Affinage

XPR1

Solute carrier family 53 member 1 · UniProt Q9UBH6

Length
696 aa
Mass
81.5 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

XPR1 is the sole known mammalian inorganic phosphate (Pi) exporter, functioning as a dimeric, voltage- and Pi-dependent phosphate-permeable ion channel at the plasma membrane that maintains cellular and systemic phosphate homeostasis. Cryo-EM structures reveal a 10-transmembrane-helix architecture with multiple sequential Pi-binding sites forming a relay translocation pathway, whose gating is controlled by high-affinity binding of the inositol pyrophosphate InsP8 to its N-terminal SPX domain; InsP8 rigidifies the SPX dimer interface, connects it to the transmembrane domains, and overcomes the inhibitory restraint imposed by the scaffold protein KIDINS220, which stabilizes XPR1 in a closed conformation (PMID:39325866, PMID:40858110, PMID:32019887). Physiologically, XPR1 mediates Pi export in astrocyte end-feet to prevent brain calcification, in pancreatic β-cells during the glucose-stimulated phosphate flush, in placental tissue for fetal Pi supply, and in fetal liver macrophages where it is required for Kupffer cell identity and erythrophagocytic clearance of pyrenocytes (PMID:39019040, PMID:32826297, PMID:31498925, PMID:41335223). Loss-of-function mutations in XPR1—in both the SPX domain and the transmembrane channel—cause primary familial brain calcification (PFBC) (PMID:25938945).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2009 High

    Mapping the retrovirus receptor function of XPR1 to specific extracellular loop residues established that ECL3 and ECL4 form the virus-binding site, defining the topology of the protein before its physiological transport role was known.

    Evidence Systematic site-directed mutagenesis and chimeric receptor analysis with multiple MLV strains in transfected hamster cells

    PMID:19811656

    Open questions at the time
    • No connection to phosphate transport was made
    • No structural model available at this stage
  2. 2013 High

    Identification of XPR1 as the first metazoan inorganic phosphate exporter resolved a long-standing gap in mammalian Pi homeostasis, demonstrating conserved export activity from Drosophila to human.

    Evidence siRNA knockdown, cross-species rescue, and pharmacological inhibition with viral envelope-derived ligand in multiple human cell lines

    PMID:23791524

    Open questions at the time
    • Mechanism of Pi translocation unknown
    • Regulatory inputs not identified
    • Physiological tissues requiring XPR1 not defined
  3. 2015 High

    Linking XPR1 mutations to primary familial brain calcification (PFBC) established that impaired Pi export causes human disease and identified the SPX domain as functionally critical.

    Evidence Family-based sequencing with in vitro phosphate export complementation assay of PFBC-associated mutants

    PMID:25938945

    Open questions at the time
    • Brain cell type(s) responsible not identified
    • Mechanism by which impaired Pi export leads to calcification unclear
  4. 2019 High

    Demonstrating that inositol pyrophosphates IP7 and InsP8—synthesized by IP6K1/2—bind the SPX domain and are required for XPR1-mediated Pi export revealed the ligand-gated regulatory mechanism, while variants outside the SPX domain showed the C-terminal transmembrane region also harbors essential transport determinants.

    Evidence IP6K1/2 double CRISPR knockout in HCT116 cells with HPLC nucleotide analysis and 32Pi flux; functional assay of non-SPX PFBC variants separating virus receptor and Pi export activities

    PMID:31043717 PMID:31186349

    Open questions at the time
    • Identity of the specific activating inositol pyrophosphate species debated (IP7 vs InsP8)
    • Structural basis of SPX–ligand interaction unknown
  5. 2020 High

    Pinpointing InsP8 as the specific high-affinity activator (Kd ~180 nM) of XPR1 and demonstrating functional coupling between the Pi importer SLC20A2 and XPR1 via inositol pyrophosphates established a homeostatic feedback circuit for cellular Pi.

    Evidence ITC binding assay, PPIP5K knockout, IP6K inhibition with PCP-InsP8 analog rescue; SLC20A2 overexpression/knockdown epistasis with XPR1 KO and PP-IP binding-pocket mutants

    PMID:32019887 PMID:32393577

    Open questions at the time
    • Structural mechanism of InsP8-induced channel opening unknown
    • Whether SLC20A2–XPR1 coupling is direct or indirect unresolved
  6. 2019 High

    Demonstrating that global Xpr1 knockout causes perinatal lethality with placental calcification and impaired fetal Pi supply established that XPR1-mediated Pi export is essential for mammalian development.

    Evidence Xpr1 knockout mouse, Pi measurement in amniotic fluid and fetal serum, skeletal mineral content analysis

    PMID:31498925

    Open questions at the time
    • Tissue-specific contributions to the lethal phenotype not dissected
    • Compensatory mechanisms not explored
  7. 2020 Medium

    Showing that XPR1 mediates the glucose-stimulated phosphate flush in pancreatic β-cells linked Pi export to insulin secretion physiology.

