EzCatDB: T00221
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DB codeT00221
RLCP classification1.15.36030.52 : Hydrolysis
CATH domainDomain 13.30.505.10 : SHC Adaptor Protein
Domain 23.30.505.10 : SHC Adaptor Protein
Domain 33.90.190.10 : Protein-Tyrosine Phosphatase; Chain ACatalytic domain
E.C.3.1.3.48

CATH domainRelated DB codes (homologues)
3.30.505.10 : SHC Adaptor ProteinM00183,M00043,M00130,M00148,T00256,M00304,M00333,M00339,M00344
3.90.190.10 : Protein-Tyrosine Phosphatase; Chain AM00169,S00458,D00154,M00149

Enzyme Name
UniProtKBKEGG

Q06124
Protein nameTyrosine-protein phosphatase non-receptor type 11protein-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
SynonymsEC 3.1.3.48
Protein-tyrosine phosphatase 2C
PTP-2C
PTP-1D
SH-PTP3
SH-PTP2
SHP-2
Shp2
RefSeqNP_002825.3 (Protein)
NM_002834.3 (DNA/RNA sequence)
NP_542168.1 (Protein)
NM_080601.1 (DNA/RNA sequence)
PfamPF00017 (SH2)
PF00102 (Y_phosphatase)
[Graphical view]


UniProtKB:Accession NumberQ06124
Entry namePTN11_HUMAN
ActivityProtein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.
SubunitInteracts 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.
Subcellular locationCytoplasm.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC01167C00001C00585C00009
CompoundProtein tyrosine phosphateH2OProtein tyrosineOrthophosphate
Typearomatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ionH2Oaromatic ring (only carbon atom),peptide/proteinphosphate group/phosphate ion
ChEBI
15377

26078
PubChem
962
22247451

22486802
1004
            
2shpA01Unbound UnboundUnbound
2shpB01Unbound UnboundUnbound
2shpA02Unbound UnboundUnbound
2shpB02Unbound UnboundUnbound
2shpA03Unbound UnboundUnbound
2shpB03Unbound UnboundUnbound

Active-site residues
resource
Swiss-prot;Q06124 & literature [10]
pdbCatalytic residuesModified residuesMain-chain involved in catalysiscomment
            
2shpA01 
 
 
mutant T2K, F41L
2shpB01 
 
 
mutant T2K, F41L
2shpA02 
 
 
 
2shpB02 
 
 
 
2shpA03ASP 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
2shpB03ASP 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
ReferencesSectionsNo. of steps in catalysis
[9]p.422-444
[10]Fig.3, p.635-638

