DB code: S00298

RLCP classification 1.15.33000.50 : Hydrolysis
CATH domain 3.40.50.270 : Rossmann fold Catalytic domain
E.C. 3.1.3.2 3.1.3.48
CSA 1pnt 1d1q
M-CSA 1pnt 1d1q
MACiE

CATH domain Related DB codes (homologues)
3.40.50.270 : Rossmann fold S00297

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P40347 Low molecular weight phosphotyrosine protein phosphatase
EC 3.1.3.48
Low molecular weight cytosolic acid phosphatase
EC 3.1.3.2
PTPase
NP_015398.1 (Protein)
NM_001184170.1 (DNA/RNA sequence)
PF01451 (LMWPc)
[Graphical View]
P11064 Low molecular weight phosphotyrosine protein phosphatase
LMW-PTPase
LMW-PTP
EC 3.1.3.48
Low molecular weight cytosolic acid phosphatase
EC 3.1.3.2
NP_776403.1 (Protein)
NM_173978.2 (DNA/RNA sequence)
PF01451 (LMWPc)
[Graphical View]
P24666 Low molecular weight phosphotyrosine protein phosphatase
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
NP_004291.1 (Protein)
NM_004300.3 (DNA/RNA sequence)
NP_009030.1 (Protein)
NM_007099.3 (DNA/RNA sequence)
PF01451 (LMWPc)
[Graphical View]

KEGG enzyme name
acid 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 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P40347 PPAL_YEAST Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. A phosphate monoester + H(2)O = an alcohol + phosphate. Cytoplasm.
P11064 PPAC_BOVIN Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. A phosphate monoester + H(2)O = an alcohol + phosphate. Interacts with the SH3 domain of SPTAN1 (By similarity). Cytoplasm.
P24666 PPAC_HUMAN Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. A phosphate monoester + H(2)O = an alcohol + phosphate. Isoform 1 interacts with the SH3 domain of SPTAN1. There is no interaction observed for isoforms 2 or 3. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00361 gamma-Hexachlorocyclohexane degradation 3.1.3.2
MAP00740 Riboflavin metabolism 3.1.3.2

Compound table
Substrates Products Intermediates
KEGG-id C01153 C01167 C00001 C00069 C00009 C00585
E.C. 3.1.3.2
3.1.3.48
3.1.3.2
3.1.3.48
3.1.3.2
3.1.3.2
3.1.3.48
3.1.3.48
Compound Orthophosphoric monoester Protein tyrosine phosphate H2O Alcohol phosphate Protein tyrosine
Type carbohydrate,phosphate group/phosphate ion aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion H2O carbohydrate phosphate group/phosphate ion aromatic ring (only carbon atom),peptide/protein
ChEBI 15377
26078
PubChem 22247451
962
1004
22486802
1d1pA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:EPE Unbound Unbound Unbound
1d1pB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:EPE Unbound Unbound Unbound
1d1qA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:4NP Unbound Unbound Unbound
1d1qB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:PO4 Unbound
1d2aA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:PO4 Unbound
1d2aB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:PO4 Unbound
1bvhA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1c0eA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:PO4 Unbound
1c0eB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:PO4 Unbound
1dg9A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:EPE Unbound Unbound Unbound
1phrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:SO4 Unbound
1pntA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:PO4 Unbound
5pntA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:MES Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1d1pA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 13;ARG 19;ASP 132
1d1pB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 13;ARG 19;ASP 132
1d1qA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ARG 19;ASP 132 mutant C13A
1d1qB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ARG 19;ASP 132 mutant C13A
1d2aA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ARG 19;ASP 132 mutant C13A
1d2aB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ARG 19;ASP 132 mutant C13A
1bvhA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 12;ARG 18;ASP 129
1c0eA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 12;ARG 18;ASP 129 mutant S19A
1c0eB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 212;ARG 218;ASP 329 mutant S219A
1dg9A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 12;ARG 18;ASP 129
1phrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 12;ARG 18;ASP 129
1pntA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 12;ARG 18;ASP 129
5pntA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 12;ARG 18;ASP 129

