D00154
type: Enzyme
rlcp: p52
cath: Protein-Tyrosine Phosphatase; Chain A
cath: Immunoglobulin-like
ec: https://purl.uniprot.org/enzyme/3.1.3.67
ec: https://purl.uniprot.org/enzyme/3.1.3.16
ec: https://purl.uniprot.org/enzyme/3.1.3.48
csa: 1d5r
uniprot: P60484
kegg enzyme: phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.67
kegg enzyme: PTEN, MMAC1
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.67
kegg enzyme: phosphatidylinositol-3,4,5-trisphosphate 3-phosphohydrolase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.67
kegg enzyme: phosphoprotein phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: protein phosphatase-1
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: protein phosphatase-2A
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: protein phosphatase-2B
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: protein phosphatase-2C
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: protein D phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphospectrin phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: casein phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: Aspergillus awamori acid protein phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: calcineurin
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphatase 2A
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphatase 2B
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphatase II
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphatase IB
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphatase C-II
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: polycation modulated (PCM-) phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphopyruvate dehydrogenase phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphatase SP
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: branched-chain alpha-keto acid dehydrogenase phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: BCKDH phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: 3-hydroxy 3-methylglutaryl coenzymeA reductase phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: HMG-CoA reductase phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphatase H-II
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphatase III
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphatase I
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: protein phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: phosphatase IV
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.16
kegg enzyme: protein-tyrosine-phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.48
kegg enzyme: phosphotyrosine phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.48
kegg enzyme: phosphoprotein phosphatase (phosphotyrosine)
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.48
kegg enzyme: phosphotyrosine histone phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.48
kegg enzyme: protein phosphotyrosine phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.48
kegg enzyme: tyrosylprotein phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.48
kegg enzyme: phosphotyrosine protein phosphatase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/3.1.3.48
kegg pathway: Inositol phosphate metabolism
kegg pathway: Phosphatidylinositol signaling system
kegg cofactor: Magnesium
kegg substrate: H2O
kegg substrate: Phosphatidylinositol-3,4,5-trisphosphate
kegg substrate: Phosphoprotein
kegg substrate: Protein tyrosine phosphate
kegg product: Orthophosphate
kegg product: Phosphatidylinositol 4,5-bisphosphate
kegg product: Protein
kegg product: Protein tyrosine
pdb: 1d5rA01
pdb: 1d5rA02
active site residues resources: P60484
references: PTEN: sometimes taking it off can be better than putting it on.
references: A family of putative tumor suppressors is structurally and functionally conserved in humans and yeast.
references: P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase.
references: Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.
references: Structural assets of a tumor suppressor.
references: Analysis 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.
references: The Cold Spring Harbor Laboratory meeting on tyrosine phosphorylation and cell signaling. Cold Spring Harbor, NY, USA, May 12-16, 1999.
references: Stabilization and productive positioning roles of the C2 domain of PTEN tumor suppressor.
references: Antagonism of PI 3-kinase-dependent signalling pathways by the tumour suppressor protein, PTEN.
references: Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383.
references: PTEN: life as a tumor suppressor.
references: The murine orthologue of the Golgi-localized TPTE protein provides clues to the evolutionary history of the human TPTE gene family.
references: PTEN 2, a Golgi-associated testis-specific homologue of the PTEN tumor suppressor lipid phosphatase.
references: Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.
references: The myotubularin family: from genetic disease to phosphoinositide metabolism.
references: Some protein tyrosine phosphatases target in part to lipid rafts and interact with caveolin-1.
references: PTEN: The down side of PI 3-kinase signalling.
references: Direct identification of PTEN phosphorylation sites.
references: Membrane-binding and activation mechanism of PTEN.
comment: 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).

Protein-Tyrosine Phosphatase; Chain A
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.90.190.10
catalytic domain: index.html

Immunoglobulin-like
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.60.40.1110

Inositol phosphate metabolism
type: KeggPathway
references: KEGG:MAP00562
ec: https://purl.uniprot.org/enzyme/3.1.3.67

Phosphatidylinositol signaling system
type: KeggPathway
references: KEGG:MAP04070
ec: https://purl.uniprot.org/enzyme/3.1.3.67

Magnesium
type: KeggCofactor
references: KEGG:C00305
compound type: divalent metal (Ca2+, Mg2+)
references: CHEBI:18420
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

