PTEN_DICDI
ID PTEN_DICDI Reviewed; 533 AA.
AC Q8T9S7; Q54LI5; Q8T658;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 131.
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=Pten 3-phosphoinositide phosphatase alpha;
GN Name=pteN; Synonyms=ptenA; ORFNames=DDB_G0286557;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=AX3;
RA Meili R., Firtel R.A.;
RT "Spatial and temporal regulation of Dictyostelium discoideum chemotaxis by
RT PTEN.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-515.
RA Iijima M., Devreotes P.N.;
RT "Dictyostelium discoideum PI3 phosphatase PTEN homolog.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [4]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=12062103; DOI=10.1016/s0092-8674(02)00745-6;
RA Iijima M., Devreotes P.;
RT "Tumor suppressor PTEN mediates sensing of chemoattractant gradients.";
RL Cell 109:599-610(2002).
RN [5]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=12062104; DOI=10.1016/s0092-8674(02)00755-9;
RA Funamoto S., Meili R., Lee S., Parry L., Firtel R.A.;
RT "Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and
RT PTEN mediates chemotaxis.";
RL Cell 109:611-623(2002).
RN [6]
RP FUNCTION.
RX PubMed=17419997; DOI=10.1016/j.devcel.2007.03.005;
RA Chen L., Iijima M., Tang M., Landree M.A., Huang Y.E., Xiong Y.,
RA Iglesias P.A., Devreotes P.N.;
RT "PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis.";
RL Dev. Cell 12:603-614(2007).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17623773; DOI=10.1242/jcs.010876;
RA Wessels D., Lusche D.F., Kuhl S., Heid P., Soll D.R.;
RT "PTEN plays a role in the suppression of lateral pseudopod formation during
RT Dictyostelium motility and chemotaxis.";
RL J. Cell Sci. 120:2517-2531(2007).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18657484; DOI=10.1016/j.arr.2008.04.003;
RA McMains V.C., Liao X.-H., Kimmel A.R.;
RT "Oscillatory signaling and network responses during the development of
RT Dictyostelium discoideum.";
RL Ageing Res. Rev. 7:234-248(2008).
RN [9]
RP FUNCTION.
RX PubMed=18676656; DOI=10.1529/biophysj.108.130179;
RA Gruver J.S., Wikswo J.P., Chung C.Y.;
RT "3'-phosphoinositides regulate the coordination of speed and accuracy
RT during chemotaxis.";
RL Biophys. J. 95:4057-4067(2008).
RN [10]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19011688; DOI=10.1371/journal.pone.0003734;
RA Maeda Y.T., Inose J., Matsuo M.Y., Iwaya S., Sano M.;
RT "Ordered patterns of cell shape and orientational correlation during
RT spontaneous cell migration.";
RL PLoS ONE 3:E3734-E3734(2008).
CC -!- FUNCTION: Acts as a dual-specificity protein phosphatase,
CC dephosphorylating tyrosine-, serine- and threonine-phosphorylated
CC proteins. Also acts as a lipid phosphatase, removing the phosphate in
CC the D3 position of the inositol ring from phosphatidylinositol 3,4,5-
CC trisphosphate, phosphatidylinositol 3,4-diphosphate,
CC phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate
CC (By similarity). Negative regulator of PI3K chemotaxis pathways.
CC Overexpression leads to a suppression of a PI3K-dependent activation of
CC pkbA, and these cells exhibit chemotaxis defects consistent with a
CC reduction in PI3K activity. {ECO:0000250|UniProtKB:P60484,
CC ECO:0000269|PubMed:12062103, ECO:0000269|PubMed:12062104,
CC ECO:0000269|PubMed:17419997, ECO:0000269|PubMed:17623773,
CC ECO:0000269|PubMed:18657484, ECO:0000269|PubMed:18676656,
CC ECO:0000269|PubMed:19011688}.
