P60483 (PTEN_CANFA) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 81. History...
Names and origin
|Protein names||Recommended name:|
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Mutated in multiple advanced cancers 1
Phosphatase and tensin homolog
|Organism||Canis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]|
|Taxonomic identifier||9615 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis ›|
|Sequence length||403 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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 By similarity.
Phosphatidylinositol 3,4,5-trisphosphate + H2O = phosphatidylinositol 4,5-bisphosphate + phosphate.
A phosphoprotein + H2O = a protein + phosphate.
Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
Magnesium By similarity.
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.
Cytoplasm By similarity. Nucleus By similarity. Nucleus › PML 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.
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.
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.
Contains 1 C2 tensin-type domain.
Contains 1 phosphatase tensin-type domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 403||403||Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN||PRO_0000215903|
|Domain||14 – 185||172||Phosphatase tensin-type|
|Domain||190 – 350||161||C2 tensin-type|
|Region||401 – 403||3||PDZ domain-binding By similarity|
|Active site||124||1||Phosphocysteine intermediate Potential|
Amino acid modifications
|Modified residue||336||1||Phosphotyrosine; by FRK By similarity|
|Modified residue||366||1||Phosphothreonine; by GSK3-beta and PLK3 By similarity|
|Modified residue||370||1||Phosphoserine; by CK2 and PLK3 By similarity|
|Modified residue||380||1||Phosphoserine; by ROCK1 By similarity|
|Modified residue||382||1||Phosphothreonine; by ROCK1 By similarity|
|Modified residue||383||1||Phosphothreonine; by ROCK1 By similarity|
|Modified residue||385||1||Phosphoserine; by CK2 By similarity|
|Modified residue||401||1||Phosphothreonine By similarity|
|Cross-link||13||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Cross-link||289||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|||"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].
|U92435 mRNA. Translation: AAC48709.1.|
|RefSeq||NP_001003192.1. NM_001003192.1. |
3D structure databases
Protocols and materials databases
Genome annotation databases
Family and domain databases
|InterPro||IPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN. |
|Pfam||PF00782. DSPc. 1 hit. |
PF10409. PTEN_C2. 1 hit.
|PIRSF||PIRSF038025. PTEN. 1 hit. |
|SUPFAM||SSF49562. C2_CaLB. 1 hit. |
|PROSITE||PS51182. C2_TENSIN. 1 hit. |
PS51181. PPASE_TENSIN. 1 hit.
|Accession||Primary (citable) accession number: P60483|
Secondary accession number(s): O00633, O02679
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families