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Protein

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

Gene

PTEN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement.
Isoform alpha: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1.

Catalytic activityi

Phosphatidylinositol 3,4,5-trisphosphate + H2O = phosphatidylinositol 4,5-bisphosphate + phosphate.
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.
Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Cofactori

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei124 – 1241Phosphocysteine intermediatePROSITE-ProRule annotation

GO - Molecular functioni

  • anaphase-promoting complex binding Source: BHF-UCL
  • enzyme binding Source: UniProtKB
  • inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity Source: UniProtKB
  • lipid binding Source: UniProtKB-KW
  • magnesium ion binding Source: InterPro
  • PDZ domain binding Source: UniProtKB
  • phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity Source: UniProtKB
  • phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity Source: UniProtKB
  • phosphatidylinositol-3-phosphatase activity Source: UniProtKB
  • phosphoprotein phosphatase activity Source: BHF-UCL
  • protein serine/threonine phosphatase activity Source: UniProtKB
  • protein tyrosine/serine/threonine phosphatase activity Source: InterPro
  • protein tyrosine phosphatase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Apoptosis, Lipid metabolism, Neurogenesis

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS10404-MONOMER.
BRENDAi3.1.3.16. 2681.
ReactomeiREACT_121025. Synthesis of PIPs at the plasma membrane.
REACT_12447. Negative regulation of the PI3K/AKT network.
REACT_12555. Downstream TCR signaling.
REACT_150312. Synthesis of IP3 and IP4 in the cytosol.
REACT_355377. TP53 Regulates Metabolic Genes.
REACT_355467. PTEN Loss of Function in Cancer.
REACT_75829. PIP3 activates AKT signaling.
SignaLinkiP60484.

Names & Taxonomyi

Protein namesi
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 namesi
Name:PTEN
Synonyms:MMAC1, TEP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:9588. PTEN.

Subcellular locationi

  • Cytoplasm
  • Nucleus
  • NucleusPML 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.
Isoform alpha :

GO - Cellular componenti

  • cell projection Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytoplasmic side of plasma membrane Source: UniProtKB
  • cytosol Source: Reactome
  • dendritic spine Source: Ensembl
  • extracellular region Source: UniProtKB-SubCell
  • mitochondrion Source: Ensembl
  • myelin sheath adaxonal region Source: BHF-UCL
  • neuron projection Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: BHF-UCL
  • plasma membrane Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
  • postsynaptic membrane Source: Ensembl
  • Schmidt-Lanterman incisure Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus, Secreted

Pathology & Biotechi

Involvement in diseasei

Cowden syndrome 1 (CWS1)13 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn autosomal dominant hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid.

See also OMIM:158350
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti33 – 331Missing in CWS1. 1 Publication
VAR_008733
Natural varianti35 – 351M → R in CWS1. 1 Publication
VAR_008036
Natural varianti47 – 471R → G in CWS1. 1 Publication
VAR_011587
Natural varianti67 – 671I → R in CWS1.
VAR_007461
Natural varianti68 – 681Y → H in CWS1 and BRRS; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes. 4 Publications
VAR_007462
Natural varianti70 – 701L → P in CWS1. 1 Publication
VAR_018102
Natural varianti71 – 711C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026254
Natural varianti93 – 931H → Y in CWS1. 1 Publication
VAR_026255
Natural varianti112 – 1121L → P in CWS1 and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. 3 Publications
VAR_007807
Natural varianti123 – 1231H → R in CWS1. 2 Publications
VAR_007463
Natural varianti124 – 1241C → R in CWS1. 3 Publications
VAR_007464
Natural varianti124 – 1241C → S in CWS1; phosphatase-dead protein with neither lipid nor protein phosphatase activity. 2 Publications
VAR_018104
Natural varianti129 – 1291G → E in CWS1; no lipid phosphatase activity but retains protein phosphatase activity; retains ability to inhibit focal adhesion formation. 5 Publications
VAR_007465
Natural varianti130 – 1301R → L in CWS1 and endometrial hyperplasia; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 2 Publications
VAR_007467
Natural varianti130 – 1301R → Q in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 2 Publications
VAR_007468
Natural varianti136 – 1361C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P3. 2 Publications
VAR_007808
Natural varianti137 – 1371A → AN in CWS1. 1 Publication
VAR_008737
Natural varianti155 – 1551Y → C in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026263
Natural varianti165 – 1651G → E in CWS1. 1 Publication
VAR_008739
Natural varianti165 – 1651G → V in CWS1.
VAR_008738
Natural varianti246 – 2461P → L in CWS1 and BRRS. 1 Publication
VAR_008740
Natural varianti289 – 2891K → E in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 2 Publications
VAR_008741
Natural varianti331 – 3311D → G in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
VAR_026275
Natural varianti341 – 3411F → V in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026276
Natural varianti342 – 3421K → N in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4 but PtdIns(3,4,5)P3 phosphatase activity is similar to wild-type. 1 Publication
VAR_026277
Natural varianti343 – 3431V → E in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
VAR_008742
Natural varianti347 – 3471F → L in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
VAR_008743
Lhermitte-Duclos disease (LDD)

