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Information on EC 3.1.3.1 - alkaline phosphatase and Organism(s) Mus musculus and UniProt Accession P09242
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3.1.3.1 alkaline phosphataseIUBMB Comments
Wide specificity. Also catalyses transphosphorylations. The human placental enzyme is a zinc protein. Some enzymes hydrolyse diphosphate (cf. EC 3.6.1.1 inorganic diphosphatase)
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Word Map
- 3.1.3.1
- osteoblast
- osteocalcin
-
osteogenic
- collagen
- aminotransferase
- bilirubin
- women
- mesenchymal
- albumin
- pancreatitis
- marrow
- parathyroid
- phosphorus
- urinary
- cholesterol
- osteoporosis
- creatinine
- resorption
- arterial
- fracture
- children
-
alt
- necrosis
- pain
- femoral
- spine
- transaminase
-
osteogenesis
-
lumbar
- biliary
-
morphogenetic
- osteopontin
- anterior
- bile
- femur
- periodontal
-
radiological
-
gamma-glutamyl
- calcification
- dental
-
postoperative
-
biocompatibility
- gg
-
preoperative
- transpeptidase
- ligament
-
admission
-
postmenopausal
- trabecular
-
hepatoprotective
- biotechnology
- agriculture
- medicine
- food industry
- environmental protection
- analysis
- molecular biology
- diagnostics
- synthesis
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
ap, alkaline phosphatase, bone alkaline phosphatase, placental alkaline phosphatase, alpase, apase, intestinal alkaline phosphatase, tnsalp, phosphomonoesterase, secreted alkaline phosphatase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alkaline phenyl phosphatase
-
-
-
-
alkaline phosphohydrolase
-
-
-
-
alkaline phosphomonoesterase
-
-
-
-
ALP
AP-TNAP
-
-
-
-
APase
-
-
-
-
APASED
-
-
-
-
BC6
-
-
-
-
EAP
-
-
-
-
Germ-cell alkaline phosphatase
-
-
-
-
glycerophosphatase
-
-
-
-
H-AP
-
-
-
-
High molecular weight phosphatase
-
-
-
-
IAP
L-AP
-
-
-
-
Liver/bone/kidney isozyme
-
-
-
-
Low molecular weight phosphatase
-
-
-
-
M-ALP
-
-
-
-
Nagao isozyme
-
-
-
-
non-specific alkaline phosphatase
-
-
-
-
phosphatase, alkaline
-
-
-
-
phosphomonoesterase
-
-
-
-
PLAP-like
-
-
-
-
RAN1
-
-
-
-
Regan isozyme
-
-
-
-
TNSALP
-
-
-
-
ALP
-
-
-
-
IAP
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a phosphate monoester + H2O = an alcohol + phosphate
Wide specificity. Also catalyses transphosphorylations. Some enzymes hydrolyse diphosphate
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-
SYSTEMATIC NAME
IUBMB Comments
phosphate-monoester phosphohydrolase (alkaline optimum)
Wide specificity. Also catalyses transphosphorylations. The human placental enzyme is a zinc protein. Some enzymes hydrolyse diphosphate (cf. EC 3.6.1.1 inorganic diphosphatase)
CAS REGISTRY NUMBER
COMMENTARY
9001-78-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
enzyme is important in bone formation and mineralization
-
?
additional information
?
-
-
the enzyme is involved in the regulation of mineralization of cartilage matrix
-
?
additional information
?
-
-
strong correlations between ALP activity and lipid accumulation. These data suggest that ALP and fat storage are tightly linked during preadipocyte maturation
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
enzyme is important in bone formation and mineralization
-
?
additional information
?
-
-
the enzyme is involved in the regulation of mineralization of cartilage matrix
-
?
additional information
?
