P60484 (PTEN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
EC=3.1.3.16
EC=3.1.3.48
EC=3.1.3.67

Alternative name(s):
Mutated in multiple advanced cancers 1
Phosphatase and tensin homolog

Gene names

Name:	PTEN
Synonyms:	MMAC1, TEP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	403 AA.
Sequence status	Complete.
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. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. Ref.1 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.21 Ref.25
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 with NDFIP1 and NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes PTEN ubiquitination. Interacts (via C2 domain) with FRK. Interacts with USP7; the interaction is direct. Interacts with ROCK1 By similarity. Interacts with XIAP/BIRC4. Ref.17 Ref.18 Ref.19 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.29 Ref.31
Subcellular location	Cytoplasm. Nucleus. Nucleus › PML body. Note: Monoubiquitinated form is nuclear. Nonubiquitinated form is cytoplasmic. Colocalized with PML and USP7 in PML nuclear bodies. XIAP/BIRC4 promotes its nuclear localization. Ref.1 Ref.25 Ref.27
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 TGFB1. 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.31
Post-translational modification	Constitutively phosphorylated by CK2 under normal conditions. 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. Phosphorylation by ROCK1 is essential for its stability and activity. Phosphorylation by PLK3 promotes its stability and prevents its degradation by the proteasome. Ref.17 Ref.20 Ref.21 Ref.22 Ref.23 Ref.26 Ref.28 Monoubiquitinated; monoubiquitination is increased in presence of retinoic acid. Deubiquitinated by USP7; leading to its nuclear exclusion. Monoubiquitination of one of either Lys-13 and Lys-289 amino acid is sufficient to modulate PTEN compartmentalization. Ubiquitinated by XIAP/BIRC4. Ref.25 Ref.27
Involvement in disease	Cowden disease (CD) [MIM:158350]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.14 Ref.32 Ref.33 Ref.35 Ref.36 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.49 Ref.52 Ref.54 Lhermitte-Duclos disease (LDD) [MIM:158350]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Bannayan-Zonana syndrome (BZS) [MIM:153480]: A rare hamartomatous disorder characterized by macrocephaly and multiple hemangiomas as well as subcutaneous and visceral lipomas. It belongs to the family of hamartomatous polyposis syndromes that includes Peutz Jeghers syndrome, juvenile polyposis, and Cowden disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37 Ref.41 Ref.48 Ref.49 Ref.54 Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.56 Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. PTEN mutations are found in a subset of patients with Proteus syndrome, a genetically heterogeneous condition. The molecular diagnosis of PTEN mutation positive cases classifies Proteus syndrome patients as part of the PTEN hamartoma syndrome spectrum. As such, patients surviving the early years of Proteus syndrome are likely at a greater risk of developing malignancies. Glioma 2 (GLM2) [MIM:613028]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. VACTERL association with hydrocephalus (VACTERL-H) [MIM:276950]: VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects. Note: The disease is caused by mutations affecting the gene represented in this entry. Prostate cancer (PC) [MIM:176807]: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Macrocephaly/autism syndrome (MCEPHAS) [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). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.58 A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.
Sequence similarities	Contains 1 C2 tensin-type domain. Contains 1 phosphatase tensin-type domain.