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA rare disease characterized by the occurrence of a slowly enlarging mass within the cerebellar cortex corresponding histologically to a cerebellar hamartoma. It manifests, most commonly in the third and fourth decades of life, with increased intracranial pressure, headache, nausea, cerebellar dysfunction, occlusive hydrocephalus, ataxia, visual disturbances and other cranial nerve palsies. Various associated abnormalities may be present such as megalencephaly, microgyria, hydromyelia, polydactyly, partial gigantism, macroglossia. LDD is part of the PTEN hamartoma tumor syndromes spectrum that also includes Cowden syndrome.

See also OMIM:158350
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti112 – 1121L → P in CWS1 and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. 3 Publications
VAR_007807
Bannayan-Riley-Ruvalcaba syndrome (BRRS)4 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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 syndrome.

See also OMIM:153480
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti34 – 341A → D in BRRS. 2 Publications
VAR_008734
Natural varianti68 – 681Y → H in CWS1 and BRRS; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes. 4 Publications
VAR_007462
Natural varianti105 – 1051C → F in BRRS; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026256
Natural varianti105 – 1051C → Y in BRRS. 2 Publications
VAR_008735
Natural varianti107 – 1071D → Y in BRRS and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
VAR_026257
Natural varianti135 – 1351I → V in BRRS. 2 Publications
VAR_008736
Natural varianti170 – 1701S → R in BRRS; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4. 5 Publications
VAR_007470
Natural varianti246 – 2461P → L in CWS1 and BRRS. 1 Publication
VAR_008740
Squamous cell carcinoma of the head and neck (HNSCC)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes.

See also OMIM:275355
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti121 – 1211A → G in HNSCC. 1 Publication
VAR_018103
Endometrial cancer (ENDMC)

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:608089

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)

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionGliomas 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.

See also OMIM:613028
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti234 – 2341R → Q in GLM2; the patient also suffered from benign 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. 1 Publication
VAR_018106
VACTERL association with hydrocephalus (VACTERL-H)

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionVACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects.

See also OMIM:276950
Prostate cancer (PC)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:176807
Macrocephaly/autism syndrome (MCEPHAS)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionPatients 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).