    Evidence XPR1 siRNA knockdown in MIN6m9 cells and pseudoislets with Pi efflux and insulin secretion assays

    PMID:32826297

    Open questions at the time
    • Effect on insulin secretion was modest
    • In vivo β-cell-specific knockout not performed
    • Whether InsP8 regulation operates in β-cells not directly tested
  8. 2022 High

    Identification of KIDINS220 as an obligate scaffold for XPR1 stability and localization revealed an additional layer of regulation and exposed a cancer-specific vulnerability in SLC34A2-high tumors where XPR1 inhibition causes lethal phosphate accumulation.

    Evidence Genome-scale CRISPR screens, genetic and pharmacologic XPR1 inhibition, co-localization studies, in vivo xenograft validation

    PMID:35437317

    Open questions at the time
    • Molecular interface between XPR1 and KIDINS220 not structurally defined at this point
    • Mechanism by which KIDINS220 loss triggers vacuolization and death unclear
  9. 2024 High

    Astrocyte-specific Xpr1 knockout recapitulated brain calcification, localizing XPR1 to astrocyte end-feet and establishing that astrocytic Pi export at the blood–brain barrier is the critical function lost in PFBC.

    Evidence Immunofluorescence localization, astrocyte-specific conditional Xpr1 knockout in mice, brain calcification quantification

    PMID:39019040

    Open questions at the time
    • Whether neuronal or other glial XPR1 contributes to brain Pi homeostasis not excluded
    • Mechanism of calcification deposit formation downstream of Pi accumulation undefined
  10. 2024 High

    The first cryo-EM structures of XPR1 resolved its dimeric 10-TM architecture with a transmembrane Pi translocation pathway, dual InsP/PP-IP binding sites, and electrophysiology confirmed channel-mode activity—transforming XPR1 from 'transporter of unknown mechanism' to a structurally defined phosphate channel.

    Evidence Cryo-EM in multiple conformations, patch clamp electrophysiology, mutagenesis

    PMID:39325866

    Open questions at the time
    • Full gating cycle not resolved
    • Role of KIDINS220 in structural context unknown
  11. 2025 High

    Multiple independent cryo-EM studies converged on a detailed gating mechanism: Pi permeates through sequential 'relay' binding sites via a knock-kiss-kick process; InsP8 bridges SPX to TM domains to open the channel; and KIDINS220 traps the α1 helix to stabilize a closed state that InsP8 must overcome—completing the structural picture of ligand-gated, scaffold-restrained Pi export.

    Evidence Cryo-EM of XPR1 alone and in complex with KIDINS220, Pi-bound/unbound states, MD simulations, proteoliposomal reconstitution, patch clamp electrophysiology, mutagenesis

    PMID:39747008 PMID:40140662 PMID:40374661 PMID:40858110

    Open questions at the time
    • How voltage dependence integrates with InsP8 gating structurally unresolved
    • Whether other cellular ligands modulate gating unknown
    • Structural basis for PFBC mutations outside SPX and channel pore not systematically mapped
  12. 2025 High

    Conditional Xpr1 knockout demonstrated that XPR1 is required for fetal liver macrophage (Kupffer cell) identity and erythrophagocytic function, expanding XPR1's physiological roles beyond epithelial/neuroglial Pi homeostasis to immune cell specification.

    Evidence Conditional Xpr1 knockout in hematopoietic and CD206+ cells, single-cell RNA-seq, pyrenocyte clearance assay

