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Lead Time
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Usage
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis. Has broad substrate specificity and can hydrolyze a considerable variety of compounds: however, only a few substrates, such as diphosphate (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate (PLP) and N-phosphocreatine are natural substrates. Plays an essential role in skeletal and dental mineralization via its ability to hydrolyze extracellular diphosphate, a potent mineralization inhibitor, to phosphate: it thereby promotes hydroxyapatite crystal formation and increases inorganic phosphate concentration. Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix. Also promotes dephosphorylation of osteopontin (SSP1), an inhibitor of hydroxyapatite crystallization in its phosphorylated state; it is however unclear whether ALPL/TNAP mediates SSP1 dephosphorylation via a direct or indirect manner. Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable form of vitamin B6, in order to provide a sufficient amount of PLP in the brain, an essential cofactor for enzymes catalyzing the synthesis of diverse neurotransmitters. Additionally, also able to mediate ATP degradation in a stepwise manner to adenosine, thereby regulating the availability of ligands for purinergic receptors. Also capable of dephosphorylating microbial products, such as lipopolysaccharides (LPS) as well as other phosphorylated small-molecules, such as poly-inosine:cytosine (poly I:C). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating hydrolysis of N-phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation. During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work.
Gene References into Functions
intestinal alkaline phosphatase knockout mice display higher intestinal Ca uptake, which over time appears to correlate with a positive effect on the biomechanical properties of trabecular bone.PMID:29234952
Study results from cerulein induced pancreatitis model in TNAP+/- mice show that altered TNAP expression results in heightened pancreatic inflammation, which may be explained by an augmented response of neutrophils and by a higher sensitivity of acinar cells to cerulein injury.PMID:30251694
TNAP activation in vascular smooth muscle cells (VSMCs) appears sufficient to induce calcification. TNAP activation in VSMCs stimulates expression of chondrocyte markers.PMID:27932058
Our results offer clear evidence that TNAP modulates T lymphocyte function and specifically T cell-dependent colitis.PMID:28039309
The results are the first to demonstrate a role for ENC1 in the control of osteoblast differentiation. Additionally, the contrasting mineralization phenotypes and transcriptional patterns seen with coordinate knockdown of both ENC1 isoforms vs selective knockdown of 67 kDa ENC1 suggest opposing roles for the isoforms in regulation of osteoblastic differentiation, through effects on Alpl expression and phosphate cellularPMID:27996212
TNAP overexpression in vascular endothelium in mice leads to an unusual course of coronary atherosclerosis and was accompanied by the reduction in body weight and left ventricular ejection fraction.PMID:29023576
Data, including data from studies using cells from transgenic/knockout mice, suggest that Med1 plays role in enamel formation; Med1 induces Alpl via stimulation of Notch1 signaling by forming Notch1-RBP-Jk complex on Alpl promoter. (Med1 = mediator complex subunit 1; Alpl = alkaline phosphatase, liver-bone-kidney; Notch1 = Notch gene homolog 1; RBP-Jk = kappa J region recombining binding protein suppressor of hairless)PMID:28673966
These analyses revealed that TNAP deficient mice present an increased proliferation of neural precursors, an altered neuronal morphology, and an augmented neuronal activity. We found that these alterations were associated with a partial downregulation of the purinergic P2X7 receptor (P2X7R).PMID:27466191
Despite similar deficiencies in alkaline phosphatase, Alpl(-/-) mice develop craniosynostosis and a brachycephalic/acrocephalic craniofacial shape of variable penetrance.PMID:26605996
Prevention of lethal murine hypophosphatasia by neonatal ex vivo gene therapy using lentivirally transduced bone marrow cells expressing Akp-2.PMID:26467745
TNAP in the vasculature contributes to the pathology of medial vascular calcification and that it is a druggable target.PMID:25428889
In cardiac fibroblasts, TNAP expression and activity is induced by sFRP2.PMID:25972450
p107 is required for the efficient recruitment of an activating SWI/SNF chromatin-remodeling complex, an essential event in Alpl induction.PMID:25182511
Inhibition of rhBMP-2-induced ALP activity by intracellular delivery of SMURF1 in murine calvarial preosteoblast cells.PMID:24288199
Findings demonstrate that Alpl(-/-) mice exhibit a craniofacial skeletal phenotype similar to that seen in infants with HPP, including true bony craniosynostosis in the context of severely diminished bone mineralizationPMID:25014884
CD73 and TNAP play interactive roles to metabolize luminally applied 5'-AMP in the renal vasculature such that inhibition of both is required to inhibit the production of adenosine.PMID:24990899
TNAP plays a role in governing the phosphorylation status of phospholamban in the sarcoplasmic reticulum.PMID:25015959
Taken together, these data indicate that ATF3 is a novel negative regulator of osteoblast differentiation by specifically suppressing ALP gene expression in preosteoblasts.PMID:24315873
data suggest that the promineralization role of TNAP may be related not only to its accepted pyrophosphatase activity but also to its ability to modify the phosphorylation status of OPN.PMID:23427088
mineralization abnormalities of dentin; reduced overall mineralization with decreased matrix vesicle mineralization in the Phospho1(-/-) mice; almost complete absence of matrix vesicles in mice; further reduction in mineralization.PMID:23694930
In the cerebral cortex, myelinated axons, while present in wild-type, were absent in the Akp2( -/- ) mice and these animals also displayed a significantly increased proportion of immature cortical synapses.PMID:22696173
a link between ATRA-induced mL/B/K-ALP gene transcription and chromatin remodelingPMID:22270475
Results demonstrate that TNAP, regulating both ligand availability and protein expression of P2X7 receptor, is essential for axonal development.PMID:21289095
Data show that alkaline phosphatase (AP) activity in brain vessels and parenchyma in which AP exhibits specific patterns is attributable to TNAP.PMID:21191615
We show that TNAP knockdown reduces cell proliferation and differentiation into neurons or oligodendrocytesPMID:20849921
These results demonstrate that calcium ions released from apatite are important in the synergistic effect of 20alpha-HC and apatite.PMID:20683129
Once the HT2B receptor is expressed, it constitutively controls tissue-nonspecific alkaline phosphatase activity at a post-translational level along the overall period of bone mineral depositionPMID:20573958
Tissue-nonspecific alkaline phosphatase is the enzyme that hydrolyzes both ATP and inorganic pyrophosate in matrix vesicles.PMID:19874193
correction of bone mineralization abnormalities in knockout mice null for both the TNAP (Akp2) and PC-1 (Enpp1) genesPMID:12082181
The Alpl (Akp2) gene is located within the quantitative trait locus region for alkaline phosphatase activity on chromosome 4.PMID:16159911
alkaline phosphatase 2(Hpp/Hpp) mice develop late-onset skeletal disease, notably defective endochondral ossification and bone mineralization that leads to arthropathies of knees and shouldersPMID:17539739
The process selectively internalizes IAP and may contribute to the appearance of the enzyme in serum and surfactant-like particles.PMID:17947448
Results show that inorganic phosphate (P(i)) levels and TNSALP activity increased in response to androgen/androgen receptor (AR), and P(i) signals increase the expression and translocation of AR.PMID:18838539
TNAP-AID mice expressed alpha-fetoprotein and had deleterious mutations in the tumour suppressor gene Trp53, some of which corresponded to those found in human cancer.PMID:18997814