See also OMIM:605309
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti93 – 931H → R in MCEPHAS. 1 Publication
VAR_032634
Natural varianti241 – 2411F → S in MCEPHAS. 1 Publication
VAR_032636
Natural varianti252 – 2521D → G in MCEPHAS. 1 Publication
VAR_032637

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.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1 – 11M → I: Expression is restricted to isoform alpha. 1 Publication
Mutagenesisi13 – 131K → E: Nuclear. Cytoplasmic; when associated with E-289. Shows less tumor suppressive ability; when associated with E-289. 1 Publication
Mutagenesisi92 – 921D → A: 700-fold reduction in phosphatase activity towards PtdIns(3,4,5)P3. Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation. 2 Publications
Mutagenesisi93 – 931H → A: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Modest reduction in phosphatase activity towards PtdIns(3,4)P2. 1 Publication
Mutagenesisi124 – 1241C → A: Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation. 1 Publication
Mutagenesisi125 – 1251K → M: Reduced phosphatase activity towards PtdIns(3,4,5)P3, PtdIns(3,4)P2 and PtdIns(3)P. 1 Publication
Mutagenesisi128 – 1281K → M: 85% reduction in phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication
Mutagenesisi128 – 1281K → R: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication
Mutagenesisi130 – 1301R → M: Does not affect the ability to inhibit AKT/PKB activation. 1 Publication
Mutagenesisi167 – 1671T → A or D: 60% reduction in phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication
Mutagenesisi171 – 1711Q → A or E: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication
Mutagenesisi263 – 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. 1 Publication
Mutagenesisi289 – 2891K → E: Nuclear. Cytoplasmic; when associated with E-13. Shows less tumor suppressive ability; when associated with E-13. 1 Publication
Mutagenesisi327 – 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. 1 Publication
Mutagenesisi336 – 3361Y → F: Significantly lower phosphatase activity, reduced protein stability and decreased growth-inhibitory effect. 1 Publication
Mutagenesisi366 – 3661T → A: Decreased stability. 1 Publication
Mutagenesisi370 – 3701S → A: Decreased stability. 1 Publication
Mutagenesisi401 – 4011T → A: Loss of DLG1-binding. No effect on MAGI2- and MAST2-binding.
Mutagenesisi402 – 4021K → A: No effect on MAGI2-, MAST2- and DLG1-binding.
Mutagenesisi402 – 4021K → W: Loss of DLG1-, MAGI2-, MAGI3- and MAST2-binding. Decrease of protein stability.
Mutagenesisi403 – 4031V → A: Loss of DLG1-, MAGI2-, MAGI3-, MAST1-, MAST2- and MAST3-binding. 1 Publication

Keywords - Diseasei

Autism spectrum disorder, Disease mutation, Tumor suppressor

Organism-specific databases

MIMi137800. phenotype.
153480. phenotype.
158350. phenotype.
176807. phenotype.
275355. phenotype.
276950. phenotype.
605309. phenotype.
608089. phenotype.
612242. phenotype.
613028. phenotype.
Orphaneti109. 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.
744. Proteus syndrome.
2969. Proteus-like syndrome.
137608. Segmental outgrowth - lipomatosis - arteriovenous malformation - epidermal nevus.
67037. Squamous cell carcinoma of head and neck.
PharmGKBiPA33942.

Polymorphism and mutation databases

BioMutaiPTEN.
DMDMi42560209.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 403402Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENPRO_0000215904Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylthreonine1 Publication
Cross-linki13 – 13Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki289 – 289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei336 – 3361Phosphotyrosine; by FRK1 Publication
Modified residuei366 – 3661Phosphothreonine; by GSK3-beta and PLK33 Publications
Modified residuei370 – 3701Phosphoserine; by CK2 and PLK33 Publications
Modified residuei380 – 3801Phosphoserine; by ROCK1 and CK21 Publication
Modified residuei382 – 3821Phosphothreonine; by ROCK1 and CK21 Publication
Modified residuei383 – 3831Phosphothreonine; by ROCK1 and CK21 Publication
Modified residuei385 – 3851Phosphoserine; by CK22 Publications
Modified residuei401 – 4011Phosphothreonine1 Publication

Post-translational modificationi

Constitutively phosphorylated by CK2 under normal conditions. Phosphorylated in vitro by MAST1, MAST2, MAST3 and STK11. 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.9 Publications
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/BIRC4.2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP60484.
PaxDbiP60484.
PRIDEiP60484.

