P60483 · PTEN_CANLF
- ProteinPhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
- GenePTEN
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids403 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also functions as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring of PtdIns(3,4,5)P3/phosphatidylinositol 3,4,5-trisphosphate, PtdIns(3,4)P2/phosphatidylinositol 3,4-diphosphate and PtdIns3P/phosphatidylinositol 3-phosphate with a preference for PtdIns(3,4,5)P3. Furthermore, this enzyme can also act as a cytosolic inositol 3-phosphatase acting on Ins(1,3,4,5,6)P5/inositol 1,3,4,5,6 pentakisphosphate and possibly Ins(1,3,4,5)P4/1D-myo-inositol 1,3,4,5-tetrakisphosphate (By similarity).
Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (By similarity).
The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation (By similarity).
Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation (By similarity).
Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation (By similarity).
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 (By similarity).
Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD) (By similarity).
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 (By similarity).
Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (By similarity).
The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation (By similarity).
Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation (By similarity).
Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation (By similarity).
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 (By similarity).
Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD) (By similarity).
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 (By similarity).
Catalytic activity
- 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) + phosphateThis reaction proceeds in the forward direction.
- 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) + phosphateThis reaction proceeds in the forward 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) + phosphateThis reaction proceeds in the forward direction.
- 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + H2O = 1D-myo-inositol 1,4,5,6-tetrakisphosphate + phosphateThis reaction proceeds in the forward direction.
- 1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + phosphateThis reaction proceeds in the forward direction.
Cofactor
Features
Showing features for active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Active site | 124 | Phosphocysteine intermediate | |||
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
- EC number
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Canidae > Canis
Accessions
- Primary accessionP60483
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Monoubiquitinated form is nuclear (By similarity).
Nonubiquitinated form is cytoplasmic (By similarity).
Colocalized with PML and USP7 in PML nuclear bodies (By similarity).
XIAP/BIRC4 promotes its nuclear localization (By similarity).
Associares with the postsynaptic density in response to NMDAR activation (By similarity).
Nonubiquitinated form is cytoplasmic (By similarity).
Colocalized with PML and USP7 in PML nuclear bodies (By similarity).
XIAP/BIRC4 promotes its nuclear localization (By similarity).
Associares with the postsynaptic density in response to NMDAR activation (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 2 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Initiator methionine | 1 | Removed | |||
Modified residue | 2 | N-acetylthreonine | |||
Chain | PRO_0000215903 | 2-403 | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN | ||
Cross-link | 13 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Cross-link | 289 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Modified residue | 294 | Phosphoserine | |||
Modified residue | 319 | Phosphothreonine | |||
Modified residue | 321 | Phosphothreonine | |||
Modified residue | 336 | Phosphotyrosine; by FRK | |||
Modified residue | 366 | Phosphothreonine; by GSK3-beta and PLK3 | |||
Modified residue | 370 | Phosphoserine; by CK2 and PLK3 | |||
Modified residue | 380 | Phosphoserine; by ROCK1 | |||
Modified residue | 382 | Phosphothreonine; by ROCK1 | |||
Modified residue | 383 | Phosphothreonine; by ROCK1 | |||
Modified residue | 385 | Phosphoserine; by CK2 | |||
Modified residue | 401 | Phosphothreonine | |||
Post-translational modification
Constitutively phosphorylated by CK2 under normal conditions. 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 (By similarity).
Phosphorylation by PLK3 promotes its stability and prevents its degradation by the proteasome. Phosphorylation by ROCK1 is essential for its stability and activity (By similarity).
Phosphorylated on Thr-319 and Thr-321 in the C2-type tensin domain following EGF stimulation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 (By similarity).
Phosphorylation by PLK3 promotes its stability and prevents its degradation by the proteasome. Phosphorylation by ROCK1 is essential for its stability and activity (By similarity).
Phosphorylated on Thr-319 and Thr-321 in the C2-type tensin domain following EGF stimulation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 (By similarity).
