PTEN_XENLA
ID PTEN_XENLA Reviewed; 402 AA.
AC Q9PUT6;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 117.
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 {ECO:0000312|EMBL:AAD46165.1};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000312|EMBL:AAD46165.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis {ECO:0000312|EMBL:AAD46165.1};
RX PubMed=10555148; DOI=10.1016/s0092-8674(00)81663-3;
RA Lee J.-O., Yang H., Georgescu M.-M., Di Cristofano A., Maehama T., Shi Y.,
RA Dixon J.E., Pandolfi P., Pavletich N.P.;
RT "Crystal structure of the PTEN tumor suppressor: implications for its
RT phosphoinositide phosphatase activity and membrane association.";
RL Cell 99:323-334(1999).
CC -!- FUNCTION: 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 neuron positioning, dendritic development and synapse
CC formation. May be a negative regulator of insulin signaling and glucose
CC metabolism in adipose tissue. In motile cells, suppresses the formation
CC of lateral pseudopods and thereby promotes cell polarization and
CC directed movement (By similarity). {ECO:0000250}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P60484};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P60484}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P60484}. Nucleus
CC {ECO:0000250|UniProtKB:P60484}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:P60484}.
CC -!- PTM: Monoubiquitinated. Deubiquitinated (By similarity). {ECO:0000250}.
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; AF144732; AAD46165.1; -; mRNA.
DR RefSeq; NP_001083831.1; NM_001090362.1.
DR AlphaFoldDB; Q9PUT6; -.
DR SMR; Q9PUT6; -.
DR GeneID; 399142; -.
DR KEGG; xla:399142; -.
DR CTD; 399142; -.
DR Xenbase; XB-GENE-491437; pten.L.
DR OrthoDB; 639380at2759; -.
DR Proteomes; UP000186698; Chromosome 7L.
DR Bgee; 399142; Expressed in spleen and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0051717; F:inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR GO; GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity; ISS:UniProtKB.
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:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; ISS:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; ISS:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Apoptosis; Cytoplasm; Hydrolase; Lipid metabolism; Lipid-binding;
KW Neurogenesis; Nucleus; Protein phosphatase; Reference proteome;
KW Tumor suppressor; Ubl conjugation.
FT CHAIN 1..402
FT /note="Phosphatidylinositol 3,4,5-trisphosphate 3-
FT phosphatase and dual-specificity protein phosphatase PTEN"
FT /id="PRO_0000227539"
FT DOMAIN 14..184
FT /note="Phosphatase tensin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590"
FT DOMAIN 189..349
FT /note="C2 tensin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00589"
FT REGION 354..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 400..402
FT /note="PDZ-binding"
FT COMPBIAS 354..369
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 370..384
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 123
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590"
SQ SEQUENCE 402 AA; 46878 MW; E61315E2DAB0850F CRC64;
MTAIIKEFVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI DDVVRFLDSK
HKNHYKIYNL CAERHYDTNK FSCRVAQYPF EDHNPPQLEL IKPFCEDLDQ LLSENENVAA
IHCKAGKGRT GVMICAYLLH RGKFPRAQEA LDFYGEVRTR DKKGVTIPSQ RRYVYYYSYL
LKNSLEYRPV PLLFHKIEFE TIPMFSGSTC NPQFVVYQLK VKIFTSTAGP KRAEKLMYFD
FPQPLPVCGD IKVEFFHKQN KVMKKEKMFH FWVNTFFIPG PEEYSEKVEN GTLVGEQELD
GIYSTERSDN DKEYLTLALT KNDLDKANKD KANRLFSPNF KVKLFFTKTV EESSNSEASS
STSVTPDVSD NEPDHYRYSD TTDSDPENEP FDEDQITQIT KV