    PMID:41335223

    Open questions at the time
    • Whether Pi export per se or a Pi-independent function of XPR1 underlies macrophage identity loss not resolved
    • Downstream transcriptional mechanism linking XPR1 to Kupffer cell program unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how voltage dependence and InsP8 gating are structurally integrated; whether additional cellular ligands or post-translational modifications modulate XPR1 channel activity; the mechanism by which loss of Pi export leads to calcification deposits in specific tissues; and whether the macrophage identity phenotype reflects Pi export or a Pi-independent scaffolding function.
  • Voltage–ligand coupling mechanism unresolved
  • No comprehensive structure–function map of all known PFBC mutations
  • Pi-dependent vs Pi-independent roles in macrophage differentiation not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0140299 molecular sensor activity 4
Localization
GO:0005886 plasma membrane 6
Pathway
R-HSA-382551 Transport of small molecules 7 R-HSA-1643685 Disease 3
Partners
IP6K1IP6K2KIDINS220SLC20A2
Complex memberships
XPR1 homodimerXPR1–KIDINS220 complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 XPR1 (a multipass membrane protein) functions as an inorganic phosphate exporter in metazoans; depletion of XPR1 decreased phosphate export, and reintroduction of XPR1 proteins from fruit fly to human rescued this defect. A soluble ligand derived from the X-MLV envelope receptor-binding domain inhibited phosphate export in human cell lines. siRNA knockdown, rescue by reintroduction of XPR1 variants, pharmacological inhibition with viral envelope-derived ligand, phosphate efflux assays Cell reports High 23791524
2015 Mutations in XPR1 cause primary familial brain calcification (PFBC) by altering phosphate export function, implicating XPR1-mediated phosphate homeostasis in the disease. Human genetics (family-based sequencing), in vitro phosphate export complementation assay with PFBC-associated XPR1 mutants Nature genetics High 25938945
2020 XPR1-mediated phosphate efflux is specifically regulated by the inositol pyrophosphate InsP8: InsP8 binds with high affinity (Kd = 180 nM) to the XPR1 N-terminal SPX domain, and genetic or pharmacological reduction of InsP8 synthesis (via PPIP5K knockout or IP6K inhibition) inhibits XPR1-dependent phosphate export. PPIP5K knockout cells, pharmacological IP6K inhibition, liposomal delivery of PCP-InsP8 analog rescue, isothermal titration calorimetry (ITC) binding assay, phosphate efflux assays Proceedings of the National Academy of Sciences of the United States of America High 32019887
2019 Inositol pyrophosphates (IP7 and IP8), synthesized by IP6K1 and IP6K2, regulate XPR1-mediated phosphate export; knockout of both kinases abolishes detectable IP7/IP8, reduces phosphate export, and increases intracellular free phosphate. The SPX domain of XPR1 binds inositol pyrophosphates. CRISPR/Cas9 knockout of IP6K1/2 in HCT116 cells, PAGE/HPLC nucleotide analysis, Malachite green phosphate assay, [32Pi] pulse-labeling flux assay, functional XPR1 analysis The Journal of biological chemistry High 31186349
2020 SLC20A2 (phosphate importer) and XPR1 (phosphate exporter) functionally interact to regulate cellular phosphate homeostasis; SLC20A2 overexpression unexpectedly increases phosphate efflux via XPR1, while SLC20A2 depletion strongly decreases XPR1-mediated efflux. This interplay depends on inositol pyrophosphates (PP-IPs) binding to the XPR1 PP-IP-binding pocket. SLC20A2 overexpression and siRNA knockdown, XPR1 KO cells, inositol pyrophosphate manipulation (IP6K1-2 KO, IP6K inhibitor), rescue with WT vs. PP-IP-binding pocket mutant XPR1, intracellular phosphate and ATP measurements The Journal of biological chemistry High 32393577
2013 XPR1-GFP expressed in tobacco leaves localizes predominantly to the endomembrane system and mediates specific phosphate export, demonstrating conserved phosphate export activity in a heterologous plant system. Transient expression in tobacco leaves, GFP localization imaging, phosphate efflux assay FEBS letters Medium 24374333
2016 An XPR1 PFBC-associated variant (p.Leu87Pro) is not detectable at the cell surface and fails to export phosphate, while still being correctly transcribed; peripheral blood cells from the patient show decreased phosphate export ex vivo. In vitro complementation assay, cell surface expression analysis, ex vivo phosphate export in patient blood cells Journal of neurology Medium 27230854
