Reviewed, UniProtKB/Swiss-Prot P60484 (PTEN_HUMAN)

Names and origin

Protein names

Recommended name:
    Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
    EC=3.1.3.67
    EC=3.1.3.16
    EC=3.1.3.48
Alternative name(s):
    Phosphatase and tensin homolog
    Mutated in multiple advanced cancers 1

Gene names

Name:	PTEN
Synonyms:	MMAC1, TEP1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	403 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (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. Ref.1 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.20
Catalytic activity	Phosphatidylinositol 3,4,5-trisphosphate + H2O = phosphatidylinositol 4,5-bisphosphate + phosphate. Ref.1 Ref.12 Ref.13 Ref.14 A phosphoprotein + H2O = a protein + phosphate. Ref.1 Ref.12 Ref.13 Ref.14 Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.1 Ref.12 Ref.13 Ref.14
Cofactor	Magnesium.
Subunit structure	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. Interacts with NEDD4. Interacts (via C2 domain) with FRK. Ref.20 Ref.17 Ref.18 Ref.19 Ref.22 Ref.23 Ref.24 Ref.26
Subcellular location	Cytoplasm. Ref.1
Tissue specificity	Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas. Ref.2
Induction	Down-regulated by transforming growth factor beta (TGF-beta). Ref.1
Domain	The C2 domain binds phospholipid membranes in vitro in a Ca2+-independent manner; this binding is important for its tumor suppressor function. Ref.16 Ref.26
Post-translational modification	Phosphorylated in vitro by MAST1, MAST2 and MAST3. Phosphorylation results in an inhibited activity towards PIP3. Phosphorylation can both inhibit or promote PDZ-binding. Phosphorylation at Tyr-336 by FRK/PTK5 protects this protein from ubiquitin-mediated degradation probably by inhibiting its binding to NEDD4. Ref.20 Ref.17 Ref.22 Ref.24 Ref.21
Involvement in disease	Mutations of PTEN are found in a large number of cancers. 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. Ref.12 Ref.14 Ref.27 Ref.28 Ref.30 Ref.31 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.44 Ref.47 Ref.49 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. Defects in PTEN are a cause of Bannayan-Zonana syndrome (BZS) [MIM:153480]; also known as Ruvalcaba-Myhre-Smith syndrome (RMSS) 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. Ref.36 Ref.44 Ref.49 Ref.32 Ref.43 Defects in PTEN are a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:275355]; also known as squamous cell carcinoma of the head and neck. Ref.51 Defects in PTEN are a cause of susceptibility to endometrial cancer [MIM:608089]. 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. Ref.52 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. Ref.50 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. Defects in PTEN are involved in prostate cancer [MIM:176807]. 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). 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. Ref.54
Sequence similarities	Contains 1 C2 tensin-type domain. Contains 1 phosphatase tensin-type domain.

Ontologies

Keywords
Biological process	Apoptosis Lipid metabolism
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation Tumor suppressor
Ligand	Lipid-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Traceable author statement. Source: UniProtKB central nervous system development Inferred from sequence or structural similarity. Source: UniProtKB induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB inositol phosphate dephosphorylation Ref.13 Inferred from direct assay. Source: UniProtKB negative regulation of cell migration Ref.15 Inferred from mutant phenotype. Source: UniProtKB negative regulation of cell proliferation Ref.16 Inferred from mutant phenotype. Source: UniProtKB negative regulation of focal adhesion formation Ref.15 Inferred from mutant phenotype. Source: UniProtKB negative regulation of protein kinase B signaling cascade Ref.19 Inferred from mutant phenotype. Source: UniProtKB phosphoinositide dephosphorylation Ref.13 Ref.14 Inferred from direct assay. Source: UniProtKB protein amino acid dephosphorylation Ref.12 Inferred from direct assay. Source: UniProtKB regulation of cyclin-dependent protein kinase activity Traceable author statement. Source: UniProtKB regulation of protein stability Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytosol Ref.13 Inferred from Experiment. Source: Reactome nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	PDZ domain binding Ref.17 Ref.19 Inferred from physical interaction. Source: UniProtKB inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity Ref.13 Inferred from direct assay. Source: UniProtKB lipid binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: InterPro phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity Ref.13 Ref.14 Inferred from direct assay. Source: UniProtKB phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity Ref.14 Inferred from direct assay. Source: UniProtKB phosphatidylinositol-3-phosphatase activity Ref.14 Inferred from direct assay. Source: UniProtKB protein serine/threonine phosphatase activity Ref.12 Inferred from direct assay. Source: UniProtKB protein tyrosine phosphatase activity Ref.12 Inferred from direct assay. Source: UniProtKB protein tyrosine/serine/threonine phosphatase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Cenpc1	P49452	1	EBI-696162,EBI-1186252	From a different organism.
Dlg1	Q62696	1	EBI-696162,EBI-389325	From a different organism.
HSPA5	P11021	1	EBI-696162,EBI-354921
Magi2	O88382	2	EBI-696162,EBI-696179	From a different organism.
Magi3	Q9JK71	1	EBI-696162,EBI-696226	From a different organism.
Mast1	Q9R1L5	2	EBI-696162,EBI-491771	From a different organism.
Mast2	Q60592	2	EBI-696162,EBI-493888	From a different organism.
MAST3	O60307	2	EBI-696162,EBI-311420
PPP1CA	P62136	2	EBI-696162,EBI-357253
Pten	O08586	1	EBI-696162,EBI-1186266	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 403

