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EC Tree
IUBMB Comments Requires active site Mg2+ but also works, to a lesser extent, with Co2+ and Mn2+. The enzyme is highly specific for phosphoethanolamine and phosphocholine.
The taxonomic range for the selected organisms is: Homo sapiens The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
phospho1, phosphorylcholine phosphatase, atpecp1, phosphoethanolamine/phosphocholine phosphatase, phosphatase phospho1, 3x11a, phospho1-3a,
more
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PHOSPHO1-3a
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splice variant, a member of the haloacid dehalogenase family
additional information
PHOSPHO1 belongs to the haloacid dehalogenase superfamily
additional information
PHOSPHO1 is a member of the haloacid dehalogenase superfamily of magnesium-dependent hydrolases
additional information
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PHOSPHO1 is a member of the haloacid dehalogenase superfamily of hydrolases
additional information
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PHOSPHO1 is a member of the haloacid dehalogenase superfamily of Mg2+-dependent hydrolases
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O-phosphoethanolamine + H2O = ethanolamine + phosphate
residues D32 and D203 of catalytic motifs are essential for catalytic activity, residues D43 and D123 are important for substrate binding and specificity
O-phosphoethanolamine + H2O = ethanolamine + phosphate
requires active site Mg2+ but also works, to a lesser extend, with Co2+ and Mn2+, the enzyme is highly specific for phosphoethanolamine and phosphocholine
-
phosphocholine + H2O = choline + phosphate
requires active site Mg2+ but also works, to a lesser extend, with Co2+ and Mn2+, the enzyme is highly specific for phosphoethanolamine and phosphocholine
-
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hydrolysis of phosphoric ester
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-
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phosphoethanolamine phosphohydrolase
Requires active site Mg2+ but also works, to a lesser extent, with Co2+ and Mn2+. The enzyme is highly specific for phosphoethanolamine and phosphocholine.
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O-phosphocholine + H2O
choline + phosphate
-
-
-
?
O-phosphoethanolamine + H2O
ethanolamine + phosphate
-
-
-
?
beta-glycerol phosphate + H2O
glycerol + phosphate
-
poor substrate
-
-
?
D-ribose 5-phosphate + H2O
D-ribose + phosphate
-
poor substrate
-
-
?
O-phosphoethanolamine + H2O
ethanolamine + phosphate
p-nitrophenyl phosphate + H2O
4-nitrophenol + phosphate
-
poor substrate
-
-
?
p-nitrophenyl phosphate + H2O
p-nitrophenol + phosphate
-
-
-
-
?
phosphocholine + H2O
choline + phosphate
pyridoxal 5'-phosphate + H2O
pyridoxal + phosphate
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poor substrate
-
-
?
additional information
?
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O-phosphoethanolamine + H2O
ethanolamine + phosphate
-
-
-
-
?
O-phosphoethanolamine + H2O
ethanolamine + phosphate
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likely a natural substrate, phosphoethanolamine metabolism, PHOSPHO1 is upregulated in mineralizing cells, enzyme is implicated in the generation of phosphate for matrix mineralization
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-
?
O-phosphoethanolamine + H2O
ethanolamine + phosphate
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PHOSPHO1 exhibits high specific activities toward phosphoethanolamine and phosphocholine, phosphoethanolamine is hydrolyzed 1.5times faster than phosphocholine
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-
?
phosphocholine + H2O
choline + phosphate
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likely a natural substrate, phosphocholine metabolism, PHOSPHO1 is upregulated in mineralizing cells, enzyme is implicated in the generation of phosphate for matrix mineralization
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-
?
phosphocholine + H2O
choline + phosphate
-
PHOSPHO1 exhibits high specific activities toward phosphoethanolamine and phosphocholine, phosphocholine is hydrolyzed 1.5times slower than phosphoethanolamine
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-
?
additional information
?
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PHOSPHO1 expression is upregulated in mineralizing cells and is implicated in the generation of inorganic phosphate for matrix mineralization
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?
additional information
?
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PHOSPHO1 expression is upregulated in mineralizing cells and is implicated in the generation of inorganic phosphate for matrix mineralization
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-
?
additional information
?
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three-dimensional model of PHOSPHO1, Asp-43 and Asp-123 may contribute to substrate specificity
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-
?
additional information
?
