T00221
type: Enzyme
rlcp: p52
cath: SHC Adaptor Protein
cath: Protein-Tyrosine Phosphatase; Chain A
ec: https://purl.uniprot.org/enzyme/3.1.3.48
uniprot: Q06124
kegg enzyme: protein-tyrosine-phosphatase
kegg enzyme: phosphotyrosine phosphatase
kegg enzyme: phosphoprotein phosphatase (phosphotyrosine)
kegg enzyme: phosphotyrosine histone phosphatase
kegg enzyme: protein phosphotyrosine phosphatase
kegg enzyme: tyrosylprotein phosphatase
kegg enzyme: phosphotyrosine protein phosphatase
kegg enzyme: phosphotyrosylprotein phosphatase
kegg enzyme: tyrosine O-phosphate phosphatase
kegg enzyme: PPT-phosphatase
kegg enzyme: PTPase
kegg enzyme: [phosphotyrosine]protein phosphatase
kegg enzyme: PTP-phosphatase
kegg substrate: Protein tyrosine phosphate
kegg substrate: H2O
kegg product: Protein tyrosine
kegg product: Orthophosphate
pdb: 2shpA01
pdb: 2shpB01
pdb: 2shpA02
pdb: 2shpB02
pdb: 2shpA03
pdb: 2shpB03
pdb bound state: Unbound
  compound: Protein tyrosine phosphate
  pdb: 2shpA01
pdb bound state: Unbound
  compound: Protein tyrosine phosphate
  pdb: 2shpB01
pdb bound state: Unbound
  compound: Protein tyrosine phosphate
  pdb: 2shpA02
pdb bound state: Unbound
  compound: Protein tyrosine phosphate
  pdb: 2shpB02
pdb bound state: Unbound
  compound: Protein tyrosine phosphate
  pdb: 2shpA03
pdb bound state: Unbound
  compound: Protein tyrosine phosphate
  pdb: 2shpB03
pdb bound state: Unbound
  compound: Protein tyrosine
  pdb: 2shpA01
pdb bound state: Unbound
  compound: Protein tyrosine
  pdb: 2shpB01
pdb bound state: Unbound
  compound: Protein tyrosine
  pdb: 2shpA02
pdb bound state: Unbound
  compound: Protein tyrosine
  pdb: 2shpB02
pdb bound state: Unbound
  compound: Protein tyrosine
  pdb: 2shpA03
pdb bound state: Unbound
  compound: Protein tyrosine
  pdb: 2shpB03
pdb bound state: Unbound
  compound: Orthophosphate
  pdb: 2shpA01
pdb bound state: Unbound
  compound: Orthophosphate
  pdb: 2shpB01
pdb bound state: Unbound
  compound: Orthophosphate
  pdb: 2shpA02
pdb bound state: Unbound
  compound: Orthophosphate
  pdb: 2shpB02
pdb bound state: Unbound
  compound: Orthophosphate
  pdb: 2shpA03
pdb bound state: Unbound
  compound: Orthophosphate
  pdb: 2shpB03
active site residues resources: SHP-2, SH2-containing protein tyrosine phosphatase-2.
active site residues resources: Q06124
reference for catalytic mechanism: ReferenceForCatalyticMechanism
  reference index: 9
  reference section: p.422-444
reference for catalytic mechanism: ReferenceForCatalyticMechanism
  reference index: 10
  reference section: Fig.3, p.635-638
references: Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras.
references: Crystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase.
references: 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.
references: Involvement of Src-homology-2-domain-containing protein-tyrosine phosphatase 2 in T cell activation.
references: Characterization of two SHP-2-associated binding proteins and potential substrates in hematopoietic cells.
references: http://ezcatdb.cbrc.jp/EzCatDB/reference/T00221#6
references: 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.
references: A family of proteins that inhibit signalling through tyrosine kinase receptors.
references: Crystal structure of the tyrosine phosphatase SHP-2.
references: Protein tyrosine phosphatases: mechanisms of catalysis and regulation.
references: SHP-2, SH2-containing protein tyrosine phosphatase-2.
references: 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.
references: Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation.
references: Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor.
references: Regulation of B cell signal transduction by SH2-containing protein-tyrosine phosphatases.
references: Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2.
references: Tyrosine phosphatase SHP-2 dephosphorylates the platelet-derived growth factor receptor but enhances its downstream signalling.
references: Immune signalling: SHP-2 docks at multiple ports.
references: Shp-2 tyrosine phosphatase: signaling one cell or many.
references: Cytoplasmic protein tyrosine phosphatases SHP-1 and SHP-2: regulators of B cell signal transduction.
references: Dissecting the interaction of SHP-2 with PZR, an immunoglobulin family protein containing immunoreceptor tyrosine-based inhibitory motifs.
references: Role of the SHP-2 tyrosine phosphatase in cytokine-induced signaling and cellular response.
references: Chemical dissection of the effects of tyrosine phosphorylation of SHP-2.
references: 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.
comment: 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.

