Affinage

XPR1

Solute carrier family 53 member 1 · UniProt Q9UBH6

Length
696 aa
Mass
81.5 kDa
Annotated
2026-06-11
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

XPR1/SLC53A1 is the principal inorganic phosphate (Pi) exporter of metazoan cells, maintaining cellular Pi homeostasis by extruding Pi across the plasma membrane (PMID:23791524). Structurally it is a dimer in which each subunit contributes a 10-transmembrane-helix core forming an ion channel-like translocation pathway, with positively charged arginine residues lining sequential Pi-recognition sites through which Pi moves by a stepwise 'relay' or 'knock-kiss-kick' process; mutation of these channel-lining residues abolishes transport (PMID:39747008, PMID:40140662, PMID:40858110). Patch-clamp recording and proteoliposomal reconstitution of purified XPR1 establish it as a bona fide voltage- and Pi-dependent ion channel with large unitary conductance (PMID:40374661). Channel activity is gated by the inositol pyrophosphate InsP8, which binds with high affinity (Kd ≈ 180 nM) to the N-terminal SPX domain and a second site between the SPX and transmembrane domains, rigidifying the SPX dimer and exposing the transport pathway; depletion of InsP8 by knockout of its synthetic kinases PPIP5K or IP6K1/2 phenocopies XPR1 loss (PMID:32019887, PMID:31186349, PMID:39325866, PMID:40113814). The scaffold protein KIDINS220 is required for XPR1 localization and activity, holding the channel in a closed state by trapping the InsP8-binding α1 helix until InsP8 releases this restraint in a stepwise 'key-to-locks' activation (PMID:40858110, PMID:35437317). XPR1 works with the Pi importer SLC20A2/PiT2 in an inositol-pyrophosphate-dependent axis that buffers intracellular Pi and ATP levels (PMID:32393577). Loss-of-function XPR1 mutations cause primary familial brain calcification by impairing Pi export, and cell-surface localization together with intact C-terminal residues is required for transport activity (PMID:25938945, PMID:27230854, PMID:31043717). Physiologically, XPR1 is essential for placental-fetal Pi homeostasis (PMID:31498925), brain Pi homeostasis via polarized localization in astrocyte end-feet (PMID:39019040), pancreatic β-cell phosphate flushing during insulin secretion (PMID:35377528), and fetal liver Kupffer cell development and erythrophagocytosis (PMID:41335223). XPR1 was independently identified as the cell-surface receptor for xenotropic and polytropic murine leukemia viruses, with extracellular loops ECL3/ECL4 forming the entry site, a function genetically separable from Pi export (PMID:31043717, PMID:19811656).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2009 High

    Before its transport role was known, XPR1 was characterized as a retrovirus receptor, and mapping its virus-entry determinants established which extracellular surfaces engage ligand.

    Evidence mutagenesis and chimera infection assays with X/PMVs in transfected hamster cells

    PMID:19811656

    Open questions at the time
    • Did not address the physiological transport function of XPR1
    • Relationship between virus-binding loops and any endogenous ligand undefined
  2. 2011 Medium

    An early mechanistic proposal linked XPR1 to G-protein signaling, framing retrovirus binding as a route to neurotoxicity via cAMP.

    Evidence chemical cross-linking of XPR1 to Gβ and adenylate cyclase rescue of XMRV toxicity in SY5Y neuroblastoma cells

    PMID:22090134

    Open questions at the time
    • Cross-linking association not validated by reciprocal or structural methods
    • Relationship to the later-established Pi-export function unresolved
  3. 2013 High

    The defining advance was establishing XPR1 as an inorganic phosphate exporter, answering what the protein actually transports.

    Evidence siRNA depletion, cross-species complementation, and soluble retroviral ligand inhibition of Pi export across multiple human cell types

    PMID:23791524 PMID:24374333

    Open questions at the time
    • Mechanism of transport (channel vs carrier) not resolved
    • Regulation of export activity unknown
  4. 2015 High

    Human genetics tied XPR1 directly to disease, showing loss of Pi-export function causes primary familial brain calcification.