Ontologies

Keywords
Biological process	Apoptosis Lipid metabolism Neurogenesis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Tumor suppressor
Ligand	Lipid-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell receptor signaling pathway Traceable author statement. Source: Reactome activation of mitotic anaphase-promoting complex activity Inferred from direct assay PubMed 21241890. Source: BHF-UCL angiogenesis Inferred from electronic annotation. Source: Compara apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 20123964. Source: BHF-UCL cardiac muscle tissue development Inferred from electronic annotation. Source: Compara cell migration Inferred from sequence or structural similarity. Source: UniProtKB cell proliferation Traceable author statement PubMed 10918569. Source: UniProtKB central nervous system myelin maintenance Inferred from sequence or structural similarity. Source: BHF-UCL central nervous system neuron axonogenesis Inferred from sequence or structural similarity. Source: BHF-UCL dendritic spine morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL dentate gyrus development Inferred from sequence or structural similarity. Source: BHF-UCL endothelial cell migration Inferred from electronic annotation. Source: Compara epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome forebrain morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL heart development Inferred from sequence or structural similarity. Source: UniProtKB induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB inositol phosphate dephosphorylation Inferred from direct assay Ref.13. Source: UniProtKB learning or memory Inferred from sequence or structural similarity. Source: BHF-UCL locomotor rhythm Inferred from sequence or structural similarity. Source: BHF-UCL long-term synaptic potentiation Inferred from electronic annotation. Source: Compara male mating behavior Inferred from electronic annotation. Source: Compara maternal behavior Inferred from electronic annotation. Source: Compara multicellular organismal response to stress Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of axonogenesis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of cell aging Inferred from electronic annotation. Source: Compara negative regulation of cell migration Inferred from mutant phenotype PubMed 17880912Ref.15. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype Ref.16PubMed 17880912. Source: UniProtKB negative regulation of cell size Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S Inferred from direct assay PubMed 21241890. Source: BHF-UCL negative regulation of dendritic spine morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of excitatory postsynaptic membrane potential Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of focal adhesion assembly Inferred from mutant phenotype Ref.15. Source: UniProtKB negative regulation of myelination Inferred from electronic annotation. Source: Compara negative regulation of organ growth Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of phosphatidylinositol 3-kinase cascade Traceable author statement PubMed 18082964. Source: BHF-UCL negative regulation of protein kinase B signaling cascade Inferred from mutant phenotype Ref.19. Source: UniProtKB negative regulation of ribosome biogenesis Inferred from electronic annotation. Source: Compara negative regulation of synaptic vesicle clustering Inferred from sequence or structural similarity. Source: BHF-UCL nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome neuron-neuron synaptic transmission Inferred from sequence or structural similarity. Source: BHF-UCL phosphatidylinositol biosynthetic process Traceable author statement. Source: Reactome phosphatidylinositol dephosphorylation Inferred from direct assay Ref.13Ref.14. Source: UniProtKB phosphatidylinositol-mediated signaling Traceable author statement. Source: Reactome positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of excitatory postsynaptic membrane potential Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from direct assay PubMed 21241890. Source: BHF-UCL positive regulation of sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype PubMed 20123964. Source: BHF-UCL postsynaptic density assembly Inferred from sequence or structural similarity. Source: BHF-UCL prepulse inhibition Inferred from sequence or structural similarity. Source: BHF-UCL presynaptic membrane assembly Inferred from sequence or structural similarity. Source: BHF-UCL prostate gland growth Inferred from electronic annotation. Source: Compara protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB protein stabilization Inferred from direct assay PubMed 20123964. Source: BHF-UCL regulation of B cell apoptotic process Inferred from electronic annotation. Source: Compara regulation of myeloid cell apoptotic process Inferred from electronic annotation. Source: Compara rhythmic synaptic transmission Inferred from sequence or structural similarity. Source: BHF-UCL social behavior Inferred from sequence or structural similarity. Source: BHF-UCL synapse maturation Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	PML body Inferred from electronic annotation. Source: UniProtKB-SubCell Schmidt-Lanterman incisure Inferred from sequence or structural similarity. Source: BHF-UCL cytosol Traceable author statement. Source: Reactome internal side of plasma membrane Inferred from direct assay PubMed 10940933. Source: UniProtKB myelin sheath adaxonal region Inferred from sequence or structural similarity. Source: BHF-UCL neuron projection Inferred from sequence or structural similarity. Source: BHF-UCL nucleus Inferred from direct assay PubMed 17218261PubMed 21241890. Source: BHF-UCL
Molecular_function	inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity Inferred from direct assay Ref.13. 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 Inferred from direct assay Ref.13Ref.14. Source: UniProtKB phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity Inferred from direct assay Ref.14. Source: UniProtKB phosphatidylinositol-3-phosphatase activity Inferred from direct assay Ref.14. Source: UniProtKB protein serine/threonine phosphatase activity Inferred from direct assay Ref.12. Source: UniProtKB protein tyrosine phosphatase activity Inferred from direct assay Ref.12. Source: UniProtKB protein tyrosine/serine/threonine phosphatase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC27	P30260	7	EBI-696162,EBI-994813
Dlg1	Q62696	2	EBI-696162,EBI-389325	From a different organism.
FRK	P42685	7	EBI-696162,EBI-1383583
Magi2	O88382	3	EBI-696162,EBI-696179	From a different organism.
Magi3	Q9JK71	3	EBI-696162,EBI-696226	From a different organism.
Mast1	Q9R1L5	3	EBI-696162,EBI-491771	From a different organism.
Mast2	Q60592	4	EBI-696162,EBI-493888	From a different organism.
MAST3	O60307	3	EBI-696162,EBI-311420
NEDD4	P46934	4	EBI-696162,EBI-726944
PPP1CA	P62136	2	EBI-696162,EBI-357253