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 -!- 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 -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein;
CC Cytoplasmic side. Cytoplasm. Cytoplasm, cell cortex. Note=Found
CC uniformly on the plasma membrane in unstimulated cells. In response to
CC chemoattractant stimulation, there is a rapid and transient release
CC from the plasma membrane. Constitutively localized in the cortex of
CC polarized cells.
CC -!- DEVELOPMENTAL STAGE: In chemotaxing cells, is on the plasma membrane
CC along the lateral sides and posterior of the cell but is absent or the
CC level is significantly reduced at the leading edge.
CC {ECO:0000269|PubMed:12062104}.
CC -!- DISRUPTION PHENOTYPE: Growth defect. Failure to aggregate. Slower
CC migration. Leads to increased F-actin polymerization. Unable to
CC suppress lateral pseudopod formation and turning. Having a direct on
CC PI(3,4,5)P3/PI(3,4)P2 levels. Significant increase in chemoattractant-
CC mediated activation of pkbA and a decrease in chemotaxis speed.
CC {ECO:0000269|PubMed:12062103, ECO:0000269|PubMed:12062104,
CC ECO:0000269|PubMed:17623773, ECO:0000269|PubMed:18657484,
CC ECO:0000269|PubMed:19011688}.
CC -!- SIMILARITY: Belongs to the PTEN phosphatase protein family.
CC {ECO:0000305}.
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DR EMBL; AF467431; AAL75566.1; -; mRNA.
DR EMBL; AF483827; AAL99958.1; -; mRNA.
DR EMBL; AAFI02000089; EAL64034.1; -; Genomic_DNA.
DR RefSeq; XP_637576.1; XM_632484.1.
DR AlphaFoldDB; Q8T9S7; -.
DR SMR; Q8T9S7; -.
DR BioGRID; 1250719; 3.
DR STRING; 44689.DDB0191093; -.
DR PaxDb; Q8T9S7; -.
DR EnsemblProtists; EAL64034; EAL64034; DDB_G0286557.
DR GeneID; 8625716; -.
DR KEGG; ddi:DDB_G0286557; -.
DR dictyBase; DDB_G0286557; pten.
DR eggNOG; KOG2283; Eukaryota.
DR HOGENOM; CLU_020105_5_1_1; -.
DR InParanoid; Q8T9S7; -.
DR OMA; FMFWINT; -.
DR PhylomeDB; Q8T9S7; -.
DR Reactome; R-DDI-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-DDI-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-DDI-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-DDI-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-DDI-202424; Downstream TCR signaling.
DR Reactome; R-DDI-5689880; Ub-specific processing proteases.
DR Reactome; R-DDI-5689896; Ovarian tumor domain proteases.
DR Reactome; R-DDI-8948747; Regulation of PTEN localization.
DR Reactome; R-DDI-8948751; Regulation of PTEN stability and activity.
DR PRO; PR:Q8T9S7; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0051285; C:cell cortex of cell tip; IDA:dictyBase.
DR GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR GO; GO:0031254; C:cell trailing edge; IDA:dictyBase.
DR GO; GO:0031257; C:cell trailing edge membrane; IDA:dictyBase.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:1990753; C:equatorial cell cortex; IDA:dictyBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:dictyBase.
DR GO; GO:0001931; C:uropod; IDA:dictyBase.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity; IBA:GO_Central.
DR GO; GO:0034485; F:phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity; IDA:dictyBase.
DR GO; GO:0051800; F:phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity; IDA:dictyBase.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:dictyBase.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:dictyBase.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0030041; P:actin filament polymerization; IMP:dictyBase.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IDA:dictyBase.
DR GO; GO:0031152; P:aggregation involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0032060; P:bleb assembly; IMP:dictyBase.
DR GO; GO:0048870; P:cell motility; IMP:dictyBase.
DR GO; GO:0006935; P:chemotaxis; IMP:dictyBase.
