ID PTEN_RAT Reviewed; 403 AA. AC O54857; DT 12-OCT-2022, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 27-MAR-2024, entry version 181. DE RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN {ECO:0000250|UniProtKB:P60484}; DE EC=3.1.3.16 {ECO:0000250|UniProtKB:P60484}; DE EC=3.1.3.48 {ECO:0000250|UniProtKB:P60484}; DE EC=3.1.3.67 {ECO:0000250|UniProtKB:P60484}; DE AltName: Full=Inositol polyphosphate 3-phosphatase {ECO:0000250|UniProtKB:P60484}; DE EC=3.1.3.- {ECO:0000250|UniProtKB:P60484}; DE AltName: Full=Phosphatase and tensin homolog {ECO:0000255|PIRNR:PIRNR038025}; GN Name=Pten {ECO:0000312|RGD:61995}; GN ORFNames=rCG_47874 {ECO:0000312|EMBL:EDM13141.1}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116 {ECO:0000312|EMBL:AAB96620.1}; RN [1] {ECO:0000312|EMBL:AAB96620.1} RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAB96620.1}; RC TISSUE=Brain {ECO:0000312|EMBL:AAB96620.1}; RA Roz L., Finocchiaro G.; RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000312|EMBL:AAO31948.1} RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Brown Norway {ECO:0000312|EMBL:AAO31948.1}; RX PubMed=12461751; DOI=10.1002/gcc.10143; RA Sjoling A., Samuelson E., Adamovic T., Behboudi A., Rohme D., Levan G.; RT "Recurrent allelic imbalance at the rat Pten locus in DMBA-induced RT fibrosarcomas."; RL Genes Chromosomes Cancer 36:70-79(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DLG4, AND MUTAGENESIS OF RP CYS-124; GLY-129 AND 400-ILE--VAL-403. RX PubMed=20628354; DOI=10.1038/emboj.2010.160; RA Jurado S., Benoist M., Lario A., Knafo S., Petrok C.N., Esteban J.A.; RT "PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent RT long-term depression."; RL EMBO J. 29:2827-2840(2010). RN [6] {ECO:0007744|PubMed:22673903} RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [7] {ECO:0007744|PDB:2K20} RP STRUCTURE BY NMR OF 393-403. RA Feng W., Wu H., Chan L., Zhang M.; RT "Solution structure of Par-3 PDZ3 in complex with PTEN peptide."; RL Submitted (MAR-2008) to the PDB data bank. CC -!- FUNCTION: Dual-specificity protein phosphatase, dephosphorylating CC tyrosine-, serine- and threonine-phosphorylated proteins. Also CC functions as a lipid phosphatase, removing the phosphate in the D3 CC position of the inositol ring of PtdIns(3,4,5)P3/phosphatidylinositol CC 3,4,5-trisphosphate, PtdIns(3,4)P2/phosphatidylinositol 3,4-diphosphate CC and PtdIns3P/phosphatidylinositol 3-phosphate with a preference for CC PtdIns(3,4,5)P3. Furthermore, this enzyme can also act as a cytosolic CC inositol 3-phosphatase acting on Ins(1,3,4,5,6)P5/inositol 1,3,4,5,6 CC pentakisphosphate and possibly Ins(1,3,4,5)P4/1D-myo-inositol 1,3,4,5- CC tetrakisphosphate. Antagonizes the PI3K-AKT/PKB signaling pathway by CC dephosphorylating phosphoinositides and thereby modulating cell cycle CC progression and cell survival. The unphosphorylated form cooperates CC with MAGI2 to suppress AKT1 activation. In motile cells, suppresses the CC formation of lateral pseudopods and thereby promotes cell polarization CC and directed movement (By similarity). Dephosphorylates tyrosine- CC phosphorylated focal adhesion kinase and inhibits cell migration and CC integrin-mediated cell spreading and focal adhesion formation. Required CC for growth factor-induced epithelial cell migration; growth factor CC stimulation induces PTEN phosphorylation which changes its binding CC preference from the p85 regulatory subunit of the PI3K kinase complex CC to DLC1 and results in translocation of the PTEN-DLC1 complex to the CC posterior of migrating cells to promote RHOA activation (By CC similarity). Meanwhile, TNS3 switches binding preference from DLC1 to CC p85 and the TNS3-p85 complex translocates to the leading edge of CC migrating cells to activate RAC1 activation (By similarity). Plays a CC role as a key modulator of the AKT-mTOR signaling pathway controlling CC the tempo of the process of newborn neurons integration during adult CC neurogenesis, including correct neuron positioning, dendritic CC development and synapse formation (By similarity). Involved in the CC regulation of synaptic function in excitatory hippocampal synapses. CC Recruited to the postsynaptic membrane upon NMDA receptor activation, CC is required for the modulation of synaptic activity during plasticity. CC