2019 XPR1 variants located outside the SPX domain (R459C, N619D, I629S) are expressed at the cell surface and can serve as retrovirus receptors, yet are impaired in phosphate export, revealing that the XPR1 C-terminal domain contains structural features required for phosphate export function. In vitro phosphate export complementation assay, cell surface expression analysis, retrovirus entry assay, ex vivo phosphate export in patient blood cells Scientific reports Medium 31043717
2022 XPR1 requires the scaffold protein KIDINS220 for proper cellular localization and activity; disruption of the XPR1–KIDINS220 complex causes formation of acidic vacuolar structures preceding cell death. In SLC34A2-high cancer cells, genetic or pharmacological inhibition of XPR1-dependent phosphate efflux leads to toxic intracellular phosphate accumulation. Genome-scale CRISPR-Cas9 screens, genetic and pharmacologic XPR1 inhibition, co-localization studies, cell viability assays in vitro and in vivo xenograft Nature cancer High 35437317
2011 XPR1 is associated with the Gβ subunit of the G-protein heterotrimer (shown by chemical cross-linking), and acts as an atypical GPCR mediating cAMP signaling; retrovirus binding to XPR1 disrupts G-protein-mediated cAMP signaling, leading to apoptosis in neuroblastoma cells. Activation of adenylate cyclase rescued cells from retrovirus-induced toxicity. Chemical cross-linking, adenylate cyclase activation rescue assay, apoptosis assay in SY5Y neuroblastoma cells Journal of virology Medium 22090134
2009 Critical amino acids in XPR1 extracellular loops (ECL3 and ECL4) mediate retrovirus entry: three residues in ECL3 (E500, T507, V508) are required for polytropic MLV entry, and specific ECL4 residues determine xenotropic MLV entry; ECL3 and ECL4 may together form a single virus receptor site. Site-directed mutagenesis of XPR1, chimeric receptor analysis in transfected hamster cells, virus infectivity assays Retrovirology High 19811656
2010 XPR1 expression is upregulated by RANKL-RANK signaling during osteoclast differentiation, and XPR1 protein translocates to the membranes of the sealing zone in mature osteoclasts. Microarray analysis, quantitative PCR validation, immunostaining with subcellular localization Biochemical and biophysical research communications Low 20633538
2019 Xpr1 deficiency in mouse placenta disrupts placental-fetal inorganic phosphate homeostasis, causing decreased Pi in amniotic fluid and fetal serum, reduced skeletal mineral content, severe placental calcification, and perinatal lethality in homozygous knockout mice. Global Xpr1 knockout mouse generation, Pi measurement in amniotic fluid and serum, skeletal mineral content analysis, RNA-seq of placental mRNA Journal of bone and mineral research High 31498925
2020 XPR1 mediates the phosphate flush in pancreatic β-cells: XPR1 knockdown prevents glucose-stimulated inorganic phosphate efflux, causes intracellular Pi accumulation, and slightly blunts first-phase glucose-stimulated insulin secretion. Basal Pi efflux is stimulated by inositol pyrophosphates via XPR1. XPR1 siRNA knockdown in MIN6m9 cells and pseudoislets, Pi efflux assay, Ca2+ signaling measurement, insulin secretion assay, IP6K knockdown Diabetes Medium 32826297
2024 Cryo-EM structures of XPR1 in multiple conformations reveal a transmembrane pathway for Pi export, a dimeric architecture, and a dual-binding activation pattern for inositol pyrophosphates: a canonical InsP binding site at the dimeric interface of SPX domains, and a second site biased toward PP-IPs between the transmembrane and SPX domains. Electrophysiological analyses confirm XPR1 as an IPs/PP-IPs-activated phosphate channel. Cryo-EM structure determination in multiple conformations, electrophysiology (patch clamp), mutagenesis Science High 39325866
2025 Cryo-EM structure of human XPR1 shows a dimeric architecture with 10 transmembrane α-helices forming an ion channel-like structure, with multiple Pi recognition sites (two phosphate-binding sites enriched with positively charged residues) along the channel. Mutations of key arginine residues lining the channel abolish Pi transport. MD simulations reveal stepwise Pi transition through sequential recognition sites via a 'relay' process. Cryo-EM structure determination (Pi-unbound and Pi-bound states), site-directed mutagenesis, molecular dynamics simulation, functional Pi transport assay Nature communications High 39747008
