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Reviewed, UniProtKB/Swiss-Prot P60484 (PTEN_HUMAN)

Last modified November 3, 2009. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length403 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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 processApoptosis
Lipid metabolism
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Tumor suppressor
   LigandLipid-binding
   Molecular functionHydrolase
Protein phosphatase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processapoptosis

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 componentcytosol Ref.13

Inferred from Experiment. Source: Reactome

nucleus

Inferred from direct assay. Source: UniProtKB

   Molecular functionPDZ 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

Cenpc1P494521EBI-696162,EBI-1186252From a different organism.
Dlg1Q626961EBI-696162,EBI-389325From a different organism.
HSPA5P110211EBI-696162,EBI-354921
Magi2O883822EBI-696162,EBI-696179From a different organism.
Magi3Q9JK711EBI-696162,EBI-696226From a different organism.
Mast1Q9R1L52EBI-696162,EBI-491771From a different organism.
Mast2Q605922EBI-696162,EBI-493888From a different organism.
MAST3O603072EBI-696162,EBI-311420
PPP1CAP621362EBI-696162,EBI-357253
PtenO085861EBI-696162,EBI-1186266From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 403403Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
PRO_0000215904

Regions

Domain14 – 185172Phosphatase tensin-type
Domain190 – 350161C2 tensin-type
Region401 – 4033PDZ domain-binding

Sites

Active site1241Phosphocysteine intermediate Potential

Amino acid modifications

Modified residue61N6-acetyllysine Ref.25
Modified residue3361Phosphotyrosine; by FRK Ref.24
Modified residue3661Phosphothreonine Ref.21
Modified residue3701Phosphoserine; by CK2 Ref.21
Modified residue3851Phosphoserine; by CK2 Ref.21
Modified residue4011Phosphothreonine Ref.17

Natural variations

Natural variant101S → 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 variant151R → S in glioma. Ref.2
VAR_007457
Natural variant161Y → C Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains the ability to bind phospholipid membranes. Ref.44
VAR_026249
Natural variant191D → N in malignant melanoma; somatic mutation. Ref.46
VAR_018100
Natural variant201G → 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 variant271Y → S Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44
VAR_026251
Natural variant331Missing in CD.
VAR_008733
Natural variant341A → D in BZS. Ref.49 Ref.43
VAR_008734
Natural variant351M → R in CD. Ref.39
VAR_008036
Natural variant361G → E in glioma. Ref.2
VAR_007458
Natural variant361G → R in endometrial hyperplasia. Ref.33
VAR_026252
Natural variant421L → 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 variant471R → G in CD. Ref.49
VAR_011587
Natural variant571L → W in glioma; loss of protein phosphatase activity. Ref.12 Ref.2
VAR_007460
Natural variant611H → D in VATER. Ref.48
VAR_018101
Natural variant611H → R Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44
VAR_026253
Natural variant671I → R in CD.
VAR_007461
Natural variant681Y → 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 variant701L → P in CD. Ref.38
VAR_018102
Natural variant711C → Y in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44
VAR_026254
Natural variant931H → R in macrocephaly/autism syndrome. Ref.53
VAR_032634
Natural variant931H → Y in CD. Ref.44
VAR_026255
Natural variant1051C → F in BZS; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44
VAR_026256
Natural variant1051C → Y in BZS. Ref.49 Ref.43
VAR_008735
Natural variant1071D → Y in BZS and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44 Ref.29
VAR_026257
Natural variant1121L → 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 variant1121L → R Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44
VAR_026258
Natural variant1191V → L in multiple cancers. Ref.45
VAR_011588
Natural variant1211A → G in HNSCC. Ref.51
VAR_018103
Natural variant1211A → P in glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44 Ref.29
VAR_026259
Natural variant1231H → R in CD. Ref.30 Ref.42
VAR_007463
Natural variant1231H → Y in endometrial cancer; loss of protein phosphatase activity. Ref.12
VAR_026260
Natural variant1241C → R in CD. Ref.30 Ref.42 Ref.44
VAR_007464
Natural variant1241C → S in CD; phosphatase-dead protein with neither lipid nor protein phosphatase activity. Ref.14 Ref.47
VAR_018104
Natural variant1291G → 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 variant1291G → 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 variant1301R → G Loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3. Ref.44
VAR_026261
Natural variant1301R → 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 variant1301R → 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 variant1321G → V in one patient with clinical findings suggesting hamartoma tumor syndrome. Ref.55
VAR_032635
Natural variant1331V → I Loss of phosphatase activity towards Ins(1,3,4,5)P3. Ref.44
VAR_026262
Natural variant1341M → 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 variant1351I → V in BZS. Ref.49 Ref.43
VAR_008736
Natural variant1361C → Y in CD; loss of phosphatase activity towards Ins(1,3,4,5)P3. Ref.37 Ref.44
VAR_007808
Natural variant1371A → AN in CD. Ref.27
VAR_008737
Natural variant1551Y → C in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44
VAR_026263
Natural variant1581V → L in multiple cancers. Ref.45
VAR_011589
Natural variant1651G → E in CD. Ref.42
VAR_008739
Natural variant1651G → 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 variant1651G → V in CD.
VAR_008738
Natural variant1671T → P in breast cancer; severely reduced protein phosphatase activity. Ref.12
VAR_026265
Natural variant1701S → N Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. Ref.44
VAR_026266
Natural variant1701S → 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 variant1731R → 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 variant1731R → H Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44
VAR_026268
Natural variant1731R → P Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44
VAR_026269
Natural variant1741Y → N Loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44
VAR_026270
Natural variant1911V → A in endometrial hyperplasia. Ref.33
VAR_026271
Natural variant2171V → I in malignant melanoma; somatic mutation. Ref.46
VAR_018105
Natural variant2271S → 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 variant2341R → 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 variant2411F → S in macrocephaly/autism syndrome. Ref.53
VAR_032636
Natural variant2461P → L in CD and BZS. Ref.43
VAR_008740
Natural variant2511G → C Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. Ref.44
VAR_026273
Natural variant2521D → G in macrocephaly/autism syndrome. Ref.53
VAR_032637
Natural variant2891K → 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 variant2901V → L: dbSNP rs35600253. Ref.9
VAR_025167
Natural variant3191Missing in glioma; reduced tumor suppressor activity; fails to inactivate AKT/PKB.
VAR_026274
Natural variant3311D → G in CD; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. Ref.44
VAR_026275
Natural variant3411F → V in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.44
VAR_026276
Natural variant3421K → 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 variant3431V → E in CD; loss of phosphatase activity towards Ins(1,3,4,5)P4. Ref.28 Ref.44
VAR_008742
Natural variant3451L → 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 variant3471F → L in CD; reduced phosphatase activity towards Ins(1,3,4,5)P4. Ref.28 Ref.44
VAR_008743
Natural variant3481T → 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 variant3691V → 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 variant4011T → 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

