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UniProtKB/Swiss-Prot entry P60484

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

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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

June 16, 2009 (Entry version 74)

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. NIEHS SNPs program; 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. 528:145-153(2002).
[20]	INTERACTION WITH MAGI2, MAGI3, MAST1, MAST2 AND MAST3, MUTAGENESIS OF VAL-403, AND PHOSPHORYLATION. DOI=10.1074/jbc.M504761200; PubMed=15951562 [NCBI, ExPASy, EBI, Israel, Japan] Valiente M., Andres-Pons A., Gomar B., Torres J., Gil A., Tapparel C., Antonarakis S.E., Pulido R.; "Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases."; J. Biol. Chem. 280:28936-28943(2005).
[21]	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).
[22]	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).
[23]	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).
[24]	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).
[25]	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).
[26]	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).
[27]	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).
[28]	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).
[29]	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).
[30]	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).
[31]	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).
[32]	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).
[33]	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).
[34]	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).
[35]	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).
[36]	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).
[37]	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).
[38]	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).
[39]	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).
[40]	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).
[41]	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).
[42]	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).
[43]	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).
[44]	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).
[45]	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).
[46]	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).
[47]	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).
[48]	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).
[49]	INVOLVEMENT IN CHROMOSOME 10Q23 DELETION SYNDROME. DOI=10.1086/513607; PubMed=17436248 [NCBI, ExPASy, EBI, Israel, Japan] Balciuniene J., Feng N., Iyadurai K., Hirsch B., Charnas L., Bill B.R., Easterday M.C., Staaf J., Oseth L., Czapansky-Beilman D., Avramopoulos D., Thomas G.H., Borg A., Valle D., Schimmenti L.A., Selleck S.B.; "Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with cognitive and behavioral abnormalities."; Am. J. Hum. Genet. 80:938-947(2007).
[50]	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 MAGI2, MAGI3, MAST1 and MAST3, but neither with MAST4 nor with DLG5. Interaction with MAGI2 increases protein stability.
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: Phosphorylated in vitro by MAST1, MAST2 and MAST3. Phosphorylation results in an inhibited activity towards PIP3. Phosphorylation can both inhibit or 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).
DISEASE: A microdeletion of chromosome 10q23 involving PTEN and BMPR1A is a cause of chromosome 10q23 deletion syndrome [MIM:612242]. This syndrome shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.
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";.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/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]

IPI00012587; -.

NP_000305.3; -.

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; 16.

PTM databases

PhosphoSite

P60484; -.

Enzyme and pathway databases

BRENDA

3.1.3.16; 247.
3.1.3.48; 247.
3.1.3.67; 247.

Pathway_Interaction_DB

bcr_5pathway; BCR signaling pathway.
pi3kcipathway; Class I PI3K signaling events.
mtor_4pathway; mTOR signaling pathway.
pdgfrbpathway; PDGFR-beta signaling pathway.
met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway; Signaling events mediated by Stem cell factor receptor (c-Kit).
tcrpathway; TCR signaling in naive CD4+ T cells.

Reactome

REACT_11061; Signalling by NGF.
REACT_6900; Signaling in Immune system.

Organism-specific databases

GeneCards

GC10P089613; -.

H-InvDB

HIX0009010; -.
HIX0025699; -.

HGNC:9588; PTEN.

CAB004076; -.

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]
612242; phenotype. [NCBI / EBI]

Orphanet

94; Astrocytoma.
109; Bannayan-Riley-Ruvalcaba syndrome.
145; Breast cancer, familial.
201; Cowden syndrome.
79076; Juvenile polyposis of infancy.
65285; Lhermitte-Duclos disease.
2495; Meningioma.
46484; Oligodendroglioma.
1331; Prostate cancer, familial.
744; Proteus syndrome.
2969; Proteus-like syndrome - intellectual deficit - eye defects.
67037; Squamous cell carcinoma of head and neck.

PharmGKB

PA33942; -.

Gene expression databases

ArrayExpress

P60484; -.

Bgee

P60484; -.

CleanEx

HS_PTEN; -.
HS_TEP1; -.

GermOnline

ENSG00000171862; Homo sapiens.

