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General Description References Comments Links Keywords Features Sequence
General information
Entry name PTEN_HUMAN
Accession number O00633, O02679
Created Rel. 35, 1-NOV-1997
Sequence update Rel. 35, 1-NOV-1997
Annotation update Rel. 41, 15-JUN-2002
Description and origin of the Protein
Description Protein-tyrosine phosphatase PTEN (EC 3.1.3.48) (Mutated in multiple advanced cancers 1).
Gene name(s) PTEN OR MMAC1 OR TEP1.
Organism source Homo sapiens (Human)
Canis familiaris (Dog).
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo.
NCBI TaxID 9606, 9615
References
[1] 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.

(1997) Nat. Genet. 15:356-363
Position SEQUENCE FROM N.A., AND VARIANTS.
Comments SPECIES=Human, and C.familiaris;
Medline 97245711
PubMed 9090379
[2] 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.

(1997) Science 275:1943-1947
Position SEQUENCE FROM N.A.
Comments SPECIES=Human;
Medline 97228181
PubMed 9072974
[3] 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.

(1997) Cancer Res. 57:2124-2129
Position SEQUENCE FROM N.A.
Comments SPECIES=Human;
Medline 97330649
PubMed 9187108
[4] Wang,S., Li,J., Liaw,D., Bose,S., Podsypanina,K., Parsons,R., Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
Position SEQUENCE FROM N.A.
Comments SPECIES=Human;
[5] 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., McCombie,W.R.,
Genomic sequence of PTEN/MMAC1.
Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
Position SEQUENCE FROM N.A.
[6] Gray,N.E., Stewart,L.M.D., Hamilton,J.A., Roberts,K.G., Watson,G., Snary,D.,
Genomic sequence of chromosome 10q23.3 containing exons 6,7,8 and 9 of the PTEN gene.
Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
Position SEQUENCE FROM N.A.
[7] Strausberg,R., Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
Position SEQUENCE FROM N.A.
Comments TISSUE=LUNG;
[8] 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.

(1997) Proc. Natl. Acad. Sci. U.S.A. 94:9052-9057
Position CHARACTERIZATION.
Medline 97404346
PubMed 9256433
[9] 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.

(1997) Am. J. Hum. Genet. 61:1036-1043
Position VARIANT CD ASN-137 INS.
Medline 98007985
PubMed 9345101
[10] 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.

(1997) Am. J. Hum. Genet. 61:1254-1260
Position VARIANTS CD GLU-343 AND LEU-347.
Medline 98153621
PubMed 9399897
[11] 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.

(1997) Hum. Mol. Genet. 6:1383-1387
Position VARIANTS CD ARG-123 AND ARG-124.
Medline 97402224
PubMed 9259288
[12] 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.

(1997) Nat. Genet. 16:64-67
Position VARIANT CD GLU-129.
Medline 97285123
PubMed 9140396
[13] 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.

(1997) Nat. Genet. 16:333-334
Position VARIANT BZS ARG-170.
Medline 97385233
PubMed 9241266
[14] 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.

(1998) Gastroenterology 115:1084-1089
Position VARIANT CD GLU-289.
Medline 99014194
PubMed 9797362
[15] 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.

(1998) Hum. Genet. 102:467-473
Position VARIANTS CD HIS-68 AND PRO-112.
Medline 98260873
PubMed 9600246
[16] 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.

(1998) Hum. Mol. Genet. 7:507-515
Position VARIANTS CD AND BZS.
Medline 98133933
PubMed 9467011
[17] 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.

(1998) Int. J. Oncol. 13:665-668
Position VARIANT CD TYR-136.
Medline 98408002
PubMed 9735393
[18] Olschwang,S., Serova-Sinilnikova,O.M., Lenoir,G.M., Thomas,G.,
PTEN germ-line mutations in juvenile polyposis coli.

(1998) Nat. Genet. 18:12-14
Position VARIANT JPC ARG-35.
Medline 98085858
PubMed 9425889
[19] 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.

(1999) Am. J. Hum. Genet. 64:308-310
Position VARIANT CD GLN-130.
Medline 99115112
PubMed 9915974
[20] 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.

(1999) Am. J. Med. Genet. 82:290-293
Position VARIANT CD/LDD PRO-112.
Medline 99158469
PubMed 10051160
[21] 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., Hoefsloot,L.H., Peeters,E.A.J., Padberg,G.W.,
Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations.

(1999) Eur. J. Hum. Genet. 7:267-273
Position VARIANTS CD ILE-33 DEL; ARG-123; ARG-124 AND GLU-165.
Medline 99250761
PubMed 10234502
[22] 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.

