| Structural highlights
Disease
S53A1_HUMAN Bilateral striopallidodentate calcinosis. The disease is caused by variants affecting the gene represented in this entry.
Function
S53A1_HUMAN Inorganic ion transporter that mediates phosphate ion export across plasma membrane. Plays a major role in phosphate homeostasis, preventing intracellular phosphate accumulation and possible calcium phosphate precipitation, ultimately preserving calcium signaling. The molecular mechanism of phosphate transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated (By similarity) (PubMed:23791524, PubMed:25938945, PubMed:31043717). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), important intracellular signaling molecules involved in regulation of phosphate flux (PubMed:27080106).[UniProtKB:Q9Z0U0][1] [2] [3] [4]
Publication Abstract from PubMed
Phosphorus is a macronutrient taken up by cells as inorganic phosphate (Pi). How cells sense cellular Pilevels is poorly characterized. Here we report that SPX domains, which are found in eukaryotic phosphate transporters, signaling proteins and inorganic polyphosphate polymerases, provide a basic binding surface for inositol polyphosphate signaling molecules (InsPs), whose concentrations change in response to Piavailability. Substitutions of critical binding surface residues impair InsP binding in vitro, inorganic polyphosphate synthesis in yeast and Pitransport inArabidopsis In plants, InsPs trigger the association of SPX proteins with transcription factors to regulate Pistarvation responses. We propose that InsPs communicate cytosolic Pilevels to SPX domains and enable them to interact with a multitude of proteins to regulate Piuptake, transport and storage in fungi, plants and animals.
Control of eukaryotic phosphate homeostasis by inositol polyphosphate sensor domains.,Wild R, Gerasimaite R, Jung JY, Truffault V, Pavlovic I, Schmidt A, Saiardi A, Jessen HJ, Poirier Y, Hothorn M, Mayer A Science. 2016 Apr 14. pii: aad9858. PMID:27080106[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Giovannini D, Touhami J, Charnet P, Sitbon M, Battini JL. Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans. Cell Rep. 2013 Jun 27;3(6):1866-73. PMID:23791524 doi:10.1016/j.celrep.2013.05.035
- ↑ Legati A, Giovannini D, Nicolas G, Lopez-Sanchez U, Quintans B, Oliveira JR, Sears RL, Ramos EM, Spiteri E, Sobrido MJ, Carracedo A, Castro-Fernandez C, Cubizolle S, Fogel BL, Goizet C, Jen JC, Kirdlarp S, Lang AE, Miedzybrodzka Z, Mitarnun W, Paucar M, Paulson H, Pariente J, Richard AC, Salins NS, Simpson SA, Striano P, Svenningsson P, Tison F, Unni VK, Vanakker O, Wessels MW, Wetchaphanphesat S, Yang M, Boller F, Campion D, Hannequin D, Sitbon M, Geschwind DH, Battini JL, Coppola G. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet. 2015 Jun;47(6):579-81. doi: 10.1038/ng.3289. Epub 2015 May 4. PMID:25938945 doi:http://dx.doi.org/10.1038/ng.3289
- ↑ Wild R, Gerasimaite R, Jung JY, Truffault V, Pavlovic I, Schmidt A, Saiardi A, Jessen HJ, Poirier Y, Hothorn M, Mayer A. Control of eukaryotic phosphate homeostasis by inositol polyphosphate sensor domains. Science. 2016 Apr 14. pii: aad9858. PMID:27080106 doi:http://dx.doi.org/10.1126/science.aad9858
- ↑ López-Sánchez U, Nicolas G, Richard AC, Maltête D, Charif M, Ayrignac X, Goizet C, Touhami J, Labesse G, Battini JL, Sitbon M. Characterization of XPR1/SLC53A1 variants located outside of the SPX domain in patients with primary familial brain calcification. Sci Rep. 2019 May 1;9(1):6776. PMID:31043717 doi:10.1038/s41598-019-43255-x
- ↑ Wild R, Gerasimaite R, Jung JY, Truffault V, Pavlovic I, Schmidt A, Saiardi A, Jessen HJ, Poirier Y, Hothorn M, Mayer A. Control of eukaryotic phosphate homeostasis by inositol polyphosphate sensor domains. Science. 2016 Apr 14. pii: aad9858. PMID:27080106 doi:http://dx.doi.org/10.1126/science.aad9858
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