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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". |
|
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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
//
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