2025 Cryo-EM structure of human XPR1 reveals a dimeric structure with TM1 at the dimer interface; a core domain forms a pore-like structure with two phosphate-binding sites; phosphate binding at the central site triggers a conformational change at TM9 opening the extracellular gate. A new SPX domain conformation (V-shaped) is also identified. Cryo-EM structure determination, site-directed mutagenesis of phosphate-binding residues, functional transport assay Nature communications High 40140662
2025 Cryo-EM structures of dimeric XPR1 plus functional characterization show that InsP8 (but not InsP6) binding rigidifies the intracellular SPX domains, bridges the XPR1 dimers and connects SPX to transmembrane domains, sequesters the C-terminal tail and reveals the entrance to the transport pathway. KIDINS220 stabilizes XPR1 in a closed conformation by trapping the XPR1 α1 helix (critical for InsP8 binding) within an interaction hub; InsP8 releases KIDINS220's restraint. Pi permeates a constriction site via a 'knock-kiss-kick' process through four gating states. Cryo-EM structure determination, functional assays, structural analysis of XPR1–KIDINS220 complex Molecular cell High 40858110
2025 Cryo-EM structure and patch clamp electrophysiology demonstrate that XPR1 functions as a voltage- and Pi-dependent phosphate-permeable ion channel with large unitary conductance, distinct from known ion transporters in topology; purified reconstituted hXPR1 in proteoliposomes catalyzes Pi transport. Cryo-EM structure determination (apo and Pi-bound), patch clamp electrophysiology, proteoliposomal Pi uptake assay, mutagenesis of Pi binding site Nature communications High 40374661
2025 XPR1 is required for the development and identity of fetal liver macrophages (Kupffer cells) and splenic/bone marrow red pulp macrophages; conditional Xpr1 knockout in hematopoietic/CD206+ cells causes loss of the Kupffer cell transcriptional program, shift to interferon-activated monocyte state, and failure to clear nuclei expelled from erythroblasts (pyrenocytes). Conditional Xpr1 knockout mice, single-cell RNA-seq, flow cytometry, functional erythroblast pyrenocyte clearance assay The Journal of experimental medicine High 41335223
2024 In astrocytes, XPR1 is specifically localized to astrocyte end-feet on blood vessels (polarized distribution), and astrocyte-specific Xpr1 knockout disrupts brain phosphate homeostasis and causes brain calcification in mice. Immunofluorescence localization, astrocyte-specific Xpr1 conditional knockout, brain calcification quantification, phosphate transport measurements Neuron High 39019040
2022 XPR1 deletion in cultured vascular smooth muscle cells (VSMCs) exacerbates extracellular matrix calcification and osteogenic phenotypic switch under calcifying conditions, demonstrating a protective role of XPR1-mediated phosphate export in vascular calcification. siRNA-mediated XPR1 deletion in cultured VSMCs, calcification assay, osteogenic marker analysis Calcified tissue international Medium 35112184
2024 A regulatory role of XPR1 in cellular Pi handling is proposed in which XPR1 senses intracellular Pi levels via its SPX domain and downregulates cellular Pi uptake via its C-terminal domain, with the SPX domain blunting the inhibitory effect of the C-terminus; however, direct Pi efflux attributable to XPR1 could not be detected in this Xenopus oocyte heterologous system. Expression in Xenopus oocytes, efflux experiments with multiple conditions, truncated XPR1 domain expression, Pi uptake assay Pflugers Archiv : European journal of physiology Low 38507112
2019 XPR1 promotes TSCC progression via activation of NF-κB signaling: XPR1 increases intracellular cAMP, activates PKA, and promotes phosphorylation and activation of NF-κB; XPR1 silencing inhibits NF-κB activation and reduces tumor growth. Luciferase reporter assay, PKA activity assay, ELISA, immunofluorescence, western blot, in vivo xenograft Journal of experimental & clinical cancer research Low 30995931
2025 RBM15 stabilizes XPR1 mRNA through m6A modification in lung adenocarcinoma cells, thereby promoting XPR1 expression and malignant progression; this was demonstrated by m6A RNA immunoprecipitation, dual-luciferase assay, and actinomycin D mRNA stability assay. m6A RNA immunoprecipitation, dual-luciferase reporter assay, actinomycin D mRNA stability assay, in vivo xenograft Naunyn-Schmiedeberg's archives of pharmacology Low 39928150

