UniProtKB - P60484 (PTEN_HUMAN)
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
PTEN
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 (PubMed:26504226, PubMed:16824732).
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 MAGI2 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.
2 PublicationsFunctional 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
- a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphate3 PublicationsEC:3.1.3.673 Publications
- EC:3.1.3.161 Publication
- EC:3.1.3.161 Publication
- EC:3.1.3.482 Publications
- 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 124 | Phosphocysteine intermediatePROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- anaphase-promoting complex binding Source: BHF-UCL
- enzyme binding Source: UniProtKB
- identical protein binding Source: IntAct
- inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity Source: UniProtKB
- lipid binding Source: UniProtKB-KW
- 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 kinase binding Source: Ensembl
- protein serine/threonine phosphatase activity Source: UniProtKB
- protein tyrosine phosphatase activity Source: UniProtKB
- ubiquitin-specific protease binding Source: MGI
GO - Biological processi
- adult behavior Source: Ensembl
- angiogenesis Source: Ensembl
- apoptotic process Source: UniProtKB-KW
- brain morphogenesis Source: BHF-UCL
- canonical Wnt signaling pathway Source: BHF-UCL
- cardiac muscle tissue development Source: Ensembl
- cell migration Source: UniProtKB
- cell motility Source: GO_Central
- cellular response to electrical stimulus Source: BHF-UCL
- cellular response to hypoxia Source: Ensembl
- central nervous system development Source: UniProtKB
- central nervous system myelin maintenance Source: BHF-UCL
- central nervous system neuron axonogenesis Source: BHF-UCL
- dendritic spine morphogenesis Source: BHF-UCL
- dentate gyrus development Source: BHF-UCL
- dephosphorylation Source: GO_Central
- endothelial cell migration Source: Ensembl
- forebrain morphogenesis Source: BHF-UCL
- heart development Source: UniProtKB
- inositol phosphate dephosphorylation Source: UniProtKB
- learning or memory Source: BHF-UCL
- locomotor rhythm Source: BHF-UCL
- locomotory behavior Source: BHF-UCL
- long-term synaptic potentiation Source: Ensembl
- male mating behavior Source: Ensembl
- maternal behavior Source: Ensembl
- multicellular organismal response to stress Source: BHF-UCL
- negative regulation of apoptotic process Source: Ensembl
- negative regulation of axonogenesis Source: BHF-UCL
- negative regulation of axon regeneration Source: Ensembl
- negative regulation of cardiac muscle cell proliferation Source: Ensembl
- negative regulation of cell aging Source: Ensembl
- negative regulation of cell cycle G1/S phase transition Source: UniProtKB
- negative regulation of cell migration Source: UniProtKB
- negative regulation of cell population proliferation Source: BHF-UCL
- negative regulation of cell size Source: BHF-UCL
- negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
- negative regulation of dendritic spine morphogenesis Source: BHF-UCL
- negative regulation of epithelial cell proliferation Source: Ensembl
- negative regulation of epithelial to mesenchymal transition Source: BHF-UCL
- negative regulation of ERK1 and ERK2 cascade Source: BHF-UCL
- negative regulation of excitatory postsynaptic potential Source: BHF-UCL
- negative regulation of focal adhesion assembly Source: UniProtKB
- negative regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
- negative regulation of keratinocyte migration Source: BHF-UCL
- negative regulation of myelination Source: Ensembl
- negative regulation of neuron projection development Source: ARUK-UCL
- negative regulation of organ growth Source: BHF-UCL
- negative regulation of peptidyl-serine phosphorylation Source: UniProtKB
- negative regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
- negative regulation of protein kinase B signaling Source: UniProtKB
- negative regulation of protein phosphorylation Source: BHF-UCL
- negative regulation of ribosome biogenesis Source: Ensembl
- negative regulation of synaptic vesicle clustering Source: BHF-UCL
- negative regulation of vascular associated smooth muscle cell proliferation Source: BHF-UCL
- negative regulation of wound healing, spreading of epidermal cells Source: BHF-UCL
- neuron-neuron synaptic transmission Source: BHF-UCL
- phosphatidylinositol 3-kinase signaling Source: GO_Central
- phosphatidylinositol biosynthetic process Source: Reactome
- phosphatidylinositol dephosphorylation Source: UniProtKB
- positive regulation of cell population proliferation Source: BHF-UCL
- positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
- positive regulation of ERK1 and ERK2 cascade Source: Ensembl
- positive regulation of excitatory postsynaptic potential Source: BHF-UCL
- positive regulation of TRAIL-activated apoptotic signaling pathway Source: BHF-UCL
- positive regulation of ubiquitin-dependent protein catabolic process Source: BHF-UCL
- positive regulation of ubiquitin protein ligase activity Source: BHF-UCL
- postsynaptic density assembly Source: BHF-UCL
- prepulse inhibition Source: BHF-UCL
- presynaptic membrane assembly Source: BHF-UCL
- prostate gland growth Source: Ensembl
- protein dephosphorylation Source: UniProtKB
- protein kinase B signaling Source: UniProtKB
- protein stabilization Source: BHF-UCL
- regulation of B cell apoptotic process Source: Ensembl
- regulation of cellular component size Source: BHF-UCL
- regulation of myeloid cell apoptotic process Source: Ensembl
- regulation of neuron projection development Source: UniProtKB
- regulation of protein kinase B signaling Source: GO_Central
- regulation of protein stability Source: UniProtKB
- regulation of synaptic transmission, GABAergic Source: Ensembl
- rhythmic synaptic transmission Source: BHF-UCL
- social behavior Source: BHF-UCL
- synapse assembly Source: BHF-UCL
- synapse maturation Source: BHF-UCL
Keywordsi
Molecular function | Hydrolase, Protein phosphatase |
Biological process | Apoptosis, Lipid metabolism, Neurogenesis |
Ligand | Lipid-binding |
Enzyme and pathway databases
BRENDAi | 3.1.3.16, 2681 3.1.3.67, 2681 |
PathwayCommonsi | P60484 |
Reactomei | R-HSA-1660499, Synthesis of PIPs at the plasma membrane R-HSA-1855204, Synthesis of IP3 and IP4 in the cytosol R-HSA-199418, Negative regulation of the PI3K/AKT network R-HSA-202424, Downstream TCR signaling R-HSA-5628897, TP53 Regulates Metabolic Genes R-HSA-5674404, PTEN Loss of Function in Cancer R-HSA-5689880, Ub-specific processing proteases R-HSA-5689896, Ovarian tumor domain proteases R-HSA-8943723, Regulation of PTEN mRNA translation R-HSA-8948747, Regulation of PTEN localization R-HSA-8948751, Regulation of PTEN stability and activity R-HSA-8986944, Transcriptional Regulation by MECP2 |
SignaLinki | P60484 |
SIGNORi | P60484 |
Chemistry databases
SwissLipidsi | SLP:000000849 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:PTEN Synonyms:MMAC1, TEP1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9588, PTEN |
MIMi | 601728, gene |
neXtProti | NX_P60484 |
VEuPathDBi | HostDB:ENSG00000171862 |
Subcellular locationi
Extracellular region or secreted
- Secreted 2 Publications
Note: May be secreted via a classical signal peptide and reenter into cells with the help of a poly-Arg motif.
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
- PML body Source: UniProtKB-SubCell
Plasma Membrane
- apical plasma membrane Source: UniProtKB
- cytoplasmic side of plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- cell projection Source: UniProtKB
- cytoplasm Source: UniProtKB
- myelin sheath adaxonal region Source: BHF-UCL
- neuron projection Source: BHF-UCL
- Schmidt-Lanterman incisure Source: BHF-UCL
- synapse Source: GOC
Keywords - Cellular componenti
Cytoplasm, Nucleus, SecretedPathology & Biotechi
Involvement in diseasei
Cowden syndrome 1 (CWS1)21 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_008733 | 33 | Missing in CWS1. 1 PublicationCorresponds to variant dbSNP:rs1554893765Ensembl. | 1 | |
Natural variantiVAR_008734 | 34 | A → D in CWS1. 2 Publications | 1 | |
Natural variantiVAR_008036 | 35 | M → R in CWS1. 1 PublicationCorresponds to variant dbSNP:rs121909225EnsemblClinVar. | 1 | |
Natural variantiVAR_011587 | 47 | R → G in CWS1. 1 PublicationCorresponds to variant dbSNP:rs786204855EnsemblClinVar. | 1 | |
Natural variantiVAR_007461 | 67 | I → R in CWS1. | 1 | |
Natural variantiVAR_007462 | 68 | Y → H in CWS1; 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 PublicationsCorresponds to variant dbSNP:rs398123317EnsemblClinVar. | 1 | |
Natural variantiVAR_018102 | 70 | L → P in CWS1. 1 PublicationCorresponds to variant dbSNP:rs121909226EnsemblClinVar. | 1 | |
Natural variantiVAR_026254 | 71 | C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication | 1 | |
Natural variantiVAR_026255 | 93 | H → Y in CWS1. 1 PublicationCorresponds to variant dbSNP:rs786204927EnsemblClinVar. | 1 | |
Natural variantiVAR_026256 | 105 | C → F in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication | 1 | |
Natural variantiVAR_008735 | 105 | C → Y in CWS1. 2 PublicationsCorresponds to variant dbSNP:rs587782343EnsemblClinVar. | 1 | |
Natural variantiVAR_026257 | 107 | D → Y in CWS1 and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 PublicationsCorresponds to variant dbSNP:rs57374291EnsemblClinVar. | 1 | |
Natural variantiVAR_007807 | 112 | L → P in CWS1 and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. 3 PublicationsCorresponds to variant dbSNP:rs121909230EnsemblClinVar. | 1 | |
Natural variantiVAR_007463 | 123 | H → R in CWS1. 2 PublicationsCorresponds to variant dbSNP:rs121909222EnsemblClinVar. | 1 | |
Natural variantiVAR_007464 | 124 | C → R in CWS1. 3 PublicationsCorresponds to variant dbSNP:rs121909223EnsemblClinVar. | 1 | |
Natural variantiVAR_018104 | 124 | C → S in CWS1; phosphatase-dead protein with neither lipid nor protein phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs121909223EnsemblClinVar. | 1 | |
Natural variantiVAR_007465 | 129 | G → E in CWS1; no lipid phosphatase activity but retains protein phosphatase activity; retains ability to inhibit focal adhesion formation. 5 PublicationsCorresponds to variant dbSNP:rs121909218EnsemblClinVar. | 1 | |
Natural variantiVAR_007467 | 130 | R → L in CWS1 and endometrial hyperplasia; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 2 PublicationsCorresponds to variant dbSNP:rs121909229EnsemblClinVar. | 1 | |
Natural variantiVAR_007468 | 130 | R → Q in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 2 PublicationsCorresponds to variant dbSNP:rs121909229EnsemblClinVar. | 1 | |
Natural variantiVAR_008736 | 135 | I → V in CWS1. 2 PublicationsCorresponds to variant dbSNP:rs587782360EnsemblClinVar. | 1 | |
Natural variantiVAR_007808 | 136 | C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P3. 2 PublicationsCorresponds to variant dbSNP:rs786204859EnsemblClinVar. | 1 | |