Ontologies

GO:0005829;	Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005634;	Cellular component: nucleus (inferred from direct assay from UniProtKB).
GO:0051717;	Molecular function: inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity (inferred from direct assay from UniProtKB).
GO:0008289;	Molecular function: lipid binding (inferred from electronic annotation from UniProtKB-KW).
GO:0000287;	Molecular function: magnesium ion binding (inferred from electronic annotation from InterPro).
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:0008138;	Molecular function: protein tyrosine/serine/threonine phosphatase activity (inferred from electronic annotation from InterPro).
GO:0007049;	Biological process: cell cycle (inferred from electronic annotation from UniProtKB-KW).
GO:0008283;	Biological process: cell proliferation (traceable author statement from UniProtKB).
GO:0007417;	Biological process: central nervous system 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:0045786;	Biological process: negative regulation of cell cycle (inferred from electronic annotation from UniProtKB-KW).
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

InterPro

IPR017361; Bifunc_PIno_P3_Pase/Pase_PTEN.
IPR014019; Phosphatase_tensin-typ.
IPR014020; Tensin_phosphatase_C2-dom.
IPR000340; Tyr_Pase_dual_specific.
Graphical view of domain structure.

Pfam

PF00782; DSPc; 1.
PF10409; PTEN_C2; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF038025; PTEN; 1.

PROSITE

PS51182; C2_TENSIN; 1.
PS51181; PPASE_TENSIN; 1.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

P60484; -.

Genome annotation databases

Ensembl

ENSG00000171862; Homo sapiens. [Contig view]

GeneID

5728; -.

KEGG

hsa:5728; -.

Phylogenomic databases

HOGENOM

P60484; -.

HOVERGEN

P60484; -.

OMA

P60484; NEPFDEE.

Other

22282; -.

P60484; -.