    Evidence mutation identification in PFBC families plus in vitro Pi export assays demonstrating loss-of-function; refined by cell-surface and C-terminal residue analyses

    PMID:25938945 PMID:27230854 PMID:31043717

    Open questions at the time
    • Mechanism linking impaired Pi efflux to brain calcification not fully defined
    • Cell-type specificity of pathology not established at this stage
  5. 2020 High

    The regulatory logic of XPR1 was solved by showing the inositol pyrophosphate InsP8 specifically activates Pi efflux through the SPX domain.

    Evidence PPIP5K/IP6K knockout, analog rescue, and ITC binding (Kd 180 nM) to the SPX domain; SLC20A2-XPR1 axis defined by flux and ATP measurements with PP-IP-pocket mutants

    PMID:31186349 PMID:32019887 PMID:32393577

    Open questions at the time
    • Structural basis of SPX-mediated gating not yet visualized
    • How InsP8 binding couples to channel opening unknown
  6. 2019 High

    Knockout mouse work demonstrated that XPR1 Pi export is physiologically essential, beginning with placental-fetal phosphate homeostasis.

    Evidence global Xpr1 knockout mice with amniotic/serum Pi, skeletal mineralization, and placental calcification phenotypes; perinatal lethality

    PMID:31498925

    Open questions at the time
    • Tissue-autonomous requirements not dissected by global knockout
    • Did not resolve molecular gating mechanism
  7. 2024 High

    Cryo-EM and electrophysiology resolved XPR1 as a dimeric, Pi-permeable ion channel with a dual InsP8-binding activation pattern, explaining how gating works.

    Evidence cryo-EM in multiple conformational states with electrophysiology, channel-lining arginine mutagenesis, and MD simulations of stepwise Pi relay

    PMID:39325866 PMID:39747008 PMID:40113814 PMID:40140662 PMID:40374661

    Open questions at the time
    • In vivo relevance of specific conformational states not directly tested
    • Role of accessory proteins in gating not addressed structurally here
  8. 2025 High

    Structural work on the XPR1-KIDINS220 complex established the scaffold's role as a brake released by InsP8, completing the activation model.

    Evidence cryo-EM of the XPR1-KIDINS220 complex showing KIDINS220 trapping the α1 helix in a closed state and InsP8-driven stepwise 'key-to-locks' release

    PMID:35437317 PMID:40858110

    Open questions at the time
    • How KIDINS220 levels are regulated physiologically unknown
    • Whether other scaffolds substitute in different tissues not addressed
  9. 2025 High

    Conditional knockouts revealed cell-type-specific physiological roles, extending XPR1 function from brain Pi homeostasis to macrophage development.

    Evidence astrocyte-, β-cell-, and hematopoietic/CD206+-specific perturbations with localization, scRNA-seq, flow cytometry, and functional Pi-flush/erythrophagocytosis readouts

    PMID:32826297 PMID:39019040 PMID:41335223

    Open questions at the time
    • Mechanism linking Pi flux to Kupffer cell transcriptional identity unclear
    • Glucose-driven β-cell phosphate flush occurs independent of inositol pyrophosphates, mechanism unresolved
  10. 2025 Medium

    Cancer studies positioned XPR1-dependent Pi efflux as a tumor dependency and connected it to metabolic regulation.