Enhancement of lipid phosphatase activity is able to drive depression CC of AMPA receptor-mediated synaptic responses, activity required for CC NMDA receptor-dependent long-term depression (LTD) (Ref.7). May be a CC negative regulator of insulin signaling and glucose metabolism in CC adipose tissue. The nuclear monoubiquitinated form possesses greater CC apoptotic potential, whereas the cytoplasmic nonubiquitinated form CC induces less tumor suppressive ability (By similarity). CC {ECO:0000250|UniProtKB:O08586, ECO:0000250|UniProtKB:P60484, CC ECO:0000269|Ref.7}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5- CC trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- CC inositol-4,5-bisphosphate) + phosphate; Xref=Rhea:RHEA:25017, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57836, CC ChEBI:CHEBI:58456; EC=3.1.3.67; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25018; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83421; EC=3.1.3.16; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20630; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:61977; EC=3.1.3.16; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620; EC=3.1.3.48; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10685; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5- CC trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- CC inositol-4,5-bisphosphate) + phosphate; Xref=Rhea:RHEA:43552, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83416, CC ChEBI:CHEBI:83419; Evidence={ECO:0000250|UniProtKB:P60484}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43553; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo- CC inositol-3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero- CC 3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphate; CC Xref=Rhea:RHEA:43560, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83420, ChEBI:CHEBI:83423; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43561; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + H2O = 1D-myo- CC inositol 1,4,5,6-tetrakisphosphate + phosphate; Xref=Rhea:RHEA:77143, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57627, CC ChEBI:CHEBI:57733; Evidence={ECO:0000250|UniProtKB:P60484}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77144; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo- CC inositol 1,4,5-trisphosphate + phosphate; Xref=Rhea:RHEA:77155, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57895, CC ChEBI:CHEBI:203600; Evidence={ECO:0000250|UniProtKB:P60484}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77156; CC Evidence={ECO:0000250|UniProtKB:P60484}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:O08586}; CC -!- SUBUNIT: Monomer. The unphosphorylated form interacts with the second CC PDZ domain of MAGI2 (By similarity). Interacts with MAGI2, MAGI3, MAST1 CC and MAST3, but neither with MAST4 nor with DLG5; interaction with MAGI2 CC increases protein stability (By similarity). Interacts with NEDD4 (By CC similarity). Interacts with NDFIP1 and NDFIP2; in the presence of NEDD4 CC or ITCH, this interaction promotes PTEN ubiquitination (By similarity). CC Interacts (via C2 domain) with FRK (By similarity). Interacts with CC USP7; the interaction is direct (By similarity). Interacts with ROCK1. CC Interacts with XIAP/BIRC4 (By similarity). Interacts with STK11; the CC interaction phosphorylates PTEN (By similarity). Interacts with CC PPP1R16B (By similarity). Interacts with NOP53; regulates PTEN CC phosphorylation and increases its stability (By similarity). Interacts CC (via PDZ domain-binding motif) with DLG4; the interaction is induced by CC NMDA and is required for PTEN location at postsynaptic density CC (PubMed:20628354). Interacts with the regulatory p85 subunit of the CC PI3K kinase complex and with Rho GTPase-activating protein DLC1; in CC resting cells, interacts (via C2 tensin-type domain) with p85 but, CC following growth factor stimulation, PTEN is phosphorylated which leads CC to weakened interaction with p85 and enhanced interaction (via C2 CC tensin-type domain) with DLC1 while p85 interaction with TNS3 increases CC (By similarity). {ECO:0000250|UniProtKB:O08586, CC ECO:0000250|UniProtKB:P60484, ECO:0000269|PubMed:20628354}. CC -!