H2O
type: KeggSubstrate
references: KEGG:C00001
ec: https://purl.uniprot.org/enzyme/3.1.3.67
ec: https://purl.uniprot.org/enzyme/3.1.3.16
ec: https://purl.uniprot.org/enzyme/3.1.3.48
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Phosphatidylinositol-3,4,5-trisphosphate
type: KeggSubstrate
references: KEGG:C05981
ec: https://purl.uniprot.org/enzyme/3.1.3.67
compound type: carbohydrate
compound type: lipid
compound type: phosphate group/phosphate ion

Phosphoprotein
type: KeggSubstrate
references: KEGG:C00562
ec: https://purl.uniprot.org/enzyme/3.1.3.16
compound type: peptide/protein
compound type: phosphate group/phosphate ion

Protein tyrosine phosphate
type: KeggSubstrate
references: KEGG:C01167
ec: https://purl.uniprot.org/enzyme/3.1.3.48
compound type: aromatic ring (only carbon atom)
compound type: peptide/protein
compound type: phosphate group/phosphate ion

Orthophosphate
type: KeggProduct
references: KEGG:C00009
ec: https://purl.uniprot.org/enzyme/3.1.3.67
ec: https://purl.uniprot.org/enzyme/3.1.3.16
ec: https://purl.uniprot.org/enzyme/3.1.3.48
compound type: phosphate group/phosphate ion
references: CHEBI:26078
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Phosphatidylinositol 4,5-bisphosphate
type: KeggProduct
references: KEGG:C04637
ec: https://purl.uniprot.org/enzyme/3.1.3.67
compound type: carbohydrate
compound type: lipid
compound type: phosphate group/phosphate ion

Protein
type: KeggProduct
references: KEGG:C00017
ec: https://purl.uniprot.org/enzyme/3.1.3.16
compound type: peptide/protein

Protein tyrosine
type: KeggProduct
references: KEGG:C00585
ec: https://purl.uniprot.org/enzyme/3.1.3.48
compound type: aromatic ring (only carbon atom)
compound type: peptide/protein

1d5rA01
type: Pdb
references: 1d5r
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1d5r
catalytic residue: ASP 92;CYS 124;ARG 130;THR 131
main chain in catalysis: LYS 125;ALA 126;LYS 128;GLY 129;ARG 130

PTEN: sometimes taking it off can be better than putting it on.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9399917
journal: Am J Hum Genet
volume: 61
pages: 1234-8
published year: 1997
authors:
  item: Myers MP
  item: Tonks NK

A family of putative tumor suppressors is structurally and functionally conserved in humans and yeast.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9367992
journal: J Biol Chem
volume: 272
pages: 29403-6
published year: 1997
authors:
  item: Li L
  item: Ernsting BR
  item: Wishart MJ
  item: Lohse DL
  item: Dixon JE

P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase.
type: BibliographicResource
comment: CHARACTERIZATION
medline id: 97404346
references: http://www.ncbi.nlm.nih.gov/pubmed/9256433
journal: Proc Natl Acad Sci U S A
volume: 94
pages: 9052-7
published year: 1997
authors:
  item: Myers MP
  item: Stolarov JP
  item: Eng C
  item: Li J
  item: Wang SI
  item: Wigler MH
  item: Parsons R
  item: Tonks NK
references: O00633

Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/10555148
journal: Cell
volume: 99
pages: 323-34
published year: 1999
authors:
  item: Lee JO
  item: Yang H
  item: Georgescu MM
  item: Di Cristofano A
  item: Maehama T
  item: Shi Y
  item: Dixon JE
  item: Pandolfi P
  item: Pavletich NP
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Structural assets of a tumor suppressor.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10617421
journal: Science
volume: 286
pages: 2096-7
published year: 1999
authors:
  item: Tonks NK
  item: Myers MP

Analysis 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.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10698713
journal: Biochem J
volume: 346 Pt 3
pages: 827-33
published year: 2000
authors:
  item: Leslie NR
  item: Gray A
  item: Pass I
  item: Orchiston EA
  item: Downes CP

The Cold Spring Harbor Laboratory meeting on tyrosine phosphorylation and cell signaling. Cold Spring Harbor, NY, USA, May 12-16, 1999.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10656991
journal: Biochim Biophys Acta
volume: 1470
pages: R17-20
published year: 2000
authors:
  item: Roussel MF

Stabilization and productive positioning roles of the C2 domain of PTEN tumor suppressor.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11156408
journal: Cancer Res
volume: 60
pages: 7033-8
published year: 2000
authors:
  item: Georgescu MM
  item: Kirsch KH
  item: Kaloudis P
  item: Yang H
  item: Pavletich NP
  item: Hanafusa H

