred from direct assay from UniProtKB).
GO:0000079; Biological process: regulation of cyclin-dependent protein kinase activity (traceable author statement from UniProtKB).
GO:0031647; Biological process: regulation of protein stability (inferred from mutant phenotype from UniProtKB).
QuickGo view.
Family and domain databases