    Evidence CRISPR/shRNA knockdown in ovarian clear cell, hepatocellular, and lung adenocarcinoma models with xenografts, epistatic PHGDH rescue, and m6A/RBM15 mRNA-stability analysis

    PMID:35377528 PMID:39928150 PMID:41592436

    Open questions at the time
    • Reliance on knockdown rather than knockout in several studies
    • Whether metabolic effects are direct consequences of altered Pi handling not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How XPR1 channel gating is coordinated with tissue-specific physiology, and whether the SPX/InsP8 mechanism applies uniformly across all its essential roles, remains open.
  • The InsP8-independent glucose-driven β-cell phosphate flush is mechanistically unexplained
  • A dissenting Xenopus oocyte study proposing a regulatory rather than direct-export role conflicts with structural and electrophysiological data and has not been reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0001618 virus receptor activity 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-382551 Transport of small molecules 3 R-HSA-1430728 Metabolism 2 R-HSA-1643685 Disease 2
Partners
GNB1KIDINS220SLC20A2
Complex memberships
XPR1-KIDINS220 complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 XPR1 (a multipass membrane molecule) 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 from the envelope-receptor-binding domain of X-MLV inhibited phosphate export in all human cell lines tested, as well as in stem cells and renal proximal tubule epithelial cells. siRNA depletion, complementation assays with XPR1 from multiple species, soluble ligand inhibition in multiple cell types including renal proximal tubule cells Cell reports High 23791524
2015 Mutations in XPR1 cause primary familial brain calcification (PFBC). Identified mutations in XPR1 alter inorganic phosphate export function, establishing XPR1's phosphate export activity as mechanistically linked to PFBC pathology. Human genetics (mutation identification in PFBC families), in vitro phosphate export assay demonstrating loss-of-function Nature genetics High 25938945
2020 XPR1-mediated inorganic phosphate (Pi) efflux is specifically regulated by inositol pyrophosphate InsP8. Genetic knockout of PPIP5Ks (which synthesize InsP8) or pharmacological inhibition of upstream IP6Ks reduced XPR1-dependent Pi efflux, phenocopying XPR1 knockout. Rescue of InsP8 levels restored Pi efflux. High-affinity binding of InsP8 to the XPR1 N-terminus (SPX domain) was demonstrated by isothermal titration calorimetry (Kd = 180 nM). PCP analogs of other PP-IP signaling molecules were ineffective, establishing functional specificity for InsP8. PPIP5K/XPR1 knockout cells, pharmacological inhibition, liposomal delivery of metabolically resistant InsP8 analog, isothermal titration calorimetry, cellular Pi efflux assays Proceedings of the National Academy of Sciences of the United States of America High 32019887
2019 IP6K1 and IP6K2 regulate XPR1-mediated phosphate export in human cells. Knockout of IP6K1/2 in HCT116 cells eliminated inositol pyrophosphates (IP7, IP8), decreased phosphate flux (both import and export), and XPR1 phosphate export function was shown to be regulated by inositol pyrophosphates binding to its SPX domain. IP6K1/2 double knockout in HCT116 cells, PAGE and HPLC analysis of inositol pyrophosphates, [32Pi] pulse labeling for phosphate flux measurement, Malachite green assay for intracellular phosphate The Journal of biological chemistry High 31186349
2020 XPR1 and SLC20A2 (phosphate importer) function in an interplay to regulate cellular phosphate homeostasis. Overexpression of WT SLC20A2 increased both phosphate uptake and efflux; PFBC-associated SLC20A2 variants did not increase efflux. SLC20A2 depletion strongly decreased XPR1-mediated phosphate efflux. The SLC20A2-XPR1 axis maintained constant intracellular phosphate and ATP levels; XPR1 harboring a mutated inositol pyrophosphate (PP-IP)-binding pocket failed to rescue elevated ATP levels, establishing that this regulation is IP-dependent. SLC20A2 overexpression/depletion, XPR1 KO, XPR1 PP-IP-binding pocket mutant, phosphate flux measurement, ATP measurement, IP6K1/2 inhibition The Journal of biological chemistry High 32393577