- INTERACTION: CC O54857; Q07266: Dbn1; NbExp=3; IntAct=EBI-8074312, EBI-918187; CC O54857; P31016: Dlg4; NbExp=5; IntAct=EBI-8074312, EBI-375655; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O08586}. Nucleus CC {ECO:0000250|UniProtKB:O08586}. Nucleus, PML body CC {ECO:0000250|UniProtKB:P60484}. Synapse, synaptosome CC {ECO:0000250|UniProtKB:O08586}. Cell projection, dendritic spine CC {ECO:0000269|PubMed:20628354}. Postsynaptic density CC {ECO:0000269|PubMed:20628354}. Note=Monoubiquitinated form is nuclear CC (By similarity). Nonubiquitinated form is cytoplasmic (By similarity). CC Colocalized with PML and USP7 in PML nuclear bodies (By similarity). CC XIAP/BIRC4 promotes its nuclear localization (By similarity). CC Associares with the postsynaptic density in response to NMDAR CC activation (PubMed:20628354). {ECO:0000250|UniProtKB:O08586, CC ECO:0000250|UniProtKB:P60484, ECO:0000269|PubMed:20628354}. CC -!- PTM: Constitutively phosphorylated by CK2 under normal conditions. CC Phosphorylation results in an inhibited activity towards PIP3. CC Phosphorylation can both inhibit or promote PDZ-binding. CC Phosphorylation at Tyr-336 by FRK/PTK5 protects this protein from CC ubiquitin-mediated degradation probably by inhibiting its binding to CC NEDD4 (By similarity). Phosphorylation by PLK3 promotes its stability CC and prevents its degradation by the proteasome. Phosphorylation by CC ROCK1 is essential for its stability and activity (By similarity). CC Phosphorylated on Thr-319 and Thr-321 in the C2-type tensin domain CC following EGF stimulation which changes its binding preference from the CC p85 regulatory subunit of the PI3K kinase complex to DLC1 (By CC similarity). {ECO:0000250|UniProtKB:O08586, CC ECO:0000250|UniProtKB:P60484}. CC -!- PTM: Monoubiquitinated; monoubiquitination is increased in presence of CC retinoic acid. Deubiquitinated by USP7; leading to its nuclear CC exclusion. Monoubiquitination of one of either Lys-13 and Lys-289 amino CC acid is sufficient to modulate PTEN compartmentalization (By CC similarity). Ubiquitinated by XIAP/BIRC4 (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:O08586}. CC -!- PTM: Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, CC leading to its degradation. {ECO:0000250|UniProtKB:P60484}. CC -!- PTM: ISGylated. ISGylation promotes PTEN degradation. CC {ECO:0000250|UniProtKB:P60484}. CC -!- SIMILARITY: Belongs to the PTEN phosphatase protein family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF017185; AAB96620.1; -; mRNA. DR EMBL; AF455569; AAO31948.1; -; mRNA. DR EMBL; CH473953; EDM13141.1; -; Genomic_DNA. DR RefSeq; NP_113794.1; NM_031606.1. DR PDB; 2K20; NMR; -; B=393-403. DR PDBsum; 2K20; -. DR AlphaFoldDB; O54857; -. DR SMR; O54857; -. DR IntAct; O54857; 4. DR MINT; O54857; -. DR STRING; 10116.ENSRNOP00000028143; -. DR iPTMnet; O54857; -. DR PhosphoSitePlus; O54857; -. DR PaxDb; 10116-ENSRNOP00000028143; -. DR Ensembl; ENSRNOT00000028143.4; ENSRNOP00000028143.1; ENSRNOG00000020723.4. DR Ensembl; ENSRNOT00055051625; ENSRNOP00055042566; ENSRNOG00055029782. DR Ensembl; ENSRNOT00060047149; ENSRNOP00060039221; ENSRNOG00060027159. DR Ensembl; ENSRNOT00065050947; ENSRNOP00065041896; ENSRNOG00065029492. DR GeneID; 50557; -. DR KEGG; rno:50557; -. DR AGR; RGD:61995; -. DR CTD; 5728; -. DR RGD; 61995; Pten. DR eggNOG; KOG2283; Eukaryota. DR GeneTree; ENSGT00940000163053; -. DR HOGENOM; CLU_020105_5_2_1; -. DR InParanoid; O54857; -. DR OrthoDB; 5477362at2759; -. DR TreeFam; TF324513; -. DR BRENDA; 3.1.3.67; 5301. DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane. DR Reactome; R-RNO-1855204; Synthesis of IP3 and IP4 in the cytosol. DR Reactome; R-RNO-199418; Negative regulation of the PI3K/AKT network. DR Reactome; R-RNO-202424; Downstream TCR signaling. DR Reactome; R-RNO-5689880; Ub-specific processing proteases. DR Reactome; R-RNO-5689896; Ovarian tumor domain proteases. DR Reactome; R-RNO-8948747; Regulation of PTEN localization. DR Reactome; R-RNO-8948751; Regulation of PTEN stability and activity. DR EvolutionaryTrace; O54857; -. DR Proteomes; UP000002494; Chromosome 1. DR Proteomes; UP000234681; Chromosome 1. DR Bgee; ENSRNOG00000020723; Expressed in duodenum and 19 other cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD. DR GO; GO:0042995; C:cell projection; ISO:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISO:RGD. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0043197; C:dendritic spine; IDA:RGD. DR GO; GO:0035749; C:myelin sheath adaxonal region; ISO:RGD. DR GO; GO:0043005; C:neuron projection; ISO:RGD. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell. DR GO; GO:0099524; C:postsynaptic cytosol; IDA:SynGO. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0045211; C:postsynaptic membrane; IDA:RGD. DR GO; GO:0043220; C:Schmidt-Lanterman incisure; ISO:RGD. DR GO; GO:0010997; F:anaphase-promoting complex binding; ISO:RGD. DR GO; GO:0019899; F:enzyme binding; ISO:RGD. DR GO; GO:0042802; F:identical protein binding; ISO:RGD. DR GO; GO:0030351; F:inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity; ISS:UniProtKB. DR GO; GO:0051717; F:inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity; ISO:RGD. DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IDA:RGD. DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0030165; F:PDZ domain binding; IPI:RGD. DR GO; GO:0052866; F:phosphatidylinositol phosphate phosphatase activity; ISO:RGD. DR GO; GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity; IDA:RGD. DR GO; GO:0051800; F:phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity; ISO:RGD. DR GO; GO:0004438; F:phosphatidylinositol-3-phosphate phosphatase activity; ISO:RGD. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; ISO:RGD. DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; IDA:RGD. DR GO; GO:0019901; F:protein kinase binding; ISO:RGD. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISO:RGD. DR GO; GO:1990782; F:protein tyrosine kinase binding; IDA:RGD. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISO:RGD. DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; TAS:RGD. DR GO; GO:1990381; F:ubiquitin-specific protease binding; ISO:RGD. DR GO; GO:0030534; P:adult behavior; ISO:RGD. DR GO; GO:0001525; P:angiogenesis; ISO:RGD. DR GO; GO:0006915; P:apoptotic process; ISO:RGD. DR GO; GO:0042100; P:B cell proliferation; ISO:RGD. DR GO; GO:0048854; P:brain morphogenesis; ISO:RGD. DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD. DR GO; GO:0048738; P:cardiac muscle tissue development; ISO:RGD. DR GO; GO:0016477; P:cell migration; ISO:RGD. DR GO; GO:0048870; P:cell motility; IBA:GO_Central. DR GO; GO:0008283; P:cell population proliferation; ISO:RGD. DR GO; GO:0036294; P:cellular response to decreased oxygen levels; ISO:RGD. DR GO; GO:0071257; P:cellular response to electrical stimulus; ISO:RGD. DR GO; GO:0071361; P:cellular response to ethanol; IDA:RGD. DR GO; GO:0071456; P:cellular response to hypoxia; ISO:RGD. DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:RGD. DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IDA:RGD. DR GO; GO:0044320; P:cellular response to leptin stimulus; IMP:RGD. DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEP:RGD. DR GO; GO:0007417; P:central nervous system development; ISO:RGD. DR GO; GO:0032286; P:central nervous system myelin maintenance; ISO:RGD. DR GO; GO:0021955; P:central nervous system neuron axonogenesis; ISO:RGD. DR GO; GO:0060997; P:dendritic spine morphogenesis; ISO:RGD. DR GO; GO:0021542; P:dentate gyrus development; ISO:RGD. DR GO; GO:0043542; P:endothelial cell migration; ISO:RGD. DR GO; GO:0048853; P:forebrain morphogenesis; ISO:RGD. DR GO; GO:0010467; P:gene expression; ISO:RGD. DR GO; GO:0007507; P:heart development; ISO:RGD. DR GO; GO:0071545; P:inositol phosphate catabolic process; IDA:RGD. DR GO; GO:0007611; P:learning or memory; ISO:RGD. DR GO; GO:0045475; P:locomotor rhythm; ISO:RGD. DR GO; GO:0007626; P:locomotory behavior; ISO:RGD. DR GO; GO:0060292; P:long-term synaptic depression; IMP:RGD. DR GO; GO:0060291; P:long-term synaptic potentiation; ISO:RGD. DR GO; GO:0060179; P:male mating behavior; ISO:RGD. DR GO; GO:0042711; P:maternal behavior; ISO:RGD. DR GO; GO:0007613; P:memory; IMP:RGD. DR GO; GO:0033555; P:multicellular organismal response to stress; ISO:RGD. DR GO; GO:0042552; P:myelination; ISO:RGD. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD. DR GO; GO:0048681; P:negative regulation of axon regeneration; ISO:RGD. DR GO; GO:0050771; P:negative regulation of axonogenesis; ISO:RGD. DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISO:RGD. DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; IMP:RGD. DR GO; GO:0045786; P:negative regulation of cell cycle; IMP:RGD. DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; ISO:RGD. DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD. DR GO; GO:0045792; P:negative regulation of cell size; ISO:RGD. DR GO; GO:2000773; P:negative regulation of cellular senescence; ISO:RGD. DR GO; GO:1900425; P:negative regulation of defense response to bacterium; IMP:RGD. DR GO; GO:1903860; P:negative regulation of dendrite extension; IMP:RGD. DR GO; GO:0061002; P:negative regulation of dendritic spine morphogenesis; ISO:RGD. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISO:RGD. DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISO:RGD. DR GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; ISO:RGD. DR GO; GO:1905450; P:negative regulation of Fc-gamma receptor signaling pathway involved in phagocytosis; IMP:RGD. DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; ISO:RGD. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISO:RGD. DR GO; GO:0051548; P:negative regulation of keratinocyte migration; ISO:RGD. DR GO; GO:0031642; P:negative regulation of myelination; ISO:RGD. DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:ARUK-UCL. DR GO; GO:0046621; P:negative regulation of organ growth; ISO:RGD. DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISO:RGD. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD. DR GO; GO:0090071; P:negative regulation of ribosome biogenesis; ISO:RGD. DR GO; GO:2000808; P:negative regulation of synaptic vesicle clustering; ISO:RGD. DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:RGD. DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:RGD. DR GO; GO:1903690; P:negative regulation of wound healing, spreading of epidermal cells; ISO:RGD. DR GO; GO:0031175; P:neuron projection development; IDA:RGD. DR GO; GO:0007270; P:neuron-neuron synaptic transmission; ISO:RGD. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD. DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:RGD. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:RGD. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:RGD. DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IMP:RGD. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD. DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISO:RGD. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:RGD. DR GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:RGD. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:RGD. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISO:RGD. DR GO; GO:0097107; P:postsynaptic density assembly; ISO:RGD. DR GO; GO:0060134; P:prepulse inhibition; ISO:RGD. DR GO; GO:0097105; P:presynaptic membrane assembly; ISO:RGD. DR GO; GO:0060736; P:prostate gland growth; ISO:RGD. DR GO; GO:0050821; P:protein stabilization; ISO:RGD. DR GO; GO:0048679; P:regulation of axon regeneration; ISO:RGD. DR GO; GO:0002902; P:regulation of B cell apoptotic process; ISO:RGD. DR GO; GO:0051726; P:regulation of cell cycle; ISO:RGD. DR GO; GO:0032535; P:regulation of cellular component size; ISO:RGD. DR GO; GO:0060341; P:regulation of cellular localization; ISO:RGD. DR GO; GO:2000109; P:regulation of macrophage apoptotic process; ISO:RGD. DR GO; GO:0010975; P:regulation of neuron projection development; ISO:RGD. DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central. DR GO; GO:0031647; P:regulation of protein stability; ISO:RGD. DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; ISO:RGD. DR GO; GO:0014823; P:response to activity; IEP:RGD. DR GO; GO:0046685; P:response to arsenic-containing substance; IEP:RGD. DR GO; GO:0033198; P:response to ATP; IEP:RGD. DR GO; GO:0032355; P:response to estradiol; IEP:RGD. DR GO; GO:0045471; P:response to ethanol; IEP:RGD. DR GO; GO:0009749; P:response to glucose; IEP:RGD. DR GO; GO:0010035; P:response to inorganic substance; IEP:RGD. DR GO; GO:0007584; P:response to nutrient; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0010033; P:response to organic substance; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0010043; P:response to zinc ion; IEP:RGD. DR GO; GO:0060024; P:rhythmic synaptic transmission; ISO:RGD. DR GO; GO:0035176; P:social behavior; ISO:RGD. DR GO; GO:0007056; P:spindle assembly involved in female meiosis; ISO:RGD. DR GO; GO:0007416; P:synapse assembly; ISO:RGD. DR GO; GO:0060074; P:synapse maturation; ISO:RGD. DR GO; GO:0042098; P:T cell proliferation; ISO:RGD. DR CDD; cd14509; PTP_PTEN; 1. DR Gene3D; 2.60.40.1110; -; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR InterPro; IPR017361; Bifunc_PIno_P3_Pase/Pase_PTEN. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR000242; PTP_cat. DR InterPro; IPR045101; PTP_PTEN. DR InterPro; IPR014020; Tensin_C2-dom. DR InterPro; IPR029023; Tensin_phosphatase. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR003595; Tyr_Pase_cat. DR InterPro; IPR000387; Tyr_Pase_dom. DR PANTHER; PTHR12305; PHOSPHATASE WITH HOMOLOGY TO TENSIN; 1. DR PANTHER; PTHR12305:SF81; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE 3-PHOSPHATASE AND DUAL-SPECIFICITY PROTEIN PHOSPHATASE PTEN; 1. DR Pfam; PF10409; PTEN_C2; 1. DR Pfam; PF00102; Y_phosphatase; 1. DR PIRSF; PIRSF038025; PTEN; 1. DR SMART; SM01326; PTEN_C2; 1. DR SMART; SM00404; PTPc_motif; 1. DR SMART; SM01301; PTPlike_phytase; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR PROSITE; PS51182; C2_TENSIN; 1. DR PROSITE; PS51181; PPASE_TENSIN; 1. DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1. DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Apoptosis; Cell projection; Cytoplasm; KW Hydrolase; Isopeptide bond; Lipid metabolism; Neurogenesis; Nucleus; KW Phosphoprotein; Protein phosphatase; Reference proteome; Synapse; KW Synaptosome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P60484" FT CHAIN 2..403 FT /note="Phosphatidylinositol 3,4,5-trisphosphate 3- FT phosphatase and dual-specificity protein phosphatase PTEN" FT /id="PRO_0000456474" FT DOMAIN 14..185 FT /note="Phosphatase tensin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590" FT DOMAIN 190..350 FT /note="C2 tensin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00589" FT REGION 338..348 FT /note="Required for interaction with NOP53" FT /evidence="ECO:0000250|UniProtKB:P60484" FT REGION 352..403 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 401..403 FT /note="PDZ domain-binding" FT /evidence="ECO:0000250|UniProtKB:O08586" FT COMPBIAS 353..370 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 371..385 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 124 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0000250|UniProtKB:P60484" FT MOD_RES 294 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08586" FT MOD_RES 319 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P60484" FT MOD_RES 321 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P60484" FT MOD_RES 336 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P60484" FT MOD_RES 366 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O08586" FT MOD_RES 370 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08586" FT MOD_RES 380 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08586" FT MOD_RES 382 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O08586" FT MOD_RES 383 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O08586" FT MOD_RES 385 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08586" FT MOD_RES 401 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P60484" FT CROSSLNK 13 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P60484" FT CROSSLNK 289 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P60484" FT MUTAGEN 124 FT /note="C->S: Dominant negative. Abolishes depression of FT AMPAR-mediated transmission. Abolishes NMDA FT receptor-dependent long-lasting depression." FT /evidence="ECO:0000269|PubMed:20628354" FT MUTAGEN 129 FT /note="G->E: Abolishes NMDA receptor-dependent long-lasting FT depression." FT /evidence="ECO:0000269|PubMed:20628354" FT MUTAGEN 400..403 FT /note="Missing: Loss of interaction with DLG4." FT /evidence="ECO:0000269|PubMed:20628354" FT STRAND 401..403 FT /evidence="ECO:0007829|PDB:2K20" SQ SEQUENCE 403 AA; 47118 MW; 243BFE35FE209FE5 CRC64; MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI DDVVRFLDSK HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL IKPFCEDLDQ WLSEDDNHVA AIHCKAGKGR TGVMICAYLL HRGKFLKAQE ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY LLKNHLDYRP VALLFHKMMF ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKLMY FEFPQPLPVC GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT VEEPSNPEAS SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHSQI TKV //