UniProt Accession

 PTEN_MOUSE; O08586; Q3UFB0; Q542G1 

Genbank Protein ID

 U92437; AK076980; AK088717; AK148736; BC021445 

Genbank Nucleotide ID

 AAC53118.1; BAC36545.1; BAC40525.1; BAE28651.1; AAH21445.1 

Protein Name

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

Protein Synonyms/Alias

 Mutated in multiple advanced cancers 1; Phosphatase and tensin homolog 

Gene Name

 Pten 

Gene Synonyms/Alias

 Mmac1 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
6	**MTAIIKEIVSRNK	acetylation	[1]
66	SKHKNHYKIYNLCAE	ubiquitination	[2]
80	ERHYDTAKFNCRVAQ	ubiquitination	[2]

Reference

 [1] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [2] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 14 185 Phosphatase tensin-type.
 DOMAIN 190 350 C2 tensin-type.
 REGION 401 403 PDZ domain-binding (By similarity).
 ACT_SITE 124 124 Phosphocysteine intermediate (Potential).
 MOD_RES 336 336 Phosphotyrosine; by FRK (By similarity).
 MOD_RES 366 366 Phosphothreonine; by GSK3-beta and PLK3.
 MOD_RES 370 370 Phosphoserine; by CK2 and PLK3.
 MOD_RES 380 380 Phosphoserine; by ROCK1.
 MOD_RES 382 382 Phosphothreonine; by ROCK1.
 MOD_RES 383 383 Phosphothreonine; by ROCK1.
 MOD_RES 385 385 Phosphoserine; by CK2 (By similarity).
 MOD_RES 401 401 Phosphothreonine (By similarity).
 CROSSLNK 13 13 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 289 289 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 Apoptosis; Complete proteome; Cytoplasm; Hydrolase; Isopeptide bond; Lipid metabolism; Neurogenesis; Nucleus; Phosphoprotein; Protein phosphatase; Reference proteome; Tumor suppressor; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 403 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; ISS:UniProtKB.
 GO:0009898; C:internal side of plasma membrane; IEA:Compara.
 GO:0035749; C:myelin sheath adaxonal region; IDA:BHF-UCL.
 GO:0043005; C:neuron projection; IDA:BHF-UCL.
 GO:0005634; C:nucleus; IDA:MGI.
 GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
 GO:0043220; C:Schmidt-Lanterman incisure; IDA:BHF-UCL.
 GO:0051717; F:inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity; ISS:UniProtKB.
 GO:0000287; F:magnesium ion binding; IEA:InterPro.
 GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
 GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity; ISS:UniProtKB.
 GO:0051800; F:phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity; ISS:UniProtKB.
 GO:0004438; F:phosphatidylinositol-3-phosphatase activity; ISS:UniProtKB.
 GO:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB.
 GO:0004725; F:protein tyrosine phosphatase activity; ISS:UniProtKB.
 GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IEA:InterPro.
 GO:0007092; P:activation of mitotic anaphase-promoting complex activity; IMP:BHF-UCL.
 GO:0001525; P:angiogenesis; IMP:MGI.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0060070; P:canonical Wnt receptor signaling pathway; IEA:Compara.
 GO:0048738; P:cardiac muscle tissue development; IMP:MGI.
 GO:0032286; P:central nervous system myelin maintenance; IMP:BHF-UCL.
 GO:0021955; P:central nervous system neuron axonogenesis; IMP:BHF-UCL.
 GO:0060997; P:dendritic spine morphogenesis; IMP:BHF-UCL.
 GO:0021542; P:dentate gyrus development; IMP:BHF-UCL.
 GO:0043542; P:endothelial cell migration; IMP:MGI.
 GO:0048853; P:forebrain morphogenesis; IMP:BHF-UCL.
 GO:0006917; P:induction of apoptosis; IMP:MGI.
 GO:0046855; P:inositol phosphate dephosphorylation; ISS:UniProtKB.
 GO:0007611; P:learning or memory; IMP:BHF-UCL.
 GO:0045475; P:locomotor rhythm; IMP:BHF-UCL.
 GO:0060291; P:long-term synaptic potentiation; IMP:BHF-UCL.
 GO:0060179; P:male mating behavior; IMP:BHF-UCL.
 GO:0042711; P:maternal behavior; IMP:BHF-UCL.
 GO:0033555; P:multicellular organismal response to stress; IMP:BHF-UCL.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0050771; P:negative regulation of axonogenesis; IMP:BHF-UCL.
 GO:0090344; P:negative regulation of cell aging; IMP:BHF-UCL.
 GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
 GO:0045792; P:negative regulation of cell size; IMP:BHF-UCL.
 GO:0031658; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IEA:Compara.
 GO:0061002; P:negative regulation of dendritic spine morphogenesis; IMP:BHF-UCL.
 GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
 GO:0090394; P:negative regulation of excitatory postsynaptic membrane potential; IMP:BHF-UCL.
 GO:0051895; P:negative regulation of focal adhesion assembly; ISS:UniProtKB.
 GO:0031642; P:negative regulation of myelination; IMP:MGI.
 GO:0046621; P:negative regulation of organ growth; IMP:BHF-UCL.
 GO:0051898; P:negative regulation of protein kinase B signaling cascade; IMP:UniProtKB.
 GO:0090071; P:negative regulation of ribosome biogenesis; IMP:BHF-UCL.
 GO:2000808; P:negative regulation of synaptic vesicle clustering; IMP:BHF-UCL.
 GO:0007270; P:neuron-neuron synaptic transmission; IMP:BHF-UCL.
 GO:0046856; P:phosphatidylinositol dephosphorylation; ISS:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL.
 GO:2000463; P:positive regulation of excitatory postsynaptic membrane potential; IMP:BHF-UCL.
 GO:2000060; P:positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IEA:Compara.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IEA:Compara.
 GO:0097107; P:postsynaptic density assembly; IMP:BHF-UCL.
 GO:0060134; P:prepulse inhibition; IMP:BHF-UCL.
 GO:0097105; P:presynaptic membrane assembly; IMP:BHF-UCL.
 GO:0060736; P:prostate gland growth; IMP:MGI.
 GO:0043491; P:protein kinase B signaling cascade; IMP:UniProtKB.
 GO:0050821; P:protein stabilization; IEA:Compara.
 GO:0002902; P:regulation of B cell apoptotic process; IMP:MGI.
 GO:0033032; P:regulation of myeloid cell apoptotic process; IMP:MGI.
 GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
 GO:0060024; P:rhythmic synaptic transmission; IMP:BHF-UCL.
 GO:0035176; P:social behavior; IMP:BHF-UCL.
 GO:0060074; P:synapse maturation; IMP:BHF-UCL. 

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. 

Pfam

 PF00782; DSPc
 PF10409; PTEN_C2 

SMART

  

PROSITE

 PS51182; C2_TENSIN
 PS51181; PPASE_TENSIN 

PRINTS