Antagonism of PI 3-kinase-dependent signalling pathways by the tumour suppressor protein, PTEN.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11709086
journal: Biochem Soc Trans
volume: 29
pages: 846-51
published year: 2001
authors:
  item: Downes CP
  item: Bennett D
  item: McConnachie G
  item: Leslie NR
  item: Pass I
  item: MacPhee C
  item: Patel L
  item: Gray A

Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11431330
journal: Cancer Res
volume: 61
pages: 4985-9
published year: 2001
authors:
  item: Tolkacheva T
  item: Boddapati M
  item: Sanfiz A
  item: Tsuchida K
  item: Kimmelman AC
  item: Chan AM

PTEN: life as a tumor suppressor.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11237521
journal: Exp Cell Res
volume: 264
pages: 29-41
published year: 2001
authors:
  item: Simpson L
  item: Parsons R

The murine orthologue of the Golgi-localized TPTE protein provides clues to the evolutionary history of the human TPTE gene family.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11810268
journal: Hum Genet
volume: 109
pages: 569-75
published year: 2001
authors:
  item: Guipponi M
  item: Tapparel C
  item: Jousson O
  item: Scamuffa N
  item: Mas C
  item: Rossier C
  item: Hutter P
  item: Meda P
  item: Lyle R
  item: Reymond A
  item: Antonarakis SE

PTEN 2, a Golgi-associated testis-specific homologue of the PTEN tumor suppressor lipid phosphatase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11279206
journal: J Biol Chem
volume: 276
pages: 21745-53
published year: 2001
authors:
  item: Wu Y
  item: Dowbenko D
  item: Pisabarro MT
  item: Dillard-Telm L
  item: Koeppen H
  item: Lasky LA

Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11494141
journal: Oncogene
volume: 20
pages: 4457-65
published year: 2001
authors:
  item: Unoki M
  item: Nakamura Y

The myotubularin family: from genetic disease to phosphoinositide metabolism.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11275328
journal: Trends Genet
volume: 17
pages: 221-8
published year: 2001
authors:
  item: Laporte J
  item: Blondeau F
  item: Buj-Bello A
  item: Mandel JL

Some protein tyrosine phosphatases target in part to lipid rafts and interact with caveolin-1.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12176037
journal: Biochem Biophys Res Commun
volume: 296
pages: 692-7
published year: 2002
authors:
  item: Caselli A
  item: Mazzinghi B
  item: Camici G
  item: Manao G
  item: Ramponi G

PTEN: The down side of PI 3-kinase signalling.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11858936
journal: Cell Signal
volume: 14
pages: 285-95
published year: 2002
authors:
  item: Leslie NR
  item: Downes CP

Direct identification of PTEN phosphorylation sites.
type: BibliographicResource
comment: PHOSPHORYLATION OF THR-366; SER-370 AND SER-385
medline id: 22233751
references: http://www.ncbi.nlm.nih.gov/pubmed/12297295
journal: FEBS Lett
volume: 528
pages: 145-53
published year: 2002
authors:
  item: Miller SJ
  item: Lou DY
  item: Seldin DC
  item: Lane WS
  item: Neel BG
references: O00633

Membrane-binding and activation mechanism of PTEN.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12808147
journal: Proc Natl Acad Sci U S A
volume: 100
pages: 7491-6
published year: 2003
authors:
  item: Das S
  item: Dixon JE
  item: Cho W

phosphotyrosylprotein phosphatase
type: KeggEnzyme
ec: https://purl.uniprot.org/enzyme/3.1.3.48

tyrosine O-phosphate phosphatase
type: KeggEnzyme
ec: https://purl.uniprot.org/enzyme/3.1.3.48

PPT-phosphatase
type: KeggEnzyme
ec: https://purl.uniprot.org/enzyme/3.1.3.48

PTPase
type: KeggEnzyme
ec: https://purl.uniprot.org/enzyme/3.1.3.48

[phosphotyrosine]protein phosphatase
type: KeggEnzyme
ec: https://purl.uniprot.org/enzyme/3.1.3.48

PTP-phosphatase
type: KeggEnzyme
ec: https://purl.uniprot.org/enzyme/3.1.3.48

Analogue
compound: Phosphatidylinositol 4,5-bisphosphate
pdb: 1d5rA01
ligand het code: TLA

ReferenceForCatalyticMechanism
reference index: 4
reference section: p.326