403

Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN

PRO_0000215904

Regions

Domain

14 – 185

172

Phosphatase tensin-type

Domain

190 – 350

161

C2 tensin-type

Region

401 – 403

3

PDZ domain-binding

Sites

Active site

124

1

Phosphocysteine intermediate Potential

Amino acid modifications

Modified residue

6

1

N6-acetyllysine Ref.25

Modified residue

336

1

Phosphotyrosine; by FRK Ref.24

Modified residue

366

1

Phosphothreonine Ref.21

Modified residue

370

1

Phosphoserine; by CK2 Ref.21

Modified residue

385

1

Phosphoserine; by CK2 Ref.21

Modified residue

401

1

Phosphothreonine Ref.17

Natural variations

Natural variant

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. Ref.44

VAR_026248

Natural variant

15

1

R → S in glioma. Ref.2

VAR_007457

Natural variant

16

1

Y → C Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains the ability to bind phospholipid membranes. Ref.44

VAR_026249

Natural variant

19

1

D → N in malignant melanoma; somatic mutation. Ref.46

VAR_018100

Natural variant

20

1

G → E Reduced phosphatase activity towards Ins(1,3,4,5)P4; retains phosphatase activity towards PtdIns(3,4,5)P3. Ref.44

VAR_026250

Natural variant

27

1

Y → S Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44

VAR_026251

Natural variant

33

1

Missing in CD.

VAR_008733

Natural variant

34

1

A → D in BZS. Ref.49 Ref.43

VAR_008734

Natural variant

35

1

M → R in CD. Ref.39

VAR_008036

Natural variant

36

1

G → E in glioma. Ref.2

VAR_007458

Natural variant

36

1

G → R in endometrial hyperplasia. Ref.33

VAR_026252

Natural variant

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. Ref.2

VAR_007459

Natural variant

47

1

R → G in CD. Ref.49

VAR_011587

Natural variant

57

1

L → W in glioma; loss of protein phosphatase activity. Ref.12 Ref.2

VAR_007460

Natural variant

61

1

H → D in VATER. Ref.48

VAR_018101

Natural variant

61

1

H → R Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44

VAR_026253

Natural variant

67

1

I → R in CD.

VAR_007461

Natural variant

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. Ref.35 Ref.44 Ref.49 Ref.43

VAR_007462

Natural variant

70

1

L → P in CD. Ref.38

VAR_018102

Natural variant

71

1

C → Y in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44

VAR_026254

Natural variant

93

1

H → R in macrocephaly/autism syndrome. Ref.53

VAR_032634

Natural variant

93

1

H → Y in CD. Ref.44

VAR_026255

Natural variant

105

1

C → F in BZS; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44

VAR_026256

Natural variant

105

1

C → Y in BZS. Ref.49 Ref.43

VAR_008735

Natural variant

107

1

D → Y in BZS and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44 Ref.29

VAR_026257

Natural variant

112

1

L → P in CD and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.35 Ref.41 Ref.44