(1999) Hum. Mol. Genet. 8:1461-1472
Position VARIANTS BZS ASP-34; HIS-68; TYR-105; VAL-135; ARG-170 AND LEU-246.
Medline 99330553
PubMed 10400993
[23] 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.

(2000) J. Med. Genet. 37:336-341
Position VARIANTS MULTIPLE CANCERS LEU-119 AND LEU-158.
Medline 20267903
PubMed 10807691
[24] 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.

(2001) Neoplasia 3:236-244
Position VARIANT CD G-47, AND VARIANTS BZS D-34; H-68; Y-105; V-135 AND R-170.
Medline 21385665
PubMed 11494117
Comments
FUNCTION POTENTIAL TUMOR SUPPRESSOR. ACTIVE AS A PHOSPHATASE ON TYROSINE, SERINE AND THREONINE RESIDUES.
CATALYTIC ACTIVITY PROTEIN TYROSINE PHOSPHATE + H(2)O = PROTEIN TYROSINE + PHOSPHATE.
DISEASE MUTATIONS OF PTEN ARE FOUND IN A LARGE NUMBER OF CANCERS.
DISEASE DEFECTS IN PTEN ARE A CAUSE OF COWDEN SYNDROME (CS), ALSO KNOWN AS COWDEN DISEASE (CD). CS IS AN AUTOSOMAL DOMINANT CANCER PREDISPOSITION SYNDROME ASSOCIATED WITH ELEVATED RISK FOR TUMORS OF THE BREAST, THYROID AND SKIN. THE PREDOMINANT PHENOTYPE FOR CS IS MULTIPLE HAMARTOMA SYNDROME, IN MANY ORGAN SYSTEMS INCLUDING THE BREAST (70% OF CS 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 CS.
DISEASE DEFECTS IN PTEN ARE A CAUSE OF BANNAYAN-ZONANA SYNDROME (BZS), 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 CS. BRR IS CHARACTERIZED BY THE CLASSIC TRIAD OF MACROCEPHALY, LIPOMATOSIS AND PIGMENTED MACULES OF THE GLAND PENIS.
DISEASE DEFECTS IN PTEN ARE A CAUSE OF JUVENILE POLYPOSIS COLI (JPC). JPC IS A DOMINANTLY INHERITED DISORDER THAT OFTEN PRESENTS WITH DIARRHEA, HEMORRHAGE AND PROTEIN-LOSING ENTEROPATHY. IT IS CHARACTERIZED BY THE DEVELOPMENT, THROUGHOUT THE DIGESTIVE TRACT, OF HAMARTOMATOUS POLYPS THAT POSSESS AN ABUNDANT LAMINA PROPRIA DEVOID OF SMOOTH MUSCLE AND A NORMAL EPITHELIAL COMPONENT, DISTINGUISHING THEM FROM THOSE THAT DEVELOP IN ADENOMATOUS POLYPOSIS COLI. JPC PREDISPOSES TO DIGESTIVE-TRACT CANCER.
DISEASE DEFECTS IN PTEN ARE A CAUSE OF LHERMITTE-DUCLOS DISEASE (LDD). LDD IS CHARACTERIZED BY DYSPLASTIC GANGLIOCYTOMA OF THE CEREBELLUM WHICH OFTEN RESULTS IN CEREBELLAR SIGNS AND SEIZURES.
SIMILARITY BELONGS TO THE NON-RECEPTOR CLASS OF THE PROTEIN- TYROSINE PHOSPHATASE FAMILY.
SIMILARITY CONTAINS 1 TENSIN DOMAIN.
DATABASE NAME=Atlas Genet. Cytogenet. Oncol. Haematol.; WWW="http://www.infobiogen.fr/services/chromcancer/Genes/PTENID158.html".
Copyright
This SWISS-PROT entry is copyright. It is produced through a collaboration between the Swiss Institute of Bioinformatics and the EMBL outstation - the European Bioinformatics Institute. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified and this statement is not removed. Usage by and for commercial entities requires a license agreement (See http://www.isb-sib.ch/announce/ or send an email to license@isb-sib.ch).
Database cross-references
EMBL
U92436;AAC51182.1;-.
U92435;AAC48709.1;-.
U93051;AAC51183.1;-.
U96180;AAB66902.1;-.
AF000734;AAC08699.1;-.
AF000726;AAC08699.1;JOINED.
AF000727;AAC08699.1;JOINED.
AF000728;AAC08699.1;JOINED.
AF000729;AAC08699.1;JOINED.
AF000730;AAC08699.1;JOINED.
AF000731;AAC08699.1;JOINED.
