DB code: D00154

RLCP classification 1.15.36030.52 : Hydrolysis
CATH domain 3.90.190.10 : Protein-Tyrosine Phosphatase; Chain A Catalytic domain
2.60.40.1110 : Immunoglobulin-like
E.C. 3.1.3.67 3.1.3.16 3.1.3.48
CSA 1d5r
M-CSA 1d5r
MACiE

CATH domain Related DB codes (homologues)
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain A M00169 S00458 M00149 T00221

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P60484 Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
EC 3.1.3.67
EC 3.1.3.16
EC 3.1.3.48
Phosphatase and tensin homolog
Mutated in multiple advanced cancers 1
NP_000305.3 (Protein)
NM_000314.4 (DNA/RNA sequence)
PF00782 (DSPc)
PF10409 (PTEN_C2)
[Graphical View]

KEGG enzyme name
phosphatidylinositol-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 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P60484 PTEN_HUMAN Phosphatidylinositol 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. Monomer. The unphosphorylated form interacts with the second PDZ domain of AIP1 and with DLG1 and MAST2 in vitro. Interacts with MAGI3. Cytoplasm. Magnesium.

KEGG Pathways
Map code Pathways E.C.
MAP00562 Inositol phosphate metabolism 3.1.3.67
MAP04070 Phosphatidylinositol signaling system 3.1.3.67

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00001 C05981 C00562 C01167 C00009 C04637 C00017 C00585
E.C. 3.1.3.67
3.1.3.16
3.1.3.48
3.1.3.67
3.1.3.16
3.1.3.48
3.1.3.67
3.1.3.16
3.1.3.48
3.1.3.67
3.1.3.16
3.1.3.48
Compound Magnesium H2O Phosphatidylinositol-3,4,5-trisphosphate Phosphoprotein Protein tyrosine phosphate Orthophosphate Phosphatidylinositol 4,5-bisphosphate Protein Protein tyrosine
Type divalent metal (Ca2+, Mg2+) H2O carbohydrate,lipid,phosphate group/phosphate ion peptide/protein,phosphate group/phosphate ion aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion phosphate group/phosphate ion carbohydrate,lipid,phosphate group/phosphate ion peptide/protein aromatic ring (only carbon atom),peptide/protein
ChEBI 18420
 18420
 		15377
 15377
 		26078
 26078
PubChem 888
 888
 		22247451
 962
 22247451
 962
 		1004
 22486802
 1004
 22486802
1d5rA01 Unbound Unbound Unbound Unbound Unbound Analogue:TLA Unbound Unbound
1d5rA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P60484

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1d5rA01 ASP 92;CYS 124;ARG 130;THR 131 LYS 125;ALA 126;LYS 128;GLY 129;ARG 130
1d5rA02