VAR_007807

Natural variant

112

1

L → R Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44

VAR_026258

Natural variant

119

1

V → L in multiple cancers. Ref.45

VAR_011588

Natural variant

121

1

A → G in HNSCC. Ref.51

VAR_018103

Natural variant

121

1

A → P in glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44 Ref.29

VAR_026259

Natural variant

123

1

H → R in CD. Ref.30 Ref.42

VAR_007463

Natural variant

123

1

H → Y in endometrial cancer; loss of protein phosphatase activity. Ref.12

VAR_026260

Natural variant

124

1

C → R in CD. Ref.30 Ref.42 Ref.44

VAR_007464

Natural variant

124

1

C → S in CD; phosphatase-dead protein with neither lipid nor protein phosphatase activity. Ref.14 Ref.47

VAR_018104

Natural variant

129

1

G → E in CD; no lipid phosphatase activity but retains protein phosphatase activity; retains ability to inhibit focal adhesion formation. Ref.14 Ref.15 Ref.31 Ref.44 Ref.47

VAR_007465

Natural variant

129

1

G → R in glioblastoma; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.12 Ref.44 Ref.29 Ref.3

VAR_007466

Natural variant

130

1

R → G Loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3. Ref.44

VAR_026261

Natural variant

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. Ref.44 Ref.33

VAR_007467

Natural variant

130

1

R → Q in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. Ref.40 Ref.44

VAR_007468

Natural variant

132

1

G → V in one patient with clinical findings suggesting hamartoma tumor syndrome. Ref.55

VAR_032635

Natural variant

133

1

V → I Loss of phosphatase activity towards Ins(1,3,4,5)P3. Ref.44

VAR_026262

Natural variant

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. Ref.12 Ref.44 Ref.3

VAR_007469

Natural variant

135

1

I → V in BZS. Ref.49 Ref.43

VAR_008736

Natural variant

136

1

C → Y in CD; loss of phosphatase activity towards Ins(1,3,4,5)P3. Ref.37 Ref.44

VAR_007808

Natural variant

137

1

A → AN in CD. Ref.27

VAR_008737

Natural variant

155

1

Y → C in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44

VAR_026263

Natural variant

158

1

V → L in multiple cancers. Ref.45

VAR_011589

Natural variant

165

1

G → E in CD. Ref.42

VAR_008739

Natural variant

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. Ref.12 Ref.44 Ref.29

VAR_026264

Natural variant

165

1

G → V in CD.

VAR_008738

Natural variant

167

1

T → P in breast cancer; severely reduced protein phosphatase activity. Ref.12

VAR_026265

Natural variant

170

1

S → N Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. Ref.44

VAR_026266

Natural variant

170

1

S → R in BZS; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.12 Ref.44 Ref.49 Ref.32 Ref.43

VAR_007470

Natural variant

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. Ref.44 Ref.33

VAR_026267

Natural variant

173

1

R → H Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44

VAR_026268

Natural variant

173

1

R → P Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44

VAR_026269

Natural variant

174

1

Y → N Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44

VAR_026270

Natural variant

191

1

V → A in endometrial hyperplasia. Ref.33

VAR_026271

Natural variant

217

1

V → I in malignant melanoma; somatic mutation. Ref.46

VAR_018105

Natural variant

227

1

S → F Reduced phosphatase activity towards Ins(1,3,4,5)P4 but retains PtdIns(3,4,5)P3 phosphatase activity. Ref.44

VAR_026272

Natural variant

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. Ref.50

VAR_018106

Natural variant

241

1

F → S in macrocephaly/autism syndrome. Ref.53

VAR_032636

Natural variant

246

1

P → L in CD and BZS. Ref.43

VAR_008740

Natural variant

251

1

G → C Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. Ref.44

VAR_026273

Natural variant

252

1

D → G in macrocephaly/autism syndrome. Ref.53

VAR_032637

Natural variant

289

1

K → E in CD; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. Ref.34 Ref.44

VAR_008741

Natural variant

290

1

V → L: dbSNP rs35600253. Ref.9

VAR_025167

Natural variant

319

1

Missing in glioma; reduced tumor suppressor activity; fails to inactivate AKT/PKB.

