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P60483

- PTEN_CANFA

UniProt

P60483 - PTEN_CANFA

Protein

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

Gene

PTEN

Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 90 (01 Oct 2014)
      Sequence version 1 (16 Feb 2004)
      Previous versions | rss
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    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. 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 By similarity.By similarity

    Catalytic activityi

    Phosphatidylinositol 3,4,5-trisphosphate + H2O = phosphatidylinositol 4,5-bisphosphate + phosphate.
    [a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.
    Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

    Cofactori

    Magnesium.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei124 – 1241Phosphocysteine intermediatePROSITE-ProRule annotation

    GO - Molecular functioni

    1. inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity Source: UniProtKB
    2. magnesium ion binding Source: InterPro
    3. PDZ domain binding Source: UniProtKB
    4. phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity Source: UniProtKB
    5. phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity Source: UniProtKB
    6. phosphatidylinositol-3-phosphatase activity Source: UniProtKB
    7. protein serine/threonine phosphatase activity Source: UniProtKB
    8. protein tyrosine/serine/threonine phosphatase activity Source: InterPro
    9. protein tyrosine phosphatase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: UniProtKB
    2. cell migration Source: UniProtKB
    3. central nervous system development Source: UniProtKB
    4. heart development Source: UniProtKB
    5. inositol phosphate dephosphorylation Source: UniProtKB
    6. negative regulation of cell migration Source: UniProtKB
    7. negative regulation of cell proliferation Source: UniProtKB
    8. negative regulation of focal adhesion assembly Source: UniProtKB
    9. negative regulation of protein kinase B signaling Source: UniProtKB
    10. peptidyl-tyrosine dephosphorylation Source: GOC
    11. phosphatidylinositol dephosphorylation Source: UniProtKB
    12. protein dephosphorylation Source: UniProtKB
    13. protein kinase B signaling Source: UniProtKB
    14. regulation of neuron projection development Source: UniProtKB
    15. regulation of protein stability Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Biological processi

    Apoptosis, Lipid metabolism, Neurogenesis

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (EC:3.1.3.16, EC:3.1.3.48, EC:3.1.3.67)
    Alternative name(s):
    Mutated in multiple advanced cancers 1
    Phosphatase and tensin homolog
    Gene namesi
    Name:PTEN
    Synonyms:MMAC1
    OrganismiCanis familiaris (Dog) (Canis lupus familiaris)
    Taxonomic identifieri9615 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
    ProteomesiUP000002254: Unplaced

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. NucleusPML body By similarity
    Note: Monoubiquitinated form is nuclear By similarity. Nonubiquitinated form is cytoplasmic. Colocalized with PML and USP7 in PML nuclear bodies. XIAP/BIRC4 promotes its nuclear localization By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. PML body Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 403402Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENPRO_0000215903Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylthreonineBy similarity
    Cross-linki13 – 13Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki289 – 289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei336 – 3361Phosphotyrosine; by FRKBy similarity
    Modified residuei366 – 3661Phosphothreonine; by GSK3-beta and PLK3By similarity
    Modified residuei370 – 3701Phosphoserine; by CK2 and PLK3By similarity
    Modified residuei380 – 3801Phosphoserine; by ROCK1By similarity
    Modified residuei382 – 3821Phosphothreonine; by ROCK1By similarity
    Modified residuei383 – 3831Phosphothreonine; by ROCK1By similarity
    Modified residuei385 – 3851Phosphoserine; by CK2By similarity
    Modified residuei401 – 4011PhosphothreonineBy similarity

    Post-translational modificationi

    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. Phosphorylation by ROCK1 is essential for its stability and activity. Phosphorylation by PLK3 promotes its stability and prevents its degradation by the proteasome By similarity.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.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiP60483.

    Interactioni

    Subunit structurei

    Monomer. The unphosphorylated form interacts with the second PDZ domain of AIP1. 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. 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 By similarity. Interacts with XIAP/BIRC4 By similarity. Interacts with STK11; the interaction phosphorylates PTEN By similarity.By similarity

    Protein-protein interaction databases

    MINTiMINT-128368.