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

336

1

Phosphotyrosine; by FRK Ref.26

Modified residue

366

1

Phosphothreonine; by GSK3-beta and PLK3 Ref.22 Ref.28

Modified residue

370

1

Phosphoserine; by CK2 and PLK3 Ref.20 Ref.22 Ref.28

Modified residue

380

1

Phosphoserine; by ROCK1 and CK2 Ref.20

Modified residue

382

1

Phosphothreonine; by ROCK1 and CK2 Ref.20

Modified residue

383

1

Phosphothreonine; by ROCK1 and CK2 Ref.20

Modified residue

385

1

Phosphoserine; by CK2 Ref.20 Ref.22

Modified residue

401

1

Phosphothreonine Ref.17

Cross-link

13

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.25

Cross-link

289

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.25

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.49

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.49

VAR_026249

Natural variant

19

1

D → N in malignant melanoma; somatic mutation. Ref.51

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.49

VAR_026250

Natural variant

27

1

Y → S Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.49

VAR_026251

Natural variant

33

1

Missing in CD. Ref.47

VAR_008733

Natural variant

34

1

A → D in BZS. Ref.48 Ref.54

VAR_008734

Natural variant

35

1

M → R in CD. Ref.44

VAR_008036

Natural variant

36

1

G → E in glioma. Ref.2

VAR_007458

Natural variant

36

1

G → R in endometrial hyperplasia. Ref.38

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.54

VAR_011587

Natural variant

57

1

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

VAR_007460

Natural variant

61

1

H → D in VATER. Ref.53

VAR_018101

Natural variant

61

1

H → R Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.49

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.40 Ref.48 Ref.49 Ref.54

VAR_007462

Natural variant

70

1

L → P in CD. Ref.43

VAR_018102

Natural variant

71

1

C → Y in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.49

VAR_026254

Natural variant

93

1

H → R in MCEPHAS. Ref.58

VAR_032634

Natural variant

93

1

H → Y in CD. Ref.49

VAR_026255

Natural variant

105

1

C → F in BZS; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.49

VAR_026256

Natural variant

105

1

C → Y in BZS. Ref.48 Ref.54

VAR_008735

Natural variant

107

1

D → Y in BZS and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.34 Ref.49

VAR_026257

Natural variant

112

1

L → P in CD and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.40 Ref.46 Ref.49

VAR_007807

Natural variant

112

1

L → R Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.49

VAR_026258

Natural variant

119

1

V → L in multiple cancers. Ref.50

VAR_011588

Natural variant

121

1

A → G in HNSCC. Ref.56

VAR_018103

Natural variant

121

1

A → P in glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.34 Ref.49

VAR_026259

Natural variant

123

1

H → R in CD. Ref.35 Ref.47

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.35 Ref.47 Ref.49

VAR_007464

Natural variant

124

1

C → S in CD; phosphatase-dead protein with neither lipid nor protein phosphatase activity. Ref.14 Ref.52

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.36 Ref.49 Ref.52

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.3 Ref.12 Ref.34 Ref.49

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.49

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.38 Ref.49

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.45 Ref.49

VAR_007468

Natural variant

132

1

G → V in one patient with clinical findings suggesting hamartoma tumor syndrome. Ref.60

VAR_032635

Natural variant

133

1

V → I Loss of phosphatase activity towards Ins(1,3,4,5)P3. Ref.49

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.3 Ref.12 Ref.49

VAR_007469

Natural variant

135

1

I → V in BZS. Ref.48 Ref.54

VAR_008736

Natural variant

136

1

C → Y in CD; loss of phosphatase activity towards Ins(1,3,4,5)P3. Ref.42 Ref.49

VAR_007808

Natural variant

137

1

A → AN in CD. Ref.32

VAR_008737

Natural variant

155

1

Y → C in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.49

VAR_026263

Natural variant

158

1

V → L in multiple cancers. Ref.50

VAR_011589

Natural variant

165

1

G → E in CD. Ref.47

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.34 Ref.49

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.49

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.37 Ref.48 Ref.49 Ref.54

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.38 Ref.49

VAR_026267

Natural variant

173

1

R → H Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.49

VAR_026268

Natural variant

173

1

R → P Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.49

VAR_026269

Natural variant

174

1

Y → N Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.49

VAR_026270

Natural variant

191

1

V → A in endometrial hyperplasia. Ref.38

VAR_026271

Natural variant

217

1

V → I in malignant melanoma; somatic mutation. Ref.51

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.49

VAR_026272

Natural variant

234

1

R → Q in a patient with glioma and meningioma; 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.55

VAR_018106

Natural variant

241

1

F → S in MCEPHAS. Ref.58

VAR_032636

Natural variant

246

1

P → L in CD and BZS. Ref.48

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.49

VAR_026273

Natural variant

252

1

D → G in MCEPHAS. Ref.58

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.39 Ref.49

VAR_008741

Natural variant

290

1

V → L. Ref.9
Corresponds to variant rs35600253 [ dbSNP | Ensembl ].