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three-dimensional model of PHOSPHO1, Asp-43 and Asp-123 may contribute to substrate specificity
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-
?
additional information
?
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high substrate specificity of PHOSPHO1, residual activity with beta-glycerol phosphate, 4-nitrophenyl phosphate, and ribose 5-phosphate, no activity with phospho-L-serine, diphosphate, fructose 6-phosphate, phospho-L-tyrosine, and ATP, overview
-
-
?
additional information
?
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high substrate specificity of PHOSPHO1, residual activity with beta-glycerol phosphate, 4-nitrophenyl phosphate, and ribose 5-phosphate, no activity with phospho-L-serine, diphosphate, fructose 6-phosphate, phospho-L-tyrosine, and ATP, overview
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-
?
additional information
?
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-
PHOSPHO1 may be involved in the mineralization process
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-
?
additional information
?
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not: diphosphate, phospho-L-serine, glycone phosphate, fructose 6-phosphate, phospho-L-tyrosine, ATP
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-
?
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O-phosphocholine + H2O
choline + phosphate
-
-
-
?
O-phosphoethanolamine + H2O
ethanolamine + phosphate
-
-
-
?
O-phosphoethanolamine + H2O
ethanolamine + phosphate
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likely a natural substrate, phosphoethanolamine metabolism, PHOSPHO1 is upregulated in mineralizing cells, enzyme is implicated in the generation of phosphate for matrix mineralization
-
-
?
phosphocholine + H2O
choline + phosphate
-
likely a natural substrate, phosphocholine metabolism, PHOSPHO1 is upregulated in mineralizing cells, enzyme is implicated in the generation of phosphate for matrix mineralization
-
-
?
additional information
?
-
additional information
?
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PHOSPHO1 expression is upregulated in mineralizing cells and is implicated in the generation of inorganic phosphate for matrix mineralization
-
-
?
additional information
?
-
-
PHOSPHO1 expression is upregulated in mineralizing cells and is implicated in the generation of inorganic phosphate for matrix mineralization
-
-
?
additional information
?
-
-
PHOSPHO1 may be involved in the mineralization process
-
-
?
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Co2+
-
stimulates to a lesser extend than Mg2+, higher activity with phosphocholine than with phosphoethanolamine in the presence of Co2+ and Mn2+ most probably due to an allosteric effect caused by a difference in the metal-binding properties of each enzyme-substrate complex
Mn2+
-
stimulates to a lesser extend than Mg2+, higher activity with phosphocholine than with phosphoethanolamine in the presence of Co2+ and Mn2+ most probably due to an allosteric effect caused by a difference in the metal-binding properties of each enzyme-substrate complex
Ni2+
-
stimulates to a lesser extend than Mg2+
additional information
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not activated by Ca2+ or Zn2+
Mg2+
-
Mg2+
Mg2+-dependent, binding site of the catalytic Mg2+
Mg2+
-
-
Mg2+
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high specific Mg2+-dependence, optimum concentration: 2 mM MgCl2
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2-(([3-(3-oxo-1,2-benzothiazol-2(3H)-yl)phenyl]sulfonyl)amino)benzoic acid
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-
2-(2,3-dimethylphenyl)-6-fluoro-1,2-benzothiazol-3(2H)-one
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-
2-(2,5-dimethylphenyl)-1,2-benzothiazol-3(2H)-one
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-
2-(2,5-dimethylphenyl)-6-fluoro-1,2-benzothiazol-3(2H)-one
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-
2-(3-chloro-4-fluorophenyl)-1,2-benzothiazol-3(2H)-one
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-
2-(3-chlorophenyl)-1,2-benzothiazol-3(2H)-one
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2-(3-methylphenyl)-1,2-benzothiazol-3(2H)-one
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2-(4-fluorophenyl)-1,2-benzothiazol-3(2H)-one
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2-(4-methylphenyl)-1,2-benzothiazol-3(2H)-one
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2-phenyl-1,2-benzoisoselenazol-3(2H)-one
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noncompetitive inhibitor
2-phenyl-1,2-benzothiazol-3(2H)-one
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2-[2-(morpholin-4-yl)-5-(morpholin-4-ylsulfonyl)phenyl]-1,2-benzothiazol-3(2H)-one
