DB code: T00221

RLCP classification 1.15.36030.52 : Hydrolysis
CATH domain 3.30.505.10 : SHC Adaptor Protein
3.30.505.10 : SHC Adaptor Protein
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)
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain A M00169 S00458 D00154 M00149
3.30.505.10 : SHC Adaptor Protein M00183 M00043 M00130 M00148 T00256 M00304 M00333 M00339 M00344

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q06124 Tyrosine-protein phosphatase non-receptor type 11
EC 3.1.3.48
Protein-tyrosine phosphatase 1D
PTP-1D
Protein-tyrosine phosphatase 2C
PTP-2C
SH-PTP2
SHP-2
Shp2
SH-PTP3
NP_002825.3 (Protein)
NM_002834.3 (DNA/RNA sequence)
NP_542168.1 (Protein)
NM_080601.1 (DNA/RNA sequence)
PF00017 (SH2)
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
Q06124 PTN11_HUMAN Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. Interacts with phosphorylated LIME1 and BCAR3. Interacts with SHB and INPP5D/SHIP1 (By similarity). Interacts with PTPNS1 and CD84. Interacts with phosphorylated SIT1 and MPZL1. Interacts with FCRL3, FCRL4, FCRL6 and ANKHD1. Cytoplasm.

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
2shpA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2shpB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2shpA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2shpB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2shpA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
2shpB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;Q06124 & literature [10]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
2shpA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant T2K, F41L
2shpB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant T2K, F41L
2shpA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2shpB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2shpA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 425;CYS 459;ARG 465;THR 466 ; (phospholylated) SER 460;ALA 461;ILE 463;GLY 464;ARG 465 mutant F513S, deletion 528-593, phosphorylated Y542/Y580
2shpB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 425;CYS 459;ARG 465;THR 466 ; (phospholylated) SER 460;ALA 461;ILE 463;GLY 464;ARG 465 mutant F513S, deletion 528-593, phosphorylated Y542/Y580

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[9]
p.422-444
[10]
Fig.3, p.635-638