PTEN; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Anti-oncogene; Cell cycle; Cytoplasm; Disease mutation; Hydrolase; Lipid metabolism; Lipid-binding; Phosphoprotein; Polymorphism; Protein phosphatase.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 403`	`403`	`Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN.`	`PRO_0000215904`
`DOMAIN`	`14 185`	`172`	`Phosphatase tensin-type.`
`DOMAIN`	`190 350`	`161`	`C2 tensin-type.`
`REGION`	`401 403`	`3`	`PDZ domain-binding.`
`ACT_SITE`	`124 124`		`Phosphocysteine intermediate (Potential).`
`MOD_RES`	`366 366`		`Phosphothreonine.`
`MOD_RES`	`370 370`		`Phosphoserine; by CK2.`
`MOD_RES`	`385 385`		`Phosphoserine; by CK2.`
`MOD_RES`	`401 401`		`Phosphothreonine.`
`VARIANT`	`10 10`	`1`	`S -> N (retains phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes).`	`VAR_026248`
`VARIANT`	`15 15`	`1`	`R -> S (in glioma).`	`VAR_007457 [3D]`
`VARIANT`	`16 16`	`1`	`Y -> C (loss of phosphatase activity towards Ins(1,3,4,5)P4; retains the ability to bind phospholipid membranes).`	`VAR_026249 [3D]`
`VARIANT`	`19 19`	`1`	`D -> N (in malignant melanoma; somatic mutation).`	`VAR_018100 [3D]`
`VARIANT`	`20 20`	`1`	`G -> E (reduced phosphatase activity towards Ins(1,3,4,5)P4; retains phosphatase activity towards PtdIns(3,4,5)P3).`	`VAR_026250 [3D]`
`VARIANT`	`27 27`	`1`	`Y -> S (loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026251 [3D]`
`VARIANT`	`33 33`	`1`	`Missing (in CD).`	`VAR_008733`
`VARIANT`	`34 34`	`1`	`A -> D (in BZS).`	`VAR_008734 [3D]`
`VARIANT`	`35 35`	`1`	`M -> R (in CD).`	`VAR_008036 [3D]`
`VARIANT`	`36 36`	`1`	`G -> E (in glioma).`	`VAR_007458 [3D]`
`VARIANT`	`36 36`	`1`	`G -> R (in endometrial hyperplasia).`	`VAR_026252 [3D]`
`VARIANT`	`42 42`	`1`	`L -> R (in glioma; retains phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes).`	`VAR_007459 [3D]`
`VARIANT`	`47 47`	`1`	`R -> G (in CD).`	`VAR_011587 [3D]`
`VARIANT`	`57 57`	`1`	`L -> W (in glioma; loss of protein phosphatase activity).`	`VAR_007460 [3D]`
`VARIANT`	`61 61`	`1`	`H -> D (in VATER).`	`VAR_018101 [3D]`
`VARIANT`	`61 61`	`1`	`H -> R (loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026253 [3D]`
`VARIANT`	`67 67`	`1`	`I -> R (in CD).`	`VAR_007461 [3D]`
`VARIANT`	`68 68`	`1`	`Y -> H (in CD and BZS; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes).`	`VAR_007462 [3D]`
`VARIANT`	`70 70`	`1`	`L -> P (in CD).`	`VAR_018102 [3D]`
`VARIANT`	`71 71`	`1`	`C -> Y (in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026254 [3D]`
`VARIANT`	`93 93`	`1`	`H -> R (in macrocephaly/autism syndrome).`	`VAR_032634 [3D]`
`VARIANT`	`93 93`	`1`	`H -> Y (in CD).`	`VAR_026255 [3D]`
`VARIANT`	`105 105`	`1`	`C -> F (in BZS; loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026256 [3D]`
`VARIANT`	`105 105`	`1`	`C -> Y (in BZS).`	`VAR_008735 [3D]`
`VARIANT`	`107 107`	`1`	`D -> Y (in BZS and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026257 [3D]`
`VARIANT`	`112 112`	`1`	`L -> P (in CD and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_007807 [3D]`
`VARIANT`	`112 112`	`1`	`L -> R (loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026258 [3D]`
`VARIANT`	`119 119`	`1`	`V -> L (in multiple cancers).`	`VAR_011588 [3D]`
`VARIANT`	`121 121`	`1`	`A -> G (in HNSCC).`	`VAR_018103 [3D]`
`VARIANT`	`121 121`	`1`	`A -> P (in glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026259 [3D]`
`VARIANT`	`123 123`	`1`	`H -> R (in CD).`	`VAR_007463 [3D]`
`VARIANT`	`123 123`	`1`	`H -> Y (in endometrial cancer; loss of protein phosphatase activity).`	`VAR_026260 [3D]`
`VARIANT`	`124 124`	`1`	`C -> R (in CD).`	`VAR_007464 [3D]`
`VARIANT`	`124 124`	`1`	`C -> S (in CD; phosphatase-dead protein with neither lipid nor protein phosphatase activity).`	`VAR_018104 [3D]`
`VARIANT`	`129 129`	`1`	`G -> E (in CD; no lipid phosphatase activity but retains protein phosphatase activity; retains ability to inhibit focal adhesion formation).`	`VAR_007465 [3D]`
`VARIANT`	`129 129`	`1`	`G -> R (in glioblastoma; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_007466 [3D]`
`VARIANT`	`130 130`	`1`	`R -> G (loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3).`	`VAR_026261 [3D]`