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2-[4-(dimethylamino)phenyl]-1,2-benzothiazol-3(2H)-one
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2-[4-chloro-3-(morpholin-4-ylsulfonyl)phenyl]-1,2-benzothiazol-3(2H)-one
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2-[4-methyl-3-(morpholin-4-ylsulfonyl)phenyl]-1,2-benzothiazol-3(2H)-one
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2-[5-(morpholin-4-ylsulfonyl)-2-(pyrrolidin-1-yl)phenyl]-1,2-benzothiazol-3(2H)-one
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3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzoic acid
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5-fluoro-2-phenyl-1,2-benzothiazol-3(2H)-one
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6-fluoro-2-(4-fluorophenyl)-1,2-benzothiazol-3(2H)-one
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6-fluoro-2-(4-methoxyphenyl)-1,2-benzothiazol-3(2H)-one
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6-fluoro-2-phenyl-1,2-benzothiazol-3(2H)-one
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ethyl 4-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzoate
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lansoprazole
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noncompetitive inhibitor, reduces activity by 28%
methyl 3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzoate
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N,N-diethyl-3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzenesulfonamide
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N,N-dimethyl-3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzamide
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N,N-dimethyl-3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzenesulfonamide
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N-benzyl-3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzamide
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-
SCH202676
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noncompetitive inhibitor, reduces activity by 16%
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Diabetes Mellitus, Type 2
DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk.
Diabetes Mellitus, Type 2
Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study.
Fractures, Spontaneous
A distinctive patchy osteomalacia characterises Phospho1-deficient mice.
Fractures, Spontaneous
Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing.
Fractures, Spontaneous
PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures.
Infections
Preparation and biophysical characterization of recombinant Pseudomonas aeruginosa phosphorylcholine phosphatase.
Infections
Pseudomonas aeruginosa cholinesterase and phosphorylcholine phosphatase: two enzymes contributing to corneal infection.
Insulin Resistance
PHOSPHO1 is a skeletal regulator of insulin resistance and obesity.
Insulin Resistance
Phosphocholine accumulation and PHOSPHO1 depletion promote adipose tissue thermogenesis.
Metabolic Syndrome
Phosphocholine accumulation and PHOSPHO1 depletion promote adipose tissue thermogenesis.
Obesity
PHOSPHO1 Gene DNA Methylations Are Associated with a Change in HDL-C Response to Simvastatin Treatment.
Obesity
PHOSPHO1 is a skeletal regulator of insulin resistance and obesity.
Obesity
Phosphocholine accumulation and PHOSPHO1 depletion promote adipose tissue thermogenesis.
Osteoarthritis
Lansoprazole is an uncompetitive inhibitor of tissue-nonspecific alkaline phosphatase.
Osteogenesis Imperfecta
An investigation of the mineral in ductile and brittle cortical mouse bone.
Osteomalacia
A distinctive patchy osteomalacia characterises Phospho1-deficient mice.
Osteomalacia
Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing.
phosphoethanolamine/phosphocholine phosphatase deficiency
Ablation of Osteopontin Improves the Skeletal Phenotype of Phospho1(-/-) Mice.
phosphoethanolamine/phosphocholine phosphatase deficiency
Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing.
phosphoethanolamine/phosphocholine phosphatase deficiency
PHOSPHO1 is essential for normal bone fracture healing: An Animal Study.
Pseudomonas Infections
Preparation and biophysical characterization of recombinant Pseudomonas aeruginosa phosphorylcholine phosphatase.
Scoliosis
Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing.
Starvation
Expression Profiles of 2 Phosphate Starvation-Inducible Phosphocholine/Phosphoethanolamine Phosphatases, PECP1 and PS2, in Arabidopsis.
Starvation
Pi starvation-dependent regulation of ethanolamine metabolism by phosphoethanolamine phosphatase PECP1 in Arabidopsis roots.
Vascular Calcification
How To Build a Bone: PHOSPHO1, Biomineralization, and Beyond.