References for Catalytic Mechanism
References Sections No. 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.7 2
[18]
p.1240
[20]
p.13580-13581, Fig.3 3

References
[1]
Resource
Comments
Medline ID
PubMed ID 8319676
Journal Eur J Biochem
Year 1993
Volume 214
Pages 647-57
Authors Cirri P, Chiarugi P, Camici G, Manao G, Raugei G, Cappugi G, Ramponi G
Title The role of Cys12, Cys17 and Arg18 in the catalytic mechanism of low-M(r) cytosolic phosphotyrosine protein phosphatase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8110762
Journal Biochemistry
Year 1994
Volume 33
Pages 1278-86
Authors Davis JP, Zhou MM, Van Etten RL
Title Spectroscopic and kinetic studies of the histidine residues of bovine low-molecular-weight phosphotyrosyl protein phosphatase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8135752
Journal Biochem J
Year 1994
Volume 298
Pages 427-33
Authors Chiarugi P, Cirri P, Camici G, Manao G, Fiaschi T, Raugei G, Cappugi G, Ramponi G
Title The role of His66 and His72 in the reaction mechanism of bovine liver low-M(r) phosphotyrosine protein phosphatase.
Related PDB
Related UniProtKB
[4]
Resource
Comments NMR
Medline ID 94227053
PubMed ID 8172896
Journal Biochemistry
Year 1994
Volume 33
Pages 5221-9
Authors Zhou MM, Logan TM, Theriault Y, Van Etten RL, Fesik SW
Title Backbone 1H, 13C, and 15N assignments and secondary structure of bovine low molecular weight phosphotyrosyl protein phosphatase.
Related PDB
Related UniProtKB P11064
[5]
Resource
Comments NMR
Medline ID
PubMed ID 7727361
Journal Biochemistry
Year 1994
Volume 33
Pages 11087-96
Authors Logan TM, Zhou MM, Nettesheim DG, Meadows RP, Van Etten RL, Fesik SW
Title Solution structure of a low molecular weight protein tyrosine phosphatase.
Related PDB 1bvh
Related UniProtKB
[6]
Resource
Comments X-ray crystallography (2.2 Angstroms)
Medline ID
PubMed ID 7537084
Journal Biochemistry
Year 1994
Volume 33
Pages 11097-105
Authors Zhang M, Van Etten RL, Stauffacher CV
Title Crystal structure of bovine heart phosphotyrosyl phosphatase at 2.2-A resolution.
Related PDB 1pnt
Related UniProtKB
[7]
Resource
Comments X-ray crystallography
Medline ID 94329182
PubMed ID 8052313
Journal Nature
Year 1994
Volume 370
Pages 575-8
Authors Su XD, Taddei N, Stefani M, Ramponi G, Nordlund P
Title The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase.
Related PDB 1phr
Related UniProtKB P11064
[8]
Resource
Comments
Medline ID
PubMed ID 7929301
Journal J Biol Chem
Year 1994
Volume 269
Pages 25947-50
Authors Zhang Z, Harms E, Van Etten RL
Title Asp129 of low molecular weight protein tyrosine phosphatase is involved in leaving group protonation.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8132604
Journal J Biol Chem
Year 1994
Volume 269
Pages 8734-40
Authors Davis JP, Zhou MM, Van Etten RL
Title Kinetic and site-directed mutagenesis studies of the cysteine residues of bovine low molecular weight phosphotyrosyl protein phosphatase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 7577995
Journal Biochemistry
Year 1995
Volume 34
Pages 13982-7
Authors Hengge AC, Sowa GA, Wu L, Zhang ZY
Title Nature of the transition state of the protein-tyrosine phosphatase-catalyzed reaction.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8611532
Journal Biochemistry
Year 1996
Volume 35
Pages 5426-34
Authors Wu L, Zhang ZY
Title Probing the function of Asp128 in the lower molecular weight protein-tyrosine phosphatase-catalyzed reaction. A pre-steady-state and steady-state kinetic investigation.