DR GO; GO:0043327; P:chemotaxis to cAMP; IMP:dictyBase.
DR GO; GO:0016311; P:dephosphorylation; IBA:GO_Central.
DR GO; GO:0030010; P:establishment of cell polarity; IMP:dictyBase.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:dictyBase.
DR GO; GO:0050919; P:negative chemotaxis; IMP:dictyBase.
DR GO; GO:1903665; P:negative regulation of asexual reproduction; IMP:dictyBase.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IMP:dictyBase.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:dictyBase.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IBA:GO_Central.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IMP:dictyBase.
DR GO; GO:1903669; P:positive regulation of chemorepellent activity; IMP:dictyBase.
DR GO; GO:0006470; P:protein dephosphorylation; IBA:GO_Central.
DR GO; GO:0036051; P:protein localization to trailing edge; IDA:dictyBase.
DR GO; GO:0036052; P:protein localization to uropod; IMP:dictyBase.
DR GO; GO:0031269; P:pseudopodium assembly; IMP:dictyBase.
DR GO; GO:0045761; P:regulation of adenylate cyclase activity; IGI:dictyBase.
DR GO; GO:0022604; P:regulation of cell morphogenesis; IMP:dictyBase.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0031272; P:regulation of pseudopodium assembly; IMP:dictyBase.
DR GO; GO:0034461; P:uropod retraction; IMP:dictyBase.
DR CDD; cd14509; PTP_PTEN; 1.
DR Gene3D; 3.90.190.10; -; 1.
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; IPR000387; Tyr_Pase_dom.
DR Pfam; PF10409; PTEN_C2; 1.
DR SMART; SM01326; PTEN_C2; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS51182; C2_TENSIN; 1.
DR PROSITE; PS51181; PPASE_TENSIN; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; Cell membrane; Chemotaxis; Cytoplasm; Hydrolase;
KW Lipid metabolism; Lipid-binding; Membrane; Protein phosphatase;
KW Reference proteome.
FT CHAIN 1..533
FT /note="Phosphatidylinositol 3,4,5-trisphosphate 3-
FT phosphatase and dual-specificity protein phosphatase PTEN"
FT /id="PRO_0000376825"
FT DOMAIN 14..185
FT /note="Phosphatase tensin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590"
FT DOMAIN 271..406
FT /note="C2 tensin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00589"
FT REGION 235..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 410..533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 235..260
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 261..298
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..506
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..533
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 124
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT CONFLICT 515
FT /note="I -> N (in Ref. 2; AAL99958)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 59831 MW; 9922F7887D6F9F6A CRC64;
MSNLLRVAVS KQKRRYQKNG YDLDLAYITD NIVAMGFPSE KVEGVFRNPM KDVQRFLDQY
HKDHFKVYNL CSERVYDHSK FYGRVGYYPF DDHNAPQFEM IDAFCRDVDA WMKEDSKNIA
VIHCKAGKGR TGLMICCWLM YCGMWKNTED SLRFYAALRT YNQKGVTIPS QIRYVGYFGR
SIRESIKYVP RNVTLKKIVL RPLPKEINLS EVQFNISVGK NCVFNSKEHN MNVVISKKKK
TVVDKNKKDP KKKLTKENSE KNIDSQQQQQ SQSSLSQSQQ GQSSPNMQSL SASGTISSGS
NVGTVNGNTL HQLGGSQFSL SDLADGNTIG NDEYISFEIG ALSLAGDIRI EFTNKQDDRM
FMFWVNTSFV QQLEIIPKSG LDKAHKDKNH KAFPEDFHVE LTFDQLDQQQ SHTTVVASAE
EQTNNQHYPQ SSNNVATSSS HHDNITVVAS DAPQNNNNNN NLNSSNSNNA TTTTTKNNIS
LASSQSNPVQ QESNPSTTTQ VSEENSAPKV EAEKIENSNA SANDSETSSN SSS