VAR_025167

Natural variant

319

1

Missing in glioma; reduced tumor suppressor activity; fails to inactivate AKT/PKB. Ref.2 Ref.16

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.49

VAR_026275

Natural variant

341

1

F → V in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.49

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.49

VAR_026277

Natural variant

343

1

V → E in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.33 Ref.49

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.34 Ref.49

VAR_026278

Natural variant

347

1

F → L in CD; reduced phosphatase activity towards Ins(1,3,4,5)P4. Ref.33 Ref.49

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.38

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.49

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.49

VAR_026281

Experimental info

Mutagenesis

13

1

K → E: Nuclear. Cytoplasmic; when associated with E-289. Shows less tumor suppressive ability; when associated with E-289. Ref.25

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.31

Mutagenesis

93

1

H → A: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Modest reduction in phosphatase activity towards PtdIns(3,4)P2. Ref.31

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, PtdIns(3,4)P2 and PtdIns(3)P. Ref.31

Mutagenesis

128

1

K → M: 85% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Ref.31

Mutagenesis

128

1

K → R: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3. Ref.31

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.31

Mutagenesis

171

1

Q → A or E: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Ref.31

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.31

Mutagenesis

289

1

K → E: Nuclear. Cytoplasmic; when associated with E-13. Shows less tumor suppressive ability; when associated with E-13. Ref.25

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.31

Mutagenesis

336

1

Y → F: Significantly lower phosphatase activity, reduced protein stability and decreased growth-inhibitory effect. Ref.26

Mutagenesis

366

1

T → A: Decreased stability. Ref.28

Mutagenesis

370

1

S → A: Decreased stability. Ref.28

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.23

Secondary structure

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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

Beta strand

395 – 403

9

Sequences

	Sequence		Length	Mass (Da)
	P60484 [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

	« Hide 'large scale' referencesShow 'large scale' references »
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AIP1.
[20]	"The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation." Torres J., Pulido R. J. Biol. Chem. 276:993-998(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-370; SER-380; THR-382; THR-383 AND SER-385.
[21]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH AIP1.
[22]	"Direct identification of PTEN phosphorylation sites." Miller S., Lou D., Seldin D., Lane W., Neel B. FEBS Lett. 528:145-153(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-366; SER-370 AND SER-385.
[23]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAGI2; MAGI3; MAST1; MAST2 AND MAST3, MUTAGENESIS OF VAL-403, PHOSPHORYLATION.
[24]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NEDD4.
[25]	"The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network." Song M.S., Salmena L., Carracedo A., Egia A., Lo-Coco F., Teruya-Feldstein J., Pandolfi P.P. Nature 455:813-817(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH USP7, UBIQUITINATION AT LYS-13 AND LYS-289, DEUBIQUITINATION BY USP7, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-13 AND LYS-289.
[26]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FRK, PHOSPHORYLATION AT TYR-336, MUTAGENESIS OF TYR-336.
[27]	"X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization." Van Themsche C., Leblanc V., Parent S., Asselin E. J. Biol. Chem. 284:20462-20466(2009) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY XIAP/BIRC4, SUBCELLULAR LOCATION, INTERACTION WITH XIAP/BIRC4.
[28]	"Regulation of PTEN stability and activity by Plk3." Xu D., Yao Y., Jiang X., Lu L., Dai W. J. Biol. Chem. 285:39935-39942(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-366 AND SER-370, MUTAGENESIS OF THR-366 AND SER-370.
[29]	"Regulation of PTEN/Akt and MAP kinase signaling pathways by the ubiquitin ligase activators Ndfip1 and Ndfip2." Mund T., Pelham H.R. Proc. Natl. Acad. Sci. U.S.A. 107:11429-11434(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NDFIP1 AND NDFIP2.
[30]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[31]	"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] [Europe PMC] [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.
[32]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CD ASN-137 INS.
[33]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS CD GLU-343 AND LEU-347.
[34]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS GLIOBLASTOMA TYR-107; PRO-121; ARG-129; ARG-165 AND GLN-345.
[35]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS CD ARG-123 AND ARG-124.
[36]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CD GLU-129.
[37]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BZS ARG-170.
[38]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ENDOMETRIAL HYPERPLASIA ARG-36; LEU-130; CYS-173; ALA-191 AND ILE-348.
[39]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CD GLU-289.
[40]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS CD HIS-68 AND PRO-112.
[41]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS CD AND BZS.
[42]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CD TYR-136.
[43]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CD PRO-70.
[44]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CD ARG-35.
[45]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CD GLN-130.
[46]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CD/LDD PRO-112.
[47]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS CD ILE-33 DEL; ARG-123; ARG-124 AND GLU-165.
[48]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS BZS ASP-34; HIS-68; TYR-105; VAL-135; ARG-170 AND LEU-246.
[49]	"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] [Europe PMC] [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.
[50]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS MULTIPLE CANCERS LEU-119 AND LEU-158.
[51]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS MALIGNANT MELANOMA ASN-19 AND ILE-217.
[52]	"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] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS CD SER-124 AND GLU-129.
[53]	"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] [Europe PMC] [Abstract] Cited for: VARIANT VATER ASP-61.
[54]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CD GLY-47, VARIANTS BZS ASP-34; HIS-68; TYR-105; VAL-135 AND ARG-170.
[55]	"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] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT GLN-234.
[56]	"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] [Europe PMC] [Abstract] Cited for: VARIANT HNSCC GLY-121.
[57]	"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] [Europe PMC] [Abstract] Cited for: DISCUSSION OF PTEN INVOLVEMENT IN PROTEUS SYNDROME.
[58]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS MCEPHAS ARG-93; SER-241 AND GLY-252.
[59]	"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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CHROMOSOME 10Q23 DELETION SYNDROME.
[60]	"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] [Europe PMC] [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