Mutagenesis921D → 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
Mutagenesis931H → A: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Modest reduction in phosphatase activity towards PtsIns(3,4)P2. Ref.26
Mutagenesis1241C → A: Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation. Ref.15
Mutagenesis1251K → M: Reduced phosphatase activity towards PtdIns(3,4,5)P3, PtsIns(3,4)P2 and PtdIns(3)P. Ref.26
Mutagenesis1281K → M: 85% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Ref.26
Mutagenesis1281K → R: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3. Ref.26
Mutagenesis1301R → M: Does not affect the ability to inhibit AKT/PKB activation. Ref.14
Mutagenesis1671T → A or D: 60% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Ref.26
Mutagenesis1711Q → A or E: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Ref.26
Mutagenesis263 – 2697KMLKKDK → 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
Mutagenesis327 – 3359KANKDKANR → 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
Mutagenesis3361Y → F: Significantly lower phosphatase activity, reduced protein stability and decreased growth-inhibitory effect. Ref.24
Mutagenesis4011T → A: Loss of DLG1-binding. No effect on MAGI2- and MAST2-binding.
Mutagenesis4021K → A: No effect on MAGI2-, MAST2- and DLG1-binding.
Mutagenesis4021K → W: Loss of DLG1-, MAGI2-, MAGI3- and MAST2-binding. Decrease of protein stability.
Mutagenesis4031V → A: Loss of DLG1-, MAGI2-, MAGI3-, MAST1-, MAST2- and MAST3-binding. Ref.22

Secondary structure

.................................................... 403
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P60484-1 [UniParc].

Last modified February 16, 2004. Version 1.
Checksum: 75F97C3DD6802BA9

FASTA40347,166
        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 

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References

« Hide '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: 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.

Cross-references

Sequence databases

U96180 mRNA. Translation: AAB66902.1.
U92436 mRNA. Translation: AAC51182.1.
U93051 mRNA. Translation: AAC51183.1.
AF143315 expand/collapse EMBL AC list , AF143312, AF143313, AF143314 Genomic DNA. Translation: AAD38372.1.
AF000734 expand/collapse EMBL AC list , 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.
IPIIPI00012587.
RefSeqNP_000305.3.
UniGeneHs.500466

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1D5RX-ray2.10A8-353[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP60484. 17 interactions.
STRINGP60484.

PTM databases

PhosphoSiteP60484.

Proteomic databases

PRIDEP60484.

Genome annotation databases

EnsemblENST00000371953; ENSP00000361021; ENSG00000171862; Homo sapiens. [Genome view]
GeneID5728.
KEGGhsa:5728.
UCSCuc001kfb.1. human.

Organism-specific databases

CTD5728.
GeneCardsGC10P089613.
H-InvDBHIX0009010.
HIX0025699.
HGNCHGNC:9588. PTEN.
HPACAB004076.
MIM137800. phenotype.
153480. phenotype.
158350. phenotype.
176807. phenotype.
176920. phenotype.
275355. phenotype.
276950. phenotype.
601728. gene.
605309. phenotype.
608089. phenotype.
612242. phenotype.
Orphanet94. 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.
PharmGKBPA33942.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP60484.
HOVERGENP60484.
OMANEPFDEE.

Enzyme and pathway databases

BRENDA3.1.3.16. 247.
3.1.3.48. 247.
3.1.3.67. 247.
Pathway_Interaction_DBbcr_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.
ReactomeREACT_11061. Signalling by NGF.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpressP60484.
BgeeP60484.
CleanExHS_PTEN.
HS_TEP1.
GenevestigatorP60484.
GermOnlineENSG00000171862. Homo sapiens.

Family and domain databases

InterProIPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR014019. Phosphatase_tensin-typ.
IPR014020. Tensin_phosphatase_C2-dom.
[Graphical view]
PfamPF00782. DSPc. 1 hit.
PF10409. PTEN_C2. 1 hit.
[Graphical view]
PIRSFPIRSF038025. PTEN. 1 hit.
PROSITEPS51182. C2_TENSIN. 1 hit.
PS51181. PPASE_TENSIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio22282.
PMAP-CutDBP60484.
SOURCESearch...

Entry information

Entry namePTEN_HUMAN
AccessionPrimary (citable) accession number: P60484
Secondary accession number(s): B2R904 expand/collapse secondary AC list , 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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

Relevant documents

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents