UniProtKB - P60484 (PTEN_HUMAN)
Protein
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Gene
PTEN
Organism
Homo sapiens (Human)
Status
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). 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.1 Publication
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
- 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) + phosphate2 PublicationsEC:3.1.3.672 Publications
- EC:3.1.3.161 Publication
- EC:3.1.3.161 Publication
- EC:3.1.3.482 Publications
Cofactori
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
- ionotropic glutamate receptor binding Source: Ensembl
- 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
- platelet-derived growth factor receptor binding Source: Ensembl
- protein serine/threonine phosphatase activity Source: UniProtKB
- protein tyrosine/serine/threonine phosphatase activity Source: InterPro
- protein tyrosine kinase binding Source: Ensembl
- protein tyrosine phosphatase activity Source: UniProtKB
- ubiquitin-specific protease binding Source: MGI
GO - Biological processi
- adult behavior Source: Ensembl
- aging 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 population proliferation Source: UniProtKB
- cellular response to electrical stimulus Source: BHF-UCL
- cellular response to ethanol Source: Ensembl
- cellular response to hypoxia Source: Ensembl
- cellular response to insulin-like growth factor stimulus Source: Ensembl
- cellular response to insulin stimulus Source: Ensembl
- cellular response to leptin stimulus Source: Ensembl
- cellular response to nerve growth factor stimulus 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
- endothelial cell migration Source: Ensembl
- forebrain morphogenesis Source: BHF-UCL
- heart development Source: UniProtKB
- inositol phosphate dephosphorylation Source: UniProtKB
- inositol phosphate metabolic process Source: Reactome
- learning or memory Source: BHF-UCL
- locomotor rhythm Source: BHF-UCL
- locomotory behavior Source: BHF-UCL
- long-term synaptic depression Source: Ensembl
- long-term synaptic potentiation Source: Ensembl
- male mating behavior Source: Ensembl
- maternal behavior Source: Ensembl
- memory 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 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 organ growth Source: BHF-UCL
- negative regulation of phagocytosis Source: Ensembl
- negative regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
- negative regulation of potassium ion transmembrane transporter activity Source: Ensembl
- 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 signaling receptor activity Source: Ensembl
- negative regulation of synaptic vesicle clustering Source: BHF-UCL
- negative regulation of vascular 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 biosynthetic process Source: Reactome
- phosphatidylinositol dephosphorylation Source: UniProtKB
- platelet-derived growth factor receptor signaling pathway Source: Ensembl
- positive regulation of cardiac muscle cell apoptotic process Source: Ensembl
- 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 gene expression Source: Ensembl
- positive regulation of neuron differentiation Source: Ensembl
- 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 deubiquitination Source: Reactome
- 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 cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
- regulation of myeloid cell apoptotic process Source: Ensembl
- regulation of neuron projection development Source: UniProtKB
- regulation of protein stability Source: UniProtKB
- regulation of synaptic transmission, GABAergic Source: Ensembl
- response to activity Source: Ensembl
- response to arsenic-containing substance Source: Ensembl
- response to ATP Source: Ensembl
- response to estradiol Source: Ensembl
- response to glucose Source: Ensembl
- response to zinc ion Source: Ensembl
- rhythmic synaptic transmission Source: BHF-UCL
- social behavior Source: BHF-UCL
- synapse assembly Source: BHF-UCL
- synapse maturation Source: BHF-UCL
- transcription initiation from RNA polymerase II promoter Source: Reactome
Keywordsi
| Molecular function | Hydrolase, Protein phosphatase |
| Biological process | Apoptosis, Lipid metabolism, Neurogenesis |
| Ligand | Lipid-binding |
Enzyme and pathway databases
| BioCyci | MetaCyc:HS10404-MONOMER |
| BRENDAi | 3.1.3.16 2681 |
| 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
| EuPathDBi | HostDB:ENSG00000171862.9 |
| HGNCi | HGNC:9588 PTEN |
| MIMi | 601728 gene |
| neXtProti | NX_P60484 |
Subcellular locationi
Isoform alpha :
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
- postsynaptic cytosol Source: Ensembl
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Mitochondrion
- mitochondrion Source: Ensembl
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
- postsynaptic membrane Source: Ensembl
Other locations
- cell projection Source: UniProtKB
- cytoplasm Source: UniProtKB
- dendritic spine Source: Ensembl
- myelin sheath adaxonal region Source: BHF-UCL
- neuron projection Source: BHF-UCL
- Schmidt-Lanterman incisure Source: BHF-UCL
Keywords - Cellular componenti
Cytoplasm, Nucleus, SecretedPathology & Biotechi
Involvement in diseasei
Cowden syndrome 1 (CWS1)21 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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_008733 | 33 | Missing in CWS1. 1 Publication | 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 Publication | 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 Publications | 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 Publications | 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:rs786204863Ensembl. | 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 Publications | 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)
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 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
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 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)
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:608089PTEN 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)1 Publication
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 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
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:176807Macrocephaly/autism syndrome (MCEPHAS)3 Publications
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 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 |
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 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 mutation, 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 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 |
Chemistry databases
| ChEMBLi | CHEMBL2052032 |
| GuidetoPHARMACOLOGYi | 2497 |
Polymorphism and mutation 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
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 conjugationProteomic databases
| EPDi | P60484 |
| jPOSTi | P60484 |
| MaxQBi | P60484 |
| PaxDbi | P60484 |
| PeptideAtlasi | P60484 |
| PRIDEi | P60484 |
| ProteomicsDBi | 57209 |
PTM databases
| CarbonylDBi | P60484 |
| DEPODi | P60484 |
| iPTMneti | P60484 |
| PhosphoSitePlusi | P60484 |
Miscellaneous databases
| PMAP-CutDBi | P60484 |
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
| Bgeei | ENSG00000171862 Expressed in 205 organ(s), highest expression level in intestine |
| ExpressionAtlasi | P60484 baseline and differential |
| Genevisiblei | P60484 HS |
Organism-specific databases
| HPAi | CAB004076 HPA031335 |
Interactioni
Subunit structurei
Monomer. The unphosphorylated form interacts with the second PDZ domain of AIP1 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 Publications
Binary interactionsi
GO - Molecular functioni
- enzyme binding Source: UniProtKB
- identical protein binding Source: IntAct
- ionotropic glutamate receptor binding Source: Ensembl
- PDZ domain binding Source: UniProtKB
- platelet-derived growth factor receptor binding Source: Ensembl
- protein tyrosine kinase binding Source: Ensembl
- ubiquitin-specific protease binding Source: MGI
Protein-protein interaction databases
| BioGridi | 111700, 407 interactors |
| ComplexPortali | CPX-3153 PTEN phosphatase complex |
| CORUMi | P60484 |
| DIPi | DIP-35019N |
| ELMi | P60484 |
| IntActi | P60484, 54 interactors |
| MINTi | P60484 |
| STRINGi | 9606.ENSP00000361021 |
Chemistry databases
| BindingDBi | P60484 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1D5R | X-ray | 2.10 | A | 8-353 | [»] | |
| 2KYL | NMR | - | B | 391-403 | [»] | |
| 4O1V | X-ray | 2.00 | B | 354-368 | [»] | |
| 5BUG | X-ray | 2.40 | A/B/C/D | 14-351 | [»] | |
| 5BZX | X-ray | 2.50 | A/B/C/D | 14-351 | [»] | |
| 5BZZ | X-ray | 2.20 | A/B/C/D | 14-351 | [»] | |
| ProteinModelPortali | P60484 | |||||
| SMRi | P60484 | |||||
| ModBasei | Search... | |||||
| MobiDBi | 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 | 401 – 403 | PDZ domain-binding | 3 |
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
Belongs to the PTEN phosphatase protein family.Curated
Phylogenomic databases
| eggNOGi | KOG2283 Eukaryota COG2453 LUCA |
| GeneTreei | ENSGT00940000154335 |
| HOGENOMi | HOG000008008 |
| HOVERGENi | HBG000239 |
| InParanoidi | P60484 |
| KOi | K01110 |
| OMAi | REDKYMY |
| OrthoDBi | 154265at2759 |
| PhylomeDBi | P60484 |
| TreeFami | TF324513 |
Family and domain databases
| Gene3Di | 3.90.190.10, 1 hit |
| InterProi | View protein in InterPro IPR017361 Bifunc_PIno_P3_Pase/Pase_PTEN IPR000340 Dual-sp_phosphatase_cat-dom IPR029021 Prot-tyrosine_phosphatase-like IPR014020 Tensin_C2-dom IPR029023 Tensin_phosphatase IPR016130 Tyr_Pase_AS IPR003595 Tyr_Pase_cat |
| Pfami | View protein in Pfam PF00782 DSPc, 1 hit 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 | SSF52799 SSF52799, 1 hit |
| PROSITEi | View protein in PROSITE PS51182 C2_TENSIN, 1 hit PS51181 PPASE_TENSIN, 1 hit |
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 basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
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.
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
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 »Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket| A0A087X033 | A0A087X033_HUMAN | Phosphatidylinositol 3,4,5-trisphos... | PTEN | 153 | 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 Publication | 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 Publication | 1 | |
| Natural variantiVAR_026252 | 36 | G → R in endometrial hyperplasia. 1 PublicationCorresponds to variant dbSNP:rs786204854Ensembl. | 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 Publication | 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 Publications | 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 PublicationsCorresponds to variant dbSNP:rs121909222EnsemblClinVar. | 1 | |
| Natural variantiVAR_026260 | 123 | H → Y in endometrial cancer; loss of protein phosphatase activity. 1 PublicationCorresponds to variant dbSNP:rs786204931EnsemblClinVar. | 1 | |
| Natural variantiVAR_007464 | 124 | C → R in CWS1. 3 Publications |