EzCatDB: S00298
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DB codeS00298
RLCP classification1.15.33000.50 : Hydrolysis
CATH domainDomain 13.40.50.270 : Rossmann foldCatalytic domain
E.C.3.1.3.2,3.1.3.48
CSA1d1q,1pnt

CATH domainRelated DB codes (homologues)
3.40.50.270 : Rossmann foldS00297

Enzyme Name
UniProtKBKEGG

P40347P11064P24666
Protein nameLow molecular weight phosphotyrosine protein phosphataseLow molecular weight phosphotyrosine protein phosphataseLow molecular weight phosphotyrosine protein phosphataseacid phosphatase
   (EC 3.1.3.2)
acid phosphomonoesterase
   (EC 3.1.3.2)
phosphomonoesterase
   (EC 3.1.3.2)
glycerophosphatase
   (EC 3.1.3.2)
acid monophosphatase
   (EC 3.1.3.2)
acid phosphohydrolase
   (EC 3.1.3.2)
acid phosphomonoester hydrolase
   (EC 3.1.3.2)
uteroferrin
   (EC 3.1.3.2)
acid nucleoside diphosphate phosphatase
   (EC 3.1.3.2)
orthophosphoric-monoester phosphohydrolase (acid optimum)
   (EC 3.1.3.2)
protein-tyrosine-phosphatase
   (EC 3.1.3.48)
phosphotyrosine phosphatase
   (EC 3.1.3.48)
phosphoprotein phosphatase (phosphotyrosine)
   (EC 3.1.3.48)
phosphotyrosine histone phosphatase
   (EC 3.1.3.48)
protein phosphotyrosine phosphatase
   (EC 3.1.3.48)
tyrosylprotein phosphatase
   (EC 3.1.3.48)
phosphotyrosine protein phosphatase
   (EC 3.1.3.48)
phosphotyrosylprotein phosphatase
   (EC 3.1.3.48)
tyrosine O-phosphate phosphatase
   (EC 3.1.3.48)
PPT-phosphatase
   (EC 3.1.3.48)
PTPase
   (EC 3.1.3.48)
[phosphotyrosine]protein phosphatase
   (EC 3.1.3.48)
PTP-phosphatase
   (EC 3.1.3.48)
SynonymsEC 3.1.3.48
Low molecular weight cytosolic acid phosphatase
EC 3.1.3.2
PTPase
LMW-PTPase
LMW-PTP
EC 3.1.3.48
Low molecular weight cytosolic acid phosphatase
EC 3.1.3.2
LMW-PTPase
LMW-PTP
EC 3.1.3.48
Low molecular weight cytosolic acid phosphatase
EC 3.1.3.2
Red cell acid phosphatase 1
Adipocyte acid phosphatase
RefSeqNP_015398.1 (Protein)
NM_001184170.1 (DNA/RNA sequence)
NP_776403.1 (Protein)
NM_173978.2 (DNA/RNA sequence)
NP_004291.1 (Protein)
NM_004300.3 (DNA/RNA sequence)
NP_009030.1 (Protein)
NM_007099.3 (DNA/RNA sequence)
PfamPF01451 (LMWPc)
[Graphical view]
PF01451 (LMWPc)
[Graphical view]
PF01451 (LMWPc)
[Graphical view]

KEGG pathways
MAP codePathwaysE.C.
MAP00361gamma-Hexachlorocyclohexane degradation3.1.3.2
MAP00740Riboflavin metabolism3.1.3.2

UniProtKB:Accession NumberP40347P11064P24666
Entry namePPAL_YEASTPPAC_BOVINPPAC_HUMAN
ActivityProtein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.,A phosphate monoester + H(2)O = an alcohol + phosphate.Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.,A phosphate monoester + H(2)O = an alcohol + phosphate.Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.,A phosphate monoester + H(2)O = an alcohol + phosphate.
Subunit
Interacts with the SH3 domain of SPTAN1 (By similarity).Isoform 1 interacts with the SH3 domain of SPTAN1. There is no interaction observed for isoforms 2 or 3.
Subcellular locationCytoplasm.Cytoplasm.Cytoplasm.
Cofactor



Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC01153C01167C00001C00069C00009C00585
E.C.3.1.3.23.1.3.483.1.3.2,3.1.3.483.1.3.23.1.3.2,3.1.3.483.1.3.48
CompoundOrthophosphoric monoesterProtein tyrosine phosphateH2OAlcoholphosphateProtein tyrosine
Typecarbohydrate,phosphate group/phosphate ionaromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ionH2Ocarbohydratephosphate group/phosphate ionaromatic ring (only carbon atom),peptide/protein
ChEBI

