PTEN_MOUSE
ID PTEN_MOUSE Reviewed; 403 AA.
AC O08586; Q3UFB0; Q542G1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN;
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=Mutated in multiple advanced cancers 1;
DE AltName: Full=Phosphatase and tensin homolog;
GN Name=Pten; Synonyms=Mmac1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9090379; DOI=10.1038/ng0497-356;
RA Steck P.A., Pershouse M.A., Jasser S.A., Lin H., Yung W.K.A., Ligon A.H.,
RA Langford L.A., Baumgard M.L., Hattier T., Davis T., Frye C., Hu R.,
RA Swedlund B., Teng D.H.-F., Tavtigian S.V.;
RT "Identification of a candidate tumour suppressor gene, MMAC1, at chromosome
RT 10q23.3 that is mutated in multiple advanced cancers.";
RL Nat. Genet. 15:356-363(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Sympathetic ganglion, Testis, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION.
RX PubMed=10339565; DOI=10.1073/pnas.96.11.6199;
RA Sun H., Lesche R., Li D.M., Liliental J., Zhang H., Gao J., Gavrilova N.,
RA Mueller B., Liu X., Wu H.;
RT "PTEN modulates cell cycle progression and cell survival by regulating
RT phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B
RT signaling pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:6199-6204(1999).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP UBIQUITINATION BY XIAP/BIRC4, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP XIAP/BIRC4.
RX PubMed=19473982; DOI=10.1074/jbc.c109.009522;
RA Van Themsche C., Leblanc V., Parent S., Asselin E.;
RT "X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN
RT ubiquitination, content, and compartmentalization.";
RL J. Biol. Chem. 284:20462-20466(2009).
RN [7]
RP FUNCTION.
RX PubMed=19778506; DOI=10.1016/j.neuron.2009.08.008;
RA Kim J.Y., Duan X., Liu C.Y., Jang M.H., Guo J.U., Pow-anpongkul N.,
RA Kang E., Song H., Ming G.L.;
RT "DISC1 regulates new neuron development in the adult brain via modulation
RT of AKT-mTOR signaling through KIAA1212.";
RL Neuron 63:761-773(2009).
RN [8]
RP PHOSPHORYLATION AT SER-380; THR-382 AND THR-383, AND INTERACTION WITH
RP ROCK1.
RX PubMed=20008297; DOI=10.1182/blood-2009-08-237222;
RA Vemula S., Shi J., Hanneman P., Wei L., Kapur R.;
RT "ROCK1 functions as a suppressor of inflammatory cell migration by
RT regulating PTEN phosphorylation and stability.";
RL Blood 115:1785-1796(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-294 AND SER-385, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP PHOSPHORYLATION AT THR-366 AND SER-370.
RX PubMed=20940307; DOI=10.1074/jbc.m110.166462;
RA Xu D., Yao Y., Jiang X., Lu L., Dai W.;
RT "Regulation of PTEN stability and activity by Plk3.";
RL J. Biol. Chem. 285:39935-39942(2010).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=25801959; DOI=10.1093/jmcb/mjv020;
RA Howitt J., Low L.H., Putz U., Doan A., Lackovic J., Goh C.P., Gunnersen J.,
RA Silke J., Tan S.S.;
RT "Ndfip1 represses cell proliferation by controlling Pten localization and
RT signaling specificity.";
RL J. Mol. Cell Biol. 7:119-131(2015).
CC -!- FUNCTION: In motile cells, suppresses the formation of lateral
CC pseudopods and thereby promotes cell polarization and directed movement
CC (By similarity). Tumor suppressor. Acts as a dual-specificity protein
CC phosphatase, dephosphorylating tyrosine-, serine- and threonine-
CC phosphorylated proteins. Also acts as a lipid phosphatase, removing the
CC phosphate in the D3 position of the inositol ring from
CC phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-
CC diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-
CC tetrakisphosphate with order of substrate preference in vitro
CC PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid
CC phosphatase activity is critical for its tumor suppressor function.
CC Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating
CC phosphoinositides and thereby modulating cell cycle progression and
CC cell survival. The unphosphorylated form cooperates with MAGI2 to
CC suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated
CC focal adhesion kinase and inhibits cell migration and integrin-mediated
CC cell spreading and focal adhesion formation. Plays a role as a key
CC modulator of the AKT-mTOR signaling pathway controlling the tempo of
CC the process of newborn neurons integration during adult neurogenesis,
CC including correct neuron positioning, dendritic development and synapse
CC formation. May be a negative regulator of insulin signaling and glucose
CC metabolism in adipose tissue. The nuclear monoubiquitinated form
CC possesses greater apoptotic potential, whereas the cytoplasmic
CC nonubiquitinated form induces less tumor suppressive ability.