VAR_026274

Natural variant

331

1

D → G in CD; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. Ref.44

VAR_026275

Natural variant

341

1

F → V in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44

VAR_026276

Natural variant

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. Ref.44

VAR_026277

Natural variant

343

1

V → E in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.28 Ref.44

VAR_008742

Natural variant

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. Ref.16 Ref.44 Ref.29

VAR_026278

Natural variant

347

1

F → L in CD; reduced phosphatase activity towards Ins(1,3,4,5)P4. Ref.28 Ref.44

VAR_008743

Natural variant

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. Ref.16 Ref.33

VAR_026279

Natural variant

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. Ref.44

VAR_026280

Natural variant

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. Ref.44

VAR_026281

Experimental info

Mutagenesis

92

1

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. Ref.15 Ref.26

Mutagenesis

93

1

H → A: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Modest reduction in phosphatase activity towards PtsIns(3,4)P2. Ref.26

Mutagenesis

124

1

C → A: Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation. Ref.15

Mutagenesis

125

1

K → M: Reduced phosphatase activity towards PtdIns(3,4,5)P3, PtsIns(3,4)P2 and PtdIns(3)P. Ref.26

Mutagenesis

128

1

K → M: 85% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Ref.26

Mutagenesis

128

1

K → R: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3. Ref.26

Mutagenesis

130

1

R → M: Does not affect the ability to inhibit AKT/PKB activation. Ref.14

Mutagenesis

167

1

T → A or D: 60% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Ref.26

Mutagenesis

171

1

Q → A or E: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Ref.26

Mutagenesis

263 – 269

7

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. Ref.26

Mutagenesis

327 – 335

9

KANKDKANR → AAGADAANA: Reduces growth suppression activity and promotes anchorage-independent growth. Reduces binding to phospholipid membranes in vitro; phosphatase activity towards PtdIns(3,4,5)P3 is not affected. Ref.26

Mutagenesis

336

1

Y → F: Significantly lower phosphatase activity, reduced protein stability and decreased growth-inhibitory effect. Ref.24

Mutagenesis

401

1

T → A: Loss of DLG1-binding. No effect on MAGI2- and MAST2-binding.

Mutagenesis

402

1

K → A: No effect on MAGI2-, MAST2- and DLG1-binding.

Mutagenesis

402

1

K → W: Loss of DLG1-, MAGI2-, MAGI3- and MAST2-binding. Decrease of protein stability.

Mutagenesis

403

1

V → A: Loss of DLG1-, MAGI2-, MAGI3-, MAST1-, MAST2- and MAST3-binding. Ref.22

Secondary structure

1

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403

Helix Strand Turn

Details...

Turn

19 – 22

4

Beta strand

23 – 29

7

Beta strand

32 – 35

4

Beta strand

39 – 41

3

Helix

50 – 60

11

Beta strand

61 – 63

3

Beta strand

65 – 73

9

Beta strand

85 – 90

6

Helix

98 – 100

3

Helix

101 – 112

12

Turn

113 – 115

3

Beta strand

118 – 123

6

Beta strand

125 – 128

4

Helix

129 – 141

13

Helix

148 – 159

12

Beta strand

161 – 163

3

Helix

169 – 184

16

Beta strand

192 – 202

11

Beta strand

213 – 219

7

Beta strand

222 – 226

5

Beta strand

232 – 235

4

Beta strand

238 – 259

22

Beta strand

268 – 276

9

Helix

277 – 279

3

Beta strand

315 – 321

7

Helix

322 – 324

3

Helix

328 – 330

3

Beta strand

335 – 337

3

Beta strand

342 – 349

8

Sequences

	Sequence		Length	Mass (Da)
	P60484-1 [UniParc]. Last modified February 16, 2004. Version 1. Checksum: 75F97C3DD6802BA9	FASTA	403	47,166
	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

