EzCatDB: D00154
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DB codeD00154
RLCP classification1.15.36030.52 : Hydrolysis
CATH domainDomain 13.90.190.10 : Protein-Tyrosine Phosphatase; Chain ACatalytic domain
Domain 22.60.40.1110 : Immunoglobulin-like
E.C.3.1.3.67,3.1.3.16,3.1.3.48
CSA1d5r

CATH domainRelated DB codes (homologues)
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain AM00169,S00458,M00149,T00221

Enzyme Name
UniProtKBKEGG

P60484
Protein namePhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENphosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
   (EC 3.1.3.67)
PTEN, MMAC1
   (EC 3.1.3.67)
phosphatidylinositol-3,4,5-trisphosphate 3-phosphohydrolase
   (EC 3.1.3.67)
phosphoprotein phosphatase
   (EC 3.1.3.16)
protein phosphatase-1
   (EC 3.1.3.16)
protein phosphatase-2A
   (EC 3.1.3.16)
protein phosphatase-2B
   (EC 3.1.3.16)
protein phosphatase-2C
   (EC 3.1.3.16)
protein D phosphatase
   (EC 3.1.3.16)
phosphospectrin phosphatase
   (EC 3.1.3.16)
casein phosphatase
   (EC 3.1.3.16)
Aspergillus awamori acid protein phosphatase
   (EC 3.1.3.16)
calcineurin
   (EC 3.1.3.16)
phosphatase 2A
   (EC 3.1.3.16)
phosphatase 2B
   (EC 3.1.3.16)
phosphatase II
   (EC 3.1.3.16)
phosphatase IB
   (EC 3.1.3.16)
phosphatase C-II
   (EC 3.1.3.16)
polycation modulated (PCM-) phosphatase
   (EC 3.1.3.16)
phosphopyruvate dehydrogenase phosphatase
   (EC 3.1.3.16)
phosphatase SP
   (EC 3.1.3.16)
branched-chain alpha-keto acid dehydrogenase phosphatase
   (EC 3.1.3.16)
BCKDH phosphatase
   (EC 3.1.3.16)
3-hydroxy 3-methylglutaryl coenzymeA reductase phosphatase
   (EC 3.1.3.16)
HMG-CoA reductase phosphatase
   (EC 3.1.3.16)
phosphatase H-II
   (EC 3.1.3.16)
phosphatase III
   (EC 3.1.3.16)
phosphatase I
   (EC 3.1.3.16)
protein phosphatase
   (EC 3.1.3.16)
phosphatase IV
   (EC 3.1.3.16)
protein-tyrosine-phosphatase
   (EC 3.1.3.48)
phosphotyrosine phosphatase
   (EC 3.1.3.48)
phosphoprotein phosphatase (phosphotyrosine)
   (EC 3.1.3.48)
phosphotyrosine histone phosphatase
   (EC 3.1.3.48)
protein phosphotyrosine phosphatase
   (EC 3.1.3.48)
tyrosylprotein phosphatase
   (EC 3.1.3.48)
phosphotyrosine protein phosphatase
   (EC 3.1.3.48)
phosphotyrosylprotein phosphatase
   (EC 3.1.3.48)
tyrosine O-phosphate phosphatase
   (EC 3.1.3.48)
PPT-phosphatase
   (EC 3.1.3.48)
PTPase
   (EC 3.1.3.48)
[phosphotyrosine]protein phosphatase
   (EC 3.1.3.48)
PTP-phosphatase
   (EC 3.1.3.48)
SynonymsEC 3.1.3.16
EC 3.1.3.48
EC 3.1.3.67
Mutated in multiple advanced cancers 1
Phosphatase and tensin homolog
RefSeqNP_000305.3 (Protein)
NM_000314.4 (DNA/RNA sequence)
PfamPF00782 (DSPc)
PF10409 (PTEN_C2)
[Graphical view]

KEGG pathways
MAP codePathwaysE.C.
MAP00562Inositol phosphate metabolism3.1.3.67
MAP04070Phosphatidylinositol signaling system3.1.3.67

