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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Tartrate-resistant acid phosphatase''' ('''TRAP''' or '''TRAPase'''), also called '''acid phosphatase 5, tartrate resistant''' ('''ACP5'''), is a [[glycosylated]] [[monomer]]ic [[metalloprotein]] [[enzyme]] expressed in mammals.<ref name="pmid1922010">{{cite journal | vauthors = Baumbach GA, Saunders PT, Ketcham CM, Bazer FW, Roberts RM | title = Uteroferrin contains complex and high mannose-type oligosaccharides when synthesized in vitro | journal =
The mechanism of phosphate ester hydrolysis by TRAP is through a nucleophilic attack mechanism,<ref name="pmid8683579">{{cite journal | vauthors = Klabunde T, Sträter N, Fröhlich R, Witzel H, Krebs B | title = Mechanism of Fe(III)-Zn(II) purple acid phosphatase based on crystal structures | journal =
==TRAP expression and cell localization==
Under normal circumstances, TRAP is highly expressed by [[osteoclast]]s, activated [[macrophages]], [[neurons]], and by the porcine endometrium during pregnancy.<ref name="pmid13664936">{{cite journal |
In osteoclasts, TRAP is localized within the ruffled border area, the lysosomes, the Golgi cisternae and vesicles.<ref name="Ljusberg2005"/>
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==TRAP gene, promoter organisation and transcription==
Mammalian TRAP is encoded by one gene, which is localized on chromosome 19 (19p13.2–13.3) in humans, and on chromosome 9 in mice. TRAP DNA is, as expected from [[protein sequencing]], highly conserved throughout the class mammalia. The TRAP gene has been cloned and sequenced in porcine, rat, human, and murine species.<ref name="pmid8359686">{{cite journal | vauthors = Cassady AI, King AG, Cross NC, Hume DA | title = Isolation and characterization of the genes encoding mouse and human type-5 acid phosphatase | journal = Gene | volume = 130 | issue = 2 | pages =
Human, murine, and porcine TRAP genes all contain 5 exons, and have the ATG codon at the beginning of exon 2, with exon 1 being non-coding. Within the exon 1 promoter, there are three distinct “tissue-specific” [[promotor (biology)|promoters]]: 1A, 1B, and 1C.<ref name="pmid12706893">{{cite journal | vauthors = Walsh NC, Cahill M, Carninci P, Kawai J, Okazaki Y, Hayashizaki Y, Hume DA, Cassady AI | display-authors = 6 | title = Multiple tissue-specific promoters control expression of the murine tartrate-resistant acid phosphatase gene | journal = Gene | volume = 307
Transcribed from this gene is a 1.5kb mRNA with an [[open reading frame]] (ORF) of 969-975 bp encoding a 323-325 amino acid protein. In the rat, the ORF is 981 bp in length and encodes for a 327-amino acid protein. TRAP is translated as a single polypeptide.
TRAP gene transcription is regulated by the [[Microphthalmia-associated transcription factor]].<ref name="pmid10750559">{{cite journal | vauthors = Luchin A, Purdom G, Murphy K, Clark MY, Angel N, Cassady AI, Hume DA, Ostrowski MC | display-authors = 6 | title = The microphthalmia transcription factor
==Physiology and pathology==
Many functions have been attributed to TRAP, and its physiologic role(s) are likely to be manifold. The mice knockout studies as well as the human disorder associated with genetic deficiency of TRAP shed some light onto its functions.
In knockout studies, TRAP<sup>−/−</sup> mice exhibit mild [[osteopetrosis]], associated with reduced osteoclast activity. These result in thickening and shortening of the cortices, formation of club-like deformities in the distal [[femur]], and widened epiphyseal growth plates with delayed mineralization of cartilage, all of which increase with age.<ref name="pmid8898228">{{cite journal | vauthors = Hayman AR, Jones SJ, Boyde A, Foster D, Colledge WH, Carlton MB, Evans MJ, Cox TM | display-authors = 6 | title = Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis | journal = Development | volume = 122 | issue = 10 | pages =
Proposed functions of TRAP include [[osteopontin]] /[[bone sialoprotein]] [[dephosphorylation]], the generation of [[reactive oxygen species]] (ROS), iron transport, and as a cell growth and [[cell differentiation|differentiation]] factor.