CC {ECO:0000250, ECO:0000269|PubMed:10339565,
CC ECO:0000269|PubMed:19778506}.
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 -!- 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 -!- 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 -!- 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 -!- 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-inositol-
CC 3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-
CC (1D-myo-inositol-4,5-bisphosphate) + phosphate; Xref=Rhea:RHEA:43560,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83420,
CC ChEBI:CHEBI:83423; Evidence={ECO:0000250|UniProtKB:P60484};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43561;
CC Evidence={ECO:0000250|UniProtKB:P60484};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
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 (PubMed:20008297). Interacts with XIAP/BIRC4 (PubMed:19473982).
CC Interacts with STK11; the interaction phosphorylates PTEN (By
CC similarity). Interacts with PPP1R16B (By similarity). Interacts with
CC NOP53; regulates PTEN phosphorylation and increases its stability (By
CC similarity). {ECO:0000250|UniProtKB:P60484,
CC ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:20008297}.
CC -!- INTERACTION:
CC O08586; P49452: Cenpc; NbExp=2; IntAct=EBI-1186266, EBI-1186252;
CC O08586; B1AZ99: Otud3; NbExp=2; IntAct=EBI-1186266, EBI-16170692;
CC O08586; Q9JHL1: Slc9a3r2; NbExp=3; IntAct=EBI-1186266, EBI-538451;
CC O08586; P02340: Tp53; NbExp=4; IntAct=EBI-1186266, EBI-474016;
CC O08586; P62991: Ubc; NbExp=2; IntAct=EBI-1186266, EBI-413074;
CC O08586; Q6A4J8: Usp7; NbExp=2; IntAct=EBI-1186266, EBI-1216254;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19473982,
CC ECO:0000269|PubMed:25801959}. Nucleus {ECO:0000269|PubMed:19473982,
CC ECO:0000269|PubMed:25801959}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:P60484}. 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 (PubMed:19473982).
CC {ECO:0000250|UniProtKB:P60484, ECO:0000269|PubMed:19473982}.
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. {ECO:0000250,
CC ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:20008297,
CC ECO:0000269|PubMed:20940307}.
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. {ECO:0000250,
CC ECO:0000269|PubMed:19473982}.
CC -!- SIMILARITY: Belongs to the PTEN phosphatase protein family.
CC {ECO:0000305}.
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DR EMBL; U92437; AAC53118.1; -; mRNA.
DR EMBL; AK076980; BAC36545.1; -; mRNA.
DR EMBL; AK088717; BAC40525.1; -; mRNA.
DR EMBL; AK148736; BAE28651.1; -; mRNA.
DR EMBL; BC021445; AAH21445.1; -; mRNA.
DR CCDS; CCDS29753.1; -.
DR RefSeq; NP_032986.1; NM_008960.2.
DR AlphaFoldDB; O08586; -.
DR SMR; O08586; -.
DR BioGRID; 202449; 39.
DR ComplexPortal; CPX-3154; PTEN phosphatase complex.
DR DIP; DIP-38740N; -.
DR IntAct; O08586; 24.
DR MINT; O08586; -.
DR STRING; 10090.ENSMUSP00000013807; -.
DR iPTMnet; O08586; -.
DR PhosphoSitePlus; O08586; -.
DR EPD; O08586; -.
DR jPOST; O08586; -.
DR MaxQB; O08586; -.
DR PaxDb; O08586; -.
DR PeptideAtlas; O08586; -.
DR PRIDE; O08586; -.
DR ProteomicsDB; 302005; -.
DR Antibodypedia; 3420; 1806 antibodies from 53 providers.
DR DNASU; 19211; -.
DR Ensembl; ENSMUST00000013807; ENSMUSP00000013807; ENSMUSG00000013663.
DR GeneID; 19211; -.
DR KEGG; mmu:19211; -.
DR UCSC; uc008hfr.1; mouse.
DR CTD; 5728; -.
DR MGI; MGI:109583; Pten.
DR VEuPathDB; HostDB:ENSMUSG00000013663; -.
DR eggNOG; KOG2283; Eukaryota.