UniProtKB:Accession NumberP60484
Entry namePTEN_HUMAN
ActivityPhosphatidylinositol 3,4,5-trisphosphate + H(2)O = phosphatidylinositol 4,5-bisphosphate + phosphate.,A phosphoprotein + H(2)O = a protein + phosphate.,Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.
SubunitMonomer. The unphosphorylated form interacts with the second PDZ domain of AIP1 and with DLG1 and MAST2 in vitro. Interacts with MAGI3.
Subcellular locationCytoplasm.
CofactorMagnesium.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00001C05981C00562C01167C00009C04637C00017C00585
E.C.
3.1.3.67,3.1.3.16,3.1.3.483.1.3.673.1.3.163.1.3.483.1.3.67,3.1.3.16,3.1.3.483.1.3.673.1.3.163.1.3.48
CompoundMagnesiumH2OPhosphatidylinositol-3,4,5-trisphosphatePhosphoproteinProtein tyrosine phosphateOrthophosphatePhosphatidylinositol 4,5-bisphosphateProteinProtein tyrosine
Typedivalent metal (Ca2+, Mg2+)H2Ocarbohydrate,lipid,phosphate group/phosphate ionpeptide/protein,phosphate group/phosphate ionaromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ionphosphate group/phosphate ioncarbohydrate,lipid,phosphate group/phosphate ionpeptide/proteinaromatic ring (only carbon atom),peptide/protein
ChEBI18420
15377



26078



PubChem888
22247451
962



1004
22486802



                 
1d5rA01Unbound UnboundUnboundUnboundUnboundAnalogue:TLAUnboundUnbound
1d5rA02Unbound UnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P60484
pdbCatalytic residuesMain-chain involved in catalysis
          
1d5rA01ASP 92;CYS 124;ARG 130;THR 131
LYS 125;ALA 126;LYS 128;GLY 129;ARG 130
1d5rA02 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]p.326

references
[1]
PubMed ID9399917
JournalAm J Hum Genet
Year1997
Volume61
Pages1234-8
AuthorsMyers MP, Tonks NK
TitlePTEN: sometimes taking it off can be better than putting it on.
[2]
PubMed ID9367992
JournalJ Biol Chem
Year1997
Volume272
Pages29403-6
AuthorsLi L, Ernsting BR, Wishart MJ, Lohse DL, Dixon JE
TitleA family of putative tumor suppressors is structurally and functionally conserved in humans and yeast.
[3]
CommentsCHARACTERIZATION
Medline ID97404346
PubMed ID9256433
JournalProc Natl Acad Sci U S A
Year1997
Volume94
Pages9052-7
AuthorsMyers MP, Stolarov JP, Eng C, Li J, Wang SI, Wigler MH, Parsons R, Tonks NK
TitleP-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase.
Related UniProtKBO00633
[4]
CommentsX-ray crystallography
PubMed ID10555148
JournalCell
Year1999
Volume99
Pages323-34
AuthorsLee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich NP
TitleCrystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.
Related PDB1d5r
[5]
PubMed ID10617421
JournalScience
Year1999
Volume286
Pages2096-7
AuthorsTonks NK, Myers MP
TitleStructural assets of a tumor suppressor.
[6]
PubMed ID10698713
JournalBiochem J
Year2000
Volume346 Pt 3
Pages827-33
AuthorsLeslie NR, Gray A, Pass I, Orchiston EA, Downes CP
TitleAnalysis of the cellular functions of PTEN using catalytic domain and C-terminal mutations: differential effects of C-terminal deletion on signalling pathways downstream of phosphoinositide 3-kinase.
[7]
PubMed ID10656991
JournalBiochim Biophys Acta
Year2000
Volume1470
PagesR17-20
AuthorsRoussel MF
TitleThe Cold Spring Harbor Laboratory meeting on tyrosine phosphorylation and cell signaling. Cold Spring Harbor, NY, USA, May 12-16, 1999.
[8]
PubMed ID11156408
JournalCancer Res
Year2000
Volume60
Pages7033-8
AuthorsGeorgescu MM, Kirsch KH, Kaloudis P, Yang H, Pavletich NP, Hanafusa H
TitleStabilization and productive positioning roles of the C2 domain of PTEN tumor suppressor.
[9]
PubMed ID11709086
JournalBiochem Soc Trans
Year2001
Volume29
Pages846-51
AuthorsDownes CP, Bennett D, McConnachie G, Leslie NR, Pass I, MacPhee C, Patel L, Gray A
TitleAntagonism of PI 3-kinase-dependent signalling pathways by the tumour suppressor protein, PTEN.
[10]
PubMed ID11431330
JournalCancer Res
Year2001
Volume61
Pages4985-9
AuthorsTolkacheva T, Boddapati M, Sanfiz A, Tsuchida K, Kimmelman AC, Chan AM
TitleRegulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383.
[11]
PubMed ID11237521
JournalExp Cell Res
Year2001
Volume264
Pages29-41
AuthorsSimpson L, Parsons R
TitlePTEN: life as a tumor suppressor.
[12]
PubMed ID11810268
JournalHum Genet
Year2001
Volume109
Pages569-75
AuthorsGuipponi M, Tapparel C, Jousson O, Scamuffa N, Mas C, Rossier C, Hutter P, Meda P, Lyle R, Reymond A, Antonarakis SE
TitleThe murine orthologue of the Golgi-localized TPTE protein provides clues to the evolutionary history of the human TPTE gene family.
[13]
PubMed ID11279206
JournalJ Biol Chem
Year2001
Volume276
Pages21745-53
AuthorsWu Y, Dowbenko D, Pisabarro MT, Dillard-Telm L, Koeppen H, Lasky LA
TitlePTEN 2, a Golgi-associated testis-specific homologue of the PTEN tumor suppressor lipid phosphatase.
[14]
PubMed ID11494141
JournalOncogene
Year2001
Volume20
Pages4457-65
AuthorsUnoki M, Nakamura Y
TitleGrowth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.
[15]
PubMed ID11275328
JournalTrends Genet
Year2001
Volume17
Pages221-8
AuthorsLaporte J, Blondeau F, Buj-Bello A, Mandel JL
TitleThe myotubularin family: from genetic disease to phosphoinositide metabolism.
[16]
PubMed ID12176037
JournalBiochem Biophys Res Commun
Year2002
Volume296
Pages692-7
AuthorsCaselli A, Mazzinghi B, Camici G, Manao G, Ramponi G
TitleSome protein tyrosine phosphatases target in part to lipid rafts and interact with caveolin-1.
[17]
PubMed ID11858936
JournalCell Signal
Year2002
Volume14
Pages285-95
AuthorsLeslie NR, Downes CP
TitlePTEN: The down side of PI 3-kinase signalling.
[18]
CommentsPHOSPHORYLATION OF THR-366; SER-370 AND SER-385
Medline ID22233751
PubMed ID12297295
JournalFEBS Lett
Year2002
Volume528
Pages145-53
AuthorsMiller SJ, Lou DY, Seldin DC, Lane WS, Neel BG
TitleDirect identification of PTEN phosphorylation sites.
Related UniProtKBO00633
[19]
PubMed ID12808147
JournalProc Natl Acad Sci U S A
Year2003
Volume100
Pages7491-6
AuthorsDas S, Dixon JE, Cho W
TitleMembrane-binding and activation mechanism of PTEN.

comments
The C-terminal of this enzyme, which seems to be phosphorylated, is not included in the PDB structure.
According to the literature [4], Cys124, Arg130 and Asp92 are catalytic residues. Asp92 acts as a general acid, to protonate the leaving, phonolic oxgen atom.
As the catalytic domain of this enzyme is homologous to dual specificity protein phosphatase 3 (Swiss-prot;P51452; S00458 in EzCatDB), the catalytic mechanism can be similar to that. In the protein phosphatase 3, Ser131 facilitates the reaction by interacting with the thiol group of Cys124. The corresponding residue, Thr131 also seems to interact with Cys124 in this enzyme structure (PDB; 1d5r).

createdupdated
2004-08-172009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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