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nature genetics 262 25938945
2003 The immunoglobulin superfamily protein SYG-1 determines the location of specific synapses in C. elegans. Cell 253 12628183
2004 Synaptic specificity is generated by the synaptic guidepost protein SYG-2 and its receptor, SYG-1. Cell 239 15035988
2013 Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans. Cell reports 151 23791524
2000 Identification of XPR-1, a progesterone receptor required for Xenopus oocyte activation. Proceedings of the National Academy of Sciences of the United States of America 145 11114187
2012 Identification and characterization of a novel incompatibility group X3 plasmid carrying bla NDM-1 in Enterobacteriaceae isolates with epidemiological links to multiple geographical areas in China. Emerging microbes & infections 117 26038408
1980 In vitro comparison of initiation properties of bacteriophage lambda wild-type PR and x3 mutant promoters. Proceedings of the National Academy of Sciences of the United States of America 102 6450417
2020 Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. Proceedings of the National Academy of Sciences of the United States of America 95 32019887
1982 Agenesis of corpus callosum, ocular, and skeletal anomalies (X-linked dominant Aicardi's syndrome) in a girl with balanced X/3 translocation. Human genetics 94 6818132
2019 The inositol hexakisphosphate kinases IP6K1 and -2 regulate human cellular phosphate homeostasis, including XPR1-mediated phosphate export. The Journal of biological chemistry 87 31186349
2011 A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and glioma migration through the secreted glycoprotein YKL-40. The Journal of biological chemistry 68 21953450
2010 The mouse "xenotropic" gammaretroviruses and their XPR1 receptor. Retrovirology 64 21118532
1977 Isolation, chemical characterization, and biophysical properties of three different abnormal lipoproteins: LP-X1, LP-X2, and LP-X3. The Journal of biological chemistry 63 191454
2016 XPR1 mutations are a rare cause of primary familial brain calcification. Journal of neurology 61 27230854
2020 Interplay between primary familial brain calcification-associated SLC20A2 and XPR1 phosphate transporters requires inositol polyphosphates for control of cellular phosphate homeostasis. The Journal of biological chemistry 60 32393577
1991 Cu(II)-binding properties of a cytochrome c with a synthetic metal-binding site: His-X3-His in an alpha-helix. Proteins 60 1654548
2022 Phosphate dysregulation via the XPR1-KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer. Nature cancer 59 35437317
2012 Characterization of a novel β-agarase from an agar-degrading bacterium Catenovulum sp. X3. Applied microbiology and biotechnology 48 22990583
2022 A novel inhibitor of monooxygenase reversed the activity of tetracyclines against tet(X3)/tet(X4)-positive bacteria. EBioMedicine 47 35306337
2016 LRRK2 modulates microglial activity through regulation of chemokine (C-X3-C) receptor 1 -mediated signalling pathways. Human molecular genetics 43 27378696
2009 Six host range variants of the xenotropic/polytropic gammaretroviruses define determinants for entry in the XPR1 cell surface receptor. Retrovirology 42 19811656
2019 Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification. Human mutation 39 30609140
2010 Evolution of functional and sequence variants of the mammalian XPR1 receptor for mouse xenotropic gammaretroviruses and the human-derived retrovirus XMRV. Journal of virology 37 20844050
2015 X-3, a mangiferin derivative, stimulates AMP-activated protein kinase and reduces hyperglycemia and obesity in db/db mice. Molecular and cellular endocrinology 33 25681564
2007 Wild mouse variants of envelope genes of xenotropic/polytropic mouse gammaretroviruses and their XPR1 receptors elucidate receptor determinants of virus entry. Journal of virology 30 17634227
2019 Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of tongue squamous cell carcinoma (TSCC) via activation of NF-κB signaling. Journal of experimental & clinical cancer research : CR 29 30995931
2008 Functional dissection of SYG-1 and SYG-2, cell adhesion molecules required for selective synaptogenesis in C. elegans. Molecular and cellular neurosciences 29 18675916
2011 Xpr1 is an atypical G-protein-coupled receptor that mediates xenotropic and polytropic murine retrovirus neurotoxicity. Journal of virology 28 22090134
1997 Arginine 52 and histidine 54 located in a conserved amino-terminal hydrophobic region (LX2-R52-G-H54-X3-V-L) are important amino acids for the functional and structural integrity of the human liver UDP-glucuronosyltransferase UGT1*6. Molecular pharmacology 28 9058595
2019 Bioimmobilization of lead by Bacillus subtilis X3 biomass isolated from lead mine soil under promotion of multiple adsorption mechanisms. Royal Society open science 27 30891281
2019 Characterization of XPR1/SLC53A1 variants located outside of the SPX domain in patients with primary familial brain calcification. Scientific reports 26 31043717
2016 Vitamin-D receptor agonist calcitriol reduces calcification in vitro through selective upregulation of SLC20A2 but not SLC20A1 or XPR1. Scientific reports 26 27184385
2013 Expression of the mammalian Xenotropic Polytropic Virus Receptor 1 (XPR1) in tobacco leaves leads to phosphate export. FEBS letters 26 24374333