2024 Cryo-EM structures of XPR1 in multiple conformations reveal a transmembrane pathway for Pi export and a dual-binding activation pattern for inositol pyrophosphates (PP-IPs). A canonical PP-IP binding site is at the dimeric interface of SPX domains, and a second site biased toward PP-IPs is between the transmembrane and SPX domains. Electrophysiological analyses confirmed XPR1 as a PP-IP/IP-activated phosphate channel. The interplay among transmembrane domains, SPX domains, and IPs/PP-IPs orchestrates conformational transitions between closed and open states. Cryo-electron microscopy (multiple conformational states), electrophysiology Science (New York, N.Y.) 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 along the channel. Pathogenic mutations in two arginine residues lining the translocation channel disrupt Pi transport. Molecular dynamics simulations reveal Pi undergoes stepwise transition through sequential recognition sites via a 'relay' process. Cryo-EM (Pi-unbound and Pi-bound states), mutagenesis of channel-lining arginines, molecular dynamics simulations, functional Pi transport assays Nature communications High 39747008
2025 Cryo-EM structure of human XPR1 shows a dimeric structure with TM1 forming the dimer interface. Each subunit has a core domain forming a pore-like structure with two phosphate-binding sites enriched with positively charged residues. Mutations of key residues at either binding site substantially diminish transport activity. Phosphate binding at the central site triggers a conformational change at TM9, opening the extracellular gate. A new conformational state with V-shaped cytoplasmic SPX domains was identified. Cryo-EM structure determination, site-directed mutagenesis of phosphate-binding site residues with functional transport assays Nature communications High 40140662
2025 Patch clamp recordings of human XPR1 reveal voltage- and Pi-dependent channel activity with large unitary conductance, characterizing XPR1 as an ion channel. Proteoliposomal uptake assays with purified reconstituted XPR1 confirmed Pi transport. Mutagenesis of a putative Pi binding site affected transport. Cryo-EM structure of hXPR1 with Pi bound identified an ion permeation pathway. Cryo-EM (apo and Pi-bound), patch clamp electrophysiology, proteoliposomal reconstitution assays, site-directed mutagenesis Nature communications High 40374661
2025 XPR1 requires the scaffold protein KIDINS220 for proper cellular localization and activity. Cryo-EM structural studies show InsP8 activates XPR1 in a stepwise manner involving profound SPX domain movements, with each XPR1 subunit having four gating states and Pi permeating via a 'knock-kiss-kick' process at a constriction site. 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, constituting a 'key-to-locks' stepwise activation mechanism. Cryo-EM structural analysis of XPR1-KIDINS220 complex, functional activity assays, structural characterization of InsP8 binding states Molecular cell High 40858110
2025 Binding of InsP8 to XPR1 (but not InsP6) rigidifies the intracellular SPX domains, with InsP8 bridging the XPR1 dimers and connecting SPX and transmembrane domains. In this state, the C-terminal tail is sequestered, revealing the entrance to the transport pathway. This explains the obligate roles of the SPX domain and InsP8 in XPR1 activity. Cryo-EM structures of dimeric XPR1 with and without InsP8/InsP6, functional characterization of substrate translocation pathway Nature communications High 40113814
2022 XPR1 requires the novel partner protein KIDINS220 for proper cellular localization and phosphate export activity. In SLC34A2-high cancer cell lines, genetic or pharmacologic inhibition of XPR1-dependent phosphate efflux leads to toxic intracellular phosphate accumulation. Disruption of the XPR1-KIDINS220 protein complex results in acidic vacuolar structures preceding cell death. Genome-scale CRISPR-Cas9 screens, genetic and pharmacological inhibition, assessment of intracellular phosphate levels, cellular localization studies, in vitro and in vivo cancer models Nature cancer High 35437317
2016 An XPR1 mutation (p.Leu87Pro) causes PFBC; the mutant XPR1 protein was not detectable at the cell surface and did not support phosphate export, indicating that cell surface localization is required for XPR1 phosphate export function. Peripheral blood cells from the patient showed decreased phosphate export ex vivo. In vitro physiological complementation assay, cell surface expression analysis, ex vivo phosphate export measurement from patient blood cells Journal of neurology Medium 27230854
