O54857 · PTEN_RAT

  • Protein
    Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
  • Gene
    Pten
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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. 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. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (By similarity).
Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. 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) (Ref.7). 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 Componentmyelin sheath adaxonal region
Cellular Componentneuron projection
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular ComponentPML body
Cellular Componentpostsynaptic cytosol
Cellular Componentpostsynaptic density
Cellular Componentpostsynaptic membrane
Cellular ComponentSchmidt-Lanterman incisure
Molecular Functionanaphase-promoting complex binding
Molecular Functionenzyme 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 Functionionotropic glutamate receptor binding
Molecular Functionmyosin phosphatase activity
Molecular FunctionPDZ domain binding
Molecular Functionphosphatidylinositol phosphate phosphatase activity
Molecular Functionphosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
Molecular Functionphosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
Molecular Functionphosphatidylinositol-3-phosphate phosphatase activity
Molecular Functionphosphoprotein phosphatase activity
Molecular Functionplatelet-derived growth factor receptor binding
Molecular Functionprotein kinase binding
Molecular Functionprotein serine/threonine phosphatase activity
Molecular Functionprotein tyrosine kinase binding
Molecular Functionprotein tyrosine phosphatase activity
Molecular Functionprotein tyrosine/serine/threonine phosphatase activity
Molecular Functionubiquitin-specific protease binding
Biological Processadult behavior
Biological Processangiogenesis
Biological Processapoptotic process
Biological ProcessB cell proliferation
Biological Processbrain morphogenesis
Biological Processcanonical Wnt signaling pathway
Biological Processcardiac muscle tissue development
Biological Processcell migration
Biological Processcell motility
Biological Processcell population proliferation
Biological Processcellular response to decreased oxygen levels
Biological Processcellular response to electrical stimulus
Biological Processcellular response to ethanol
Biological Processcellular response to hypoxia
Biological Processcellular response to insulin stimulus
Biological Processcellular response to insulin-like growth factor stimulus
Biological Processcellular response to leptin stimulus
Biological Processcellular response to nerve growth factor stimulus
Biological Processcellular response to sorbitol
Biological Processcentral nervous system development
Biological Processcentral nervous system myelin maintenance
Biological Processcentral nervous system neuron axonogenesis
Biological Processdendritic spine morphogenesis
Biological Processdentate gyrus development
Biological Processendothelial cell migration
Biological Processforebrain morphogenesis
Biological Processgene expression
Biological Processheart development
Biological Processinositol phosphate catabolic process
Biological Processlearning or memory
Biological Processlocomotor rhythm
Biological Processlocomotory behavior
Biological Processlong-term synaptic depression
Biological Processlong-term synaptic potentiation
Biological Processmale mating behavior
Biological Processmaternal behavior
Biological Processmemory
Biological Processmulticellular organismal response to stress
Biological Processmyelination
Biological Processnegative regulation of apoptotic process
Biological Processnegative regulation of axon regeneration
Biological Processnegative regulation of axonogenesis
Biological Processnegative regulation of B cell proliferation
Biological Processnegative regulation of cardiac muscle cell proliferation
Biological Processnegative regulation of cell cycle
Biological Processnegative regulation of cell cycle G1/S phase transition
Biological Processnegative regulation of cell migration
Biological Processnegative regulation of cell population proliferation
Biological Processnegative regulation of cell size
Biological Processnegative regulation of cellular senescence
Biological Processnegative regulation of defense response to bacterium
Biological Processnegative regulation of dendrite extension
Biological Processnegative regulation of dendritic spine morphogenesis
Biological Processnegative regulation of epithelial cell proliferation
Biological Processnegative regulation of epithelial to mesenchymal transition
Biological Processnegative regulation of excitatory postsynaptic potential
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 myelination
Biological Processnegative regulation of neuron projection development
Biological Processnegative regulation of organ growth
Biological Processnegative regulation of phagocytosis
Biological Processnegative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processnegative regulation of ribosome biogenesis
Biological Processnegative regulation of synaptic vesicle clustering
Biological Processnegative regulation of T cell proliferation
Biological Processnegative regulation of vascular associated smooth muscle cell proliferation
Biological Processnegative regulation of wound healing, spreading of epidermal cells
Biological Processneuron projection development
Biological Processneuron-neuron synaptic transmission
Biological Processphosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processphosphatidylinositol dephosphorylation
Biological Processplatelet-derived growth factor receptor signaling pathway
Biological Processpositive regulation of apoptotic process
Biological Processpositive regulation of apoptotic signaling pathway
Biological Processpositive regulation of cardiac muscle cell apoptotic process
Biological Processpositive regulation of cell population proliferation
Biological Processpositive regulation of ERK1 and ERK2 cascade
Biological Processpositive regulation of excitatory postsynaptic potential
Biological Processpositive regulation of gene expression
Biological Processpositive regulation of interleukin-6 production
Biological Processpositive regulation of neuron differentiation
Biological Processpositive regulation of tumor necrosis factor production
Biological Processpositive regulation of ubiquitin-dependent protein catabolic process
Biological Processpostsynaptic density assembly
Biological Processprepulse inhibition
Biological Processpresynaptic membrane assembly
Biological Processprostate gland growth
Biological Processprotein stabilization
Biological Processregulation of axon regeneration
Biological Processregulation of B cell apoptotic process
Biological Processregulation of cell cycle
Biological Processregulation of cellular component size
Biological Processregulation of cellular localization
Biological Processregulation of Fc receptor mediated stimulatory signaling pathway
Biological Processregulation of macrophage apoptotic process
Biological Processregulation of neuron projection development
Biological Processregulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processregulation of protein stability
Biological Processregulation of synaptic transmission, GABAergic
Biological Processresponse to activity
Biological Processresponse to arsenic-containing substance
Biological Processresponse to ATP
Biological Processresponse to estradiol
Biological Processresponse to ethanol
Biological Processresponse to glucose
Biological Processresponse to nutrient
Biological Processresponse to organic cyclic compound
Biological Processresponse to xenobiotic stimulus
Biological Processresponse to zinc ion
Biological Processrhythmic synaptic transmission
Biological Processsocial behavior
Biological Processspindle assembly involved in female meiosis
Biological Processsynapse assembly
Biological Processsynapse maturation
Biological ProcessT cell proliferation

