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 15377		26078 26078
PubChem		22247451 962 22247451 962		1004 22486802 1004 22486802

1d5gA	Unbound		Unbound	Unbound
1q7xA	Unbound		Unbound	Unbound
3pdzA	Unbound		Unbound	Unbound
1wchA	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
1q7xA
3pdzA
1wchA	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.

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