PTM databases

DEPODiP60484.
PhosphoSiteiP60484.

Miscellaneous databases

PMAP-CutDBP60484.

Expressioni

Tissue specificityi

Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas.1 Publication

Inductioni

Down-regulated by TGFB1.1 Publication

Gene expression databases

BgeeiP60484.
CleanExiHS_PTEN.
HS_TEP1.
ExpressionAtlasiP60484. baseline and differential.
GenevisibleiP60484. HS.

Organism-specific databases

HPAiCAB004076.
HPA031335.

Interactioni

Subunit structurei

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. Interacts with STK11; the interaction phosphorylates PTEN.By similarity12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BMI1P352263EBI-696162,EBI-2341576
CDC27P302607EBI-696162,EBI-994813
DBN1Q166435EBI-696162,EBI-351394
Dlg1Q626962EBI-696162,EBI-389325From a different organism.
FRKP426857EBI-696162,EBI-1383583
Magi2O883823EBI-696162,EBI-696179From a different organism.
Magi3Q9JK713EBI-696162,EBI-696226From a different organism.
Mast1Q9R1L53EBI-696162,EBI-491771From a different organism.
Mast2Q605924EBI-696162,EBI-493888From a different organism.
MAST3O603073EBI-696162,EBI-311420
NCOA3Q9Y6Q92EBI-696162,EBI-81196
NEDD4P469344EBI-696162,EBI-726944
PDGFRBP096193EBI-696162,EBI-641237
PPP1CAP621362EBI-696162,EBI-357253
PRDX1Q068307EBI-696162,EBI-353193
SLC9A3R1O147455EBI-696162,EBI-349787
SLC9A3R2Q155995EBI-696162,EBI-1149760
Slc9a3r2Q9JHL12EBI-696162,EBI-538451From a different organism.
SPOPO437914EBI-696162,EBI-743549

Protein-protein interaction databases

BioGridi111700. 91 interactions.
DIPiDIP-35019N.
IntActiP60484. 49 interactions.
MINTiMINT-127351.
STRINGi9606.ENSP00000361021.

Structurei

Secondary structure

1
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni19 – 224Combined sources
Beta strandi23 – 297Combined sources
Beta strandi32 – 354Combined sources
Beta strandi39 – 413Combined sources
Helixi50 – 6011Combined sources
Beta strandi61 – 633Combined sources
Beta strandi65 – 739Combined sources
Beta strandi85 – 906Combined sources
Helixi98 – 1003Combined sources
Helixi101 – 11212Combined sources
Turni113 – 1153Combined sources
Beta strandi118 – 1236Combined sources
Beta strandi125 – 1284Combined sources
Helixi129 – 14113Combined sources
Helixi148 – 15912Combined sources
Beta strandi161 – 1633Combined sources
Helixi169 – 18416Combined sources
Beta strandi192 – 20211Combined sources
Beta strandi213 – 2197Combined sources
Beta strandi222 – 2265Combined sources
Beta strandi232 – 2354Combined sources
Beta strandi238 – 25922Combined sources
Beta strandi268 – 2769Combined sources
Helixi277 – 2793Combined sources
Beta strandi315 – 3217Combined sources
Helixi322 – 3243Combined sources
Helixi328 – 3303Combined sources
Beta strandi335 – 3373Combined sources
Beta strandi342 – 3498Combined sources
Beta strandi395 – 4039Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1D5RX-ray2.10A8-353[»]
2KYLNMR-B391-403[»]
4O1VX-ray2.00B354-368[»]
ProteinModelPortaliP60484.
SMRiP60484. Positions 14-351.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP60484.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 185172Phosphatase tensin-typePROSITE-ProRule annotationAdd
BLAST
Domaini190 – 350161C2 tensin-typePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni401 – 4033PDZ domain-binding

Domaini

The C2 domain binds phospholipid membranes in vitro in a Ca2+-independent manner; this binding is important for its tumor suppressor function.2 Publications