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)
    • Phosphatase and tensin homolog

Gene names

    • Name
      Pten
    • ORF names
      rCG_47874

Organism names

  • Taxonomic identifier
  • Organism
  • Strains
    • Sprague-Dawley
    • Brown Norway
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    O54857

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Nucleus
Nucleus, PML body
Synapse, synaptosome
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 (PubMed:20628354).

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis124Dominant negative. Abolishes depression of AMPAR-mediated transmission. Abolishes NMDA receptor-dependent long-lasting depression.
Mutagenesis129Abolishes NMDA receptor-dependent long-lasting depression.
Mutagenesis400-403Loss of interaction with DLG4.

PTM/Processing

Features

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

TypeIDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylthreonine
ChainPRO_00004564742-403Phosphatidylinositol 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
Modified residue366Phosphothreonine
Modified residue370Phosphoserine
Modified residue380Phosphoserine
Modified residue382Phosphothreonine
Modified residue383Phosphothreonine
Modified residue385Phosphoserine
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

PTM databases

Expression

Gene expression 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 (PubMed:20628354).
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).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY O54857Dbn1 Q072663EBI-8074312, EBI-918187
BINARY O54857Dlg4 P310165EBI-8074312, EBI-375655

Protein-protein interaction databases

Family & Domains

Features

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

TypeIDPosition(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)
    47,118
  • Last updated
    1998-06-01 v1
  • Checksum
    243BFE35FE209FE5
MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSYLLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKLMYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEASSSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHSQITKV

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8I6AU71A0A8I6AU71_RATPten414

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
AF017185
EMBL· GenBank· DDBJ
AAB96620.1
EMBL· GenBank· DDBJ
mRNA
AF455569
EMBL· GenBank· DDBJ
AAO31948.1
EMBL· GenBank· DDBJ
mRNA
CH473953
EMBL· GenBank· DDBJ
EDM13141.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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