AF000732;AAC08699.1;JOINED.
AF000733;AAC08699.1;JOINED.
AF067844;AAD13528.1;-.
AF143315;AAD38372.1;-.
AF143312;AAD38372.1;JOINED.
AF143313;AAD38372.1;JOINED.
AF143314;AAD38372.1;JOINED.
BC005821;AAH05821.1;-.
Genew
HGNC:9588;PTEN.
MIM
601728;-.
158350;-.
153480;-.
174900;-.
InterPro
IPR000340;DS_phosphatase.
IPR000387;TYR_phosphatase.
SMART
SM00012;PTPc_DSPc;1.
PROSITE
PS00383;TYR_PHOSPHATASE_1;1.
PS50056;TYR_PHOSPHATASE_2;1.
Keywords
Hydrolase; Anti-oncogene; Disease mutation;
Features
Key Begin End Length Description
DOMAIN 22 303 282 TENSIN.
ACT_SITE 124 124 1 POTENTIAL.
VARIANT 15 15 1 R -> S (IN A GLIOMA). /FTID=VAR_007457.
VARIANT 33 33 1 MISSING (IN CD). /FTID=VAR_008733.
VARIANT 34 34 1 A -> D (IN BZS). /FTID=VAR_008734.
VARIANT 35 35 1 M -> R (IN JPC). /FTID=VAR_008036.
VARIANT 36 36 1 G -> E (IN A GLIOMA). /FTID=VAR_007458.
VARIANT 42 42 1 L -> R (IN A GLIOMA). /FTID=VAR_007459.
VARIANT 47 47 1 R -> G (IN CD). /FTID=VAR_011587.
VARIANT 57 57 1 L -> W (IN A GLIOMA). /FTID=VAR_007460.
VARIANT 67 67 1 I -> R (IN CD). /FTID=VAR_007461.
VARIANT 68 68 1 Y -> H (IN CD AND BZS). /FTID=VAR_007462.
VARIANT 105 105 1 C -> Y (IN BZS). /FTID=VAR_008735.
VARIANT 112 112 1 L -> P (IN CD AND LDD). /FTID=VAR_007807.
VARIANT 119 119 1 V -> L (IN MULTIPLE CANCERS). /FTID=VAR_011588.
VARIANT 123 123 1 H -> R (IN CD). /FTID=VAR_007463.
VARIANT 124 124 1 C -> R (IN CD). /FTID=VAR_007464.
VARIANT 129 129 1 G -> E (IN CD). /FTID=VAR_007465.
VARIANT 129 129 1 G -> R (IN A GLIOBLASTOMA). /FTID=VAR_007466.
VARIANT 130 130 1 R -> L (IN CD). /FTID=VAR_007467.
VARIANT 130 130 1 R -> Q (IN CD). /FTID=VAR_007468.
VARIANT 134 134 1 M -> L (IN A PROSTATE CANCER). /FTID=VAR_007469.
VARIANT 135 135 1 I -> V (IN BZS). /FTID=VAR_008736.
VARIANT 136 136 1 C -> Y (IN CD). /FTID=VAR_007808.
VARIANT 137 137 1 A -> AN (IN CD). /FTID=VAR_008737.
VARIANT 158 158 1 V -> L (IN MULTIPLE CANCERS). /FTID=VAR_011589.
VARIANT 165 165 1 G -> V (IN CD). /FTID=VAR_008738.
VARIANT 165 165 1 G -> E (IN CD). /FTID=VAR_008739.
VARIANT 170 170 1 S -> R (IN BZS). /FTID=VAR_007470.
VARIANT 246 246 1 P -> L (IN CD AND BZS). /FTID=VAR_008740.
VARIANT 289 289 1 K -> E (IN CD). /FTID=VAR_008741.
VARIANT 343 343 1 V -> E (IN CD). /FTID=VAR_008742.
VARIANT 347 347 1 F -> L (IN CD). /FTID=VAR_008743.
Sequence information
Length: 403 aa, molecular weight: 47166 Da, CRC64 checksum: 75F97C3DD6802BA9
     MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI DDVVRFLDSK        60
     HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL IKPFCEDLDQ WLSEDDNHVA       120
     AIHCKAGKGR TGVMICAYLL HRGKFLKAQE ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY       180
     LLKNHLDYRP VALLFHKMMF ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY       240
     FEFPQPLPVC GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI       300
     DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT VEEPSNPEAS       360
     SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHTQI TKV                         403
//
General Description References Comments Links Keywords Features Sequence
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