-
-
strong correlations between ALP activity and lipid accumulation. These data suggest that ALP and fat storage are tightly linked during preadipocyte maturation
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide
SBI-425, potent inhibitor
5-chloro-2-methoxy-N-[5-(2-methylphenyl)pyridin-3-yl]benzene-1-sulfonamide
-
5-chloro-2-methoxy-N-[5-(3-methylphenyl)pyridin-3-yl]benzene-1-sulfonamide
-
5-chloro-2-methoxy-N-[5-(4-methoxyphenyl)pyridin-3-yl]benzene-1-sulfonamide
-
5-chloro-2-methoxy-N-[5-(4-methylphenyl)pyridin-3-yl]benzene-1-sulfonamide
-
5-chloro-2-methoxy-N-[5-(4-methylpiperazine-1-carbonyl)pyridin-3-yl]benzene-1-sulfonamide
-
5-chloro-N-[5-(4-chlorophenyl)pyridin-3-yl]-2-methoxybenzene-1-sulfonamide
-
5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]-N-ethylpyridine-3-carboxamide
-
5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]-N-methylpyridine-3-carboxamide
-
5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]-N-phenylpyridine-3-carboxamide
-
5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]pyridine-3-carboxamide
SBI-425, potent inhibitor
5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]pyridine-3-carboxylic acid
-
5-[[2-methoxy-5-(trifluoromethoxy)benzene-1-sulfonyl]amino]pyridine-3-carboxamide
-
5-[[5-chloro-2-(trifluoromethoxy)benzene-1-sulfonyl]amino]pyridine-3-carboxamide
-
6-(5-nitro-1-benzothiophen-2-yl)-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole
-
methyl 5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]pyridine-3-carboxylate
-
2-([(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)sulfonyl]amino)-N-(2,5-dimethylphenyl)acetamide
potent inhibitor with good selectivity against both placental and tissue-nonspecific alkaline phosphatase, competitive inhibition. A dose of 10 microM completley inhibits the enzyme expressed by transfected COS-1 cells
N-(3-cyanophenyl)-3-([(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)sulfonyl]amino)propanamide
potent inhibitor with good selectivity against both placental and tissue-nonspecific alkaline phosphatase
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0032
2-([(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)sulfonyl]amino)-N-(2,5-dimethylphenyl)acetamide
pH not specified in the publication, temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0103
2,5-dimethoxy-N-(pyridin-3-yl)benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000322
2-cyano-6-methoxy-N-(pyridin-3-yl)benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000896
2-methoxy-5-methyl-N-(pyridin-3-yl)benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.00149
3-methoxy-2-[(pyridin-3-yl)sulfamoyl]benzamide
Mus musculus
pH and temperature not specified in the publication
0.000876
3-methoxy-N-(pyridin-3-yl)[1,1'-biphenyl]-2-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.00417
5-chloro-2-methoxy-N-(pyridin-3-yl)benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000178
5-chloro-2-methoxy-N-[5-(2-methylphenyl)pyridin-3-yl]benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.00016
5-chloro-2-methoxy-N-[5-(3-methylphenyl)pyridin-3-yl]benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000023
5-chloro-2-methoxy-N-[5-(4-methoxyphenyl)pyridin-3-yl]benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000147
5-chloro-2-methoxy-N-[5-(4-methylphenyl)pyridin-3-yl]benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000671
5-chloro-2-methoxy-N-[5-(4-methylpiperazine-1-carbonyl)pyridin-3-yl]benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000198
5-chloro-N-[5-(4-chlorophenyl)pyridin-3-yl]-2-methoxybenzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000183
5-methyl-3-[3-[3-(trifluoromethyl)phenyl]prop-2-yn-1-yl]oxolan-2-one
Mus musculus
pH and temperature not specified in the publication
0.000014
5-[(5-bromo-2-methoxybenzene-1-sulfonyl)amino]pyridine-3-carboxamide
Mus musculus
pH and temperature not specified in the publication
0.000193
5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]-N-ethylpyridine-3-carboxamide
Mus musculus
pH and temperature not specified in the publication
0.000109
5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]-N-methylpyridine-3-carboxamide
Mus musculus
pH and temperature not specified in the publication
0.00031
5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]-N-phenylpyridine-3-carboxamide
Mus musculus
pH and temperature not specified in the publication
0.000016
5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]pyridine-3-carboxamide
Mus musculus
pH and temperature not specified in the publication
0.000134
5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]pyridine-3-carboxylic acid
Mus musculus
pH and temperature not specified in the publication
0.000019
5-[(5-fluoro-2-methoxybenzene-1-sulfonyl)amino]pyridine-3-carboxamide
Mus musculus
pH and temperature not specified in the publication
0.000131
5-[[2-methoxy-5-(trifluoromethoxy)benzene-1-sulfonyl]amino]pyridine-3-carboxamide
Mus musculus