Natural variantiVAR_008737 | 137 | A → AN in CWS1. 1 Publication | 1 | |
Natural variantiVAR_026263 | 155 | Y → C in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 PublicationCorresponds to variant dbSNP:rs1060500126EnsemblClinVar. | 1 | |
Natural variantiVAR_008739 | 165 | G → E in CWS1. 1 Publication | 1 | |
Natural variantiVAR_008738 | 165 | G → V in CWS1. Corresponds to variant dbSNP:rs786204863EnsemblClinVar. | 1 | |
Natural variantiVAR_007470 | 170 | S → R in CWS1; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4. 5 PublicationsCorresponds to variant dbSNP:rs121909221EnsemblClinVar. | 1 | |
Natural variantiVAR_008740 | 246 | P → L in CWS1. 1 PublicationCorresponds to variant dbSNP:rs587782350EnsemblClinVar. | 1 | |
Natural variantiVAR_008741 | 289 | K → E in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes; predominantly nuclear. 3 PublicationsCorresponds to variant dbSNP:rs562015640EnsemblClinVar. | 1 | |
Natural variantiVAR_026275 | 331 | D → G in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes. 1 Publication | 1 | |
Natural variantiVAR_026276 | 341 | F → V in CWS1; loss of interaction with NOP53; decreased phosphorylation at S-380; decreased stability; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 PublicationsCorresponds to variant dbSNP:rs1554825652EnsemblClinVar. | 1 | |
Natural variantiVAR_026277 | 342 | K → 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 PublicationCorresponds to variant dbSNP:rs398123314EnsemblClinVar. | 1 | |
Natural variantiVAR_008742 | 343 | V → E in CWS1; loss of interaction with NOP53; decreased phosphorylation at S-380; decreased stability; loss of phosphatase activity towards Ins(1,3,4,5)P4. 3 Publications | 1 | |
Natural variantiVAR_008743 | 347 | F → L in CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications | 1 |
Lhermitte-Duclos disease (LDD)
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_007807 | 112 | L → P in CWS1 and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. 3 PublicationsCorresponds to variant dbSNP:rs121909230EnsemblClinVar. | 1 |
Squamous cell carcinoma of the head and neck (HNSCC)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_018103 | 121 | A → G in HNSCC. 1 PublicationCorresponds to variant dbSNP:rs121909237EnsemblClinVar. | 1 |
Endometrial cancer (ENDMC)
Glioma 2 (GLM2)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_018106 | 234 | R → 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 PublicationCorresponds to variant dbSNP:rs121909235EnsemblClinVar. | 1 |
Prostate cancer (PC)2 Publications
Macrocephaly/autism syndrome (MCEPHAS)3 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078705 | 65 – 403 | Missing in MCEPHAS. 1 PublicationAdd BLAST | 339 | |
Natural variantiVAR_032634 | 93 | H → R in MCEPHAS. 1 PublicationCorresponds to variant dbSNP:rs121909238EnsemblClinVar. | 1 | |
Natural variantiVAR_076762 | 131 | T → I in MCEPHAS. 1 PublicationCorresponds to variant dbSNP:rs397514560EnsemblClinVar. | 1 | |
Natural variantiVAR_076763 | 167 | T → N in MCEPHAS. 1 PublicationCorresponds to variant dbSNP:rs397514559EnsemblClinVar. | 1 | |
Natural variantiVAR_032636 | 241 | F → S in MCEPHAS. 1 PublicationCorresponds to variant dbSNP:rs121909240EnsemblClinVar. | 1 | |
Natural variantiVAR_032637 | 252 | D → G in MCEPHAS. 1 PublicationCorresponds to variant dbSNP:rs121909239EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 | M → I: Expression is restricted to isoform alpha. 1 Publication | 1 | |
Mutagenesisi | 13 | K → E: Nuclear. Cytoplasmic; when associated with E-289. Shows less tumor suppressive ability; when associated with E-289. 1 Publication | 1 | |