`VARIANT`	`130 130`	`1`	`R -> L (in CD and endometrial hyperplasia; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes).`	`VAR_007467 [3D]`
`VARIANT`	`130 130`	`1`	`R -> Q (in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes).`	`VAR_007468 [3D]`
`VARIANT`	`132 132`	`1`	`G -> V (in one patient with clinical findings suggesting hamartoma tumor syndrome).`	`VAR_032635 [3D]`
`VARIANT`	`133 133`	`1`	`V -> I (loss of phosphatase activity towards Ins(1,3,4,5)P3).`	`VAR_026262 [3D]`
`VARIANT`	`134 134`	`1`	`M -> L (in prostate cancer; no effect on protein phosphatase activity; reduced phosphatase activity towards Ins(1,3,4,5)P3 but retains PtdIns(3,4,5)P3 phosphatase activity).`	`VAR_007469 [3D]`
`VARIANT`	`135 135`	`1`	`I -> V (in BZS).`	`VAR_008736 [3D]`
`VARIANT`	`136 136`	`1`	`C -> Y (in CD; loss of phosphatase activity towards Ins(1,3,4,5)P3).`	`VAR_007808 [3D]`
`VARIANT`	`137 137`	`1`	`A -> AN (in CD).`	`VAR_008737`
`VARIANT`	`155 155`	`1`	`Y -> C (in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026263 [3D]`
`VARIANT`	`158 158`	`1`	`V -> L (in multiple cancers).`	`VAR_011589 [3D]`
`VARIANT`	`165 165`	`1`	`G -> E (in CD).`	`VAR_008739 [3D]`
`VARIANT`	`165 165`	`1`	`G -> R (in glioblastoma; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes).`	`VAR_026264 [3D]`
`VARIANT`	`165 165`	`1`	`G -> V (in CD).`	`VAR_008738 [3D]`
`VARIANT`	`167 167`	`1`	`T -> P (in breast cancer; severely reduced protein phosphatase activity).`	`VAR_026265 [3D]`
`VARIANT`	`170 170`	`1`	`S -> N (loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes).`	`VAR_026266 [3D]`
`VARIANT`	`170 170`	`1`	`S -> R (in BZS; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_007470 [3D]`
`VARIANT`	`173 173`	`1`	`R -> C (in endometrial hyperplasia; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains ability to bind phospholipid membranes).`	`VAR_026267 [3D]`
`VARIANT`	`173 173`	`1`	`R -> H (loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026268 [3D]`
`VARIANT`	`173 173`	`1`	`R -> P (loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026269 [3D]`
`VARIANT`	`174 174`	`1`	`Y -> N (loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026270 [3D]`
`VARIANT`	`191 191`	`1`	`V -> A (in endometrial hyperplasia).`	`VAR_026271 [3D]`
`VARIANT`	`217 217`	`1`	`V -> I (in malignant melanoma; somatic mutation).`	`VAR_018105 [3D]`
`VARIANT`	`227 227`	`1`	`S -> F (reduced phosphatase activity towards Ins(1,3,4,5)P4 but retains PtdIns(3,4,5)P3 phosphatase activity).`	`VAR_026272 [3D]`
`VARIANT`	`234 234`	`1`	`R -> Q (in oligodendroglioma; not capable of inducing apoptosis; induced increased cell proliferation; led to high constitutive AKT1 activation which could not be increased further by stimulation with insulin).`	`VAR_018106 [3D]`
`VARIANT`	`241 241`	`1`	`F -> S (in macrocephaly/autism syndrome).`	`VAR_032636 [3D]`
`VARIANT`	`246 246`	`1`	`P -> L (in CD and BZS).`	`VAR_008740 [3D]`
`VARIANT`	`251 251`	`1`	`G -> C (loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes).`	`VAR_026273 [3D]`
`VARIANT`	`252 252`	`1`	`D -> G (in macrocephaly/autism syndrome).`	`VAR_032637 [3D]`
`VARIANT`	`289 289`	`1`	`K -> E (in CD; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes).`	`VAR_008741 [3D]`
`VARIANT`	`290 290`	`1`	`V -> L (in dbSNP:rs35600253 [NCBI]).`	`VAR_025167 [3D]`
`VARIANT`	`319 319`	`1`	`Missing (in glioma; reduced tumor suppressor activity; fails to inactivate AKT/PKB).`	`VAR_026274`
`VARIANT`	`331 331`	`1`	`D -> G (in CD; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes).`	`VAR_026275 [3D]`
`VARIANT`	`341 341`	`1`	`F -> V (in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_026276 [3D]`
`VARIANT`	`342 342`	`1`	`K -> N (in CD; reduced phosphatase activity towards Ins(1,3,4,5)P4 but PtdIns(3,4,5)P3 phosphatase activity is similar to wild-type).`	`VAR_026277 [3D]`
`VARIANT`	`343 343`	`1`	`V -> E (in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_008742 [3D]`
`VARIANT`	`345 345`	`1`	`L -> Q (in glioblastoma; reduced tumor suppressor activity; loss of phosphatase activity towards Ins(1,3,4,5)P4; reduced ability to inactivate AKT/PKB; retains ability to bind phospholipid membranes).`	`VAR_026278 [3D]`
`VARIANT`	`347 347`	`1`	`F -> L (in CD; reduced phosphatase activity towards Ins(1,3,4,5)P4).`	`VAR_008743 [3D]`