    Structurei

    3D structure databases

    ProteinModelPortaliP60483.
    SMRiP60483. Positions 14-351.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini14 – 185172Phosphatase tensin-typePROSITE-ProRule annotationAdd
    BLAST
    Domaini190 – 350161C2 tensin-typePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni401 – 4033PDZ domain-bindingBy similarity

    Sequence similaritiesi

    Contains 1 C2 tensin-type domain.PROSITE-ProRule annotation
    Contains 1 phosphatase tensin-type domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG2453.
    HOGENOMiHOG000008008.
    HOVERGENiHBG000239.
    InParanoidiP60483.
    KOiK01110.

    Family and domain databases

    Gene3Di3.90.190.10. 1 hit.
    InterProiIPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN.
    IPR000008. C2_dom.
    IPR000340. Dual-sp_phosphatase_cat-dom.
    IPR029021. Prot-tyrosine_phosphatase-like.
    IPR014020. Tensin_C2-dom.
    IPR029023. Tensin_lipid_phosphatase_dom.
    IPR016130. Tyr_Pase_AS.
    [Graphical view]
    PfamiPF00782. DSPc. 1 hit.
    PF10409. PTEN_C2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF038025. PTEN. 1 hit.
    SUPFAMiSSF49562. SSF49562. 1 hit.
    SSF52799. SSF52799. 1 hit.
    PROSITEiPS51182. C2_TENSIN. 1 hit.
    PS51181. PPASE_TENSIN. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P60483-1 [UniParc]FASTAAdd to Basket

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    MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI    50
    DDVVRFLDSK HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL 100
    IKPFCEDLDQ WLSEDDNHVA AIHCKAGKGR TGVMICAYLL HRGKFLKAQE 150
    ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY LLKNHLDYRP VALLFHKMMF 200
    ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY FEFPQPLPVC 250
    GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI 300
    DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT 350
    VEEPSNPEAS SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHTQI 400
    TKV 403
    Length:403
    Mass (Da):47,166
    Last modified:February 16, 2004 - v1
    Checksum:i75F97C3DD6802BA9
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U92435 mRNA. Translation: AAC48709.1.
    RefSeqiNP_001003192.1. NM_001003192.1.
    UniGeneiCfa.3695.

    Genome annotation databases

    GeneIDi403832.
    KEGGicfa:403832.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U92435 mRNA. Translation: AAC48709.1 .
    RefSeqi NP_001003192.1. NM_001003192.1.
    UniGenei Cfa.3695.

    3D structure databases

    ProteinModelPortali P60483.
    SMRi P60483. Positions 14-351.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-128368.

    Proteomic databases

    PRIDEi P60483.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 403832.
    KEGGi cfa:403832.

    Organism-specific databases

    CTDi 5728.

    Phylogenomic databases

    eggNOGi COG2453.
    HOGENOMi HOG000008008.
    HOVERGENi HBG000239.
    InParanoidi P60483.
    KOi K01110.

    Miscellaneous databases

    NextBioi 20817328.

    Family and domain databases

    Gene3Di 3.90.190.10. 1 hit.
    InterProi IPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN.
    IPR000008. C2_dom.
    IPR000340. Dual-sp_phosphatase_cat-dom.
    IPR029021. Prot-tyrosine_phosphatase-like.
    IPR014020. Tensin_C2-dom.
    IPR029023. Tensin_lipid_phosphatase_dom.
    IPR016130. Tyr_Pase_AS.
    [Graphical view ]
    Pfami PF00782. DSPc. 1 hit.
    PF10409. PTEN_C2. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF038025. PTEN. 1 hit.
    SUPFAMi SSF49562. SSF49562. 1 hit.
    SSF52799. SSF52799. 1 hit.
    PROSITEi PS51182. C2_TENSIN. 1 hit.
    PS51181. PPASE_TENSIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers."
      Steck P.A., Pershouse M.A., Jasser S.A., Lin H., Yung W.K.A., Ligon A.H., Langford L.A., Baumgard M.L., Hattier T., Davis T., Frye C., Hu R., Swedlund B., Teng D.H.-F., Tavtigian S.V.
      Nat. Genet. 15:356-363(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].

    Entry informationi

    Entry nameiPTEN_CANFA
    AccessioniPrimary (citable) accession number: P60483
    Secondary accession number(s): O00633, O02679
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 16, 2004
    Last sequence update: February 16, 2004
    Last modified: October 1, 2014
    This is version 90 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3