Mutagenesisi | 92 | 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. 2 Publications | 1 | |
Mutagenesisi | 93 | H → A: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Modest reduction in phosphatase activity towards PtdIns(3,4)P2. 1 Publication | 1 | |
Mutagenesisi | 124 | C → A: Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation. 1 Publication | 1 | |
Mutagenesisi | 125 | K → M: Reduced phosphatase activity towards PtdIns(3,4,5)P3, PtdIns(3,4)P2 and PtdIns(3)P. 1 Publication | 1 | |
Mutagenesisi | 126 | A → P: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 1 Publication | 1 | |
Mutagenesisi | 126 | A → S: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 1 Publication | 1 | |
Mutagenesisi | 126 | A → V: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 1 Publication | 1 | |
Mutagenesisi | 128 | K → M: 85% reduction in phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication | 1 | |
Mutagenesisi | 128 | K → R: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication | 1 | |
Mutagenesisi | 130 | R → M: Does not affect the ability to inhibit AKT/PKB activation. 1 Publication | 1 | |
Mutagenesisi | 167 | T → A or D: 60% reduction in phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication | 1 | |
Mutagenesisi | 171 | Q → A or E: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. 1 Publication | 1 | |
Mutagenesisi | 263 – 269 | 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. 1 Publication | 7 | |
Mutagenesisi | 289 | K → E: Cytoplasmic; when associated with E-13. Shows less tumor suppressive ability; when associated with E-13. 1 Publication | 1 | |
Mutagenesisi | 327 – 335 | 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. 1 Publication | 9 | |
Mutagenesisi | 336 | Y → F: Significantly lower phosphatase activity, reduced protein stability and decreased growth-inhibitory effect. 1 Publication | 1 | |
Mutagenesisi | 366 | T → A: Decreased stability. 1 Publication | 1 | |
Mutagenesisi | 370 | S → A: Decreased stability. 1 Publication | 1 | |
Mutagenesisi | 401 | T → A: Loss of DLG1-binding. No effect on MAGI2- and MAST2-binding. | 1 | |
Mutagenesisi | 402 | K → A: No effect on MAGI2-, MAST2- and DLG1-binding. | 1 | |
Mutagenesisi | 402 | K → W: Loss of DLG1-, MAGI2-, MAGI3- and MAST2-binding. Decrease of protein stability. | 1 | |
Mutagenesisi | 403 | V → A: Loss of DLG1-, MAGI2-, MAGI3-, MAST1-, MAST2- and MAST3-binding. 1 Publication | 1 |
Keywords - Diseasei
Autism spectrum disorder, Disease variant, Tumor suppressorOrganism-specific databases
DisGeNETi | 5728 |
GeneReviewsi | PTEN |
MalaCardsi | PTEN |
MIMi | 137800, phenotype 158350, phenotype 176807, phenotype 275355, phenotype 605309, phenotype 608089, phenotype 612242, phenotype 613028, phenotype |
OpenTargetsi | ENSG00000171862 |
Orphaneti | 397596, Activated PI3K-delta syndrome 109, Bannayan-Riley-Ruvalcaba syndrome 101070, Bilateral frontoparietal polymicrogyria 201, Cowden syndrome 145, Hereditary breast and ovarian cancer syndrome 79076, Juvenile polyposis of infancy 65285, Lhermitte-Duclos disease 210548, Macrocephaly-intellectual disability-autism syndrome 744, Proteus syndrome 2969, Proteus-like syndrome 137608, Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome 500481, Squamous cell carcinoma of salivary glands 494547, Squamous cell carcinoma of the hypopharynx 494550, Squamous cell carcinoma of the larynx 502366, Squamous cell carcinoma of the lip 500464, Squamous cell carcinoma of the nasal cavity and paranasal sinuses 502363, Squamous cell carcinoma of the oral cavity 500478, Squamous cell carcinoma of the oropharynx |
