xenotropic and polytropic retrovirus receptor 1

Xenotropic and polytropic retrovirus receptor 1 is a protein that in humans is encoded by the XPR1 gene.

{{cite web

| title = Entrez Gene: Xenotropic and polytropic retrovirus receptor 1

| url = https://www.ncbi.nlm.nih.gov/gene/9213

| access-date = 2017-03-31

}} It is a member of the solute carrier (SLC) family, specifically classified as SLC53A1. XPR1 is crucial for maintaining cellular phosphate homeostasis by facilitating the efflux of inorganic phosphate (Pi) from cells.{{Cite journal |last1=Giovannini |first1=Donatella |last2=Touhami |first2=Jawida |last3=Charnet |first3=Pierre |last4=Sitbon |first4=Marc |last5=Battini |first5=Jean-Luc |date=2013 |title=Inorganic Phosphate Export by the Retrovirus Receptor XPR1 in Metazoans |url=https://linkinghub.elsevier.com/retrieve/pii/S2211124713002684 |journal=Cell Reports |language=en |volume=3 |issue=6 |pages=1866–1873 |doi=10.1016/j.celrep.2013.05.035|pmid=23791524 }} Mutations in XPR1 that disrupt its phosphate export function are linked to Primary familial brain calcification (PFBC),{{Cite journal |last1=Legati |first1=Andrea |last2=Giovannini |first2=Donatella |last3=Nicolas |first3=Gaël |last4=López-Sánchez |first4=Uriel |last5=Quintáns |first5=Beatriz |last6=Oliveira |first6=João R M |last7=Sears |first7=Renee L |last8=Ramos |first8=Eliana Marisa |last9=Spiteri |first9=Elizabeth |last10=Sobrido |first10=María-Jesús |last11=Carracedo |first11=Ángel |last12=Castro-Fernández |first12=Cristina |last13=Cubizolle |first13=Stéphanie |last14=Fogel |first14=Brent L |last15=Goizet |first15=Cyril |date=2015 |title=Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export |journal=Nature Genetics |language=en |volume=47 |issue=6 |pages=579–581 |doi=10.1038/ng.3289 |issn=1061-4036 |pmc=4516721 |pmid=25938945}} a neurological condition characterized by abnormal hydroxyapatite deposits in the brain.

XPR1 is characterized by a unique architecture that includes a transmembrane domain (TMD) and a cytoplasmic SPX domain. The TMD is composed of multiple transmembrane helices that form a channel-like structure. Recent cryo-electron microscopy (cryo-EM) studies have revealed various conformational states of XPR1, including inactive (closed) and active (open) forms, as well as intermediate states.{{Cite journal |last1=Yan |first1=Rui |last2=Chen |first2=Huiwen |last3=Liu |first3=Chuanyu |last4=Zhao |first4=Jun |last5=Wu |first5=Di |last6=Jiang |first6=Juquan |last7=Gong |first7=Jianke |last8=Jiang |first8=Daohua |date=2024 |title=Human XPR1 structures reveal phosphate export mechanism |url=https://www.nature.com/articles/s41586-024-07852-9 |journal=Nature |language=en |volume=633 |issue=8031 |pages=960–967 |doi=10.1038/s41586-024-07852-9 |issn=0028-0836 |pmid=39169184}}{{Cite journal |last1=Lu |first1=Yi |last2=Yue |first2=Chen-Xi |last3=Zhang |first3=Li |last4=Yao |first4=Deqiang |last5=Xia |first5=Ying |last6=Zhang |first6=Qing |last7=Zhang |first7=Xinchen |last8=Li |first8=Shaobai |last9=Shen |first9=Yafeng |last10=Cao |first10=Mi |last11=Guo |first11=Chang-Run |last12=Qin |first12=An |last13=Zhao |first13=Jie |last14=Zhou |first14=Lu |last15=Yu |first15=Ye |date=2024 |title=Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1 |url=https://www.science.org/doi/10.1126/science.adp3252 |journal=Science |language=en |doi=10.1126/science.adp3252 |issn=0036-8075 |pmid=39325866}} Notably, XPR1 features dual binding sites for Inositol phosphate(IPs) and inositol pyrophosphates (PP-IPs), which regulate its activity.

Electrophysiological studies on XPR1 showed that XPR1 functions primarily as a PP-IPs gated Pi channel, playing a pivotal role in preventing the accumulation of excess intracellular phosphate, which can lead to metabolic disorders. It responds to the cellular levels of IPs and PP-IPs, with PP-IPs acting as more potent activators of XPR1 compared to IPs. The binding of these signaling molecules induces conformational changes in XPR1, facilitating the opening of the channel and allowing phosphate ions to exit the cell.

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