pH and temperature not specified in the publication
0.000432
5-[[5-chloro-2-(trifluoromethoxy)benzene-1-sulfonyl]amino]pyridine-3-carboxamide
Mus musculus
pH and temperature not specified in the publication
0.000084
6-(1-benzofuran-2-yl)-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole
Mus musculus
pH and temperature not specified in the publication
0.000043
6-(5-nitro-1-benzothiophen-2-yl)-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole
Mus musculus
pH and temperature not specified in the publication
0.000038
6-(thiophen-3-yl)-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole
Mus musculus
pH and temperature not specified in the publication
0.00151
methyl 3-methoxy-2-[(pyridin-3-yl)sulfamoyl]benzoate
Mus musculus
pH and temperature not specified in the publication
0.000065
methyl 5-[(5-chloro-2-methoxybenzene-1-sulfonyl)amino]pyridine-3-carboxylate
Mus musculus
pH and temperature not specified in the publication
0.000026
N-(2-hydroxyethyl)-3-(2,3,4-trichlorophenyl)-1H-pyrazole-5-carboxamide
Mus musculus
pH and temperature not specified in the publication
0.00012
N-([3,3'-bipyridin]-5-yl)-2,5-dimethoxybenzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000073
N-([3,3'-bipyridin]-5-yl)-5-chloro-2-methoxybenzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000073
N-([3,4'-bipyridin]-5-yl)-2,5-dimethoxybenzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.000073
N-([3,4'-bipyridin]-5-yl)-5-chloro-2-methoxybenzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
0.00054
2-([(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)sulfonyl]amino)-N-(2,5-dimethylphenyl)acetamide
Mus musculus
pH not specified in the publication, temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
the placental isoenzyme is encoded by a gene identical to the gene expressed in mouse, liver, kidney, and tetracarcinoma stem cells
-
endothelial cells exclusively express the bone TNAP transcript
-
restricted mesenchymal and epithelial regions. Its localization and strength changes during the hair cycle. Activity in the dermal papilla is moderate in very early anagen, reaches a maximal level in early anagen, decreases at the proximal region of dermal papilla after mid anagen, and is kept at a low level during catagen. The bulbar dermal sheath shows intense alkaline phosphatase activity only in early anagen. Most bulbar epithelium does not show alkaline phosphatase activity, germinative epidermal cells that are adjacent to the alkaline phosphatase-negative dermal papilla cells become alkaline phosphatase-positive in mid anagen and rearrange in a single layer so as to encapsulate the dermal papilla in mid catagen. During catagen, the outermost layer of bulbar epithelium becomes alkaline phosphatase-positive, which could be follicular epithelial precursors migrating from the bulge. Before the initiation of hair formation, alkaline phosphatase activity in the bulbar epithelium rapidly decreases and that in dermal papilla increases. These dynamic changes of alkaline phosphatase expression might be related to functions of the dermal papilla in hair induction and also to reconstruction of the bulbar structure during the hair cycle
-
matrix, articular, of proximal tibiae, highest activity in the hypertrophic zone
-
matrix, during early-stages of mineralization, in the proliferative and the hypertrophic zones
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
the enzyme is crucial for bone matrix mineralization
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PPBT_MOUSE
524
0
57514
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
side-chain modification
disparities in the molecular mass of the mouse enzyme from placenta, 86000 Da, liver, 76000 Da, and kidney, 79000 Da, are probably due to differences in glycosylation
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
hydrolysis of pyrophosphate by rat aortic rings is reduced about half in aortas from mice lacking TNAP
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
56
-
50% inactivation of the placental enzyme after 2.3 min, 50% inactivation of the liver enzyme after 5.8 min
65
-
50% inactivation of the placental enzyme after 0.58 min, 50% inactivation of the liver enzyme after 0.8 min
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
the placental isoenzyme is encoded by a gene identical to the gene expressed in mouse, liver, kidney, and tetracarcinoma stem cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
ALP and fat storage are tightly linked during preadipocyte maturation. Measurement of ALP activity may be a sensitive and rapid technique for the quantification of intracellular lipid accumulation
medicine
-
a circulating factor causes pyrophosphate deficiency by regulating TNAP activity and vascular calcification in renal failure may result from the action of this factor
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Manning, J.P.; Inglis, N.R.; Green, S.; Fishman, W.H.