References

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[1]	"TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta." Li D.M., Sun H. Cancer Res. 57:2124-2129(1997) [PubMed: 9187108] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INDUCTION. Tissue: Epithelium.
[2]	"Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers." 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. Nat. Genet. 15:356-363(1997) [PubMed: 9090379] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANTS GLIOMA SER-15; GLU-36; ARG-42; TRP-57 AND THR-319 DEL.
[3]	"PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer." 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. Science 275:1943-1947(1997) [PubMed: 9072974] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLIOBLASTOMA ARG-129 AND PROSTATE CANCER LEU-134.
[4]	"The expression profile for the tumour suppressor gene PTEN and associated polymorphic markers." 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. Br. J. Cancer 82:1671-1676(2000) [PubMed: 10817502] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	Wang S., Li J., Liaw D., Bose S., Podsypanina K., Parsons R. Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Genomic sequence of PTEN/MMAC1." 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. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Spleen.
[9]	NIEHS SNPs program Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-290.
[10]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[12]	"P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase." Myers M.P., Stolarov J.P., Eng C., Li J., Wang S.I., Wigler M.H., Parsons R., Tonks N.K. Proc. Natl. Acad. Sci. U.S.A. 94:9052-9057(1997) [PubMed: 9256433] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, 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.
[13]	"The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate." Maehama T., Dixon J.E. J. Biol. Chem. 273:13375-13378(1998) [PubMed: 9593664] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY.
[14]	"The lipid phosphatase activity of PTEN is critical for its tumor supressor function." 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. Proc. Natl. Acad. Sci. U.S.A. 95:13513-13518(1998) [PubMed: 9811831] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-130, CHARACTERIZATION OF VARIANTS CD SER-124 AND CD GLU-129.
[15]	"Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN." Tamura M., Gu J., Matsumoto K., Aota S., Parsons R., Yamada K.M. Science 280:1614-1617(1998) [PubMed: 9616126] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-92 AND CYS-124, CHARACTERIZATION OF VARIANT GLU-129.
[16]	"The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region." Georgescu M.-M., Kirsch K.H., Akagi T., Shishido T., Hanafusa H. Proc. Natl. Acad. Sci. U.S.A. 96:10182-10187(1999) [PubMed: 10468583] [Abstract] Cited for: FUNCTION, DOMAIN, CHARACTERIZATION OF VARIANTS THR-319 DEL; GLN-345 AND ILE-348.
[17]	"Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding." Adey N.B., Huang L., Ormonde P.A., Baumgard M.L., Pero R., Byreddy D.V., Tavtigian S.V., Bartel P.L. Cancer Res. 60:35-37(2000) [PubMed: 10646847] [Abstract] Cited for: INTERACTION WITH DLG1 AND MAST2, PHOSPHORYLATION AT THR-401.
[18]	"Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase." Wu Y., Dowbenko D., Spencer S., Laura R., Lee J., Gu Q., Lasky L.A. J. Biol. Chem. 275:21477-21485(2000) [PubMed: 10748157] [Abstract] Cited for: INTERACTION WITH MAGI3.
[19]	"Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2." 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. Proc. Natl. Acad. Sci. U.S.A. 97:4233-4238(2000) [PubMed: 10760291] [Abstract] Cited for: INTERACTION WITH AIP1.
[20]	"Phosphorylation of the PTEN tail acts as an inhibitory switch by preventing its recruitment into a protein complex." Vazquez F., Grossman S.R., Takahashi Y., Rokas M.V., Nakamura N., Sellers W.R. J. Biol. Chem. 276:48627-48630(2001) [PubMed: 11707428] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH AIP1.
[21]	"Direct identification of PTEN phosphorylation sites." Miller S., Lou D., Seldin D., Lane W., Neel B. FEBS Lett. 528:145-153(2002) [PubMed: 12297295] [Abstract] Cited for: PHOSPHORYLATION AT THR-366; SER-370 AND SER-385.
[22]	"Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases." Valiente M., Andres-Pons A., Gomar B., Torres J., Gil A., Tapparel C., Antonarakis S.E., Pulido R. J. Biol. Chem. 280:28936-28943(2005) [PubMed: 15951562] [Abstract] Cited for: INTERACTION WITH MAGI2; MAGI3; MAST1; MAST2 AND MAST3, MUTAGENESIS OF VAL-403, PHOSPHORYLATION.
