Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN


NamePhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Synonyms3.1.3.16 MMAC1 Mutated in multiple advanced cancers 1 Phosphatase and tensin homolog TEP1
Gene NamePTEN
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009278|Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSK
HKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVA
AIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY
LLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMY
FEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEI
DSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEAS
SSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV
Number of residues403
Molecular Weight47165.92
Theoretical pINone
GO Classification
Functions
    anaphase-promoting complex binding
    lipid binding
    phosphoprotein phosphatase activity
    protein tyrosine phosphatase activity
    phosphatidylinositol-3-phosphatase activity
    inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
    magnesium ion binding
    phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
    enzyme binding
    phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
    protein tyrosine/serine/threonine phosphatase activity
    identical protein binding
    protein serine/threonine phosphatase activity
    PDZ domain binding
Processes
    negative regulation of excitatory postsynaptic potential
    apoptotic process
    inositol phosphate dephosphorylation
    cardiac muscle tissue development
    negative regulation of cell size
    response to drug
    negative regulation of ribosome biogenesis
    protein kinase B signaling
    transcription initiation from RNA polymerase II promoter
    phospholipid metabolic process
    multicellular organismal response to stress
    synapse maturation
    fibroblast growth factor receptor signaling pathway
    inositol phosphate metabolic process
    endothelial cell migration
    neuron-neuron synaptic transmission
    negative regulation of synaptic vesicle clustering
    angiogenesis
    response to ethanol
    negative regulation of organ growth
    negative regulation of phosphatidylinositol 3-kinase signaling
    heart development
    canonical Wnt signaling pathway
    adult behavior
    negative regulation of axonogenesis
    postsynaptic density assembly
    long term synaptic depression
    response to zinc ion
    negative regulation of epithelial cell proliferation
    negative regulation of cell aging
    central nervous system neuron axonogenesis
    negative regulation of apoptotic process
    central nervous system development
    locomotor rhythm
    regulation of cellular component size
    maternal behavior
    cell migration
    T cell receptor signaling pathway
    male mating behavior
    activation of APC-Cdc20 complex activity
    forebrain morphogenesis
    negative regulation of cell proliferation
    positive regulation of sequence-specific DNA binding transcription factor activity
    rhythmic synaptic transmission
    phosphatidylinositol dephosphorylation
    social behavior
    epidermal growth factor receptor signaling pathway
    protein dephosphorylation
    positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
    protein stabilization
    neurotrophin TRK receptor signaling pathway
    prostate gland growth
    synapse assembly
    dendritic spine morphogenesis
    phosphatidylinositol-mediated signaling
    innate immune response
    aging
    regulation of protein stability
    phosphatidylinositol biosynthetic process
    positive regulation of cell proliferation
    positive regulation of ERK1 and ERK2 cascade
    positive regulation of excitatory postsynaptic potential
    regulation of cyclin-dependent protein serine/threonine kinase activity
    dentate gyrus development
    platelet-derived growth factor receptor signaling pathway
    positive regulation of apoptotic signaling pathway
    negative regulation of myelination
    locomotory behavior
    response to ATP
    cellular response to hypoxia
    learning or memory
    regulation of neuron projection development
    cell proliferation
    regulation of myeloid cell apoptotic process
    Fc-epsilon receptor signaling pathway
    negative regulation of phagocytosis
    central nervous system myelin maintenance
    response to glucose
    memory
    long-term synaptic potentiation
    brain morphogenesis
    regulation of B cell apoptotic process
    negative regulation of protein phosphorylation
    response to arsenic-containing substance
    negative regulation of protein kinase B signaling
    negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle
    negative regulation of cell migration
    negative regulation of focal adhesion assembly
    presynaptic membrane assembly
    gene expression
    negative regulation of G1/S transition of mitotic cell cycle
    response to estradiol
    peptidyl-tyrosine dephosphorylation
    regulation of synaptic transmission, GABAergic
    negative regulation of dendritic spine morphogenesis
    small molecule metabolic process
    response to nutrient
    prepulse inhibition
    regulation of axon regeneration
Components
    cytosol
    cytoplasmic side of plasma membrane
    plasma membrane
    nucleoplasm
    PML body
    cell projection
    cytoplasm
    dendritic spine
    myelin sheath adaxonal region
    mitochondrion
    Schmidt-Lanterman incisure
    extracellular region
    neuron projection
    postsynaptic membrane
    apical plasma membrane
    nucleus
General FunctionProtein tyrosine/serine/threonine phosphatase activity
Specific FunctionTumor 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. 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.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.
Transmembrane Regions
GenBank Protein ID
UniProtKB IDP60484
UniProtKB Entry NamePTEN_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0021732|Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)
ATGACAGCCATCATCAAAGAGATCGTTAGCAGAAACAAAAGGAGATATCAAGAGGATGGA
TTCGACTTAGACTTGACCTATATTTATCCAAACATTATTGCTATGGGATTTCCTGCAGAA
AGACTTGAAGGCGTATACAGGAACAATATTGATGATGTAGTAAGGTTTTTGGATTCAAAG
CATAAAAACCATTACAAGATATACAATCTTTGTGCTGAAAGACATTATGACACCGCCAAA
TTTAATTGCAGAGTTGCACAATATCCTTTTGAAGACCATAACCCACCACAGCTAGAACTT
ATCAAACCCTTTTGTGAAGATCTTGACCAATGGCTAAGTGAAGATGACAATCATGTTGCA
GCAATTCACTGTAAAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCATATTTATTA
CATCGGGGCAAATTTTTAAAGGCACAAGAGGCCCTAGATTTCTATGGGGAAGTAAGGACC
AGAGACAAAAAGGGAGTAACTATTCCCAGTCAGAGGCGCTATGTGTATTATTATAGCTAC
CTGTTAAAGAATCATCTGGATTATAGACCAGTGGCACTGTTGTTTCACAAGATGATGTTT
GAAACTATTCCAATGTTCAGTGGCGGAACTTGCAATCCTCAGTTTGTGGTCTGCCAGCTA
AAGGTGAAGATATATTCCTCCAATTCAGGACCCACACGACGGGAAGACAAGTTCATGTAC
TTTGAGTTCCCTCAGCCGTTACCTGTGTGTGGTGATATCAAAGTAGAGTTCTTCCACAAA
CAGAACAAGATGCTAAAAAAGGACAAAATGTTTCACTTTTGGGTAAATACATTCTTCATA
CCAGGACCAGAGGAAACCTCAGAAAAAGTAGAAAATGGAAGTCTATGTGATCAAGAAATC
GATAGCATTTGCAGTATAGAGCGTGCAGATAATGACAAGGAATATCTAGTACTTACTTTA
ACAAAAAATGATCTTGACAAAGCAAATAAAGACAAAGCCAACCGATACTTTTCTCCAAAT
TTTAAGGTGAAGCTGTACTTCACAAAAACAGTAGAGGAGCCGTCAAATCCAGAGGCTAGC
AGTTCAACTTCTGTAACACCAGATGTTAGTGACAATGAACCTGATCATTATAGATATTCT
GACACCACTGACTCTGATCCAGAGAATGAACCTTTTGATGAAGATCAGCATACACAAATT
ACAAAAGTCTGA
GenBank Gene ID
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:9588
Chromosome Location10
LocusNone
References
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