P60483 · PTEN_CANLF

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).

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) + phosphate
    This reaction proceeds in the forward direction.
    EC:3.1.3.67 (UniProtKB | ENZYME | Rhea)
  • O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate
    This reaction proceeds in the forward direction.
    EC:3.1.3.16 (UniProtKB | ENZYME | Rhea)
  • O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate
    This reaction proceeds in the forward direction.
    EC:3.1.3.16 (UniProtKB | ENZYME | Rhea)
  • O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate
    This reaction proceeds in the forward direction.
    EC:3.1.3.48 (UniProtKB | ENZYME | Rhea)
  • 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) + phosphate
    This 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) + phosphate
    This reaction proceeds in the forward direction.
  • 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + H2O = 1D-myo-inositol 1,4,5,6-tetrakisphosphate + phosphate
    This reaction proceeds in the forward direction.
  • 1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + phosphate
    This reaction proceeds in the forward direction.

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site124Phosphocysteine intermediate

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentcell projection
Cellular Componentcytoplasm
Cellular Componentcytoplasmic side of plasma membrane
Cellular Componentcytosol
Cellular Componentdendritic spine
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular ComponentPML body
Cellular Componentpostsynaptic density
Molecular Functionanaphase-promoting complex binding
Molecular Functionidentical protein binding
Molecular Functioninositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity
Molecular Functioninositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
Molecular Functionmyosin phosphatase activity
Molecular FunctionPDZ domain binding
Molecular Functionphosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
Molecular Functionphosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
Molecular Functionphosphatidylinositol-3-phosphate phosphatase activity
Molecular Functionprotein serine/threonine phosphatase activity
Molecular Functionprotein tyrosine phosphatase activity
Molecular Functionubiquitin-specific protease binding
Biological Processapoptotic process
Biological Processcanonical Wnt signaling pathway
Biological Processcell migration
Biological Processcell motility
Biological Processcellular response to electrical stimulus
Biological Processcentral nervous system development
Biological Processheart development
Biological Processnegative regulation of cell migration
Biological Processnegative regulation of cell population proliferation
Biological Processnegative regulation of cyclin-dependent protein serine/threonine kinase activity
Biological Processnegative regulation of epithelial to mesenchymal transition
Biological Processnegative regulation of focal adhesion assembly
Biological Processnegative regulation of G1/S transition of mitotic cell cycle
Biological Processnegative regulation of keratinocyte migration
Biological Processnegative regulation of osteoblast differentiation
Biological Processnegative regulation of peptidyl-serine phosphorylation
Biological Processnegative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processnegative regulation of vascular associated smooth muscle cell proliferation
Biological Processnegative regulation of wound healing, spreading of epidermal cells
Biological Processphosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processphosphatidylinositol dephosphorylation
Biological Processpositive regulation of DNA-binding transcription factor activity
Biological Processpositive regulation of ubiquitin protein ligase activity
Biological Processpositive regulation of ubiquitin-dependent protein catabolic process
Biological Processprotein dephosphorylation
Biological Processprotein stabilization
Biological Processregulation of neuron projection development
Biological Processregulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processregulation of protein stability
Biological Processspindle assembly involved in female meiosis

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
  • EC number
  • Alternative names
    • Inositol polyphosphate 3-phosphatase
      (EC:3.1.3.-
      ) . EC:3.1.3.- (UniProtKB | ENZYME | Rhea)
    • Mutated in multiple advanced cancers 1
    • Phosphatase and tensin homolog

Gene names

    • Name
      PTEN
    • Synonyms
      MMAC1

Organism names

Accessions

  • Primary accession
    P60483
  • Secondary accessions
    • O00633
    • O02679

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Nucleus
Nucleus, PML body
Postsynaptic density
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).

Keywords

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.

Go to variant viewer

Keywords

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, cross-link.

Type
IDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylthreonine
ChainPRO_00002159032-403Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Cross-link13Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue294Phosphoserine
Modified residue319Phosphothreonine
Modified residue321Phosphothreonine
Modified residue336Phosphotyrosine; by FRK
Modified residue366Phosphothreonine; by GSK3-beta and PLK3
Modified residue370Phosphoserine; by CK2 and PLK3
Modified residue380Phosphoserine; by ROCK1
Modified residue382Phosphothreonine; by ROCK1
Modified residue383Phosphothreonine; by ROCK1
Modified residue385Phosphoserine; by CK2
Modified residue401Phosphothreonine

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).
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 the DCX(DCAF13) E3 ubiquitin ligase complex, leading to its degradation.
ISGylated. ISGylation promotes PTEN degradation.

Keywords

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).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for domain, region, compositional bias, motif.

Type
IDPosition(s)Description
Domain14-185Phosphatase tensin-type
Domain190-350C2 tensin-type
Region338-348Required for interaction with NOP53
Region352-403Disordered
Compositional bias353-370Polar residues
Compositional bias371-385Basic and acidic residues
Motif401-403PDZ domain-binding

Sequence similarities

Belongs to the PTEN phosphatase protein family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    403
  • Mass (Da)
    47,166
  • Last updated
    2004-02-16 v1
  • Checksum
    75F97C3DD6802BA9
MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSYLLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEASSSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8I3Q1J4A0A8I3Q1J4_CANLFPTEN369

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias353-370Polar residues
Compositional bias371-385Basic and acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U92435
EMBL· GenBank· DDBJ
AAC48709.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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