Characterization of placental alkaline phosphatase from the rabbit, guinea pig, mouse and hamster
Enzymologia
39
307-318
1970
Cavia porcellus, Oryctolagus cuniculus, Mesocricetus auratus, Mus musculus
Terao, M.; Mintz, B.
Cloning and characterization of a cDNA coding for mouse placental alkaline phosphatase
Proc. Natl. Acad. Sci. USA
84
7051-7055
1987
Mus musculus (P09242), Mus musculus
Goldstein, D.J.; Harris, H.
Human placental alkaline phosphatase differs from that of other species
Nature
280
602-605
1979
Bos taurus, Canis lupus familiaris, Cavia porcellus, Felis catus, Ovis aries, Homo sapiens, Macaca mulatta, Mesocricetus auratus, Mus musculus, Rattus norvegicus, Sus scrofa
Sasaki, T.; Amizuka, N.; Irie, K.; Ejiri, S.; Ozawa, H.
Localization of alkaline phosphatase and osteopontin during matrix mineralization in the developing cartilage of coccygeal vertebrae
Arch. Histol. Cytol.
63
271-284
2000
Mus musculus
Miao, D.; Scutt, A.
Histochemical localization of alkaline phosphatase activity in decalcified bone and cartilage
J. Histochem. Cytochem.
50
333-340
2002
Homo sapiens, Mus musculus, Rattus norvegicus
Ali, A.T.; Penny, C.B.; Paiker, J.E.; Psaras, G.; Ikram, F.; Crowther, N.J.
The relationship between alkaline phosphatase activity and intracellular lipid accumulation in murine 3T3-L1 cells and human preadipocytes
Anal. Biochem.
354
247-254
2006
Homo sapiens, Mus musculus
Iida, M.; Ihara, S.; Matsuzaki, T.
Hair cycle-dependent changes of alkaline phosphatase activity in the mesenchyme and epithelium in mouse vibrissal follicles
Dev. Growth Differ.
49
185-195
2007
Mus musculus, Mus musculus C57BL/6N
Lomashvili, K.A.; Garg, P.; Narisawa, S.; Millan, J.L.; ONeill, W.C.
Upregulation of alkaline phosphatase and pyrophosphate hydrolysis: potential mechanism for uremic vascular calcification
Kidney Int.
73
1024-1030
2008
Mus musculus, Rattus norvegicus
Brun-Heath, I.; Ermonval, M.; Chabrol, E.; Xiao, J.; Palkovits, M.; Lyck, R.; Miller, F.; Couraud, P.; Mornet, E.; Fonta, C.
Differential expression of the bone and the liver tissue non-specific alkaline phosphatase isoforms in brain tissues
Cell Tissue Res.
343
521-536
2011
Callithrix jacchus, Homo sapiens, Mus musculus
Ardecky, R.J.; Bobkova, E.V.; Kiffer-Moreira, T.; Brown, B.; Ganji, S.; Zou, J.; Pass, I.; Narisawa, S.; Iano, F.G.; Rosenstein, C.; Cheltsov, A.; Rascon, J.; Hedrick, M.; Gasior, C.; Forster, A.; Shi, S.; Dahl, R.; Vasile, S.; Su, Y.; Sergienko, E.; Chung, T.D.; Kaunitz, J.; Hoylaerts, M.F.; Pinkerton, A.B.
Identification of a selective inhibitor of murine intestinal alkaline phosphatase (ML260) by concurrent ultra-high throughput screening against human and mouse isozymes
Bioorg. Med. Chem. Lett.
24
1000-1004
2014
Mus musculus (P24822), Mus musculus
Pinkerton, A.B.; Sergienko, E.; Bravo, Y.; Dahl, R.; Ma, C.T.; Sun, Q.; Jackson, M.R.; Cosford, N.D.P.; Millan, J.L.
Discovery of 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425), a potent and orally bioavailable tissue-nonspecific alkaline phosphatase (TNAP) inhibitor
Bioorg. Med. Chem. Lett.
28
31-34
2018
Mus musculus (P09242)
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