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0.003
O-Phosphoethanolamine
-
pH 6.7, 37°C, 2 mM Mg2+
0.0114
phosphocholine
-
pH 6.7, 37°C, 2 mM Mg2+
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2.27
O-Phosphoethanolamine
-
pH 6.7, 37°C, 2 mM Mg2+
1.98
phosphocholine
-
pH 6.7, 37°C, 2 mM Mg2+
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0.00081
2-(([3-(3-oxo-1,2-benzothiazol-2(3H)-yl)phenyl]sulfonyl)amino)benzoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0047
2-(2,3-dimethylphenyl)-6-fluoro-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.004
2-(2,5-dimethylphenyl)-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.003
2-(2,5-dimethylphenyl)-6-fluoro-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0018
2-(3-chloro-4-fluorophenyl)-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0052
2-(3-chlorophenyl)-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0027
2-(3-methylphenyl)-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0049
2-(4-fluorophenyl)-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0013
2-(4-methylphenyl)-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00094
2-phenyl-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0012
2-[2-(morpholin-4-yl)-5-(morpholin-4-ylsulfonyl)phenyl]-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.011
2-[4-(dimethylamino)phenyl]-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0011
2-[4-chloro-3-(morpholin-4-ylsulfonyl)phenyl]-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0018
2-[4-methyl-3-(morpholin-4-ylsulfonyl)phenyl]-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0075
2-[5-(morpholin-4-ylsulfonyl)-2-(pyrrolidin-1-yl)phenyl]-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0011
3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00094
5-fluoro-2-phenyl-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.01
6-fluoro-2-(4-fluorophenyl)-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0067
6-fluoro-2-(4-methoxyphenyl)-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00074
6-fluoro-2-phenyl-1,2-benzothiazol-3(2H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00281
ebselen
Homo sapiens
-
-
0.0012
ethyl 4-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzoate
Homo sapiens
-
pH and temperature not specified in the publication
0.00471
lansoprazole
Homo sapiens
-
-
0.00082
methyl 3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzoate
Homo sapiens
-
pH and temperature not specified in the publication
0.00056
N,N-diethyl-3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzenesulfonamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00014
N,N-dimethyl-3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0005
N,N-dimethyl-3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzenesulfonamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0023
N-benzyl-3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00197
SCH202676
Homo sapiens
-
-
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0.092
purified recombinant mutant D43N enzyme fragment M19-C267, substrate O-phosphoethanolamine
0.28
purified recombinant mutant D123N enzyme fragment M19-C267, substrate O-phosphoethanolamine
4.96
purified recombinant wild-type enzyme fragment M19-C267, substrate O-phosphoethanolamine
0.0176
-
pH 7.2, 37°C, hydrolysis of pyridoxal 5-phosphate
0.0396
-
pH 7.2, 37°C, hydrolysis of beta-glycerol phosphate
0.0645
-
pH 7.2, 37°C, hydrolysis of p-nitrophenyl phosphate
0.0748
-
pH 7.2, 37°C, hydrolysis of ribose 5-phosphate
2.98
-
pH 7.2, 37°C, hydrolysis of phosphocholine
4.6
-
pH 7.2, 37°C, hydrolysis of phosphoethanolamine
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6 - 7.5
-
above 70% of maximum activity between pH 6 and 7.2, activity with phosphocholine declines significantly above pH 7.2, activity with phosphoethanolamine declines above pH 7.5
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SwissProt
brenda
PHOSPHO1
SwissProt
brenda
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expression of PHOSPHO1
brenda
expression of PHOSPHO1
brenda
expression of PHOSPHO1
brenda
expression of PHOSPHO1
brenda
-
brenda
fetal, expression of PHOSPHO1
brenda
expression of PHOSPHO1
brenda
expression of PHOSPHO1
brenda
osteoblast-like cells, expression of PHOSPHO1
brenda
expression of PHOSPHO1
brenda
expression of PHOSPHO1
brenda
expression of PHOSPHO1
brenda
-
-
brenda
additional information
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no PHOSPHO1 gene expression in non-mineralizing MG-63 osteoblast-like cells
brenda
-
osteoblast-like cells
brenda
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mineralizing osteoblast-like cells, PHOSPHO1 gene expression profile
brenda
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-
brenda
-
-
brenda
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physiological function
transcription of PHOSPHO1 is strongly upregulated during the terminal stages of erythropoiesis, concomitant with increased catabolism of phosphatidylcholine and phosphocholine. Depletion of PHOSPHO1 impairs differentiation of fetal erythroblasts
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PHOP1_HUMAN
267
0
29713
Swiss-Prot
Mitochondrion (Reliability: 3 )
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29700
x * 29700, sequence calculation
32000
-
x * 32000, recombinant PHOSPHO1, SDS-PAGE, Western blot analysis
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?
x * 29700, sequence calculation
?