PharmGKBi | PA33942 |
Miscellaneous databases
Pharosi | P60484, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2052032 |
DrugBanki | DB04327, Phosphatidylethanolamine |
GuidetoPHARMACOLOGYi | 2497 |
Genetic variation databases
BioMutai | PTEN |
DMDMi | 42560209 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000215904 | 2 – 403 | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENAdd BLAST | 402 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylthreonineCombined sources | 1 | |
Cross-linki | 13 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 289 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Modified residuei | 294 | PhosphoserineBy similarity | 1 | |
Modified residuei | 336 | Phosphotyrosine; by FRK1 Publication | 1 | |
Modified residuei | 366 | Phosphothreonine; by GSK3-beta and PLK3Combined sources2 Publications | 1 | |
Modified residuei | 370 | Phosphoserine; by CK2 and PLK33 Publications | 1 | |
Modified residuei | 380 | Phosphoserine; by ROCK1 and CK21 Publication | 1 | |
Modified residuei | 382 | Phosphothreonine; by ROCK1 and CK21 Publication | 1 | |
Modified residuei | 383 | Phosphothreonine; by ROCK1 and CK21 Publication | 1 | |
Modified residuei | 385 | Phosphoserine; by CK22 Publications | 1 | |
Modified residuei | 401 | Phosphothreonine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P60484 |
jPOSTi | P60484 |
MassIVEi | P60484 |
MaxQBi | P60484 |
PaxDbi | P60484 |
PeptideAtlasi | P60484 |
PRIDEi | P60484 |
ProteomicsDBi | 57209 [P60484-1] |
PTM databases
CarbonylDBi | P60484 |
DEPODi | PTEN |
iPTMneti | P60484 |
MetOSitei | P60484 |
PhosphoSitePlusi | P60484 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000171862, Expressed in calcaneal tendon and 219 other tissues |
ExpressionAtlasi | P60484, baseline and differential |
Genevisiblei | P60484, HS |
Organism-specific databases
HPAi | ENSG00000171862, Low tissue specificity |
Interactioni
Subunit structurei
Monomer. The unphosphorylated form interacts with the second PDZ domain of MAGI2 and with DLG1 and MAST2 in vitro (PubMed:10646847, PubMed:10760291, PubMed:11707428).
Interacts with MAGI2, MAGI3, MAST1 and MAST3, but neither with MAST4 nor with DLG5; interaction with MAGI2 increases protein stability (PubMed:10748157, PubMed:15951562).
Interacts with NEDD4 (PubMed:17218260).
Interacts with NDFIP1 and NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes PTEN ubiquitination (PubMed:25801959, PubMed:20534535).
Interacts (via C2 domain) with FRK (PubMed:19345329).
Interacts with USP7; the interaction is direct (PubMed:18716620).
Interacts with ROCK1 (By similarity).
Interacts with XIAP/BIRC4 (PubMed:19473982).
Interacts with STK11; the interaction phosphorylates PTEN (PubMed:15987703).
Interacts with PPP1R16B (PubMed:25007873).
Interacts with NOP53; regulates PTEN phosphorylation and increases its stability (PubMed:15355975).
By similarity15 PublicationsBinary interactionsi
P60484
PTEN - isoform 1 [P60484-1]
With | #Exp. | IntAct |
---|---|---|
ECSCR [Q19T08] | 4 | EBI-15722967,EBI-15778214 |
OTUD3 [Q5T2D3] | 9 | EBI-15722967,EBI-16170539 |
itself | 3 | EBI-15722967,EBI-15722967 |
USP7 [Q93009] | 5 | EBI-15722967,EBI-302474 |
GO - Molecular functioni
- enzyme binding Source: UniProtKB
- identical protein binding Source: IntAct
- PDZ domain binding Source: UniProtKB
- protein kinase binding Source: Ensembl
- ubiquitin-specific protease binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 111700, 807 interactors |
ComplexPortali | CPX-3153, PTEN phosphatase complex |