2019 XPR1 variants located outside the SPX domain (p.R459C, p.N619D, p.I629S) are impaired in phosphate export function but are normally expressed at the cell surface and retain function as retrovirus receptors. Peripheral blood cells from the p.N619D patient displayed significantly impaired phosphate export ex vivo, establishing that C-terminal domain residues are required for phosphate export. In vitro physiological complementation assay, cell surface expression analysis, retrovirus entry assay, ex vivo phosphate export from patient blood cells Scientific reports Medium 31043717
2011 XPR1 is associated with the Gβ subunit of the G-protein heterotrimer by chemical cross-linking, and xenotropic/polytropic retrovirus binding to XPR1 disrupts cAMP-mediated signaling, leading to apoptosis of infected cells. Activation of adenylate cyclase rescued cells from XMRV toxicity, establishing XPR1-mediated G-protein signaling as a mechanism of retrovirus-induced neurotoxicity. Chemical cross-linking studies showing XPR1-Gβ association, adenylate cyclase activation rescue experiments, apoptosis assays in SY5Y human neuroblastoma cells Journal of virology Medium 22090134
2013 XPR1-GFP expressed in tobacco leaves localizes predominantly to the endomembrane system and leads to specific phosphate export, demonstrating phosphate export activity of XPR1 in a heterologous plant system. Transient expression of XPR1-GFP in tobacco leaves, phosphate export measurement, subcellular localization by fluorescence imaging FEBS letters Medium 24374333
2009 Critical amino acids in XPR1 extracellular loops (ECL3 and ECL4) mediate entry of xenotropic and polytropic mouse leukemia viruses. Specifically, three residues in ECL3 (E500, T507, V508) are involved in PMV entry and can influence AKR6 and Cz524 infectivity. ECL3 and ECL4 may contribute to formation of a single virus receptor site. Generation of Xpr1 mutants and chimeras, infection assays with panel of X/PMVs in transfected hamster cells expressing chimeric/mutated XPR1s Retrovirology High 19811656
2010 RANKL-RANK signaling upregulates XPR1 expression during osteoclast differentiation, and XPR1 protein translocates to the membranes of the sealing zone in mature osteoclasts. Microarray analysis, quantitative PCR validation, immunostaining for XPR1 localization in differentiating osteoclasts from primary bone marrow cells and RAW 264.7 macrophage cell line Biochemical and biophysical research communications Medium 20633538
2019 Global Xpr1 knockout in mice causes phosphate dyshomeostasis: heterozygous and homozygous Xpr1-deficient fetuses have lower inorganic phosphate levels in amniotic fluid and serum, decreased skeletal mineral content, and severely calcified placentas. Homozygous Xpr1-/- mice die perinatally, establishing XPR1 as essential for placental-fetal phosphate homeostasis. Global Xpr1 knockout mouse generation, measurement of inorganic phosphate in amniotic fluid and serum, skeletal mineral content analysis, RNA-seq of placental mRNA Journal of bone and mineral research High 31498925
2020 XPR1 knockdown in pancreatic β-cells (MIN6m9 cell line and pseudoislets) prevents the glucose-stimulated phosphate flush (inorganic phosphate efflux accompanying insulin secretion). XPR1 silencing leads to intracellular Pi accumulation and affects Ca2+ signaling. Basal Pi efflux was stimulated by inositol pyrophosphates; however, the glucose-driven phosphate flush occurred despite inositol pyrophosphate depletion. XPR1 knockdown in MIN6m9 β-cells and pseudoislets, measurement of phosphate efflux, intracellular Pi accumulation, Ca2+ signaling analysis, IP6K inhibition Diabetes Medium 32826297
2022 Knockdown of XPR1 in ovarian clear cell carcinoma (OCCC) cells induces growth arrest and apoptosis in vitro and inhibits proliferation of OCCC xenografts in vivo, establishing a role for XPR1-dependent phosphate efflux in OCCC tumorigenicity. CRISPR/Cas9 screen, shRNA knockdown, xenograft model in immunocompromised mice Cancer science Medium 35377528
