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Information on EC 3.1.3.48 - protein-tyrosine-phosphatase

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EC Tree
     3 Hydrolases
         3.1 Acting on ester bonds
             3.1.3 Phosphoric-monoester hydrolases
                3.1.3.48 protein-tyrosine-phosphatase
IUBMB Comments
Dephosphorylates O-phosphotyrosine groups in phosphoproteins, such as the products of EC 2.7.10.2, non-specific protein-tyrosine kinase.
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UNIPROT: Q8X270
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Word Map
The enzyme appears in viruses and cellular organisms
Synonyms
ptp1b, protein tyrosine phosphatase, shp-1, shp-2, tyrosine phosphatase, protein phosphatase 2a, acid phosphatase activity, mkp-1, cdc25a, ptpn22, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dual-specificity phosphatase
-
protein tyrosine phosphatase
-
70Z-SHP
-
-
-
-
Brain-derived phosphatase
-
-
-
-
BVP
-
-
-
-
CD148 antigen
-
-
-
-
CD45
-
-
-
-
CD45 antigen
-
-
-
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Cdc25-like protein
-
-
-
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CDK2-associated dual specificity phosphatase
-
-
-
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Ch-1PTPase
-
-
-
-
CPTP1
-
-
-
-
DLAR
-
-
-
-
Dual specificity phosphatase Cdc25A
-
-
-
-
Dual specificity phosphatase Cdc25B
-
-
-
-
Dual specificity phosphatase Cdc25C
-
-
-
-
Dual specificity protein phosphatase hVH1
-
-
-
-
Dual specificity protein phosphatase hVH2
-
-
-
-
Dual specificity protein phosphatase hVH3
-
-
-
-
Dual specificity protein phosphatase PYST1
-
-
-
-
Dual specificity protein phosphatase PYST2
-
-
-
-
Dual specificity protein phosphatase VHR
-
-
-
-
Dual-specificity tyrosine phosphatase TS-DSP6
-
-
-
-
Dual-specificity tyrosine phosphatase YVH1
-
-
-
-
ES cell phosphatase
-
-
-
-
HCP
-
-
-
-
Hematopoietic cell protein-tyrosine phosphatase
-
-
-
-
Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP
-
-
-
-
Hematopoietic protein-tyrosine phosphatase
-
-
-
-
HEPTP
-
-
-
-
HPTP beta-like tyrosine phosphatase
-
-
-
-
HPTP eta
-
-
-
-
hPTPE1
-
-
-
-
ICAAR
-
-
-
-
Islet cell autoantigen related protein
-
-
-
-
kinase associated phosphatase
-
-
-
-
L-CA
-
-
-
-
Late protein H1
-
-
-
-
LCA
-
-
-
-
LCA-related phosphatase
-
-
-
-
Leukocyte antigen related
-
-
-
-
Low molecular weight cytosolic acid phosphatase
-
-
-
-
LRP
-
-
-
-
Lymphoid phosphatase
-
-
-
-
LyP
-
-
-
-
M1851
-
-
-
-
MAP-kinase phosphatase CPG21
-
-
-
-
MEG
-
-
-
-
Mitosis initiation protein
-
-
-
-
Mitosis initiation protein MIH1
-
-
-
-
Mitotic inducer homolog
-
-
-
-
MKP-1 like protein tyrosine phosphatase
-
-
-
-
MPTP
-
-
-
-
MPTP-PEST
-
-
-
-
NC-PTPCOM1
-
-
-
-
Neural-specific protein-tyrosine phosphatase
-
-
-
-
ORF5
-
-
-
-
OST-PTP
-
-
-
-
P19-PTP
-
-
-
-
P80
-
-
-
-
PC12-PTP1
-
-
-
-
Phogrin
-
-
-
-
Phosphacan
-
-
-
-
phosphatase, phosphoprotein (phosphotyrosine)
-
-
-
-
phosphatase, phosphotyrosine
-
-
-
-
phosphoprotein phosphatase (phosphotyrosine)
-
-
-
-
phosphotyrosine histone phosphatase
-
-
-
-
phosphotyrosine phosphatase
-
-
-
-
Phosphotyrosine phosphatase 13
-
-
-
-
phosphotyrosine protein phosphatase
-
-
-
-
phosphotyrosylprotein phosphatase
-
-
-
-
protein phosphotyrosine phosphatase
-
-
-
-
Protein tyrosine phosphatase-NP
-
-
-
-
Protein-protein-tyrosine phosphatase HA2
-
-
-
-
Protein-tyrosine phosphatase 1B
-
-
-
-
Protein-tyrosine phosphatase 1C
-
-
-
-
Protein-tyrosine phosphatase 1E
-
-
-
-
Protein-tyrosine phosphatase 2C
-
-
-
-
Protein-tyrosine phosphatase 2E
-
-
-
-
Protein-tyrosine phosphatase 3CH134
-
-
-
-
Protein-tyrosine phosphatase CL100
-
-
-
-
Protein-tyrosine phosphatase D1
-
-
-
-
Protein-tyrosine phosphatase ERP
-
-
-
-
Protein-tyrosine phosphatase G1
-
-
-
-
Protein-tyrosine phosphatase H1
-
-
-
-
Protein-tyrosine phosphatase LC-PTP
-
-
-
-
Protein-tyrosine phosphatase MEG1
-
-
-
-
Protein-tyrosine phosphatase MEG2
-
-
-
-
Protein-tyrosine phosphatase P19
-
-
-
-
Protein-tyrosine phosphatase PCPTP1
-
-
-
-
Protein-tyrosine phosphatase pez
-
-
-
-
Protein-tyrosine phosphatase PTP-RL10
-
-
-
-
Protein-tyrosine phosphatase PTP36
-
-
-
-
Protein-tyrosine phosphatase PTPL1