SHC Adaptor Protein
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.30.505.10

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

Protein tyrosine phosphate
type: KeggSubstrate
references: KEGG:C01167
compound type: aromatic ring (only carbon atom)
compound type: peptide/protein
compound type: phosphate group/phosphate ion

H2O
type: KeggSubstrate
references: KEGG:C00001
compound type: H2O
references: CHEBI:15377
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Protein tyrosine
type: KeggProduct
references: KEGG:C00585
compound type: aromatic ring (only carbon atom)
compound type: peptide/protein

Orthophosphate
type: KeggProduct
references: KEGG:C00009
compound type: phosphate group/phosphate ion
references: CHEBI:26078
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

2shpA01
type: Pdb
references: 2shp
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2shp
comment: mutant T2K, F41L

2shpB01
type: Pdb
references: 2shp
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2shp
comment: mutant T2K, F41L

2shpA03
type: Pdb
references: 2shp
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2shp
catalytic residue: ASP 425;CYS 459;ARG 465;THR 466
modified residue: ; (phospholylated)
main chain in catalysis: SER 460;ALA 461;ILE 463;GLY 464;ARG 465
comment: mutant F513S, deletion 528-593, phosphorylated Y542/Y580

2shpB03
type: Pdb
references: 2shp
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:2shp
catalytic residue: ASP 425;CYS 459;ARG 465;THR 466
modified residue: ; (phospholylated)
main chain in catalysis: SER 460;ALA 461;ILE 463;GLY 464;ARG 465
comment: mutant F513S, deletion 528-593, phosphorylated Y542/Y580

Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras.
type: BibliographicResource
comment: PHOSPHORYLATION BY PDGFR.
medline id: 94316690
references: http://www.ncbi.nlm.nih.gov/pubmed/8041791
journal: Proc Natl Acad Sci U S A
volume: 91
pages: 7335-9
published year: 1994
authors:
  item: Bennett AM
  item: Tang TL
  item: Sugimoto S
  item: Walsh CT
  item: Neel BG
references: Q06124

Crystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7521735
journal: Structure
volume: 2
pages: 423-38
published year: 1994
authors:
  item: Lee CH
  item: Kominos D
  item: Jacques S
  item: Margolis B
  item: Schlessinger J
  item: Shoelson SE
  item: Kuriyan J

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.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8895367
journal: Endocrinology
volume: 137
pages: 4944-52
published year: 1996
authors:
  item: Rocchi S
  item: Tartare-Deckert S
  item: Sawka-Verhelle D
  item: Gamha A
  item: van Obberghen E

Involvement of Src-homology-2-domain-containing protein-tyrosine phosphatase 2 in T cell activation.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8647120
journal: Eur J Biochem
volume: 237
pages: 736-42
published year: 1996
authors:
  item: Tailor P
  item: Jascur T
  item: Williams S
  item: von Willebrand M
  item: Couture C
  item: Mustelin T

Characterization of two SHP-2-associated binding proteins and potential substrates in hematopoietic cells.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9195950
journal: J Biol Chem
volume: 272
pages: 16421-30
published year: 1997
authors:
  item: Gu H
  item: Griffin JD
  item: Neel BG

http://ezcatdb.cbrc.jp/EzCatDB/reference/T00221#6
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9312087
journal: J Biol Chem
volume: 272
pages: 24868-75
published year: 1997
authors:
  item: Jackson DE
  item: Kupcho KR
  item: 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.