[23]	"NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN." Wang X., Trotman L.C., Koppie T., Alimonti A., Chen Z., Gao Z., Wang J., Erdjument-Bromage H., Tempst P., Cordon-Cardo C., Pandolfi P.P., Jiang X. Cell 128:129-139(2007) [PubMed: 17218260] [Abstract] Cited for: INTERACTION WITH NEDD4.
[24]	"Rak functions as a tumor suppressor by regulating PTEN protein stability and function." Yim E.-K., Peng G., Dai H., Hu R., Li K., Lu Y., Mills G.B., Meric-Bernstam F., Hennessy B.T., Craven R.J., Lin S.-Y. Cancer Cell 15:304-314(2009) [PubMed: 19345329] [Abstract] Cited for: INTERACTION WITH FRK, PHOSPHORYLATION AT TYR-336, MUTAGENESIS OF TYR-336.
[25]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6, MASS SPECTROMETRY.
[26]	"Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association." Lee J.-O., Yang H., Georgescu M.-M., Di Cristofano A., Maehama T., Shi Y., Dixon J.E., Pandolfi P., Pavletich N.P. Cell 99:323-334(1999) [PubMed: 10555148] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 8-353 IN COMPLEX WITH L(+)-TARTRATE, SUBUNIT, DOMAIN, MUTAGENESIS OF ASP-92; HIS-93; LYS-125; LYS-128; THR-167; GLN-171; 263-LYS--ALA-269 AND 327-LYS--ALA-335.
[27]	"The role of MMAC1 mutations in early-onset breast cancer: causative in association with Cowden syndrome and excluded in BRCA1-negative cases." 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. Am. J. Hum. Genet. 61:1036-1043(1997) [PubMed: 9345101] [Abstract] Cited for: VARIANT CD ASN-137 INS.
[28]	"Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis." 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. Am. J. Hum. Genet. 61:1254-1260(1997) [PubMed: 9399897] [Abstract] Cited for: VARIANTS CD GLU-343 AND LEU-347.
[29]	"Somatic mutations of PTEN in glioblastoma multiforme." Wang S.I., Puc J., Li J., Bruce J.N., Cairns P., Sidransky D., Parsons R. Cancer Res. 57:4183-4186(1997) [PubMed: 9331071] [Abstract] Cited for: VARIANTS GLIOBLASTOMA TYR-107; PRO-121; ARG-129; ARG-165 AND GLN-345.
[30]	"Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease." 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. Hum. Mol. Genet. 6:1383-1387(1997) [PubMed: 9259288] [Abstract] Cited for: VARIANTS CD ARG-123 AND ARG-124.
[31]	"Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome." 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. Nat. Genet. 16:64-67(1997) [PubMed: 9140396] [Abstract] Cited for: VARIANT CD GLU-129.
[32]	"Germline mutations in PTEN are present in Bannayan-Zonana syndrome." Marsh D.J., Dahia P.L.M., Zheng Z., Liaw D., Parsons R., Gorlin R.J., Eng C. Nat. Genet. 16:333-334(1997) [PubMed: 9241266] [Abstract] Cited for: VARIANT BZS ARG-170.
[33]	"Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias." Maxwell G.L., Risinger J.I., Gumbs C., Shaw H., Bentley R.C., Barrett J.C., Berchuck A., Futreal P.A. Cancer Res. 58:2500-2503(1998) [PubMed: 9635567] [Abstract] Cited for: VARIANTS ENDOMETRIAL HYPERPLASIA ARG-36; LEU-130; CYS-173; ALA-191 AND ILE-348.
[34]	"Mutational abrogation of the PTEN/MMAC1 gene in gastrointestinal polyps in patients with Cowden disease." 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. Gastroenterology 115:1084-1089(1998) [PubMed: 9797362] [Abstract] Cited for: VARIANT CD GLU-289.
[35]	"The genetic basis of Cowden's syndrome: three novel mutations in PTEN/MMAC1/TEP1." 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. Hum. Genet. 102:467-473(1998) [PubMed: 9600246] [Abstract] Cited for: VARIANTS CD HIS-68 AND PRO-112.
[36]	"Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation." 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. Hum. Mol. Genet. 7:507-515(1998) [PubMed: 9467011] [Abstract] Cited for: VARIANTS CD AND BZS.
[37]	"Novel mutation of the PTEN gene in an Italian Cowden's disease kindred." Scala S., Bruni P., Lo Muzio L., Mignogna M., Viglietto G., Fusco A. Int. J. Oncol. 13:665-668(1998) [PubMed: 9735393] [Abstract] Cited for: VARIANT CD TYR-136.
[38]	"Germline PTEN mutations in Cowden syndrome-like families." 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. J. Med. Genet. 35:881-885(1998) [PubMed: 9832031] [Abstract] Cited for: VARIANT CD PRO-70.
[39]	"PTEN germ-line mutations in juvenile polyposis coli." Olschwang S., Serova-Sinilnikova O.M., Lenoir G.M., Thomas G. Nat. Genet. 18:12-14(1998) [PubMed: 9425889] [Abstract] Cited for: VARIANT CD ARG-35.