-
-
-
-
Protein-tyrosine phosphatase striatum-enriched
-
-
-
-
Protein-tyrosine phosphatase SYP
-
-
-
-
Protein-tyrosine-phosphatase SL
-
-
-
-
Protein-tyrosine-phosphate phosphohydrolase
-
-
-
-
PTP IA-2beta
-
-
-
-
PTP-1B
-
-
-
-
PTP-1C
-
-
-
-
PTP-1D
-
-
-
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PTP-2C
-
-
-
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PTP-BAS
-
-
-
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PTP-E1
-
-
-
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PTP-H1
-
-
-
-
PTP-HA2
-
-
-
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PTP-NP
-
-
-
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PTP-SH2beta
-
-
-
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PTP1C
-
-
-
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PTP1D
-
-
-
-
PTP2C
-
-
-
-
PTPase YVH1
-
-
-
-
PTPase-MEG1
-
-
-
-
PTPase-MEG2
-
-
-
-
PTPG1
-
-
-
-
PTPN6
-
-
-
-
PTPNE6
-
-
-
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PY protein phosphatase
-
-
-
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R-PTP-alpha
-
-
-
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R-PTP-beta
-
-
-
-
R-PTP-delta
-
-
-
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R-PTP-epsilon
-
-
-
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R-PTP-eta
-
-
-
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R-PTP-gamma
-
-
-
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R-PTP-kappa
-
-
-
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R-PTP-mu
-
-
-
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R-PTP-zeta
-
-
-
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Receptor-linked protein-tyrosine phosphatase 10D
-
-
-
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Receptor-linked protein-tyrosine phosphatase 99A
-
-
-
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RNA/RNP complex-intereracting phosphatase
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-
-
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ROL B protein
-
-
-
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RPTPalpha
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-
-
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SH-PTP1
-
-
-
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SH-PTP2
-
-
-
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SH-PTP3
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-
-
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SHP
-
-
-
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Small tyrosine phosphatase
-
-
-
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Small, acidic phosphotyrosine protein phosphatase
-
-
-
-
STEP
-
-
-
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String protein
-
-
-
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Syp
-
-
-
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T-cell protein-tyrosine phosphatase
-
-
-
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T-DSP11
-
-
-
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T200
-
-
-
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TCPTP
-
-
-
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Testis-and skeletal-muscle-specific DSP
-
-
-
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tyrosine O-phosphate phosphatase
-
-
-
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Tyrosine phosphatase CBPTP
-
-
-
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tyrosylprotein phosphatase
-
-
-
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[phosphotyrosine]protein phosphatase
-
-
-
-
additional information
cf. EC 3.1.3.16
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
protein-tyrosine-phosphate phosphohydrolase
Dephosphorylates O-phosphotyrosine groups in phosphoproteins, such as the products of EC 2.7.10.2, non-specific protein-tyrosine kinase.
CAS REGISTRY NUMBER
COMMENTARY hide
79747-53-8
-
97162-86-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
6,8-difluoro-4-methylumbelliferyl phosphate + H2O
6,8-difluoro-4-methylumbelliferone + phosphate
show the reaction diagram
-
-
-
?
[a protein]-tyrosine phosphate + H2O
[a protein]-tyrosine + phosphate
show the reaction diagram
-
-
-
?
additional information
?