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.326

References
[1]
Resource
Comments
Medline ID
PubMed ID 9399917
Journal Am J Hum Genet
Year 1997
Volume 61
Pages 1234-8
Authors Myers MP, Tonks NK
Title PTEN: sometimes taking it off can be better than putting it on.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9367992
Journal J Biol Chem
Year 1997
Volume 272
Pages 29403-6
Authors Li L, Ernsting BR, Wishart MJ, Lohse DL, Dixon JE
Title A family of putative tumor suppressors is structurally and functionally conserved in humans and yeast.
Related PDB
Related UniProtKB
[3]
Resource
Comments CHARACTERIZATION
Medline ID 97404346
PubMed ID 9256433
Journal Proc Natl Acad Sci U S A
Year 1997
Volume 94
Pages 9052-7
Authors Myers MP, Stolarov JP, Eng C, Li J, Wang SI, Wigler MH, Parsons R, Tonks NK
Title P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase.
Related PDB
Related UniProtKB O00633
[4]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10555148
Journal Cell
Year 1999
Volume 99
Pages 323-34
Authors Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich NP
Title Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.
Related PDB 1d5r
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10617421
Journal Science
Year 1999
Volume 286
Pages 2096-7
Authors Tonks NK, Myers MP
Title Structural assets of a tumor suppressor.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10698713
Journal Biochem J
Year 2000
Volume 346 Pt 3
Pages 827-33
Authors Leslie NR, Gray A, Pass I, Orchiston EA, Downes CP
Title 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.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10656991
Journal Biochim Biophys Acta
Year 2000
Volume 1470
Pages R17-20
Authors Roussel MF
Title The Cold Spring Harbor Laboratory meeting on tyrosine phosphorylation and cell signaling. Cold Spring Harbor, NY, USA, May 12-16, 1999.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11156408
Journal Cancer Res
Year 2000
Volume 60
Pages 7033-8
Authors Georgescu MM, Kirsch KH, Kaloudis P, Yang H, Pavletich NP, Hanafusa H
Title Stabilization and productive positioning roles of the C2 domain of PTEN tumor suppressor.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11709086
Journal Biochem Soc Trans
Year 2001
Volume 29
Pages 846-51
Authors Downes CP, Bennett D, McConnachie G, Leslie NR, Pass I, MacPhee C, Patel L, Gray A
Title Antagonism of PI 3-kinase-dependent signalling pathways by the tumour suppressor protein, PTEN.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11431330
Journal Cancer Res
Year 2001
Volume 61
Pages 4985-9
Authors Tolkacheva T, Boddapati M, Sanfiz A, Tsuchida K, Kimmelman AC, Chan AM
Title Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11237521
Journal Exp Cell Res
Year 2001
Volume 264
Pages 29-41
Authors Simpson L, Parsons R
Title PTEN: life as a tumor suppressor.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11810268
Journal Hum Genet
Year 2001
Volume 109
Pages 569-75
Authors Guipponi M, Tapparel C, Jousson O, Scamuffa N, Mas C, Rossier C, Hutter P, Meda P, Lyle R, Reymond A, Antonarakis SE
Title The murine orthologue of the Golgi-localized TPTE protein provides clues to the evolutionary history of the human TPTE gene family.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11279206
Journal J Biol Chem
Year 2001
Volume 276
Pages 21745-53
Authors Wu Y, Dowbenko D, Pisabarro MT, Dillard-Telm L, Koeppen H, Lasky LA
Title PTEN 2, a Golgi-associated testis-specific homologue of the PTEN tumor suppressor lipid phosphatase.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11494141
Journal Oncogene
Year 2001
Volume 20
Pages 4457-65
Authors Unoki M, Nakamura Y
Title Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11275328
Journal Trends Genet
Year 2001
Volume 17
Pages 221-8
Authors Laporte J, Blondeau F, Buj-Bello A, Mandel JL
Title The myotubularin family: from genetic disease to phosphoinositide metabolism.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 12176037
Journal Biochem Biophys Res Commun
Year 2002
Volume 296
Pages 692-7
Authors Caselli A, Mazzinghi B, Camici G, Manao G, Ramponi G
Title Some protein tyrosine phosphatases target in part to lipid rafts and interact with caveolin-1.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11858936
Journal Cell Signal
Year 2002
Volume 14
Pages 285-95
Authors Leslie NR, Downes CP
Title PTEN: The down side of PI 3-kinase signalling.
Related PDB
Related UniProtKB
[18]
Resource
Comments PHOSPHORYLATION OF THR-366; SER-370 AND SER-385
Medline ID 22233751
PubMed ID 12297295
Journal FEBS Lett
Year 2002
Volume 528
Pages 145-53
Authors Miller SJ, Lou DY, Seldin DC, Lane WS, Neel BG
Title Direct identification of PTEN phosphorylation sites.
Related PDB
Related UniProtKB O00633
[19]
Resource
Comments
Medline ID
PubMed ID 12808147
Journal Proc Natl Acad Sci U S A
Year 2003
Volume 100
Pages 7491-6
Authors Das S, Dixon JE, Cho W
Title Membrane-binding and activation mechanism of PTEN.
Related PDB
Related UniProtKB

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).

Created Updated
2004-08-17 2009-02-26