[40]	"Variant manifestation of Cowden disease in Japan: hamartomatous polyposis of the digestive tract with mutation of the PTEN gene." Kurose K., Araki T., Matsunaka T., Takada Y., Emi M. Am. J. Hum. Genet. 64:308-310(1999) [PubMed: 9915974] [Abstract] Cited for: VARIANT CD GLN-130.
[41]	"Severe Lhermitte-Duclos disease with unique germline mutation of PTEN." Sutphen R., Diamond T.M., Minton S.E., Peacocke M., Tsou H.C., Root A.W. Am. J. Med. Genet. 82:290-293(1999) [PubMed: 10051160] [Abstract] Cited for: VARIANT CD/LDD PRO-112.
[42]	"Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations." 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. Eur. J. Hum. Genet. 7:267-273(1999) [PubMed: 10234502] [Abstract] Cited for: VARIANTS CD ILE-33 DEL; ARG-123; ARG-124 AND GLU-165.
[43]	"PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome." 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. Hum. Mol. Genet. 8:1461-1472(1999) [PubMed: 10400993] [Abstract] Cited for: VARIANTS BZS ASP-34; HIS-68; TYR-105; VAL-135; ARG-170 AND LEU-246.
[44]	"Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay." Han S.-Y., Kato H., Kato S., Suzuki T., Shibata H., Ishii S., Shiiba K., Matsuno S., Kanamaru R., Ishioka C. Cancer Res. 60:3147-3151(2000) [PubMed: 10866302] [Abstract] Cited for: 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.
[45]	"Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers." De Vivo I., Gertig D.M., Nagase S., Hankinson S.E., O'Brien R., Speizer F.E., Parsons R., Hunter D.J. J. Med. Genet. 37:336-341(2000) [PubMed: 10807691] [Abstract] Cited for: VARIANTS MULTIPLE CANCERS LEU-119 AND LEU-158.
[46]	"Identification of PTEN mutations in metastatic melanoma specimens." Celebi J.T., Shendrik I., Silvers D.N., Peacocke M. J. Med. Genet. 37:653-657(2000) [PubMed: 10978354] [Abstract] Cited for: VARIANTS MALIGNANT MELANOMA ASN-19 AND ILE-217.
[47]	"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." Weng L.-P., Brown J.L., Eng C. Hum. Mol. Genet. 10:599-604(2001) [PubMed: 11230179] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS CD SER-124 AND GLU-129.
[48]	"A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association." Reardon W., Zhou X.-P., Eng C. J. Med. Genet. 38:820-823(2001) [PubMed: 11748304] [Abstract] Cited for: VARIANT VATER ASP-61.
[49]	"Rapid mutation scanning of genes associated with familial cancer syndromes using denaturing high-performance liquid chromatography." Marsh D.J., Theodosopoulos G., Howell V., Richardson A.-L., Benn D.E., Proos A.L., Eng C., Robinson B.G. Neoplasia 3:236-244(2001) [PubMed: 11494117] [Abstract] Cited for: VARIANT CD GLY-47, VARIANTS BZS ASP-34; HIS-68; TYR-105; VAL-135 AND ARG-170.
[50]	"A novel germline mutation of PTEN associated with brain tumours of multiple lineages." 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. Br. J. Cancer 86:1586-1591(2002) [PubMed: 12085208] [Abstract] Cited for: CHARACTERIZATION OF VARIANT OLIGODENDROGLIOMA GLN-234.
[51]	"Detection of new PTEN/MMAC1 mutations in head and neck squamous cell carcinomas with loss of chromosome 10." Poetsch M., Lorenz G., Kleist B. Cancer Genet. Cytogenet. 132:20-24(2002) [PubMed: 11801303] [Abstract] Cited for: VARIANT HNSCC GLY-121.
[52]	"Germline mutation of the tumour suppressor PTEN in Proteus syndrome." Smith J.M., Kirk E.P.E., Theodosopoulos G., Marshall G.M., Walker J., Rogers M., Field M., Brereton J.J., Marsh D.J. J. Med. Genet. 39:937-940(2002) [PubMed: 12471211] [Abstract] Cited for: INVOLVEMENT IN PROTEUS SYNDROME.
[53]	"Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations." 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. J. Med. Genet. 42:318-321(2005) [PubMed: 15805158] [Abstract] Cited for: VARIANTS MACROCEPHALY/AUTISM SYNDROME ARG-93; SER-241 AND GLY-252.
[54]	"Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with cognitive and behavioral abnormalities." 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. Am. J. Hum. Genet. 80:938-947(2007) [PubMed: 17436248] [Abstract] Cited for: INVOLVEMENT IN CHROMOSOME 10Q23 DELETION SYNDROME.
[55]	"A germline PTEN mutation with manifestations of prenatal onset and verrucous epidermal nevus." 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. Am. J. Med. Genet. A 140:1472-1475(2006) [PubMed: 16752378] [Abstract] Cited for: VARIANT VAL-132.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