15377

26078

PubChem

22247451
962

1004
22486802

              
1d1pAUnboundAnalogue:EPE UnboundUnboundUnbound
1d1pBUnboundAnalogue:EPE UnboundUnboundUnbound
1d1qAUnboundAnalogue:4NP UnboundUnboundUnbound
1d1qBUnboundUnbound UnboundBound:PO4Unbound
1d2aAUnboundUnbound UnboundBound:PO4Unbound
1d2aBUnboundUnbound UnboundBound:PO4Unbound
1bvhAUnboundUnbound UnboundUnboundUnbound
1c0eAUnboundUnbound UnboundBound:PO4Unbound
1c0eBUnboundUnbound UnboundBound:PO4Unbound
1dg9AUnboundAnalogue:EPE UnboundUnboundUnbound
1phrAUnboundUnbound UnboundAnalogue:SO4Unbound
1pntAUnboundUnbound UnboundBound:PO4Unbound
5pntAUnboundAnalogue:MES UnboundUnboundUnbound

Active-site residues
pdbCatalytic residuescomment
          
1d1pACYS  13;ARG  19;ASP 132
 
1d1pBCYS  13;ARG  19;ASP 132
 
1d1qA       ;ARG  19;ASP 132
mutant C13A
1d1qB       ;ARG  19;ASP 132
mutant C13A
1d2aA       ;ARG  19;ASP 132
mutant C13A
1d2aB       ;ARG  19;ASP 132
mutant C13A
1bvhACYS  12;ARG  18;ASP 129
 
1c0eACYS  12;ARG  18;ASP 129
mutant S19A
1c0eBCYS 212;ARG 218;ASP 329
mutant S219A
1dg9ACYS  12;ARG  18;ASP 129
 
1phrACYS  12;ARG  18;ASP 129
 
1pntACYS  12;ARG  18;ASP 129
 
5pntACYS  12;ARG  18;ASP 129
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.652, p.654
[5]p.11094
[6]p.11101-11104
[7]p.576
[8]p.25948-25950
[10]Fig.3
[11]p.5432-5433
[12]p.20-22
[13]p.284-286
[14]p.7933-7935
[15]Fig.72
[18]p.1240
[20]p.13580-13581, Fig.33