references
[1]
CommentsPHOSPHORYLATION BY PDGFR.
Medline ID94316690
PubMed ID8041791
JournalProc Natl Acad Sci U S A
Year1994
Volume91
Pages7335-9
AuthorsBennett AM, Tang TL, Sugimoto S, Walsh CT, Neel BG
TitleProtein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras.
Related UniProtKBQ06124
[2]
PubMed ID7521735
JournalStructure
Year1994
Volume2
Pages423-38
AuthorsLee CH, Kominos D, Jacques S, Margolis B, Schlessinger J, Shoelson SE, Kuriyan J
TitleCrystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase.
[3]
PubMed ID8895367
JournalEndocrinology
Year1996
Volume137
Pages4944-52
AuthorsRocchi S, Tartare-Deckert S, Sawka-Verhelle D, Gamha A, van Obberghen E
TitleInteraction 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.
[4]
PubMed ID8647120
JournalEur J Biochem
Year1996
Volume237
Pages736-42
AuthorsTailor P, Jascur T, Williams S, von Willebrand M, Couture C, Mustelin T
TitleInvolvement of Src-homology-2-domain-containing protein-tyrosine phosphatase 2 in T cell activation.
[5]
PubMed ID9195950
JournalJ Biol Chem
Year1997
Volume272
Pages16421-30
AuthorsGu H, Griffin JD, Neel BG
TitleCharacterization of two SHP-2-associated binding proteins and potential substrates in hematopoietic cells.
[6]
PubMed ID9312087
JournalJ Biol Chem
Year1997
Volume272
Pages24868-75
AuthorsJackson DE, Kupcho KR, Newman PJ
TitleCharacterization 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.
[7]
PubMed ID9038217
JournalJ Biol Chem
Year1997
Volume272
Pages5966-73
AuthorsTenev T, Keilhack H, Tomic S, Stoyanov B, Stein-Gerlach M, Lammers R, Krivtsov AV, Ullrich A, Bohmer FD
TitleBoth 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.
[8]
CommentsINTERACTION WITH PTPNS1.
Medline ID97215901
PubMed ID9062191
JournalNature
Year1997
Volume386
Pages181-6
AuthorsKharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A
TitleA family of proteins that inhibit signalling through tyrosine kinase receptors.
Related UniProtKBQ06124
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-526.
Medline ID98150850
PubMed ID9491886
JournalCell
Year1998
Volume92
Pages441-50
AuthorsHof P, Pluskey S, Dhe-Paganon S, Eck MJ, Shoelson SE
TitleCrystal structure of the tyrosine phosphatase SHP-2.
Related PDB2shp
Related UniProtKBQ06124
[10]
PubMed ID9818190
JournalCurr Opin Chem Biol
Year1998
Volume2
Pages633-41
AuthorsDenu JM, Dixon JE
TitleProtein tyrosine phosphatases: mechanisms of catalysis and regulation.
[11]
PubMed ID9693956
JournalInt J Biochem Cell Biol
Year1998
Volume30
Pages559-66
AuthorsStein-Gerlach M, Wallasch C, Ullrich A
TitleSHP-2, SH2-containing protein tyrosine phosphatase-2.
[12]
PubMed ID9660791
JournalJ Biol Chem
Year1998
Volume273
Pages18273-81
AuthorsGesbert F, Guenzi C, Bertoglio J
TitleA new tyrosine-phosphorylated 97-kDa adaptor protein mediates interleukin-2-induced association of SHP-2 with p85-phosphatidylinositol 3-kinase in human T lymphocytes.
[13]
PubMed ID9535915
JournalJ Biol Chem
Year1998
Volume273
Pages9234-42
AuthorsTakada T, Matozaki T, Takeda H, Fukunaga K, Noguchi T, Fujioka Y, Okazaki I, Tsuda M, Yamao T, Ochi F, Kasuga M
TitleRoles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen-activated protein kinase activation.
[14]
PubMed ID9600917
JournalProc Natl Acad Sci U S A
Year1998
Volume95
Pages6061-6
AuthorsCarpenter LR, Farruggella TJ, Symes A, Karow ML, Yancopoulos GD, Stahl N
TitleEnhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor.
[15]
PubMed ID9695189
JournalSemin Immunol
Year1998
Volume10
Pages329-47
AuthorsSiminovitch KA, Neel BG
TitleRegulation of B cell signal transduction by SH2-containing protein-tyrosine phosphatases.
[16]
PubMed ID9551546
JournalStructure
Year1998
Volume6
Pages249-54
AuthorsBarford D, Neel BG
TitleRevealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2.
[17]
PubMed ID9931295
JournalBiochem J
Year1999
Volume338
Pages35-9
AuthorsZhao R, Zhao ZJ
TitleTyrosine phosphatase SHP-2 dephosphorylates the platelet-derived growth factor receptor but enhances its downstream signalling.
[18]
PubMed ID10074424
JournalCurr Biol
Year1999
Volume9
PagesR129-32
AuthorsHuyer G, Alexander DR
TitleImmune signalling: SHP-2 docks at multiple ports.
[19]
PubMed ID10579910
JournalExp Cell Res
Year1999
Volume253
Pages47-54
AuthorsFeng GS
TitleShp-2 tyrosine phosphatase: signaling one cell or many.
[20]
PubMed ID10781410
JournalCurr Opin Immunol
Year2000
Volume12
Pages307-15
AuthorsTamir I, Dal Porto JM, Cambier JC
TitleCytoplasmic protein tyrosine phosphatases SHP-1 and SHP-2: regulators of B cell signal transduction.
[21]
PubMed ID10681522
JournalJ Biol Chem
Year2000
Volume275
Pages5453-9
AuthorsZhao R, Zhao ZJ
TitleDissecting the interaction of SHP-2 with PZR, an immunoglobulin family protein containing immunoreceptor tyrosine-based inhibitory motifs.
[22]
PubMed ID12421673
JournalBiochim Biophys Acta
Year2002
Volume1592
Pages297-301
AuthorsQu CK
TitleRole of the SHP-2 tyrosine phosphatase in cytokine-induced signaling and cellular response.
[23]
PubMed ID12731888
JournalBiochemistry
Year2003
Volume42
Pages5461-8
AuthorsLu W, Shen K, Cole PA
TitleChemical dissection of the effects of tyrosine phosphorylation of SHP-2.
[24]
PubMed ID12707331
JournalJ Immunol
Year2003
Volume170
Pages4539-47
AuthorsYusa S, Campbell KS
TitleSrc 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.

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.

createdupdated
2005-03-082009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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