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P60483

- PTEN_CANFA

UniProt

P60483 - PTEN_CANFA

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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

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
Complete GO annotation...

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. nucleus Source: UniProtKB-KW
Complete GO annotation...

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

« Hide

        10         20         30         40         50
MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI
60 70 80 90 100
DDVVRFLDSK HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL
110 120 130 140 150
IKPFCEDLDQ WLSEDDNHVA AIHCKAGKGR TGVMICAYLL HRGKFLKAQE
160 170 180 190 200
ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY LLKNHLDYRP VALLFHKMMF
210 220 230 240 250
ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY FEFPQPLPVC
260 270 280 290 300
GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI
310 320 330 340 350
DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT
360 370 380 390 400
VEEPSNPEAS SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHTQI

TKV
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 29, 2014
This is version 91 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