EMBL
GenBank
DDBJ

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 Genomic 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. NM_000314.4.

UniGene

Hs.500466.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D5R	X-ray	2.10	A	8-353	[»]
2KYL	NMR	-	B	391-403	[»]

ProteinModelPortal

P60484.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35019N.

IntAct

P60484. 24 interactions.

MINT

MINT-127351.

STRING

9606.ENSP00000361021.

PTM databases

PhosphoSite

P60484.

Polymorphism databases

DMDM

42560209.

Proteomic databases

PaxDb

P60484.

PRIDE

P60484.

Protocols and materials databases

DNASU

5728.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000371953; ENSP00000361021; ENSG00000171862.

GeneID

5728.

KEGG

hsa:5728.

UCSC

uc001kfb.3. human.

Organism-specific databases

CTD

5728.

GeneCards

GC10P089613.

HGNC

HGNC:9588. PTEN.

HPA

CAB004076.

MIM

137800. phenotype.
153480. phenotype.
158350. phenotype.
176807. phenotype.
275355. phenotype.
276950. phenotype.
601728. gene.
605309. phenotype.
608089. phenotype.
612242. phenotype.
613028. phenotype.

neXtProt

NX_P60484.

Orphanet

109. Bannayan-Riley-Ruvalcaba syndrome.
201. Cowden syndrome.
145. Hereditary breast and ovarian cancer syndrome.
79076. Juvenile polyposis of infancy.
65285. Lhermitte-Duclos disease.
210548. Macrocephaly-autism syndrome.
2969. Proteus-like syndrome - intellectual deficit - eye defects.
137608. Segmental outgrowth - lipomatosis - arteriovenous malformation - epidermal nevus.

PharmGKB

PA33942.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2453.

HOGENOM

HOG000008008.

HOVERGEN

HBG000239.

InParanoid

P60484.

KO

K01110.

OMA

TRREDKH.

OrthoDB

EOG434W64.

PhylomeDB

P60484.

Enzyme and pathway databases

BioCyc

MetaCyc:HS10404-MONOMER.

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_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_6900. 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.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR014019. Phosphatase_tensin-typ.
IPR014020. Tensin_phosphatase_C2-dom.
IPR016130. Tyr_Pase_AS.
[Graphical view]

Pfam

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

PIRSF

PIRSF038025. PTEN. 1 hit.

SUPFAM

SSF49562. C2_CaLB. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

ChiTaRS

PTEN. human.

EvolutionaryTrace

P60484.

GenomeRNAi

5728.

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:	May 1, 2013
This is version 121 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.