Genetic deficiency of TRAP, determined by biallelic recessive mutations in the ACP5 gene, are the basis of the human disorder spondylenchondrodysplasia.<ref>{{cite web | title = Spondyloenchondrodysplasia With Immune Dysregulation; Spencdi | work = OMIM | url = https://omim.org/entry/607944}}</ref> The clinical phenotype involves the bone, the central nervous system, and the immune system.<ref>{{cite journal | vauthors = Lausch E, Janecke A, Bros M, Trojandt S, Alanay Y, De Laet C, Hübner CA, Meinecke P, Nishimura G, Matsuo M, Hirano Y, Tenoutasse S, Kiss A, Rosa RF, Unger SL, Renella R, Bonafé L, Spranger J, Unger S, Zabel B, Superti-Furga A | display-authors = 6 | title = Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity | journal = Nature Genetics | volume = 43 | issue = 2 | pages = 132–137 | date = February 2011 | pmid = 21217752 | doi = 10.1038/ng.749 | s2cid = 205357235 }}</ref> The pathogenesis probably includes a defect in bone reabsorption as well as immune dysregulation because of impaired dephosphorylation of osteopontin, but may be more complex and needs to be elucidated further.
==Protein dephosphorylation and osteoclast migration==
It has been shown that osteopontin and bone sialoprotein, bone matrix phosphoproteins, are highly efficient ''in vitro'' TRAP [[Substrate (biochemistry)|substrates]], which bind to osteoclasts when phosphorylated.<ref name="pmid8195113">{{cite journal | vauthors = Ek-Rylander B, Flores M, Wendel M, Heinegård D, Andersson G | title = Dephosphorylation of osteopontin and bone sialoprotein by osteoclastic tartrate-resistant acid phosphatase. Modulation of osteoclast adhesion in vitro | journal =
==ROS generation==
Reactive oxygen species (ROS) are generated in macrophages and osteoclasts from [[superoxide]] (O<sub>2</sub><sup>−.</sup>), which forms from the action of NADPH-oxidase on oxygen (O<sub>2</sub>).<ref name="pmid9157782">{{cite journal | vauthors = Darden AG, Ries WL, Wolf WC, Rodriguiz RM, Key LL | title = Osteoclastic superoxide production and bone resorption: stimulation and inhibition by modulators of NADPH oxidase | journal =
TRAP, containing a redox active iron, catalyzes the generation of ROS through Fenton chemistry:<ref>{{cite journal | vauthors = Fenton
: O<sub>2</sub> → (NADPH-oxidase) O<sup>2− ∙</sup> → (superoxide dismutase) H<sub>2</sub>O<sub>2</sub> → (catalase) H<sub>2</sub>O + O<sub>2</sub>
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==Iron transport==
In the pregnant sow, uteroferrin is highly expressed in the uterine fluids.<ref name="pmid3527760">{{cite journal | vauthors = Roberts RM, Raub TJ, Bazer FW | title = Role of uteroferrin in transplacental iron transport in the pig | journal =
==Cell growth and differentiation factor==
TRAP is associated with osteoclast [[cell migration|migration]] to bone resorption sites, and, once there, TRAP is believed to initiate osteoclast differentiation, activation, and [[cell proliferation|proliferation]]. This hypothesis was formed from the examination of the bone structure of TRAP-null mice. It was noted that, in addition to [[osteopetrosis]], bone formation occurred in a haphazard manner, where the microarchitecture was highly irregular.<ref name="pmid12403789">{{cite journal | vauthors = Sheu TJ, Schwarz EM, Martinez DA, O'Keefe RJ, Rosier RN, Zuscik MJ, Puzas JE | title = A phage display technique identifies a novel regulator of cell differentiation | journal =
In TRAP overexpressing mice, it has been found that the affected mice are grossly obese. This has led to the hypothesis that TRAP has involvement in hyperplastic obesity.
== References ==
{{Reflist}}
== External links ==
* {{MeshName|tartrate-resistant+acid+phosphatase}}
{{Esterases}}
{{Enzymes}}
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