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Information on EC 3.1.3.16 - protein-serine/threonine phosphatase

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EC Tree
     3 Hydrolases
         3.1 Acting on ester bonds
             3.1.3 Phosphoric-monoester hydrolases
                3.1.3.16 protein-serine/threonine phosphatase
IUBMB Comments
A group of enzymes removing the serine- or threonine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes that have been phosphorylated under the action of a kinase (cf. EC 3.1.3.48 protein-tyrosine-phosphatase). The spleen enzyme also acts on phenolic phosphates and phosphamides (cf. EC 3.9.1.1, phosphoamidase).
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This record set is specific for:
UNIPROT: Q8X270
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Word Map
The enzyme appears in viruses and cellular organisms
Synonyms
calcineurin, protein phosphatase, pac-1, dusp1, dusp6, serine/threonine phosphatase, pp2ac, ppm1d, phosphoprotein phosphatase, laforin, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dual-specificity phosphatase
-
3-hydroxy 3-methylglutaryl CoenzymeA reductase phosphatase
-
-
-
-
Aspergillus awamori acid protein phosphatase
-
-
-
-
BCKDH phosphatase
-
-
-
-
branched-chain alpha-keto acid dehydrogenase phosphatase
-
-
-
-
calcineurin
-
-
-
-
Calcineurin A1
-
-
-
-
Calcineurin A2
-
-
-
-
CaM-kinase phosphatase
-
-
-
-
CaMKPase
-
-
-
-
casein phosphatase
-
-
-
-
DRES10
-
-
-
-
Fibroblast growth factor inducible protein 13
-
-
-
-
FIN13
-
-
-
-
Flap wing protein
-
-
-
-
HMG-CoA reductase phosphatase
-
-
-
-
Magnesium-dependent calcium inhibitable phosphatase
-
-
-
-
MCPP
-
-
-
-
Microtubule star protein
-
-
-
-
phosphatase 2A
-
-
-
-
phosphatase 2B
-
-
-
-
phosphatase C-II
-
-
-
-
Phosphatase esp1
-
-
-
-
phosphatase H-II
-
-
-
-
phosphatase I
-
-
-
-
phosphatase IB
-
-
-
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phosphatase II
-
-
-
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phosphatase III
-
-
-
-
phosphatase IV
-
-
-
-
phosphatase SP
-
-
-
-
phosphoprotein phosphatase
-
-
-
-
phosphopyruvate dehydrogenase phosphatase
-
-
-
-
phosphospectrin phosphatase
-
-
-
-
PK-Pase
-
-
-
-
polycation modulated (PCM-) phosphatase
-
-
-
-
PP-1A
-
-
-
-
PP-1B
-
-
-
-
PP-1G
-
-
-
-
PP2A-alpha
-
-
-
-
PP2A-beta
-
-
-
-
PP2C
-
-
-
-
PP2C-alpha
-
-
-
-
PP2C-beta
-
-
-
-
PP2C-delta
-
-
-
-
PP2C-gamma
-
-
-
-
Pp4
-
-
-
-
PP5
-
-
-
-
PP6
-
-
-
-
PPEF
-
-
-
-
PPN
-
-
-
-
PPT
-
-
-
-
protein D phosphatase
-
-
-
-
protein phosphatase
-
-
-
-
Protein phosphatase 1A
-
-
-
-
Protein phosphatase 1B
-
-
-
-
Protein phosphatase 1C
-
-
-
-
Protein phosphatase magnesium-dependent 1 delta
-
-
-
-
Protein phosphatase magnesium-dependent 1 gamma
-
-
-
-
Protein phosphatase with EF calcium-binding domain
-
-
-
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PSPase
-
-
-
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Retinal degeneration C protein
-
-
-
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Suppressor protein SDS21
-
-
-
-
additional information
cf. EC 3.1.3.48
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
protein-serine/threonine-phosphate phosphohydrolase
A group of enzymes removing the serine- or threonine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes that have been phosphorylated under the action of a kinase (cf. EC 3.1.3.48 protein-tyrosine-phosphatase). The spleen enzyme also acts on phenolic phosphates and phosphamides (cf. EC 3.9.1.1, phosphoamidase).
CAS REGISTRY NUMBER
COMMENTARY hide
9025-75-6
-
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]-serine/threonine phosphate + H2O
[a protein]-serine/threonine + 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]-serine/threonine phosphate + H2O
[a protein]-serine/threonine + 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 in 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 mixing 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