U96180 mRNA. Translation: AAB66902.1.
U92436 mRNA. Translation: AAC51182.1.
U93051 mRNA. Translation: AAC51183.1.
AF143315 , AF143312, AF143313, AF143314 Genomic DNA. Translation: AAD38372.1.
AF000734 , AF000726, AF000727, AF000728, AF000729, AF000730, AF000731, AF000732, AF000733 Genomic DNA. Translation: AAC08699.1.
AF067844 Unassigned DNA. Translation: AAD13528.1.
CR450306 mRNA. Translation: CAG29302.1.
AK313581 mRNA. Translation: BAG36351.1.
DQ073384 Genomic DNA. Translation: AAY57327.1.
CH471066 Genomic DNA. Translation: EAW50174.1.
BC005821 mRNA. Translation: AAH05821.1.

IPI

IPI00012587.

RefSeq

NP_000305.3.

UniGene

Hs.500466

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D5R	X-ray	2.10	A	8-353	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P60484. 17 interactions.

STRING

P60484.

PTM databases

PhosphoSite

P60484.

Proteomic databases

PRIDE

P60484.

Genome annotation databases

Ensembl

ENST00000371953; ENSP00000361021; ENSG00000171862; Homo sapiens. [Genome view]

GeneID

5728.

KEGG

hsa:5728.

UCSC

uc001kfb.1. human.

Organism-specific databases

CTD

5728.

GeneCards

GC10P089613.

H-InvDB

HIX0009010.
HIX0025699.

HGNC

HGNC:9588. PTEN.

HPA

CAB004076.

MIM

137800. phenotype.
153480. phenotype.
158350. phenotype.
176807. phenotype.
176920. phenotype.
275355. phenotype.
276950. phenotype.
601728. gene.
605309. phenotype.
608089. phenotype.
612242. phenotype.

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.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P60484.

HOVERGEN

P60484.

OMA

NEPFDEE.

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.

Gene expression databases

ArrayExpress

P60484.

Bgee

P60484.

CleanEx

HS_PTEN.
HS_TEP1.

Genevestigator

P60484.

GermOnline

ENSG00000171862. Homo sapiens.

Family and domain databases

InterPro

IPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR014019. Phosphatase_tensin-typ.
IPR014020. Tensin_phosphatase_C2-dom.
[Graphical view]

Pfam

PF00782. DSPc. 1 hit.
PF10409. PTEN_C2. 1 hit.
[Graphical view]

PIRSF

PIRSF038025. PTEN. 1 hit.

PROSITE

PS51182. C2_TENSIN. 1 hit.
PS51181. PPASE_TENSIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

22282.

PMAP-CutDB

P60484.

SOURCE

Search...

Entry information

Entry name

PTEN_HUMAN

Accession

Primary (citable) accession number: P60484
Secondary accession number(s): B2R904 , O00633, O02679, Q6ICT7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 16, 2004
Last sequence update:	February 16, 2004
Last modified:	November 3, 2009
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.