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Synonyms
phospho1, phosphorylcholine phosphatase, atpecp1, phosphoethanolamine/phosphocholine phosphatase, phosphatase phospho1, 3x11a, phospho1-3a,
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presence in the enamel layer, ameloblast Tomes' processes, and in the walls of ameloblast secretory vesicles
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expressed by active alveolar bone osteoblasts and cementoblasts during cellular cementum formation
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low expression, 3.38fold higher than in liver
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PHOSPHO1 is restricted to mineralizing regions of bone and growth plate. 120fold higher level of PHOSPHO1 expression in bone compared with liver. Enzyme present within matrix vesicles is in an active state. Present in early hypertrophic chondrocytes of the growth plate, and in osteoblasts of trabecular surfaces and infilling primary osteons of cortical bone
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low expression, 1.96fold higher than in liver
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low expression, 1.2fold higher than in liver
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low expression, 5.67fold higher than in liver
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lowest expression
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malfunction
both male and female Phospho1-/- mice are smaller than age-matched heterozygous and wild-type controls and exhibit growth retardation, where bones from 1-month-old male mice are shorter, phenotypes, overview
malfunction
long bones from Phospho1-/- mice do not fracture during 3-point bending but deform plastically. With dynamic loading nanoindentation the elastic modulus and hardness of Phospho1-/- tibiae are significantly lower than wild-type tibia. Mutant mice show significantly lower mineral:matrix ratios and lower carbonate substitutions in Phospho1-/- tibia, phenotype, overview
physiological function
PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase involved in the generation of inorganic phosphate for bone mineralization
physiological function
role of PHOSPHO1 during endochondral ossification, overview
physiological function
calli of Phospho1-/- mice display a mild reduction of bone volume and an increase in trabecular number and a decrease in trabecular thickness and separation. There is a marked increase of osteoid volume over bone volume in the Phospho1-/- callus. Phospho1-/- fractured bone is more elastic than the wild-type bone
physiological function
cell line MC3T3-E1 clone 14 cells express high levels of Phospho1 and low levels of tissue-nonspecific alkalinephosphatase TNAP and they mineralize their matrix strongly. Clone 24 cells express high levels of TNAP and low levels of Phospho1 and mineralize their matrix poorly. Lentiviral Phospho1 overexpression in clone 24 cells results in higher Phospho1 and TNAP protein expression and increased levels of matrix mineralization. specific inhibition of Phospho1 individually reduces mineralization levels of Phospho1 overexpressing C24 cells, whereas the simultaneous addition of inhibitors of both Phospho1 and TNAP essentially abolishes matrix mineralization
physiological function
in Phospho1-/- mice, acellular cementum formation and mineralization are unaffected, whereas cellular cementum deposition increases despite delayed mineralization and cementoid. Phospho1-/- mice feature disturbances in alveolar bone mineralization. Parallel to other skeletal sites, deposition of mineral-regulating protein osteopontin is increased in alveolar bone in Phospho1-/- mice. Genetic ablation of Spp1, the gene encoding osteopontin, does not ameliorate dentoalveolar defects in Phospho1-/- mice
physiological function
Phospho1-/- mice lack sharp incisal tips, show a 25% increase in total enamel volume, and a 2fold reduction in silver grain density of von Kossa stained ground sections. Phospho1-/- mouse enamel reveals a loss of the prominent enamel prism picket fence structure, a loss of parallel crystal organization within prisms, and a 1.56fold increase in enamel prism width. Phospho1-/- mice display a significant decrease in phosphate incorporation in the enamel layer when compared to controls
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, and in adult mice depletion impairs phenylhydrazine-induced stress erythropoiesis. Loss of PHOSPHO1 also impairs phosphocholine catabolism in mouse fetal liver progenitors and results in accumulation of several lipids, and ATP production is reduced as a result of decreased oxidative phosphorylation. Glycolysis replaces oxidative phosphorylation in PHOSPHO1 knockout erythroblasts and the increased glycolysis is used for the production of serine or glycine
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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
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Huesa, C.; Yadav, M.; Finnilae, M.; Goodyear, S.; Robins, S.; Tanner, K.; Aspden, R.; Millan, J.; Farquharson, C.
PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures
Bone
48
1066-1074
2011
Mus musculus (Q8R2H9)
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Yadav, M.; Simao, A.; Narisawa, S.; Huesa, C.; McKee, M.; Farquharson, C.; Millan, J.
Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: A unified model of the mechanisms of initiation of skeletal calcification
J. Bone Miner. Res.
26
286-297
2011
Mus musculus (Q8R2H9), Mus musculus C57BL/6 (Q8R2H9)
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Huesa, C.; Houston, D.; Kiffer-Moreira, T.; Yadav, M.M.; Millan, J.L.; Farquharson, C.
The functional co-operativity of tissue-nonspecific alkaline phosphatase (TNAP) and PHOSPHO1 during initiation of skeletal mineralization
Biochem. Biophys. Rep.
4
196-201
2015
Mus musculus (Q8R2H9)
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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
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Morcos, M.W.; Al-Jallad, H.; Li, J.; Farquharson, C.; Millan, J.L.; Hamdy, R.C.; Murshed, M.
PHOSPHO1 is essential for normal bone fracture healing an animal study
Bone Joint Res.
7
397-405
2018
Mus musculus (Q8R2H9)
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Pandya, M.; Rosene, L.; Farquharson, C.; Millan, J.; Diekwisch, T.
Intravesicular phosphatase PHOSPHO1 function in enamel mineralization and prism formation
Front. Physiol.
8
805
2017
Mus musculus (Q8R2H9)
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Zweifler, L.E.; Ao, M.; Yadav, M.; Kuss, P.; Narisawa, S.; Kolli, T.N.; Wimer, H.F.; Farquharson, C.; Somerman, M.J.; Millan, J.L.; Foster, B.L.
Role of PHOSPHO1 in periodontal development and function
J. Dent. Res.
95
742-751
2016
Mus musculus (Q8R2H9)
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