Sequence similaritiesi

Contains 1 C2 tensin-type domain.PROSITE-ProRule annotation
Contains 1 phosphatase tensin-type domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG2453.
GeneTreeiENSGT00760000119113.
HOGENOMiHOG000008008.
HOVERGENiHBG000239.
InParanoidiP60484.
KOiK01110.
OMAiRSINENK.
OrthoDBiEOG7R2BJ5.
PhylomeDBiP60484.
TreeFamiTF324513.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN.
IPR000008. C2_dom.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR014020. Tensin_C2-dom.
IPR029023. Tensin_lipid_phosphatase_dom.
IPR016130. Tyr_Pase_AS.
[Graphical view]
PfamiPF00782. DSPc. 1 hit.
PF10409. PTEN_C2. 1 hit.
[Graphical view]
PIRSFiPIRSF038025. PTEN. 1 hit.
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEiPS51182. C2_TENSIN. 1 hit.
PS51181. PPASE_TENSIN. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P60484-1) [UniParc]FASTAAdd to basket

Also known as: 55kDa

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI
60 70 80 90 100
DDVVRFLDSK HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL
110 120 130 140 150
IKPFCEDLDQ WLSEDDNHVA AIHCKAGKGR TGVMICAYLL HRGKFLKAQE
160 170 180 190 200
ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY LLKNHLDYRP VALLFHKMMF
210 220 230 240 250
ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY FEFPQPLPVC
260 270 280 290 300
GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI
310 320 330 340 350
DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT
360 370 380 390 400
VEEPSNPEAS SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHTQI

TKV
Length:403
Mass (Da):47,166
Last modified:February 16, 2004 - v1
Checksum:i75F97C3DD6802BA9
GO
Isoform alpha (identifier: P60484-2) [UniParc]FASTAAdd to basket

Also known as: 70kDa, PTEN-long

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MERGGEAAAA...FFFSHRLPDM

Note: Produced by alternative initiation at a CTG start codon of isoform 1. May contain a signal peptide at positions 1-21.
Show »
Length:576
Mass (Da):64,882
Checksum:iE0A3C5E42AEC150D
GO
Isoform 3 (identifier: P60484-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     55-70: RFLDSKHKNHYKIYNL → S
     165-190: GVTIPSQRRYVYYYSYLLKNHLDYRP → ADPTGGIPDKGIIVIGDGSSMDVIAP
     191-403: Missing.