2024 XPR1 is required for proper localization (polarized distribution) in astrocytes: XPR1 (phosphate exporter) localizes to astrocyte end-feet on blood vessels while PiT2 (importer) is distributed over the entire astrocyte processes. Astrocyte-specific knockout of Xpr1 disrupts this polarized distribution and impairs brain phosphate homeostasis, demonstrating that astrocyte XPR1 is pivotal for brain phosphate homeostasis. Astrocyte-specific Xpr1 and Pit2 conditional knockout mice, immunofluorescence for subcellular localization, phosphate transport measurements Neuron High 39019040
2025 XPR1 is required for development of fetal liver macrophages (Kupffer cells). Conditional knockout of Xpr1 in hematopoietic or CD206+ cells causes loss of the Kupffer cell transcriptional program, a shift toward interferon-activated monocyte/macrophage state, and failure to clear nuclei expelled from erythroblasts. Splenic red pulp and bone marrow macrophages are also reduced in adult mice lacking intrinsic Xpr1. Conditional Xpr1 knockout in hematopoietic/CD206+ cells, single-cell RNA-seq, flow cytometry, functional analysis of pyrenocyte clearance The Journal of experimental medicine High 41335223
2024 A regulatory role for XPR1 in cellular Pi handling rather than direct Pi export was proposed based on Xenopus oocyte expression experiments. Expression of truncated XPR1 constructs showed that the C-terminal domain downregulates cellular Pi uptake. Tethering the C-terminus to the transmembrane core changed kinetics of inhibition; the SPX domain blunted the inhibitory effect. Note: this finding contradicts the prevailing exporter model and may reflect species-incompatibility issues in the Xenopus system. Xenopus oocyte expression system, Pi efflux and uptake assays, expression of truncated XPR1 constructs and individual domains Pflugers Archiv : European journal of physiology Low 38507112
2025 XPR1 knockdown in hepatocellular carcinoma cells disrupts MNX1-mediated regulation of PHGDH expression, impairing serine biosynthesis, compromising redox homeostasis, and inducing mitochondrial fragmentation and apoptosis. Re-expression of PHGDH in XPR1-knockdown cells restored serine levels and tumorigenic capacity, placing XPR1 upstream of the MNX1-PHGDH-serine metabolism axis. XPR1 knockdown, PHGDH/MNX1 rescue experiments, serine biosynthesis measurement, redox assays, in vivo xenograft Redox biology Medium 41592436
2024 XPR1 deletion in cultured vascular smooth muscle cells (VSMCs) exacerbates calcification of extracellular matrix and promotes the osteogenic phenotypic switch under calcifying conditions, establishing a protective role for XPR1 in vascular calcification. XPR1 deletion in cultured VSMCs, extracellular matrix calcification assay, osteogenic marker analysis Calcified tissue international Medium 35112184
2025 RBM15 stabilizes XPR1 mRNA through m6A modification in lung adenocarcinoma cells, increasing XPR1 expression and promoting cancer cell proliferation and invasion. Actinomycin D assays and m6A RNA immunoprecipitation confirmed the m6A-dependent stabilization mechanism. m6A RNA immunoprecipitation, dual-luciferase reporter assay, actinomycin D mRNA stability assay, RBM15 silencing with XPR1 rescue Naunyn-Schmiedeberg's archives of pharmacology Medium 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 264 25938945
2003 The immunoglobulin superfamily protein SYG-1 determines the location of specific synapses in C. elegans. Cell 254 12628183
2004 Synaptic specificity is generated by the synaptic guidepost protein SYG-2 and its receptor, SYG-1. Cell 240 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 96 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 70 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
2022 A novel inhibitor of monooxygenase reversed the activity of tetracyclines against tet(X3)/tet(X4)-positive bacteria. EBioMedicine 49 35306337
2012 Characterization of a novel β-agarase from an agar-degrading bacterium Catenovulum sp. X3. Applied microbiology and biotechnology 49 22990583
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 41 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
2016 Vitamin-D receptor agonist calcitriol reduces calcification in vitro through selective upregulation of SLC20A2 but not SLC20A1 or XPR1. Scientific reports 27 27184385