DR GeneTree; ENSGT00940000154335; -.
DR HOGENOM; CLU_020105_5_2_1; -.
DR InParanoid; O08586; -.
DR OMA; HARTMNG; -.
DR OrthoDB; 639380at2759; -.
DR PhylomeDB; O08586; -.
DR TreeFam; TF324513; -.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-MMU-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR Reactome; R-MMU-8948747; Regulation of PTEN localization.
DR Reactome; R-MMU-8948751; Regulation of PTEN stability and activity.
DR BioGRID-ORCS; 19211; 19 hits in 82 CRISPR screens.
DR ChiTaRS; Pten; mouse.
DR PRO; PR:O08586; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; O08586; protein.
DR Bgee; ENSMUSG00000013663; Expressed in retrosplenial region and 280 other tissues.
DR ExpressionAtlas; O08586; baseline and differential.
DR Genevisible; O08586; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0035749; C:myelin sheath adaxonal region; IDA:BHF-UCL.
DR GO; GO:0043005; C:neuron projection; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0099524; C:postsynaptic cytosol; ISO:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IDA:BHF-UCL.
DR GO; GO:0010997; F:anaphase-promoting complex binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051717; F:inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISO:MGI.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR GO; GO:0016791; F:phosphatase activity; ISO:MGI.
DR GO; GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity; IDA:MGI.
DR GO; GO:0051800; F:phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; ISO:MGI.
DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:MGI.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISS:UniProtKB.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; ISO:MGI.
DR GO; GO:0030534; P:adult behavior; IMP:CACAO.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0042100; P:B cell proliferation; IMP:MGI.
DR GO; GO:0048854; P:brain morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0048738; P:cardiac muscle tissue development; IMP:MGI.
DR GO; GO:0016477; P:cell migration; IMP:MGI.
DR GO; GO:0048870; P:cell motility; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0036294; P:cellular response to decreased oxygen levels; IDA:MGI.
DR GO; GO:0071257; P:cellular response to electrical stimulus; ISO:MGI.
DR GO; GO:0071361; P:cellular response to ethanol; ISO:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:MGI.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI.
DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; ISO:MGI.
DR GO; GO:0044320; P:cellular response to leptin stimulus; ISO:MGI.
DR GO; GO:0007417; P:central nervous system development; IMP:MGI.
DR GO; GO:0032286; P:central nervous system myelin maintenance; IMP:BHF-UCL.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; IMP:BHF-UCL.
DR GO; GO:0060997; P:dendritic spine morphogenesis; IMP:BHF-UCL.
DR GO; GO:0021542; P:dentate gyrus development; IMP:BHF-UCL.
DR GO; GO:0016311; P:dephosphorylation; IBA:GO_Central.
DR GO; GO:0043542; P:endothelial cell migration; IMP:MGI.
DR GO; GO:0048853; P:forebrain morphogenesis; IMP:BHF-UCL.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; ISS:UniProtKB.
DR GO; GO:0007611; P:learning or memory; IMP:BHF-UCL.
DR GO; GO:0045475; P:locomotor rhythm; IMP:BHF-UCL.
DR GO; GO:0007626; P:locomotory behavior; IMP:BHF-UCL.
DR GO; GO:0060292; P:long-term synaptic depression; ISO:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:BHF-UCL.
DR GO; GO:0060179; P:male mating behavior; IMP:BHF-UCL.
DR GO; GO:0042711; P:maternal behavior; IMP:BHF-UCL.
DR GO; GO:0007613; P:memory; ISO:MGI.
DR GO; GO:0033555; P:multicellular organismal response to stress; IMP:BHF-UCL.
DR GO; GO:0042552; P:myelination; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0048681; P:negative regulation of axon regeneration; IMP:ParkinsonsUK-UCL.
DR GO; GO:0050771; P:negative regulation of axonogenesis; IMP:BHF-UCL.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:MGI.
DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; IGI:BHF-UCL.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:MGI.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; ISO:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0045792; P:negative regulation of cell size; IMP:BHF-UCL.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IMP:BHF-UCL.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:1900425; P:negative regulation of defense response to bacterium; ISO:MGI.
DR GO; GO:0061002; P:negative regulation of dendritic spine morphogenesis; IMP:BHF-UCL.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; IMP:BHF-UCL.
DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0051548; P:negative regulation of keratinocyte migration; ISO:MGI.