Show »
Length:175
Mass (Da):19,796
Checksum:iEB3BBB17D7302085
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti10 – 101S → N Retains phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes. 1 Publication
VAR_026248
Natural varianti15 – 151R → S in glioma. 1 Publication
VAR_007457
Natural varianti16 – 161Y → C Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains the ability to bind phospholipid membranes. 1 Publication
VAR_026249
Natural varianti19 – 191D → N in malignant melanoma; somatic mutation. 1 Publication
VAR_018100
Natural varianti20 – 201G → E Reduced phosphatase activity towards Ins(1,3,4,5)P4; retains phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication
VAR_026250
Natural varianti27 – 271Y → S Loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026251
Natural varianti33 – 331Missing in CWS1. 1 Publication
VAR_008733
Natural varianti34 – 341A → D in BRRS. 2 Publications
VAR_008734
Natural varianti35 – 351M → R in CWS1. 1 Publication
VAR_008036
Natural varianti36 – 361G → E in glioma. 1 Publication
VAR_007458
Natural varianti36 – 361G → R in endometrial hyperplasia. 1 Publication
VAR_026252
Natural varianti42 – 421L → 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. 1 Publication
VAR_007459
Natural varianti47 – 471R → G in CWS1. 1 Publication
VAR_011587
Natural varianti57 – 571L → W in glioma; loss of protein phosphatase activity. 2 Publications
VAR_007460
Natural varianti61 – 611H → D in VATER. 1 Publication
VAR_018101
Natural varianti61 – 611H → R Loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026253
Natural varianti67 – 671I → R in CWS1.
VAR_007461
Natural varianti68 – 681Y → H in CWS1 and BRRS; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes. 4 Publications
VAR_007462
Natural varianti70 – 701L → P in CWS1. 1 Publication
VAR_018102
Natural varianti71 – 711C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026254
Natural varianti93 – 931H → R in MCEPHAS. 1 Publication
VAR_032634
Natural varianti93 – 931H → Y in CWS1. 1 Publication
VAR_026255
Natural varianti105 – 1051C → F in BRRS; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026256
Natural varianti105 – 1051C → Y in BRRS. 2 Publications
VAR_008735
Natural varianti107 – 1071D → Y in BRRS and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
VAR_026257
Natural varianti112 – 1121L → P in CWS1 and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. 3 Publications
VAR_007807
Natural varianti112 – 1121L → R Loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026258
Natural varianti119 – 1191V → L in multiple cancers. 1 Publication
VAR_011588
Natural varianti121 – 1211A → G in HNSCC. 1 Publication
VAR_018103
Natural varianti121 – 1211A → P in glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
VAR_026259
Natural varianti123 – 1231H → R in CWS1. 2 Publications
VAR_007463
Natural varianti123 – 1231H → Y in endometrial cancer; loss of protein phosphatase activity. 1 Publication
VAR_026260
Natural varianti124 – 1241C → R in CWS1. 3 Publications
VAR_007464
Natural varianti124 – 1241C → S in CWS1; phosphatase-dead protein with neither lipid nor protein phosphatase activity. 2 Publications
VAR_018104
Natural varianti129 – 1291G → E in CWS1; no lipid phosphatase activity but retains protein phosphatase activity; retains ability to inhibit focal adhesion formation. 5 Publications
VAR_007465
Natural varianti129 – 1291G → R in glioblastoma; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4. 4 Publications
VAR_007466
Natural varianti130 – 1301R → G Loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3. 1 Publication
VAR_026261
Natural varianti130 – 1301R → L in CWS1 and endometrial hyperplasia; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 2 Publications
VAR_007467
Natural varianti130 – 1301R → Q in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 2 Publications
VAR_007468
Natural varianti132 – 1321G → V in one patient with clinical findings suggesting hamartoma tumor syndrome. 1 Publication
VAR_032635
Natural varianti133 – 1331V → I Loss of phosphatase activity towards Ins(1,3,4,5)P3. 1 Publication
VAR_026262
Natural varianti134 – 1341M → 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. 3 Publications
VAR_007469
Natural varianti135 – 1351I → V in BRRS. 2 Publications
VAR_008736
Natural varianti136 – 1361C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P3. 2 Publications
VAR_007808
Natural varianti137 – 1371A → AN in CWS1. 1 Publication
VAR_008737
Natural varianti155 – 1551Y → C in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026263
Natural varianti158 – 1581V → L in multiple cancers. 1 Publication
VAR_011589
Natural varianti165 – 1651G → E in CWS1. 1 Publication
VAR_008739
Natural varianti165 – 1651G → 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. 3 Publications
VAR_026264
Natural varianti165 – 1651G → V in CWS1.
VAR_008738
Natural varianti167 – 1671T → P in breast cancer; severely reduced protein phosphatase activity. 1 Publication
VAR_026265
Natural varianti170 – 1701S → N Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
VAR_026266
Natural varianti170 – 1701S → R in BRRS; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4. 5 Publications
VAR_007470
Natural varianti173 – 1731R → 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. 2 Publications
VAR_026267
Natural varianti173 – 1731R → H Loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026268
Natural varianti173 – 1731R → P Loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026269
Natural varianti174 – 1741Y → N Loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026270
Natural varianti191 – 1911V → A in endometrial hyperplasia. 1 Publication
VAR_026271
Natural varianti217 – 2171V → I in malignant melanoma; somatic mutation. 1 Publication
VAR_018105
Natural varianti227 – 2271S → F Reduced phosphatase activity towards Ins(1,3,4,5)P4 but retains PtdIns(3,4,5)P3 phosphatase activity. 1 Publication
VAR_026272
Natural varianti234 – 2341R → Q in GLM2; the patient also suffered from benign 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. 1 Publication
VAR_018106
Natural varianti241 – 2411F → S in MCEPHAS. 1 Publication
VAR_032636
Natural varianti246 – 2461P → L in CWS1 and BRRS. 1 Publication
VAR_008740
Natural varianti251 – 2511G → C Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
VAR_026273
Natural varianti252 – 2521D → G in MCEPHAS. 1 Publication
VAR_032637
Natural varianti289 – 2891K → E in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 2 Publications
VAR_008741
Natural varianti290 – 2901V → L.1 Publication
Corresponds to variant rs35600253 [ dbSNP | Ensembl ].
VAR_025167
Natural varianti319 – 3191Missing in glioma; reduced tumor suppressor activity; fails to inactivate AKT/PKB. 2 Publications
VAR_026274
Natural varianti331 – 3311D → G in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication
VAR_026275
Natural varianti341 – 3411F → V in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication
VAR_026276
Natural varianti342 – 3421K → N in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4 but PtdIns(3,4,5)P3 phosphatase activity is similar to wild-type. 1 Publication
VAR_026277
Natural varianti343 – 3431V → E in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
VAR_008742
Natural varianti345 – 3451L → 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. 3 Publications
VAR_026278
Natural varianti347 – 3471F → L in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications
VAR_008743
Natural varianti348 – 3481T → I in endometrial hyperplasia; reduced phosphatase activity towards PtdIns(3,4,5)P3; mildly reduced tumor suppressor activity; reduced ability to inactivate AKT/PKB. 2 Publications
VAR_026279
Natural varianti369 – 3691V → G Retains Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 phosphatase activity; retains ability to bind phospholipid membranes. 1 Publication
VAR_026280
Natural varianti401 – 4011T → I Retains Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 phosphatase activity; retains ability to bind phospholipid membranes. 1 Publication
VAR_026281