references
[1]
PubMed ID8319676
JournalEur J Biochem
Year1993
Volume214
Pages647-57
AuthorsCirri P, Chiarugi P, Camici G, Manao G, Raugei G, Cappugi G, Ramponi G
TitleThe role of Cys12, Cys17 and Arg18 in the catalytic mechanism of low-M(r) cytosolic phosphotyrosine protein phosphatase.
[2]
PubMed ID8110762
JournalBiochemistry
Year1994
Volume33
Pages1278-86
AuthorsDavis JP, Zhou MM, Van Etten RL
TitleSpectroscopic and kinetic studies of the histidine residues of bovine low-molecular-weight phosphotyrosyl protein phosphatase.
[3]
PubMed ID8135752
JournalBiochem J
Year1994
Volume298
Pages427-33
AuthorsChiarugi P, Cirri P, Camici G, Manao G, Fiaschi T, Raugei G, Cappugi G, Ramponi G
TitleThe role of His66 and His72 in the reaction mechanism of bovine liver low-M(r) phosphotyrosine protein phosphatase.
[4]
CommentsNMR
Medline ID94227053
PubMed ID8172896
JournalBiochemistry
Year1994
Volume33
Pages5221-9
AuthorsZhou MM, Logan TM, Theriault Y, Van Etten RL, Fesik SW
TitleBackbone 1H, 13C, and 15N assignments and secondary structure of bovine low molecular weight phosphotyrosyl protein phosphatase.
Related UniProtKBP11064
[5]
CommentsNMR
PubMed ID7727361
JournalBiochemistry
Year1994
Volume33
Pages11087-96
AuthorsLogan TM, Zhou MM, Nettesheim DG, Meadows RP, Van Etten RL, Fesik SW
TitleSolution structure of a low molecular weight protein tyrosine phosphatase.
Related PDB1bvh
[6]
CommentsX-ray crystallography (2.2 Angstroms)
PubMed ID7537084
JournalBiochemistry
Year1994
Volume33
Pages11097-105
AuthorsZhang M, Van Etten RL, Stauffacher CV
TitleCrystal structure of bovine heart phosphotyrosyl phosphatase at 2.2-A resolution.
Related PDB1pnt
[7]
CommentsX-ray crystallography
Medline ID94329182
PubMed ID8052313
JournalNature
Year1994
Volume370
Pages575-8
AuthorsSu XD, Taddei N, Stefani M, Ramponi G, Nordlund P
TitleThe crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase.
Related PDB1phr
Related UniProtKBP11064
[8]
PubMed ID7929301
JournalJ Biol Chem
Year1994
Volume269
Pages25947-50
AuthorsZhang Z, Harms E, Van Etten RL
TitleAsp129 of low molecular weight protein tyrosine phosphatase is involved in leaving group protonation.
[9]
PubMed ID8132604
JournalJ Biol Chem
Year1994
Volume269
Pages8734-40
AuthorsDavis JP, Zhou MM, Van Etten RL
TitleKinetic and site-directed mutagenesis studies of the cysteine residues of bovine low molecular weight phosphotyrosyl protein phosphatase.
[10]
PubMed ID7577995
JournalBiochemistry
Year1995
Volume34
Pages13982-7
AuthorsHengge AC, Sowa GA, Wu L, Zhang ZY
TitleNature of the transition state of the protein-tyrosine phosphatase-catalyzed reaction.
[11]
PubMed ID8611532
JournalBiochemistry
Year1996
Volume35
Pages5426-34
AuthorsWu L, Zhang ZY
TitleProbing the function of Asp128 in the lower molecular weight protein-tyrosine phosphatase-catalyzed reaction. A pre-steady-state and steady-state kinetic investigation.
[12]
CommentsX-ray crystallography (2.2 Angstroms) (with the transition state analog vanadate)
Medline ID97146457
PubMed ID8993313
JournalBiochemistry
Year1997
Volume36
Pages15-23
AuthorsZhang M, Zhou M, Van Etten RL, Stauffacher CV
TitleCrystal structure of bovine low molecular weight phosphotyrosyl phosphatase complexed with the transition state analog vanadate.
Related UniProtKBP11064
[13]
CommentsReview
PubMed ID9147129
JournalInt J Biochem Cell Biol
Year1997
Volume29
Pages279-92
AuthorsRamponi G, Stefani M
TitleStructural, catalytic, and functional properties of low M(r), phosphotyrosine protein phosphatases. Evidence of a long evolutionary history.
[14]
PubMed ID9201938
JournalBiochemistry
Year1997
Volume36
Pages7928-36
AuthorsHengge AC, Zhao Y, Wu L, Zhang ZY
TitleExamination of the transition state of the low-molecular mass small tyrosine phosphatase 1. Comparisons with other protein phosphatases.
[15]
PubMed ID9488671
JournalJ Biol Chem
Year1998
Volume273
Pages5484-92
AuthorsZhao Y, Wu L, Noh SJ, Guan KL, Zhang ZY
TitleAltering the nucleophile specificity of a protein-tyrosine phosphatase-catalyzed reaction. Probing the function of the invariant glutamine residues.
[16]
CommentsX-ray crystallography (2.2 Angstroms)
Medline ID98371007
PubMed ID9705307
JournalJ Biol Chem
Year1998
Volume273
Pages21714-20
AuthorsZhang M, Stauffacher CV, Lin D, Van Etten RL
TitleCrystal structure of a human low molecular weight phosphotyrosyl phosphatase. Implications for substrate specificity.
Related PDB5pnt
Related UniProtKBP24666
[17]
CommentsX-ray crystallography (S19A mutant)
PubMed ID10512620
JournalBiochemistry
Year1999
Volume38
Pages11651-8
AuthorsTabernero L, Evans BN, Tishmack PA, Van Etten RL, Stauffacher CV
TitleThe structure of the bovine protein tyrosine phosphatase dimer reveals a potential self-regulation mechanism.
Related PDB1c0e
[18]
CommentsX-ray crystallography (with adenine which acts as an activator.)
PubMed ID10684601
JournalBiochemistry
Year2000
Volume39
Pages1234-42
AuthorsWang S, Stauffacher CV, Van Etten RL
TitleStructural and mechanistic basis for the activation of a low-molecular weight protein tyrosine phosphatase by adenine.
Related PDB1d2a
[19]
CommentsX-ray crystallography (wild type;2.2 Angstroms, mutant;1.7 Angstroms)
PubMed ID10684639
JournalBiochemistry
Year2000
Volume39
Pages1903-14
AuthorsWang S, Tabernero L, Zhang M, Harms E, Van Etten RL, Stauffacher CV
TitleCrystal structures of a low-molecular weight protein tyrosine phosphatase from Saccharomyces cerevisiae and its complex with the substrate p-nitrophenyl phosphate.
Related PDB1d1p,1d1q
[20]
CommentsX-ray crystallography (of the other but similar protein)
PubMed ID11698660
JournalProc Natl Acad Sci U S A
Year2001
Volume98
Pages13577-82
AuthorsBennett MS, Guan Z, Laurberg M, Su XD
TitleBacillus subtilis arsenate reductase is structurally and functionally similar to low molecular weight protein tyrosine phosphatases.

comments
This enzyme hydrolyzes the tyrosine phosphate.
The paper [6] described the catalytic role of the Arg18, Cys12 and Asp129 (PDB; 1pnt). According to the paper, Arg18 can serve in the orientation and stabilization of the substrate phosphate, whilst Cys12 is the nucleophilic residue, whose thiolate anion will attack the phosphorous atom of substrate phosphate, leading to the phosphoenzyme. During the phosphorylation event, Asp129 can protonate to the leaving group [6]. After the formation of a phosphoenzyme intermediate, the dephosphorylation reaction, which is the rate-limiting step, would occur by attack of water molecule on the phosphorylated cysteine with the subsequent release of the inorganic phosphate [6]. Here, the paper [6] mentioned that the water attacks the intermediate without the assistance of a general base, whilst the literature [7] suggested that Asp129 can serve as ageneral base for the water nucleophile in the dephosphorylation event.
The papers on crystal structures ([6], [7] & [12]) suggested that the phosphorylation reaction proceeds in an in-line associative mechanism (SN2-like reaction), whilst other papers on the biochemical data ([10], [11] & [14]) indicated that this reaction is rather a dissociative one (SN1-like reaction).

createdupdated
2002-08-012009-04-03
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
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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)
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