CORUMi | P60484 |
DIPi | DIP-35019N |
ELMi | P60484 |
IntActi | P60484, 68 interactors |
MINTi | P60484 |
STRINGi | 9606.ENSP00000361021 |
Chemistry databases
BindingDBi | P60484 |
Miscellaneous databases
RNActi | P60484, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P60484 |
SMRi | P60484 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P60484 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 14 – 185 | Phosphatase tensin-typePROSITE-ProRule annotationAdd BLAST | 172 | |
Domaini | 190 – 350 | C2 tensin-typePROSITE-ProRule annotationAdd BLAST | 161 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 338 – 348 | Required for interaction with NOP531 PublicationAdd BLAST | 11 | |
Regioni | 352 – 403 | DisorderedSequence analysisAdd BLAST | 52 | |
Regioni | 401 – 403 | PDZ domain-binding | 3 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 353 – 370 | Polar residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 371 – 385 | Basic and acidic residuesSequence analysisAdd BLAST | 15 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2283, Eukaryota |
GeneTreei | ENSGT00940000154335 |
HOGENOMi | CLU_020105_5_2_1 |
InParanoidi | P60484 |
OMAi | HARTMNG |
OrthoDBi | 639380at2759 |
PhylomeDBi | P60484 |
TreeFami | TF324513 |
Family and domain databases
CDDi | cd14509, PTP_PTEN, 1 hit |
Gene3Di | 3.90.190.10, 1 hit |
InterProi | View protein in InterPro IPR017361, Bifunc_PIno_P3_Pase/Pase_PTEN IPR035892, C2_domain_sf IPR029021, Prot-tyrosine_phosphatase-like IPR045101, PTP_PTEN IPR014020, Tensin_C2-dom IPR029023, Tensin_phosphatase IPR016130, Tyr_Pase_AS IPR003595, Tyr_Pase_cat IPR000387, Tyr_Pase_dom |
Pfami | View protein in Pfam PF10409, PTEN_C2, 1 hit |
PIRSFi | PIRSF038025, PTEN, 1 hit |
SMARTi | View protein in SMART SM01326, PTEN_C2, 1 hit SM00404, PTPc_motif, 1 hit |
SUPFAMi | SSF49562, SSF49562, 1 hit SSF52799, SSF52799, 1 hit |
PROSITEi | View protein in PROSITE PS51182, C2_TENSIN, 1 hit PS51181, PPASE_TENSIN, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing and alternative initiation. AlignAdd to basketThis entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
The sequence of this isoform differs from the canonical sequence as follows:
1-1: M → MERGGEAAAA...FFFSHRLPDM
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087X033 | A0A087X033_HUMAN | Phosphatidylinositol 3,4,5-trisphos... | PTEN | 153 | Annotation score: | ||
A0A8I5KR36 | A0A8I5KR36_HUMAN | Phosphatidylinositol 3,4,5-trisphos... | PTEN | 30 | Annotation score: | ||
A0A8I5KSF9 | A0A8I5KSF9_HUMAN | Phosphatidylinositol 3,4,5-trisphos... | PTEN | 576 | Annotation score: | ||
A0A8I5KVQ8 | A0A8I5KVQ8_HUMAN | Phosphatidylinositol 3,4,5-trisphos... | PTEN | 190 | Annotation score: | ||
A0A8I5QKR2 | A0A8I5QKR2_HUMAN | Phosphatidylinositol 3,4,5-trisphos... | PTEN | 44 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_026248 | 10 | 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. 1 Publication | 1 | |
Natural variantiVAR_007457 | 15 | R → S in glioma. 1 PublicationCorresponds to variant dbSNP:rs1064794096EnsemblClinVar. | 1 | |
Natural variantiVAR_026249 | 16 | Y → C Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains the ability to bind phospholipid membranes. 1 Publication | 1 | |
Natural variantiVAR_018100 | 19 | D → N in malignant melanoma; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121909233EnsemblClinVar. | 1 | |
Natural variantiVAR_026250 | 20 | G → E Reduced phosphatase activity towards Ins(1,3,4,5)P4; retains phosphatase activity towards PtdIns(3,4,5)P3. 1 PublicationCorresponds to variant dbSNP:rs1064795967EnsemblClinVar. | 1 | |
