DB code: M00169

RLCP classification 1.15.36030.52 : Hydrolysis
CATH domain -.-.-.- :
-.-.-.- :
-.-.-.- :
2.30.42.10 : Pdz3 Domain
-.-.-.- :
2.30.42.10 : Pdz3 Domain
-.-.-.- :
2.30.42.10 : Pdz3 Domain
-.-.-.- :
2.30.42.10 : Pdz3 Domain
2.30.42.10 : Pdz3 Domain
-.-.-.- :
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain A Catalytic domain
E.C. 3.1.3.48
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.30.42.10 : Pdz3 Domain T00411
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain A S00458 D00154 M00149 T00221

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q12923 Tyrosine-protein phosphatase non-receptor type 13
EC 3.1.3.48
Protein-tyrosine phosphatase 1E
PTP-E1
hPTPE1
PTP-BAS
Protein-tyrosine phosphatase PTPL1
Fas-associated protein-tyrosine phosphatase 1
FAP-1
NP_006255.1 (Protein)
NM_006264.2 (DNA/RNA sequence)
NP_542414.1 (Protein)
NM_080683.2 (DNA/RNA sequence)
NP_542415.1 (Protein)
NM_080684.2 (DNA/RNA sequence)
NP_542416.1 (Protein)
NM_080685.2 (DNA/RNA sequence)
PF09380 (FERM_C)
PF00373 (FERM_M)
PF09379 (FERM_N)
PF00595 (PDZ)
PF00102 (Y_phosphatase)
[Graphical View]

KEGG enzyme name
protein-tyrosine-phosphatase
phosphotyrosine phosphatase
phosphoprotein phosphatase (phosphotyrosine)
phosphotyrosine histone phosphatase
protein phosphotyrosine phosphatase
tyrosylprotein phosphatase
phosphotyrosine protein phosphatase
phosphotyrosylprotein phosphatase
tyrosine O-phosphate phosphatase
PPT-phosphatase
PTPase
[phosphotyrosine]protein phosphatase
PTP-phosphatase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q12923 PTN13_HUMAN Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. Interacts with TRIP6 and TNFRSF6 (Fas receptor) through its second PDZ domain. Interacts with the C-terminal SVP motif of NGFR through its third PDZ domain. Interacts with the LIM domain of PDLIM4 through its second and fourth PDZ domains. Binds PLEKHA1 and PLEKHA2 through its first PDZ domain. Interacts with BRD7 and ARHGAP29. Cytoplasm, cytoskeleton (By similarity).

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C01167 C00001 C00585 C00009
E.C.
Compound Protein tyrosine phosphate H2O Protein tyrosine Orthophosphate
Type aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion H2O aromatic ring (only carbon atom),peptide/protein phosphate group/phosphate ion
ChEBI 15377
26078
PubChem 22247451
962
1004
22486802
1d5gA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1q7xA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
3pdzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1wchA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:PO4_3478

Reference for Active-site residues
resource references E.C.
Swissprot;Q12923 & literature [13]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1d5gA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1q7xA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
3pdzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1wchA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 2378;CYS 2408;ARG 2414;SER 2415 SER 2409;ALA 2410;ILE 2412;GLY 2413;ARG 2414