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.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9038217
journal: J Biol Chem
volume: 272
pages: 5966-73
published year: 1997
authors:
  item: Tenev T
  item: Keilhack H
  item: Tomic S
  item: Stoyanov B
  item: Stein-Gerlach M
  item: Lammers R
  item: Krivtsov AV
  item: Ullrich A
  item: Bohmer FD

A family of proteins that inhibit signalling through tyrosine kinase receptors.
type: BibliographicResource
comment: INTERACTION WITH PTPNS1.
medline id: 97215901
references: http://www.ncbi.nlm.nih.gov/pubmed/9062191
journal: Nature
volume: 386
pages: 181-6
published year: 1997
authors:
  item: Kharitonenkov A
  item: Chen Z
  item: Sures I
  item: Wang H
  item: Schilling J
  item: Ullrich A
references: Q06124

Crystal structure of the tyrosine phosphatase SHP-2.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-526.
medline id: 98150850
references: http://www.ncbi.nlm.nih.gov/pubmed/9491886
journal: Cell
volume: 92
pages: 441-50
published year: 1998
authors:
  item: Hof P
  item: Pluskey S
  item: Dhe-Paganon S
  item: Eck MJ
  item: Shoelson SE
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: Q06124

Protein tyrosine phosphatases: mechanisms of catalysis and regulation.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9818190
journal: Curr Opin Chem Biol
volume: 2
pages: 633-41
published year: 1998
authors:
  item: Denu JM
  item: Dixon JE

SHP-2, SH2-containing protein tyrosine phosphatase-2.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9693956
journal: Int J Biochem Cell Biol
volume: 30
pages: 559-66
published year: 1998
authors:
  item: Stein-Gerlach M
  item: Wallasch C
  item: Ullrich A

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.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9660791
journal: J Biol Chem
volume: 273
pages: 18273-81
published year: 1998
authors:
  item: Gesbert F
  item: Guenzi C
  item: Bertoglio J

Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9535915
journal: J Biol Chem
volume: 273
pages: 9234-42
published year: 1998
authors:
  item: Takada T
  item: Matozaki T
  item: Takeda H
  item: Fukunaga K
  item: Noguchi T
  item: Fujioka Y
  item: Okazaki I
  item: Tsuda M
  item: Yamao T
  item: Ochi F
  item: Kasuga M

Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9600917
journal: Proc Natl Acad Sci U S A
volume: 95
pages: 6061-6
published year: 1998
authors:
  item: Carpenter LR
  item: Farruggella TJ
  item: Symes A
  item: Karow ML
  item: Yancopoulos GD
  item: Stahl N

Regulation of B cell signal transduction by SH2-containing protein-tyrosine phosphatases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9695189
journal: Semin Immunol
volume: 10
pages: 329-47
published year: 1998
authors:
  item: Siminovitch KA
  item: Neel BG

Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9551546
journal: Structure
volume: 6
pages: 249-54
published year: 1998
authors:
  item: Barford D
  item: Neel BG

Tyrosine phosphatase SHP-2 dephosphorylates the platelet-derived growth factor receptor but enhances its downstream signalling.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9931295
journal: Biochem J
volume: 338
pages: 35-9
published year: 1999
authors:
  item: Zhao R
  item: Zhao ZJ

Immune signalling: SHP-2 docks at multiple ports.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10074424
journal: Curr Biol
volume: 9
pages: R129-32
published year: 1999
authors:
  item: Huyer G
  item: Alexander DR

Shp-2 tyrosine phosphatase: signaling one cell or many.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10579910
journal: Exp Cell Res
volume: 253
pages: 47-54
published year: 1999
authors:
  item: Feng GS

Cytoplasmic protein tyrosine phosphatases SHP-1 and SHP-2: regulators of B cell signal transduction.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10781410
journal: Curr Opin Immunol
volume: 12
pages: 307-15
published year: 2000
authors:
  item: Tamir I
  item: Dal Porto JM
  item: Cambier JC

Dissecting the interaction of SHP-2 with PZR, an immunoglobulin family protein containing immunoreceptor tyrosine-based inhibitory motifs.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10681522
journal: J Biol Chem
volume: 275
pages: 5453-9
published year: 2000
authors:
  item: Zhao R
  item: Zhao ZJ

Role of the SHP-2 tyrosine phosphatase in cytokine-induced signaling and cellular response.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12421673
journal: Biochim Biophys Acta
volume: 1592
pages: 297-301
published year: 2002
authors:
  item: Qu CK

Chemical dissection of the effects of tyrosine phosphorylation of SHP-2.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12731888
journal: Biochemistry
volume: 42
pages: 5461-8
published year: 2003
authors:
  item: Lu W
  item: Shen K
  item: Cole PA

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.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12707331
journal: J Immunol
volume: 170
pages: 4539-47
published year: 2003
authors:
  item: Yusa S
  item: Campbell KS