-
the enzyme shows dual specificity, protein tyrosine/serine/threonine phosphatase activity
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
[a protein]-tyrosine phosphate + H2O
[a protein]-tyrosine + phosphate
show the reaction diagram
-
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Sodium vanadate
a PTP inhibitor targeting the catalytic site pocket. Vanadate is anchored in the active site of Tk-PTP(form II), stabilized by electrostatic interaction with the guanidinium group of Arg109 and by its oxygen atom-mediated hydrogen bonds with the main chain amides of Met94, Gly95, Leu97, Gly98, and Arg99. The Tk-PTP(form II) P-loop is structurally similar to those of catalytically active DUSP proteins
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.023 - 0.862
6,8-difluoro-4-methylumbelliferyl phosphate
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0143 - 35.8
6,8-difluoro-4-methylumbelliferyl phosphate
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.102 - 338
6,8-difluoro-4-methylumbelliferyl phosphate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
i.e. Pyrococcus kodakaraensis
UniProt
Manually annotated by BRENDA team
i.e. Pyrococcus kodakaraensis
UniProt
Manually annotated by BRENDA team
i.e. Pyrococcus kodakaraensis
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
Tk-PTP adopts a common dual-specificity phosphatase (DUSP) fold, but it undergoes an atypical temperature-dependent conformational change in its P-loop and alpha4-alpha5 loop regions, switching between the inactive and active forms. Tk-PTP contains a PTP signature motif HCxxGxxR, HC93MGGLGR99 in Tk-PTP constituting the phosphate binding loop (or simply called P-loop), contains the catalytic cysteine residue (Cys93) that functions as a nucleophile for dephosphorylation and the conserved arginine residue (Arg99) that anchors the phosphate group of the substrate during the enzyme reaction. Tk-PTP contains dual general acid/base residues, Asp63 or Glu132. Structural analysis of the conformation of the P-loop of Tk-PTP(form I), structure comparisons of PTPs, structure-function analysis of the two enzyme forms, overview. Molecular dynamics simulations
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
Q8X270_THEKO
Thermococcus kodakarensis (strain ATCC BAA-918 / JCM 12380 / KOD1)
147
0
16955
TrEMBL
-
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme Tk-PTP(form I) Tk-PTP(form II) Tk-PTP(G95A), sitting-drop vapor diffusion method, for enzyme form I: mixing 0.001 ml of 10 mg/ml protein solution with 0.001 ml of precipitant solution containing 0.1 M sodium citrate, pH 5.4, 8% w/v PEG 10000, and 14% v/v dioxane, for enzyme form II: mixing of 0.001 ml of 10 mg/ml protein solution with 0.001 ml of precipitant solution containing 0.03 M citric acid, 0.07 M Bis-Tris propane, pH 7.6, 8% w/v PEG 3350, and 0.08 M spermine tetrahydrochloride, and for mutant Tk-PTP(G95A): mixing of 0.001 ml of 10 mg/ml protein solution with 0.001 ml of precipitant solution containing 0.1 M Bis-Tris, pH 6.25, and 0.8 M magnesium formate dehydrate, all at 18°C, X-ray diffraction structure determination and analysis at 1.7-2.3 A resolution, molecular replacement method, model building
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C93S
site-directed mutagenesis, inactive mutant
D63A
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type
D63N
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type
D63N/E132A
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type
E132A
site-directed mutagenesis, the mutant shows about 1.5fold increased activity compared to wild-type
E132L
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type
E132Q
site-directed mutagenesis, the mutant shows about 2.5fold increased activity compared to wild-type
G95A
site-directed mutagenesis, the mutant shows about 10fold increased activity compared to wild-type
Q136A
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type
R124A
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type
R124E
site-directed mutagenesis, the mutant shows reduced activity compared to wild-type
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60
the enzymatic activity of Tk-PTP is not affected by pre-heating the protein at 60°C for 3 h
additional information
the hyperthermostability of Tk-PTP depends on its intramolecular hydrophobic interactions, structure comparisons, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) RIL by nickel affinity chromatography, tag cleavage by thrombin, and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3) RIL
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yun, H.Y.; Lee, J.; Kim, H.; Ryu, H.; Shin, H.C.; Oh, B.H.; Ku, B.; Kim, S.J.
Structural study reveals the temperature-dependent conformational flexibility of Tk-PTP, a protein tyrosine phosphatase from Thermococcus kodakaraensis KOD1
PLoS ONE
13
e0197635
2018
Thermococcus kodakarensis (Q8X270), Thermococcus kodakarensis JCM 12380 (Q8X270), Thermococcus kodakarensis ATCC BAA-918 (Q8X270)
Manually annotated by BRENDA team