2022 PHOSPHATE exporter XPR1/SLC53A1 is required for the tumorigenicity of epithelial ovarian cancer. Cancer science 25 35377528
2020 Circ-XPR1 promotes osteosarcoma proliferation through regulating the miR-214-5p/DDX5 axis. Human cell 24 32920730
2024 Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1. Science (New York, N.Y.) 23 39325866
2021 miR-375 Inhibits the Proliferation, Migration and Invasion of Esophageal Squamous Cell Carcinoma by Targeting XPR1. Current gene therapy 23 33372873
2019 Murine Placental-Fetal Phosphate Dyshomeostasis Caused by an Xpr1 Deficiency Accelerates Placental Calcification and Restricts Fetal Growth in Late Gestation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 22 31498925
2020 Characterization of Three Porcine Acinetobacter towneri Strains Co-Harboring tet(X3) and blaOXA-58. Frontiers in cellular and infection microbiology 21 33363052
2017 Common polymorphisms of chemokine (C-X3-C motif) receptor 1 gene modify amyotrophic lateral sclerosis outcome: A population-based study. Muscle & nerve 20 28342179
2010 Several tetratricopeptide repeat (TPR) motifs of FANCG are required for assembly of the BRCA2/D1-D2-G-X3 complex, FANCD2 monoubiquitylation and phleomycin resistance. Mutation research 19 20450923
2022 The miR-4732-5p/XPR1 axis suppresses the invasion, metastasis, and epithelial-mesenchymal transition of lung adenocarcinoma via the PI3K/Akt/GSK3β/Snail pathway. Molecular omics 18 35388387
2011 Functional and spatial analysis of C. elegans SYG-1 and SYG-2, orthologs of the Neph/nephrin cell adhesion module directing selective synaptogenesis. PloS one 18 21858180
2008 Therapeutic RNA silencing of Cys-X3-Cys chemokine ligand 1 gene prevents mice from adenovirus vector-induced acute liver injury. Hepatology (Baltimore, Md.) 18 18098313
2013 The avian XPR1 gammaretrovirus receptor is under positive selection and is disabled in bird species in contact with virus-infected wild mice. Journal of virology 17 23843647
2010 RANKL-RANK signaling regulates expression of xenotropic and polytropic virus receptor (XPR1) in osteoclasts. Biochemical and biophysical research communications 17 20633538
2024 Astrocytes modulate brain phosphate homeostasis via polarized distribution of phosphate uptake transporter PiT2 and exporter XPR1. Neuron 16 39019040
2013 Endogenous gammaretrovirus acquisition in Mus musculus subspecies carrying functional variants of the XPR1 virus receptor. Journal of virology 16 23824809
2015 Genetically engineered Pseudomonas putida X3 strain and its potential ability to bioremediate soil microcosms contaminated with methyl parathion and cadmium. Applied microbiology and biotechnology 14 26521245
1994 Identification of -R-X-(X)-S/T-X3-S/T- as consensus sequence motif for autophosphorylation-dependent protein kinase. The Journal of biological chemistry 14 7961979
2022 Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter Species. Microbiology spectrum 13 36409072
2024 XPR1: a regulator of cellular phosphate homeostasis rather than a Pi exporter. Pflugers Archiv : European journal of physiology 11 38507112
2022 MicroRNA (miR)-590-3p alleviates high-glucose induced renal tubular epithelial cell damage by targeting C-X3-C motif chemokine ligand 1 (CX3CL1) in diabetic nephropathy. Bioengineered 11 34898373
2020 Biallelic XPR1 mutation associated with primary familial brain calcification presenting as paroxysmal kinesigenic dyskinesia with infantile convulsions. Brain & development 11 33433330
2011 Naturally Occurring Polymorphisms of the Mouse Gammaretrovirus Receptors CAT-1 and XPR1 Alter Virus Tropism and Pathogenicity. Advances in virology 11 22312361
2005 Distribution of human chemokine (C-X3-C) receptor 1 (CX3CR1) gene polymorphisms and haplotypes of the CC chemokine receptor 5 (CCR5) promoter in Chinese people, and the effects of CCR5 haplotypes on CCR5 expression. International journal of immunogenetics 11 15787642
2023 CircGNB1 facilitates the malignant phenotype of GSCs by regulating miR-515-5p/miR-582-3p-XPR1 axis. Cancer cell international 10 37407973
2022 Protective Roles of Xenotropic and Polytropic Retrovirus Receptor 1 (XPR1) in Uremic Vascular Calcification. Calcified tissue international 10 35112184
2021 C-X3-C motif chemokine ligand 1/receptor 1 regulates the M1 polarization and chemotaxis of macrophages after hypoxia/reoxygenation injury. Chronic diseases and translational medicine 10 34786544
2020 XPR1 Mediates the Pancreatic β-Cell Phosphate Flush. Diabetes 9 32826297
2019 Interfacial Engineering by Indium-Doped CdS for High Efficiency Solution Processed Sb2(S1- xSe x)3 Solar Cells. ACS applied materials & interfaces 9 30589526
2025 RBM15-mediated m6A modification of XPR1 promotes the malignant progression of lung adenocarcinoma. Naunyn-Schmiedeberg's archives of pharmacology 8 39928150
2022 Occurrence and Characterization of NDM-1-Producing Shewanella spp. and Acinetobacter portensis Co-Harboring tet(X3) in a Chinese Dairy Farm. Antibiotics (Basel, Switzerland) 8 36290080
2015 XPR1: a Gene Linked to Primary Familial Brain Calcification Might Help Explain a Spectrum of Neuropsychiatric Disorders. Journal of molecular neuroscience : MN 8 26231937
2025 Structural insights into the mechanism of phosphate recognition and transport by XPR1. Nature communications 7 39747008