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments
Medline ID
PubMed ID 7528537
Journal Biochemistry
Year 1994
Volume 33
Pages 15483-93
Authors Pei D, Lorenz U, Klingmuller U, Neel BG, Walsh CT
Title Intramolecular regulation of protein tyrosine phosphatase SH-PTP1: a new function for Src homology 2 domains.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9417985
Journal J Struct Biol
Year 1997
Volume 120
Pages 201-3
Authors Liang X, Meng W, Niu T, Zhao Z, Zhou GW
Title Expression, purification, and crystallization of the catalytic domain of protein tyrosine phosphatase SHP-1.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9835052
Journal J Biomol NMR
Year 1998
Volume 12
Pages 455-6
Authors Ekiel I, Banville D, Shen SH, Slon-Usakiewicz JJ, Koshy A, Gehring K
Title Main-chain signal assignment for the PDZ2 domain from human protein tyrosine phosphatase hPTP1E and its complex with a C-terminal peptide from the Fas receptor.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9632781
Journal Mol Cell Biol
Year 1998
Volume 18
Pages 3966-73
Authors Hadari YR, Kouhara H, Lax I, Schlessinger J
Title Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation.
Related PDB
Related UniProtKB
[5]
Resource
Comments STRUCTURE BY NMR OF 1361-1456 UNCOMPLEXED AND IN COMPLEX WITH THE C-TERMINUS OF TNFRSF6.
Medline ID 20170882
PubMed ID 10704206
Journal Biochemistry
Year 2000
Volume 39
Pages 2572-80
Authors Kozlov G, Gehring K, Ekiel I
Title Solution structure of the PDZ2 domain from human phosphatase hPTP1E and its interactions with C-terminal peptides from the Fas receptor.
Related PDB 3pdz
Related UniProtKB Q12923
[6]
Resource
Comments
Medline ID
PubMed ID 11500950
Journal J Cell Biochem
Year 2001
Volume 83
Pages 14-20
Authors Yang J, Cheng Z, Niu T, Liang X, Zhao ZJ, Zhou GW
Title Protein tyrosine phosphatase SHP-1 specifically recognizes C-terminal residues of its substrates via helix alpha0.
Related PDB
Related UniProtKB
[7]
Resource
Comments STRUCTURE BY NMR OF 1361-1456 IN COMPLEX WITH THE C-TERMINUS OF THE GUANINE NUCLEOTIDE EXCHANGE FACTOR RA-GEF-2.
Medline ID 22090786
PubMed ID 12095257
Journal J Mol Biol
Year 2002
Volume 320
Pages 813-20
Authors Kozlov G, Banville D, Gehring K, Ekiel I
Title Solution structure of the PDZ2 domain from cytosolic human phosphatase hPTP1E complexed with a peptide reveals contribution of the beta2-beta3 loop to PDZ domain-ligand interactions.
Related PDB 1d5g
Related UniProtKB Q12923
[8]
Resource
Comments
Medline ID
PubMed ID 11884147
Journal J Mol Biol
Year 2002
Volume 316
Pages 1101-10
Authors Walma T, Spronk CA, Tessari M, Aelen J, Schepens J, Hendriks W, Vuister GW
Title Structure, dynamics and binding characteristics of the second PDZ domain of PTP-BL.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 12870871
Journal Biochem Cell Biol
Year 2003
Volume 81
Pages 71-80
Authors Papp R, Ekiel I, English AM
Title ESI-MS and FTIR studies of the interaction between the second PDZ domain of hPTP1E and target peptides.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 14653806
Journal Eur J Biochem
Year 2003
Volume 270
Pages 4789-98
Authors Erdmann KS
Title The protein tyrosine phosphatase PTP-Basophil/Basophil-like. Interacting proteins and molecular functions.
Related PDB
Related UniProtKB
[11]
Resource
Comments NMR Structure
Medline ID
PubMed ID 14596806
Journal J Mol Biol
Year 2003
Volume 334
Pages 143-55
Authors Kachel N, Erdmann KS, Kremer W, Wolff P, Gronwald W, Heumann R, Kalbitzer HR
Title Structure determination and ligand interactions of the PDZ2b domain of PTP-Bas (hPTP1E): splicing-induced modulation of ligand specificity.
Related PDB 1q7x
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 14725761
Journal Structure (Camb)
Year 2004
Volume 12
Pages 11-20
Authors Walma T, Aelen J, Nabuurs SB, Oostendorp M, van den Berk L, Hendriks W, Vuister GW
Title A closed binding pocket and global destabilization modify the binding properties of an alternatively spliced form of the second PDZ domain of PTP-BL.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 15611135
Journal J Biol Chem
Year 2005
Volume 280
Pages 8180-7
Authors Villa F, Deak M, Bloomberg GB, Alessi DR, van Aalten DM
Title Crystal structure of the PTPL1/FAP-1 human tyrosine phosphatase mutated in colorectal cancer: evidence for a second phosphotyrosine substrate recognition pocket.
Related PDB 1wch
Related UniProtKB

Comments
This enzyme is composed of the N-terminal kinase non-noncatalytic domain (KIND), FERM domain, five PDZ domains, and the C-terminal catalytic domain (see [10]). The FERM domain is usually involved in localizing itself to the plasma membrane.
The structures of 1d5g, 1q7x, 3pdz (from PDB) correspond to the second PDZ domain, whilst 1wch corresponds to the catalytic domain.
As the catalytic domain is homologous to other phosphatase domains (S00458, D00154, M00149 in EzCatDB) and the catalytic residues are conserved, the mechanism must be similar to those of the counterparts.

Created Updated
2004-03-19 2009-02-26