Xenotropic and polytropic retrovirus receptor 1

XPR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5IJH
Identifiers
Aliases	XPR1 , SYG1, X3, IBGC6, xenotropic and polytropic retrovirus receptor 1, SLC53A1
External IDs	OMIM: 605237; MGI: 97932; HomoloGene: 134226; GeneCards: XPR1; OMA:XPR1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1q25.3 Start 180,632,022 bp [1] End 180,890,279 bp [1]
Gene location (Mouse) Chr. Chromosome 1 (mouse) [2] Band 1 G3|1 66.49 cM Start 155,151,447 bp [2] End 155,293,161 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in myocardium of left ventricle ganglionic eminence secondary oocyte endothelial cell nasal epithelium pancreatic epithelial cell cardiac muscle tissue of right atrium islet of Langerhans Brodmann area 23 right ventricle Top expressed in median eminence ventromedial nucleus lateral septal nucleus arcuate nucleus habenula ascending aorta dorsomedial hypothalamic nucleus extensor digitorum longus muscle mammillary body triceps brachii muscle More reference expression data BioGPS n/a
Gene ontology Molecular function G protein-coupled receptor activity transmembrane signaling receptor activity phosphate ion transmembrane transporter activity inositol hexakisphosphate binding virus receptor activity efflux transmembrane transporter activity signaling receptor activity Cellular component integral component of membrane membrane intrinsic component of plasma membrane plasma membrane cytoplasm Golgi apparatus Biological process viral entry into host cell G protein-coupled receptor signaling pathway response to virus cellular phosphate ion homeostasis phosphate ion transmembrane transport phosphate ion transport cellular response to phosphate starvation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9213 19775 Ensembl ENSG00000143324 ENSMUSG00000026469 UniProt Q9UBH6 Q9Z0U0 RefSeq (mRNA) NM_004736 NM_001135669 NM_001328662 NM_011273 RefSeq (protein) NP_001129141 NP_001315591 NP_004727 NP_035403 Location (UCSC) Chr 1: 180.63 – 180.89 Mb Chr 1: 155.15 – 155.29 Mb PubMed search [3] [4]
Wikidata
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Gene and physiological roles

Xenotropic and polytropic retrovirus receptor 1 is a protein that in humans is encoded by the XPR1 gene. ^[5] 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. ^[6] Mutations in XPR1 that disrupt its phosphate export function are linked to Primary familial brain calcification (PFBC), ^[7] a neurological condition characterized by abnormal hydroxyapatite deposits in the brain.

Structures and functions

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. ^{[8] [9]} 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, ^[9] 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.

References

1. GRCh38: Ensembl release 89: ENSG00000143324 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026469 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: Xenotropic and polytropic retrovirus receptor 1" . Retrieved 2017-03-31.
6. Giovannini, Donatella; Touhami, Jawida; Charnet, Pierre; Sitbon, Marc; Battini, Jean-Luc (2013). "Inorganic Phosphate Export by the Retrovirus Receptor XPR1 in Metazoans". Cell Reports . 3 (6): 1866–1873. doi:10.1016/j.celrep.2013.05.035. PMID   23791524.
7. Legati, Andrea; Giovannini, Donatella; Nicolas, Gaël; López-Sánchez, Uriel; Quintáns, Beatriz; Oliveira, João R M; Sears, Renee L; Ramos, Eliana Marisa; Spiteri, Elizabeth; Sobrido, María-Jesús; Carracedo, Ángel; Castro-Fernández, Cristina; Cubizolle, Stéphanie; Fogel, Brent L; Goizet, Cyril (2015). "Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export". Nature Genetics . 47 (6): 579–581. doi:10.1038/ng.3289. ISSN   1061-4036. PMC   4516721 . PMID   25938945.
8. Yan, Rui; Chen, Huiwen; Liu, Chuanyu; Zhao, Jun; Wu, Di; Jiang, Juquan; Gong, Jianke; Jiang, Daohua (2024). "Human XPR1 structures reveal phosphate export mechanism" . Nature. 633 (8031): 960–967. doi:10.1038/s41586-024-07852-9. ISSN   0028-0836. PMID   39169184.
9. Lu, Yi; Yue, Chen-Xi; Zhang, Li; Yao, Deqiang; Xia, Ying; Zhang, Qing; Zhang, Xinchen; Li, Shaobai; Shen, Yafeng; Cao, Mi; Guo, Chang-Run; Qin, An; Zhao, Jie; Zhou, Lu; Yu, Ye (2024). "Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1" . Science. doi:10.1126/science.adp3252. ISSN   0036-8075. PMID   39325866.

Further reading

• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Mol. Med. 16 (7–8): 247–53. doi:10.2119/molmed.2009.00159. PMC   2896464 . PMID   20379614.
• Bhosle S, Suppiah S, Molinaro R, Liang Y, Arnold R, Diehl W, Makarova N, Blackwell J, Petros J, Liotta D, Hunter E, Ly H (2010). "Evaluation of cellular determinants required for in vitro xenotropic murine leukemia virus-related virus entry into human prostate cancer and noncancerous cells". J. Virol. 84 (13): 6288–96. doi:10.1128/JVI.00274-10. PMC   2903252 . PMID   20410264.