2024 Nosocomial transmission of tet(x3), bla NDM-1 and bla OXA-97-carrying Acinetobacter baumannii conferring resistance to eravacycline and omadacycline, the Netherlands, March to August 2021. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 7 38994602
2015 Selective sweeps versus introgression - population genetic dynamics of the murine leukemia virus receptor Xpr1 in wild populations of the house mouse (Mus musculus). BMC evolutionary biology 7 26555287
2022 Long noncoding RNA regulatory factor X3- antisense RNA 1 promotes non-small cell lung cancer via the microRNA-577/signal transducer and activator of transcription 3 axis. Bioengineered 6 35475457
2020 A novel incompatibility group X3 plasmid carrying blaNDM-1 encodes a small RNA that regulates host fucose metabolism and biofilm formation. RNA biology 6 32594845
2015 Biodegradation of Navy N5RL1 carpet dye by Staphylococcus saprophyticus strain BHUSS X3. 3 Biotech 5 28324529
2023 Establishment and characterization of a new intrahepatic cholangiocarcinoma cell line, ICC-X3. Human cell 4 36662372
2023 The Effect of Lactiplantibacillus plantarum x3-2b Bacterial Powder on the Physicochemical Quality and Biogenic Amines of Fermented Lamb Jerky. Foods (Basel, Switzerland) 4 38002204
2025 Structure and function of human XPR1 in phosphate export. Nature communications 3 40140662
2022 The Immunoglobulin Superfamily Members syg-2 and syg-1 Regulate Neurite Development in C. elegans. Journal of developmental biology 3 35076532
2021 2D constraint modifies packing behaviour: a halobenzene monolayer with X3 halogen-bonding motif. Molecular physics 3 34848893
2000 Immunohistochemical studies on regulation of alternative splicing of fast skeletal muscle troponin T: non-uniform distribution of the exon x3 epitope in a single muscle fiber. Cell and tissue research 3 10741467
2025 Transport and InsP8 gating mechanisms of the human inorganic phosphate exporter XPR1. Nature communications 2 40113814
2025 Diverse Acinetobacter in retail meat: a hidden vector of novel species and antimicrobial resistance genes, including plasmid-borne blaOXA-58, mcr-4.3 and tet(X3). International journal of food microbiology 2 40513431
2025 KIDINS220 and InsP8 safeguard the stepwise regulation of phosphate exporter XPR1. Molecular cell 2 40858110
2024 Earliest observation of the tetracycline destructase tet(X3). Microbiology spectrum 2 38412527
2024 Inhibition of XPR1-dependent phosphate efflux induces mitochondrial dysfunction: A potential molecular target therapy for hepatocellular carcinoma? Molecular carcinogenesis 2 39136583
2024 Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of papillary thyroid carcinoma via the BRAF-ERK1/2-P53 signaling pathway. Journal of endocrinological investigation 2 39487939
2024 The putative polyamine transporter Shp2 facilitates phosphate export in an Xpr1-independent manner and contributes to high phosphate tolerance. The Journal of biological chemistry 2 39662831
2024 Establishment and characterization of a new intestinal-type ampullary carcinoma cell line, DPC-X3. BMC cancer 2 39707230
2014 Escape variants of the XPR1 gammaretrovirus receptor are rare due to reliance on a splice donor site and a short hypervariable loop. Virology 2 25151060
2025 The identification of XPR1 as a voltage- and phosphate-activated phosphate-permeable ion channel. Nature communications 1 40374661
2025 STAT3 regulates NK and NKT cell differentiation through C-X3-C motif chemokine receptor 1  (CX3CR1) in hyper-IgE syndrome. Molecular biomedicine 1 41212476
2024 Upregulation of granzyme B and C-X3-C motif receptor 1 in circulating plasmablasts was negatively regulated by Notch signal in patients with systemic lupus erythematosus. Journal of leukocyte biology 1 38833584
2019 Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species. Virology 1 31302509
2016 Permissive XPR1 gammaretrovirus receptors in four mammalian species are functionally distinct in interference tests. Virology 1 27423269
2006 Charge transfer study through the determination of the ionization energies of tetrapeptides X3-Tyr, X = Gly, Ala, or Leu. Influence of the inclusion of one glycine in alanine and leucine containing peptides. The journal of physical chemistry. A 1 17064186
1986 Characterization of the stability functions and inverted repeat structure X3 of the IncFI plasmid ColV2-K94. Canadian journal of microbiology 1 3024792
2025 Characterization of the expression of XPR1 in ovine utero-placental tissues. Reproduction (Cambridge, England) 0 40310868
2025 Exogenous adenosine counteracts tigecycline resistance in tet(X3)-harboring Escherichia coli. Microbiology spectrum 0 40622216
2025 The genetic polymorphism of XPR1 associated with Fanconi syndrome in Chinese patients with X-linked hypophosphatemia. Journal of endocrinological investigation 0 40768184
2025 XPR1 regulates fetal liver macrophage development, identity, and pyrenocyte clearance. The Journal of experimental medicine 0 41335223
2025 Innovative application of mefloquine and Methacycline in combating Tet(X3/X4)-positive Escherichia coli infections. BMC microbiology 0 41462086
2025 Transfer and Fitness of ISAba52-Mediated tet(X3) Transposon in Acinetobacter spp. Microorganisms 0 41471861
2024 The identification of XPR1 as a voltage- and phosphate-activated phosphate-permeable ion channel. Research square 0 39711567
2024 XPR1 promotes ovarian cancer growth and regulates MHC-I through autophagy. Genes & diseases 0 40641524