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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
The mechanism of phosphate ester hydrolysis by TRAP is through a nucleophilic attack mechanism,<ref name="pmid8683579">{{cite 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,
==TRAP gene, promoter organisation and transcription==
Mammalian TRAP is encoded by one gene, which is localized on chromosome 19 (19p13.
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 |
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 |
==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
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 |
==ROS generation==
Reactive oxygen species (ROS) are generated in macrophages and osteoclasts from [[superoxide]] (O<sub>2</sub><sup>
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>
: TRAP-Fe<sup>3+</sup> (purple) + O<sup>
: H<sub>2</sub>O<sub>2</sub> + TRAP-Fe<sup>2+</sup> (pink) → HO<sup>∙</sup> + HO<sup>−</sup> + TRAP-Fe<sup>3+</sup>
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==Iron transport==
In the pregnant sow, uteroferrin is highly expressed in the uterine fluids.<ref name="pmid3527760">{{cite journal |
==Cell growth and differentiation factor==
TRAP is associated with
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}}
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[[Category:EC 3.1.3.2]] ▼
{{PDB_Gallery|geneid=54}}
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