Natural variantiVAR_026251 | 27 | Y → S Loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 PublicationCorresponds to variant dbSNP:rs886041877EnsemblClinVar. | 1 | |
Natural variantiVAR_008733 | 33 | Missing in CWS1. 1 PublicationCorresponds to variant dbSNP:rs1554893765Ensembl. | 1 | |
Natural variantiVAR_008734 | 34 | A → D in CWS1. 2 Publications | 1 | |
Natural variantiVAR_008036 | 35 | M → R in CWS1. 1 PublicationCorresponds to variant dbSNP:rs121909225EnsemblClinVar. | 1 | |
Natural variantiVAR_007458 | 36 | G → E in glioma. 1 PublicationCorresponds to variant dbSNP:rs1554893792EnsemblClinVar. | 1 | |
Natural variantiVAR_026252 | 36 | G → R in endometrial hyperplasia. 1 PublicationCorresponds to variant dbSNP:rs786204854EnsemblClinVar. | 1 | |
Natural variantiVAR_007459 | 42 | 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. 1 Publication | 1 | |
Natural variantiVAR_011587 | 47 | R → G in CWS1. 1 PublicationCorresponds to variant dbSNP:rs786204855EnsemblClinVar. | 1 | |
Natural variantiVAR_007460 | 57 | L → W in glioma; loss of protein phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs786202398EnsemblClinVar. | 1 | |
Natural variantiVAR_018101 | 61 | H → D Foun in a patient with macrocephaly, ventriculomegaly, vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia and other limb defects; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs121909236EnsemblClinVar. | 1 | |
Natural variantiVAR_026253 | 61 | H → R Loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 PublicationCorresponds to variant dbSNP:rs398123316EnsemblClinVar. | 1 | |
Natural variantiVAR_078705 | 65 – 403 | Missing in MCEPHAS. 1 PublicationAdd BLAST | 339 | |
Natural variantiVAR_007461 | 67 | I → R in CWS1. | 1 | |
Natural variantiVAR_007462 | 68 | Y → H in CWS1; 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 PublicationsCorresponds to variant dbSNP:rs398123317EnsemblClinVar. | 1 | |
Natural variantiVAR_018102 | 70 | L → P in CWS1. 1 PublicationCorresponds to variant dbSNP:rs121909226EnsemblClinVar. | 1 | |
Natural variantiVAR_026254 | 71 | C → Y in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication | 1 | |
Natural variantiVAR_032634 | 93 | H → R in MCEPHAS. 1 PublicationCorresponds to variant dbSNP:rs121909238EnsemblClinVar. | 1 | |
Natural variantiVAR_026255 | 93 | H → Y in CWS1. 1 PublicationCorresponds to variant dbSNP:rs786204927EnsemblClinVar. | 1 | |
Natural variantiVAR_026256 | 105 | C → F in CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication | 1 | |
Natural variantiVAR_008735 | 105 | C → Y in CWS1. 2 PublicationsCorresponds to variant dbSNP:rs587782343EnsemblClinVar. | 1 | |
Natural variantiVAR_026257 | 107 | D → Y in CWS1 and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 PublicationsCorresponds to variant dbSNP:rs57374291EnsemblClinVar. | 1 | |
Natural variantiVAR_007807 | 112 | L → P in CWS1 and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4. 3 PublicationsCorresponds to variant dbSNP:rs121909230EnsemblClinVar. | 1 | |
Natural variantiVAR_026258 | 112 | L → R Loss of phosphatase activity towards Ins(1,3,4,5)P4. 1 Publication | 1 | |
Natural variantiVAR_011588 | 119 | V → L in multiple cancers. 1 PublicationCorresponds to variant dbSNP:rs139767111EnsemblClinVar. | 1 | |
Natural variantiVAR_018103 | 121 | A → G in HNSCC. 1 PublicationCorresponds to variant dbSNP:rs121909237EnsemblClinVar. | 1 | |
Natural variantiVAR_026259 | 121 | A → P in glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4. 2 Publications | 1 | |
Natural variantiVAR_007463 | 123 | H → R in CWS1. 2 Publications |