-
x * 32000, recombinant PHOSPHO1, SDS-PAGE, Western blot analysis
additional information
structure motif analysis using the amino acid sequence structural modelling and ligand docking
additional information
-
structure motif analysis using the amino acid sequence structural modelling and ligand docking
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D123N
site-directed mutagenesis, the mutant enzyme fragment shows reduced activity compared to the wild-type enzyme fragment
D203S
site-directed mutagenesis, inactive mutant enzyme fragment
D32N
site-directed mutagenesis, inactive mutant enzyme fragment
D43N
site-directed mutagenesis, the mutant enzyme fragment shows reduced activity compared to the wild-type enzyme fragment
D43N/D123N
site-directed mutagenesis, inactive mutant enzyme fragment
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recombinant His-tagged wild-type and mutant fragments M19-C267 from Escherichia coli by nickel affinity chromatography to homogeneity
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expression of His-tagged wild-type and mutant fragment comprising residues M19-C267 in Escherichia coli
expression in Escherichia coli TOP10
-
into vector pBAD TOPO TA, expressed in Escherichia coli
-
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medicine
-
may have implications for the diagnosis of hypophosphatasia and treatment of bone mineralization abnormalities such as osteomalacia and pathological soft-tissue ossification, a process clinically significant in atheroscleosis and heart failure
medicine
-
PHOSPHO1 plays a role in the initiation of matrix mineralization
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Roberts, S.J.; Stewart, A.J.; Sadler, P.J.; Farquharson, C.
Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities
Biochem. J.
382
59-65
2004
Homo sapiens
brenda
Houston, B.; Stewart, A.J.; Farquharson, C.
PHOSPHO1-a novel phosphatase specifically expressed at sites of mineralisation in bone and cartilage
Bone
34
629-637
2004
Homo sapiens, Gallus gallus (O73884)
brenda
Stewart, A.J.; Schmid, R.; Blindauer, C.A.; Paisey, S.J.; Farquharson, C.
Comparative modelling of human PHOSPHO1 reveals a new group of phosphatases within the haloacid dehalogenase superfamily
Protein Eng.
16
889-895
2003
Homo sapiens (Q8TCT1), Homo sapiens
brenda
Roberts, S.J.; Stewart, A.J.; Schmid, R.; Blindauer, C.A.; Bond, S.R.; Sadler, P.J.; Farquharson, C.
Probing the substrate specificities of human PHOSPHO1 and PHOSPHO2
Biochim. Biophys. Acta
1752
73-82
2005
Homo sapiens (Q8TCT1), Homo sapiens
brenda
Roberts, S.; Narisawa, S.; Harmey, D.; Millan, J.L.; Farquharson, C.
Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal mineralization
J. Bone Miner. Res.
22
617-627
2007
Gallus gallus, Homo sapiens, Mus musculus
brenda
Roberts, S.J.; Owen, H.C.; Farquharson, C.
Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1
Biochem. Biophys. Res. Commun.
371
872-876
2008
Homo sapiens
brenda
Bravo, Y.; Teriete, P.; Dhanya, R.P.; Dahl, R.; Lee, P.S.; Kiffer-Moreira, T.; Ganji, S.R.; Sergienko, E.; Smith, L.H.; Farquharson, C.; Millan, J.L.; Cosford, N.D.
Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1
Bioorg. Med. Chem. Lett.
24
4308-4311
2014
Homo sapiens
brenda
Huang, N.J.; Lin, Y.C.; Lin, C.Y.; Pishesha, N.; Lewis, C.A.; Freinkman, E.; Farquharson, C.; Millan, J.L.; Lodish, H.
Enhanced phosphocholine metabolism is essential for terminal erythropoiesis
Blood
131
2955-2966
2018
Mus musculus (Q8R2H9), Mus musculus, Homo sapiens (Q8TCT1), Homo sapiens
brenda