DR GO; GO:0031642; P:negative regulation of myelination; IMP:MGI.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:MGI.
DR GO; GO:0046621; P:negative regulation of organ growth; IMP:BHF-UCL.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0050765; P:negative regulation of phagocytosis; ISO:MGI.
DR GO; GO:0060101; P:negative regulation of phagocytosis, engulfment; ISO:MGI.
DR GO; GO:1901017; P:negative regulation of potassium ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0090071; P:negative regulation of ribosome biogenesis; IMP:BHF-UCL.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; ISO:MGI.
DR GO; GO:2000808; P:negative regulation of synaptic vesicle clustering; IMP:BHF-UCL.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:MGI.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:1903690; P:negative regulation of wound healing, spreading of epidermal cells; ISO:MGI.
DR GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR GO; GO:0007270; P:neuron-neuron synaptic transmission; IMP:BHF-UCL.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; ISS:UniProtKB.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:MGI.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:MGI.
DR GO; GO:1903984; P:positive regulation of TRAIL-activated apoptotic signaling pathway; ISO:MGI.
DR GO; GO:1904668; P:positive regulation of ubiquitin protein ligase activity; IMP:BHF-UCL.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0097107; P:postsynaptic density assembly; IMP:BHF-UCL.
DR GO; GO:0060134; P:prepulse inhibition; IMP:BHF-UCL.
DR GO; GO:0097105; P:presynaptic membrane assembly; IMP:BHF-UCL.
DR GO; GO:0060736; P:prostate gland growth; IMP:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:0048679; P:regulation of axon regeneration; IGI:MGI.
DR GO; GO:0002902; P:regulation of B cell apoptotic process; IMP:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IGI:MGI.
DR GO; GO:0032535; P:regulation of cellular component size; IMP:BHF-UCL.
DR GO; GO:0060341; P:regulation of cellular localization; IMP:CACAO.
DR GO; GO:2000109; P:regulation of macrophage apoptotic process; IMP:MGI.
DR GO; GO:0010975; P:regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; IMP:MGI.
DR GO; GO:0060024; P:rhythmic synaptic transmission; IMP:BHF-UCL.
DR GO; GO:0035176; P:social behavior; IMP:BHF-UCL.
DR GO; GO:0007416; P:synapse assembly; IMP:BHF-UCL.
DR GO; GO:0060074; P:synapse maturation; IMP:BHF-UCL.
DR GO; GO:0042098; P:T cell proliferation; IMP:MGI.
DR CDD; cd14509; PTP_PTEN; 1.
DR Gene3D; 3.90.190.10; -; 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; 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 Pfam; PF10409; PTEN_C2; 1.
DR PIRSF; PIRSF038025; PTEN; 1.
DR SMART; SM01326; PTEN_C2; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS51182; C2_TENSIN; 1.
DR PROSITE; PS51181; PPASE_TENSIN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Apoptosis; Cytoplasm; Hydrolase; Isopeptide bond;
KW Lipid metabolism; Neurogenesis; Nucleus; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Tumor suppressor; 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_0000215905"
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 REGION 401..403
FT /note="PDZ domain-binding"
FT /evidence="ECO:0000250"
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:0007744|PubMed:21183079"
FT MOD_RES 336
FT /note="Phosphotyrosine; by FRK"
FT /evidence="ECO:0000250|UniProtKB:P60484"
FT MOD_RES 366
FT /note="Phosphothreonine; by GSK3-beta and PLK3"
FT /evidence="ECO:0000269|PubMed:20940307"
FT MOD_RES 370
FT /note="Phosphoserine; by CK2 and PLK3"
FT /evidence="ECO:0000269|PubMed:20940307"
FT MOD_RES 380
FT /note="Phosphoserine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:20008297"
FT MOD_RES 382
FT /note="Phosphothreonine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:20008297"
FT MOD_RES 383
FT /note="Phosphothreonine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:20008297"
FT MOD_RES 385
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
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 CONFLICT 50
FT /note="Missing (in Ref. 2; BAE28651)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 403 AA; 47152 MW; 75F97C3DD6843BA9 CRC64;
MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI DDVVRFLDSK
HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL IKPFCEDLDQ WLSEDDNHVA
AIHCKAGKGR TGVMICAYLL HRGKFLKAQE ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY
LLKNHLDYRP VALLFHKMMF ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY
FEFPQPLPVC GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI
DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT VEEPSNPEAS
SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHSQI TKV