Related PDB
Related UniProtKB
[12]
Resource
Comments X-ray crystallography (2.2 Angstroms) (with the transition state analog vanadate)
Medline ID 97146457
PubMed ID 8993313
Journal Biochemistry
Year 1997
Volume 36
Pages 15-23
Authors Zhang M, Zhou M, Van Etten RL, Stauffacher CV
Title Crystal structure of bovine low molecular weight phosphotyrosyl phosphatase complexed with the transition state analog vanadate.
Related PDB
Related UniProtKB P11064
[13]
Resource
Comments Review
Medline ID
PubMed ID 9147129
Journal Int J Biochem Cell Biol
Year 1997
Volume 29
Pages 279-92
Authors Ramponi G, Stefani M
Title Structural, catalytic, and functional properties of low M(r), phosphotyrosine protein phosphatases. Evidence of a long evolutionary history.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9201938
Journal Biochemistry
Year 1997
Volume 36
Pages 7928-36
Authors Hengge AC, Zhao Y, Wu L, Zhang ZY
Title Examination of the transition state of the low-molecular mass small tyrosine phosphatase 1. Comparisons with other protein phosphatases.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9488671
Journal J Biol Chem
Year 1998
Volume 273
Pages 5484-92
Authors Zhao Y, Wu L, Noh SJ, Guan KL, Zhang ZY
Title Altering the nucleophile specificity of a protein-tyrosine phosphatase-catalyzed reaction. Probing the function of the invariant glutamine residues.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-ray crystallography (2.2 Angstroms)
Medline ID 98371007
PubMed ID 9705307
Journal J Biol Chem
Year 1998
Volume 273
Pages 21714-20
Authors Zhang M, Stauffacher CV, Lin D, Van Etten RL
Title Crystal structure of a human low molecular weight phosphotyrosyl phosphatase. Implications for substrate specificity.
Related PDB 5pnt
Related UniProtKB P24666
[17]
Resource
Comments X-ray crystallography (S19A mutant)
Medline ID
PubMed ID 10512620
Journal Biochemistry
Year 1999
Volume 38
Pages 11651-8
Authors Tabernero L, Evans BN, Tishmack PA, Van Etten RL, Stauffacher CV
Title The structure of the bovine protein tyrosine phosphatase dimer reveals a potential self-regulation mechanism.
Related PDB 1c0e
Related UniProtKB
[18]
Resource
Comments X-ray crystallography (with adenine which acts as an activator.)
Medline ID
PubMed ID 10684601
Journal Biochemistry
Year 2000
Volume 39
Pages 1234-42
Authors Wang S, Stauffacher CV, Van Etten RL
Title Structural and mechanistic basis for the activation of a low-molecular weight protein tyrosine phosphatase by adenine.
Related PDB 1d2a
Related UniProtKB
[19]
Resource
Comments X-ray crystallography (wild type;2.2 Angstroms, mutant;1.7 Angstroms)
Medline ID
PubMed ID 10684639
Journal Biochemistry
Year 2000
Volume 39
Pages 1903-14
Authors Wang S, Tabernero L, Zhang M, Harms E, Van Etten RL, Stauffacher CV
Title Crystal structures of a low-molecular weight protein tyrosine phosphatase from Saccharomyces cerevisiae and its complex with the substrate p-nitrophenyl phosphate.
Related PDB 1d1p 1d1q
Related UniProtKB
[20]
Resource
Comments X-ray crystallography (of the other but similar protein)
Medline ID
PubMed ID 11698660
Journal Proc Natl Acad Sci U S A
Year 2001
Volume 98
Pages 13577-82
Authors Bennett MS, Guan Z, Laurberg M, Su XD
Title Bacillus subtilis arsenate reductase is structurally and functionally similar to low molecular weight protein tyrosine phosphatases.
Related PDB
Related UniProtKB

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).

Created Updated
2002-08-01 2009-04-03