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 (By similarity).
Ubiquitinated by XIAP/BIRC4 (By similarity).
Ubiquitinated by XIAP/BIRC4 (By similarity).
Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, leading to its degradation.
ISGylated. ISGylation promotes PTEN degradation.
Keywords
- PTM
Proteomic databases
Interaction
Subunit
Monomer. The unphosphorylated form interacts with the second PDZ domain of MAGI2 (By similarity).
Interacts with MAGI2, MAGI3, MAST1 and MAST3, but neither with MAST4 nor with DLG5; interaction with MAGI2 increases protein stability (By similarity).
Interacts with NEDD4 (By similarity).
Interacts with NDFIP1 and NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes PTEN ubiquitination (By similarity).
Interacts (via C2 domain) with FRK (By similarity).
Interacts with USP7; the interaction is direct (By similarity).
Interacts with ROCK1. Interacts with XIAP/BIRC4 (By similarity).
Interacts with STK11; the interaction phosphorylates PTEN (By similarity).
Interacts with PPP1R16B (By similarity).
Interacts with NOP53; regulates PTEN phosphorylation and increases its stability (By similarity).
Interacts (via PDZ domain-binding motif) with DLG4; the interaction is induced by NMDA and is required for PTEN location at postsynaptic density (By similarity).
Interacts with the regulatory p85 subunit of the PI3K kinase complex and with Rho GTPase-activating protein DLC1; in resting cells, interacts (via C2 tensin-type domain) with p85 but, following growth factor stimulation, PTEN is phosphorylated which leads to weakened interaction with p85 and enhanced interaction (via C2 tensin-type domain) with DLC1 while p85 interaction with TNS3 increases (By similarity).
Interacts with MAGI2, MAGI3, MAST1 and MAST3, but neither with MAST4 nor with DLG5; interaction with MAGI2 increases protein stability (By similarity).
Interacts with NEDD4 (By similarity).
Interacts with NDFIP1 and NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes PTEN ubiquitination (By similarity).
Interacts (via C2 domain) with FRK (By similarity).
Interacts with USP7; the interaction is direct (By similarity).
Interacts with ROCK1. Interacts with XIAP/BIRC4 (By similarity).
Interacts with STK11; the interaction phosphorylates PTEN (By similarity).
Interacts with PPP1R16B (By similarity).
Interacts with NOP53; regulates PTEN phosphorylation and increases its stability (By similarity).
Interacts (via PDZ domain-binding motif) with DLG4; the interaction is induced by NMDA and is required for PTEN location at postsynaptic density (By similarity).
Interacts with the regulatory p85 subunit of the PI3K kinase complex and with Rho GTPase-activating protein DLC1; in resting cells, interacts (via C2 tensin-type domain) with p85 but, following growth factor stimulation, PTEN is phosphorylated which leads to weakened interaction with p85 and enhanced interaction (via C2 tensin-type domain) with DLC1 while p85 interaction with TNS3 increases (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias, motif.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 14-185 | Phosphatase tensin-type | |||
Domain | 190-350 | C2 tensin-type | |||
Region | 338-348 | Required for interaction with NOP53 | |||
Region | 352-403 | Disordered | |||
Compositional bias | 353-370 | Polar residues | |||
Compositional bias | 371-385 | Basic and acidic residues | |||
Motif | 401-403 | PDZ domain-binding | |||
Sequence similarities
Belongs to the PTEN phosphatase protein family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length403
- Mass (Da)47,166
- Last updated2004-02-16 v1
- Checksum75F97C3DD6802BA9
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I3Q1J4 | A0A8I3Q1J4_CANLF | PTEN | 369 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Compositional bias | 353-370 | Polar residues | |||
Compositional bias | 371-385 | Basic and acidic residues | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U92435 EMBL· GenBank· DDBJ | AAC48709.1 EMBL· GenBank· DDBJ | mRNA |