2019 Characterization of XPR1/SLC53A1 variants located outside of the SPX domain in patients with primary familial brain calcification. Scientific reports 26 31043717
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
2021 miR-375 Inhibits the Proliferation, Migration and Invasion of Esophageal Squamous Cell Carcinoma by Targeting XPR1. Current gene therapy 25 33372873
2024 Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1. Science (New York, N.Y.) 24 39325866
2020 Circ-XPR1 promotes osteosarcoma proliferation through regulating the miR-214-5p/DDX5 axis. Human cell 24 32920730
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
2024 Astrocytes modulate brain phosphate homeostasis via polarized distribution of phosphate uptake transporter PiT2 and exporter XPR1. Neuron 18 39019040
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
2013 Endogenous gammaretrovirus acquisition in Mus musculus subspecies carrying functional variants of the XPR1 virus receptor. Journal of virology 16 23824809
2022 Identification of Novel tet(X3) Variants Resistant To Tigecycline in Acinetobacter Species. Microbiology spectrum 15 36409072
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 15 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 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 12 34898373
2024 XPR1: a regulator of cellular phosphate homeostasis rather than a Pi exporter. Pflugers Archiv : European journal of physiology 11 38507112
2023 CircGNB1 facilitates the malignant phenotype of GSCs by regulating miR-515-5p/miR-582-3p-XPR1 axis. Cancer cell international 11 37407973
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 11 34786544
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
2022 Protective Roles of Xenotropic and Polytropic Retrovirus Receptor 1 (XPR1) in Uremic Vascular Calcification. Calcified tissue international 10 35112184
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) 10 36290080
2019 Interfacial Engineering by Indium-Doped CdS for High Efficiency Solution Processed Sb2(S1- xSe x)3 Solar Cells. ACS applied materials & interfaces 10 30589526
2025 Structural insights into the mechanism of phosphate recognition and transport by XPR1. Nature communications 9 39747008
2020 XPR1 Mediates the Pancreatic β-Cell Phosphate Flush. Diabetes 9 32826297
2025 RBM15-mediated m6A modification of XPR1 promotes the malignant progression of lung adenocarcinoma. Naunyn-Schmiedeberg's archives of pharmacology 8 39928150
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
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
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 4 40513431
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
2025 KIDINS220 and InsP8 safeguard the stepwise regulation of phosphate exporter XPR1. Molecular cell 3 40858110
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 3 39662831
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
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 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 The genetic polymorphism of XPR1 associated with Fanconi syndrome in Chinese patients with X-linked hypophosphatemia. Journal of endocrinological investigation 1 40768184
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
2003 Crystallization and preliminary crystallographic analysis of extracellular fragment X3 of YWK-II/APPH: a human sperm membrane protein related to the Alzheimer betaA4-amyloid precursor protein. Acta crystallographica. Section D, Biological crystallography 1 12595709
1986 Characterization of the stability functions and inverted repeat structure X3 of the IncFI plasmid ColV2-K94. Canadian journal of microbiology 1 3024792
2026 XPR1 downregulation inhibits hepatocellular carcinoma progression by suppressing serine metabolism. Redox biology 0 41592436
2025 Characterization of the expression of XPR1 in ovine utero-placental tissues. Reproduction (Cambridge, England) 0 40310868
2025 XPR1 regulates fetal liver macrophage development, identity, and pyrenocyte clearance. The Journal of experimental medicine 0 41335223
2024 Establishment and characterization of the PDAC-X3 cell line: a novel Chinese-origin pancreatic ductal adenocarcinoma cell line. Human cell 0 39012569
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

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