O08586 (PTEN_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 137. 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||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||403 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement By similarity. 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. Ref.4 Ref.7
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.
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. Interacts with XIAP/BIRC4. Ref.6 Ref.8
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. Ref.6
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 By similarity. Phosphorylation by PLK3 promotes its stability and prevents its degradation by the proteasome. Phosphorylation by ROCK1 is essential for its stability and activity. Ref.8 Ref.9
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. Ref.6
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|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 403||402||Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN||PRO_0000215905|
|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||2||1||N-acetylthreonine By similarity|
|Modified residue||336||1||Phosphotyrosine; by FRK By similarity|
|Modified residue||366||1||Phosphothreonine; by GSK3-beta and PLK3 Ref.9|
|Modified residue||370||1||Phosphoserine; by CK2 and PLK3 Ref.9|
|Modified residue||380||1||Phosphoserine; by ROCK1 Ref.8|
|Modified residue||382||1||Phosphothreonine; by ROCK1 Ref.8|
|Modified residue||383||1||Phosphothreonine; by ROCK1 Ref.8|
|Modified residue||385||1||Phosphoserine; alternate Ref.5|
|Modified residue||385||1||Phosphoserine; by CK2; alternate 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|
|Sequence conflict||50||1||Missing in BAE28651. Ref.2|
|||"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].
|||"The transcriptional landscape of the mammalian genome."|
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Sympathetic ganglion, Testis and Thymus.
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Czech II.
Tissue: Mammary gland.
|||"PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway."|
Sun H., Lesche R., Li D.M., Liliental J., Zhang H., Gao J., Gavrilova N., Mueller B., Liu X., Wu H.
Proc. Natl. Acad. Sci. U.S.A. 96:6199-6204(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Large-scale phosphorylation analysis of mouse liver."|
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, MASS SPECTROMETRY.
|||"X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization."|
Van Themsche C., Leblanc V., Parent S., Asselin E.
J. Biol. Chem. 284:20462-20466(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY XIAP/BIRC4, SUBCELLULAR LOCATION, INTERACTION WITH XIAP/BIRC4.
|||"DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212."|
Kim J.Y., Duan X., Liu C.Y., Jang M.H., Guo J.U., Pow-anpongkul N., Kang E., Song H., Ming G.L.
Neuron 63:761-773(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"ROCK1 functions as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability."|
Vemula S., Shi J., Hanneman P., Wei L., Kapur R.
Blood 115:1785-1796(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-380; THR-382 AND THR-383, INTERACTION WITH ROCK1.
|||"Regulation of PTEN stability and activity by Plk3."|
Xu D., Yao Y., Jiang X., Lu L., Dai W.
J. Biol. Chem. 285:39935-39942(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-366 AND SER-370.
|+||Additional computationally mapped references.|
|U92437 mRNA. Translation: AAC53118.1.|
AK076980 mRNA. Translation: BAC36545.1.
AK088717 mRNA. Translation: BAC40525.1.
AK148736 mRNA. Translation: BAE28651.1.
BC021445 mRNA. Translation: AAH21445.1.
|RefSeq||NP_032986.1. NM_008960.2. |
3D structure databases
|SMR||O08586. Positions 14-351. |
Protein-protein interaction databases
|BioGrid||202449. 6 interactions.|
|IntAct||O08586. 8 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000013807; ENSMUSP00000013807; ENSMUSG00000013663. |
|UCSC||uc008hfr.1. mouse. |
|MGI||MGI:109583. Pten. |
Gene expression 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. SSF49562. 1 hit. |
|PROSITE||PS51182. C2_TENSIN. 1 hit. |
PS51181. PPASE_TENSIN. 1 hit.
|ChiTaRS||PTEN. mouse. |
|Accession||Primary (citable) accession number: O08586|
Secondary accession number(s): Q3UFB0, Q542G1
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|