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MERGGEAAAAAAAAAAAPGR GSESPVTISRAGNAGELVSP LLLPPTRRRRRRHIQGPGPV LNLPSAAAAPPVARAPEAAG GGSRSEDYSSSPHSAAAAAR PLAAEEKQAQSLQPSSSRRS SHYPAAVQSQAAAERGASAT AKSRAISILQKKPRHQQLLP SLSSFFFSHRLPDM in isoform alpha. CuratedVSP_055420
Alternative sequencei55 – 7016RFLDS…KIYNL → S in isoform 3. 1 PublicationVSP_055421Add
BLAST
Alternative sequencei165 – 19026GVTIP…LDYRP → ADPTGGIPDKGIIVIGDGSS MDVIAP in isoform 3. 1 PublicationVSP_055422Add
BLAST
Alternative sequencei191 – 403213Missing in isoform 3. 1 PublicationVSP_055423Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
JF268690 mRNA. Translation: ADZ48535.1.
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.
CCDSiCCDS31238.1. [P60484-1]
RefSeqiNP_000305.3. NM_000314.6. [P60484-1]
UniGeneiHs.500466.
Hs.729457.

Genome annotation databases

EnsembliENST00000371953; ENSP00000361021; ENSG00000171862. [P60484-1]
GeneIDi5728.
KEGGihsa:5728.
UCSCiuc001kfb.3. human. [P60484-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
JF268690 mRNA. Translation: ADZ48535.1.
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.
CCDSiCCDS31238.1. [P60484-1]
RefSeqiNP_000305.3. NM_000314.6. [P60484-1]
UniGeneiHs.500466.
Hs.729457.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1D5RX-ray2.10A8-353[»]
2KYLNMR-B391-403[»]
4O1VX-ray2.00B354-368[»]
ProteinModelPortaliP60484.
SMRiP60484. Positions 14-351.
ModBasei