Reviewed,
UniProtKB/Swiss-Prot P60483 (PTEN_CANFA)
Last modified
January 19, 2010.
Version 53.
History...
Clusters with 100%,
90%,
50% identity |
Documents (1) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN EC=3.1.3.67 EC=3.1.3.16 EC=3.1.3.48 Alternative name(s): Phosphatase and tensin homolog Mutated in multiple advanced cancers 1 | ||||
| Gene names |
| ||||
| Organism | Canis familiaris (Dog) | ||||
| Taxonomic identifier | 9615 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis |
Protein attributes
| Sequence length | 403 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at transcript level. |
General annotation (Comments)
| Function | 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. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue By similarity. |
| Catalytic activity | Phosphatidylinositol 3,4,5-trisphosphate + H2O = phosphatidylinositol 4,5-bisphosphate + phosphate. A phosphoprotein + H2O = a protein + phosphate. Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. |
| Cofactor | Magnesium By similarity. |
| Subunit structure | 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 (via C2 domain) with FRK By similarity. |
| Subcellular location | Cytoplasm By similarity. |
| Post-translational modification | 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. |
| Sequence similarities | Contains 1 C2 tensin-type domain. Contains 1 phosphatase tensin-type domain. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 403 | 403 | Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN | PRO_0000215903 | |||||
Regions | |||||||||
| Domain | 14 – 185 | 172 | Phosphatase tensin-type | ||||||
| Domain | 190 – 350 | 161 | C2 tensin-type | ||||||
| Region | 401 – 403 | 3 | PDZ domain-binding By similarity | ||||||
Sites | |||||||||
| Active site | 124 | 1 | Phosphocysteine intermediate Potential | ||||||
Amino acid modifications | |||||||||
| Modified residue | 6 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 336 | 1 | Phosphotyrosine; by FRK By similarity | ||||||
| Modified residue | 366 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 370 | 1 | Phosphoserine; by CK2 By similarity | ||||||
| Modified residue | 385 | 1 | Phosphoserine; by CK2 By similarity | ||||||
| Modified residue | 401 | 1 | Phosphothreonine By similarity | ||||||
Sequences
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References
| [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: 9090379] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U92435 mRNA. Translation: AAC48709.1. |
| RefSeq | NP_001003192.1. |
| UniGene | Cfa.3695 |
3D structure databases | |
| SMR | P60483. Positions 14-351. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | P60483. |
Genome annotation databases | |
| Ensembl | ENSCAFT00000024821; ENSCAFP00000023027; ENSCAFG00000015670; Canis familiaris. [Genome view] |
| GeneID | 403832. |
| KEGG | cfa:403832. |
Organism-specific databases | |
| CTD | 403832. |
Phylogenomic databases | |
| eggNOG | maNOG08348. |
| HOVERGEN | P60483. |
| InParanoid | P60483. |
| OrthoDB | EOG908QTZ. |
Enzyme and pathway databases | |
| BRENDA | 3.1.3.67. 463. |
Family and domain databases | |
| InterPro | IPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR000340. Dual-sp_phosphatase_cat-dom. IPR014019. Phosphatase_tensin-typ. IPR014020. Tensin_phosphatase_C2-dom. IPR016130. Tyr_Pase_AS. [Graphical view] |
| Pfam | PF00782. DSPc. 1 hit. PF10409. PTEN_C2. 1 hit. [Graphical view] |
| PIRSF | PIRSF038025. PTEN. 1 hit. |
| PROSITE | PS51182. C2_TENSIN. 1 hit. PS51181. PPASE_TENSIN. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Entry information
| Entry name | PTEN_CANFA | ||||||||
| Accession | Primary (citable) accession number: P60483 Secondary accession number(s): O00633, O02679 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||

Clusters with