References
[1]
Resource
Comments PHOSPHORYLATION BY PDGFR.
Medline ID 94316690
PubMed ID 8041791
Journal Proc Natl Acad Sci U S A
Year 1994
Volume 91
Pages 7335-9
Authors Bennett AM, Tang TL, Sugimoto S, Walsh CT, Neel BG
Title Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras.
Related PDB
Related UniProtKB Q06124
[2]
Resource
Comments
Medline ID
PubMed ID 7521735
Journal Structure
Year 1994
Volume 2
Pages 423-38
Authors Lee CH, Kominos D, Jacques S, Margolis B, Schlessinger J, Shoelson SE, Kuriyan J
Title Crystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8895367
Journal Endocrinology
Year 1996
Volume 137
Pages 4944-52
Authors Rocchi S, Tartare-Deckert S, Sawka-Verhelle D, Gamha A, van Obberghen E
Title Interaction of SH2-containing protein tyrosine phosphatase 2 with the insulin receptor and the insulin-like growth factor-I receptor: studies of the domains involved using the yeast two-hybrid system.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8647120
Journal Eur J Biochem
Year 1996
Volume 237
Pages 736-42
Authors Tailor P, Jascur T, Williams S, von Willebrand M, Couture C, Mustelin T
Title Involvement of Src-homology-2-domain-containing protein-tyrosine phosphatase 2 in T cell activation.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9195950
Journal J Biol Chem
Year 1997
Volume 272
Pages 16421-30
Authors Gu H, Griffin JD, Neel BG
Title Characterization of two SHP-2-associated binding proteins and potential substrates in hematopoietic cells.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9312087
Journal J Biol Chem
Year 1997
Volume 272
Pages 24868-75
Authors Jackson DE, Kupcho KR, Newman PJ
Title Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of platelet/endothelial cell adhesion molecule-1 (PECAM-1) that are required for the cellular association and activation of the protein-tyrosine phosphatase, SHP-2.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9038217
Journal J Biol Chem
Year 1997
Volume 272
Pages 5966-73
Authors Tenev T, Keilhack H, Tomic S, Stoyanov B, Stein-Gerlach M, Lammers R, Krivtsov AV, Ullrich A, Bohmer FD
Title Both SH2 domains are involved in interaction of SHP-1 with the epidermal growth factor receptor but cannot confer receptor-directed activity to SHP-1/SHP-2 chimera.
Related PDB
Related UniProtKB
[8]
Resource
Comments INTERACTION WITH PTPNS1.
Medline ID 97215901
PubMed ID 9062191
Journal Nature
Year 1997
Volume 386
Pages 181-6
Authors Kharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A
Title A family of proteins that inhibit signalling through tyrosine kinase receptors.
Related PDB
Related UniProtKB Q06124
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-526.
Medline ID 98150850
PubMed ID 9491886
Journal Cell
Year 1998
Volume 92
Pages 441-50
Authors Hof P, Pluskey S, Dhe-Paganon S, Eck MJ, Shoelson SE
Title Crystal structure of the tyrosine phosphatase SHP-2.
Related PDB 2shp
Related UniProtKB Q06124
[10]
Resource
Comments
Medline ID
PubMed ID 9818190
Journal Curr Opin Chem Biol
Year 1998
Volume 2
Pages 633-41
Authors Denu JM, Dixon JE
Title Protein tyrosine phosphatases: mechanisms of catalysis and regulation.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 9693956
Journal Int J Biochem Cell Biol
Year 1998
Volume 30
Pages 559-66
Authors Stein-Gerlach M, Wallasch C, Ullrich A
Title SHP-2, SH2-containing protein tyrosine phosphatase-2.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9660791
Journal J Biol Chem
Year 1998
Volume 273
Pages 18273-81
Authors Gesbert F, Guenzi C, Bertoglio J
Title A new tyrosine-phosphorylated 97-kDa adaptor protein mediates interleukin-2-induced association of SHP-2 with p85-phosphatidylinositol 3-kinase in human T lymphocytes.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9535915
Journal J Biol Chem
Year 1998
Volume 273
Pages 9234-42
Authors Takada T, Matozaki T, Takeda H, Fukunaga K, Noguchi T, Fujioka Y, Okazaki I, Tsuda M, Yamao T, Ochi F, Kasuga M
Title Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9600917
Journal Proc Natl Acad Sci U S A
Year 1998
Volume 95
Pages 6061-6
Authors Carpenter LR, Farruggella TJ, Symes A, Karow ML, Yancopoulos GD, Stahl N
Title Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9695189
Journal Semin Immunol
Year 1998
Volume 10
Pages 329-47
Authors Siminovitch KA, Neel BG
Title Regulation of B cell signal transduction by SH2-containing protein-tyrosine phosphatases.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9551546
Journal Structure
Year 1998
Volume 6
Pages 249-54
Authors Barford D, Neel BG
Title Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9931295
Journal Biochem J
Year 1999
Volume 338
Pages 35-9
Authors Zhao R, Zhao ZJ
Title Tyrosine phosphatase SHP-2 dephosphorylates the platelet-derived growth factor receptor but enhances its downstream signalling.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 10074424
Journal Curr Biol
Year 1999
Volume 9
Pages R129-32
Authors Huyer G, Alexander DR
Title Immune signalling: SHP-2 docks at multiple ports.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 10579910
Journal Exp Cell Res
Year 1999
Volume 253
Pages 47-54
Authors Feng GS
Title Shp-2 tyrosine phosphatase: signaling one cell or many.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 10781410
Journal Curr Opin Immunol
Year 2000
Volume 12
Pages 307-15
Authors Tamir I, Dal Porto JM, Cambier JC
Title Cytoplasmic protein tyrosine phosphatases SHP-1 and SHP-2: regulators of B cell signal transduction.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 10681522
Journal J Biol Chem
Year 2000
Volume 275
Pages 5453-9
Authors Zhao R, Zhao ZJ
Title Dissecting the interaction of SHP-2 with PZR, an immunoglobulin family protein containing immunoreceptor tyrosine-based inhibitory motifs.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 12421673
Journal Biochim Biophys Acta
Year 2002
Volume 1592
Pages 297-301
Authors Qu CK
Title Role of the SHP-2 tyrosine phosphatase in cytokine-induced signaling and cellular response.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 12731888
Journal Biochemistry
Year 2003
Volume 42
Pages 5461-8
Authors Lu W, Shen K, Cole PA
Title Chemical dissection of the effects of tyrosine phosphorylation of SHP-2.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 12707331
Journal J Immunol
Year 2003
Volume 170
Pages 4539-47
Authors Yusa S, Campbell KS
Title Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2) can play a direct role in the inhibitory function of killer cell Ig-like receptors in human NK cells.
Related PDB
Related UniProtKB

Comments
This enzyme is composed of two SH2 domains, and the C-terminal catalytic domain. According to the literature [9], the N-terminal SH2 domain seems to inhibit the catalytic reaction by interacting directly with the active site.
As the catalytic domain is homologous to other phosphatase domains (S00458, D00154, M00149, M00169 in EzCatDB) and the catalytic residues are conserved, the mechanism must be similar to those of the counterparts. The literature [10] confirmed that Cys459, Asp425 and Arg465 act as nucleophile, acid-base, and stabilizer for the phosphate group, respectively, and that loop 460-465 also stabilizes the phosphate group during the catalysis.

Created Updated
2005-03-08 2009-02-26