`VARIANT`	`348 348`	`1`	`T -> I (in endometrial hyperplasia; reduced phosphatase activity towards PtdIns(3,4,5)P3; mildly reduced tumor suppressor activity; reduced ability to inactivate AKT/PKB).`	`VAR_026279 [3D]`
`VARIANT`	`369 369`	`1`	`V -> G (retains Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 phosphatase activity; retains ability to bind phospholipid membranes).`	`VAR_026280`
`VARIANT`	`401 401`	`1`	`T -> I (retains Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 phosphatase activity; retains ability to bind phospholipid membranes).`	`VAR_026281`
`MUTAGEN`	`92 92`		`D->A: 700-fold reduction in phosphatase activity towards PtdIns(3,4,5)P3. Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation.`
`MUTAGEN`	`93 93`		`H->A: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Modest reduction in phosphatase activity towards PtsIns(3,4)P2.`
`MUTAGEN`	`124 124`		`C->A: Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation.`
`MUTAGEN`	`125 125`		`K->M: Reduced phosphatase activity towards PtdIns(3,4,5)P3, PtsIns(3,4)P2 and PtdIns(3)P.`
`MUTAGEN`	`128 128`		`K->M: 85% reduction in phosphatase activity towards PtdIns(3,4,5)P3.`
`MUTAGEN`	`128 128`		`K->R: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3.`
`MUTAGEN`	`130 130`		`R->M: Does not affect the ability to inhibit AKT/PKB activation.`
`MUTAGEN`	`167 167`		`T->A,D: 60% reduction in phosphatase activity towards PtdIns(3,4,5)P3.`
`MUTAGEN`	`171 171`		`Q->A,E: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3.`
`MUTAGEN`	`263 269`		`KMLKKDK->AAGAADA: Reduces the growth suppression activity and cells show anchorage-independent growth. Reduces binding to phospholipid membranes in vitro. Phosphatase activity towards PtdIns(3,4,5)P3 is not affected.`
`MUTAGEN`	`327 335`		`KANKDKANR->AAGADAANA: Reduces the growth suppression activity and cells show anchorage-independent growth. Reduces binding to phospholipid membranes in vitro; phosphatase activity towards PtdIns(3,4,5)P3 is not affected.`
`MUTAGEN`	`401 401`		`T->A: Loss of DLG1-binding. No effect on MAGI2- and MAST2-binding.`
`MUTAGEN`	`402 402`		`K->A: No effect on MAGI2-, MAST2- and DLG1-binding.`
`MUTAGEN`	`402 402`		`K->W: Loss of DLG1-, MAGI2-, MAGI3- and MAST2-binding. Decrease of protein stability.`
`MUTAGEN`	`403 403`		`V->A: Loss of DLG1-, MAGI2-, MAGI3-, MAST1-, MAST2- and MAST3-binding.`
`TURN`	`19 22`	`4`
`STRAND`	`23 29`	`7`
`STRAND`	`32 35`	`4`
`STRAND`	`39 41`	`3`
`HELIX`	`50 60`	`11`
`STRAND`	`61 63`	`3`
`STRAND`	`65 73`	`9`
`STRAND`	`85 90`	`6`
`HELIX`	`98 100`	`3`
`HELIX`	`101 112`	`12`
`TURN`	`113 115`	`3`
`STRAND`	`118 123`	`6`
`STRAND`	`125 128`	`4`
`HELIX`	`129 141`	`13`
`HELIX`	`148 159`	`12`
`STRAND`	`161 163`	`3`
`HELIX`	`169 184`	`16`
`STRAND`	`192 202`	`11`
`STRAND`	`213 219`	`7`
`STRAND`	`222 226`	`5`
`STRAND`	`232 235`	`4`
`STRAND`	`238 259`	`22`
`STRAND`	`268 276`	`9`
`HELIX`	`277 279`	`3`
`STRAND`	`315 321`	`7`
`HELIX`	`322 324`	`3`
`HELIX`	`328 330`	`3`
`STRAND`	`335 337`	`3`
`STRAND`	`342 349`	`8`

Sequence information

Length: 403 AA [This is the length of the unprocessed precursor]

Molecular weight: 47166 Da [This is the MW of the unprocessed precursor]

CRC64: 75F97C3DD6802BA9 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI DDVVRFLDSK 

        70         80         90        100        110        120 
HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL IKPFCEDLDQ WLSEDDNHVA 

       130        140        150        160        170        180 
AIHCKAGKGR TGVMICAYLL HRGKFLKAQE ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY 

       190        200        210        220        230        240 
LLKNHLDYRP VALLFHKMMF ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY 

       250        260        270        280        290        300 
FEFPQPLPVC GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI 

       310        320        330        340        350        360 
DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT VEEPSNPEAS 

       370        380        390        400 
SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHTQI TKV

P60484 in FASTA format

View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools