Affinage

P2RX5

P2X purinoceptor 5 · UniProt Q93086

Length
444 aa
Mass
49.3 kDa
Annotated
2026-04-29
100 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

P2RX5 encodes the P2X5 subunit of ligand-gated ion channels that assemble as homotrimers or heterotrimers to mediate extracellular ATP signaling in diverse cell types including neurons, astrocytes, skeletal muscle satellite cells, osteoclasts, and adipocytes. The full-length homomeric P2X5 channel conducts slowly desensitizing cation currents with Ca²⁺ permeability and large-pore (YO-PRO-1-permeable) properties, and its assembly requires the second transmembrane domain encoded by exon 10—a common human splice-site SNP (G allele) causes exon 10 skipping, producing a cytoplasm-retained, non-functional isoform carried by most non-African populations (PMID:20223879, PMID:17001079, PMID:12761352). P2X5 preferentially co-assembles with P2X1 to form heteromeric channels with nanomolar ATP sensitivity and biphasic kinetics in cortical astrocytes, and with P2X2 to produce channels exhibiting P2X7-like pore dilation and membrane blebbing in neurons (PMID:9855626, PMID:18495881, PMID:22442090). Functionally, P2X5 activation on skeletal muscle satellite cells drives exit from proliferation and myogenic differentiation via p38 MAPK (PMID:12135987), while in osteoclasts P2X5 is required for ATP-induced inflammasome activation and IL-1β release that mediates inflammatory bone loss (PMID:28298636, PMID:30103845).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 High

    Cloning of P2RX5 established that it encodes a new member of the ATP-gated ion channel family with a distinctive slowly desensitizing current and unique pharmacology, answering whether there were additional P2X subtypes with non-redundant properties.

    Evidence cDNA cloning from rat, heterologous expression in Xenopus oocytes and HEK cells, whole-cell electrophysiology

    PMID:8786426

    Open questions at the time
    • No native tissue function demonstrated
    • Subunit stoichiometry and oligomeric state unknown
    • Human ortholog not yet characterized
  2. 1999 High

    Demonstration that P2X5 co-assembles with P2X1 into heteromeric channels with hybrid kinetics (fast P2X1 peak plus sustained P2X5 plateau) revealed that P2X subunit mixing diversifies purinergic signaling beyond what homomers provide.

    Evidence Co-expression in HEK293 and Xenopus oocytes, reciprocal co-purification of epitope-tagged subunits, electrophysiology

    PMID:10336430 PMID:9855626

    Open questions at the time
    • Native tissue relevance of P2X1/5 heteromers not shown
    • Stoichiometry of heteromeric assembly unknown
    • Whether P2X5 forms heteromers with other P2X subunits untested
  3. 2002 High

    Identification of P2X5 on skeletal muscle satellite cells and demonstration that its activation suppresses proliferation and promotes myogenic differentiation via p38 MAPK provided the first physiological function for P2X5 homomeric signaling.

    Evidence Primary rat satellite cell culture with RT-PCR, electrophysiology, immunocytochemistry, Western blot for p38, and pharmacological p38 inhibition

    PMID:12135987

    Open questions at the time
    • In vivo muscle regeneration phenotype not tested
    • Whether the effect requires homomeric or heteromeric P2X5 channels is unresolved
    • Downstream effectors beyond p38 not identified
  4. 2003 High

    Full biophysical characterization of human full-length P2X5 revealed Ca²⁺ permeability and large-pore (NMDG/YO-PRO-1 permeable) properties previously associated only with P2X7, expanding the functional repertoire of this channel.

    Evidence Patch-clamp and fluorescence dye uptake in HEK293 cells expressing full-length human P2X5

    PMID:12761352

    Open questions at the time
    • Structural basis for pore dilation unknown
    • Physiological relevance of large-pore state not demonstrated in native cells
  5. 2005 High

    Discovery that a frameshift polymorphism in P2RX5 generates the minor histocompatibility antigen LRH-1, with CTL responses correlating with CML remission after donor lymphocyte infusion, linked P2RX5 genetic variation to graft-versus-leukemia immunity.

    Evidence Genetic linkage analysis, HLA-B7 tetramer staining of CD8⁺ T cells, functional CTL assays in patient samples

    PMID:16322791

    Open questions at the time
    • Whether LRH-1-directed CTL activity is sufficient for remission versus a correlate is unclear
    • Broader HLA context not explored
  6. 2006 High

    Mutagenesis of TM2 showed that Asp355 and full-length TM2 are required for homotrimerization, explaining why the exon-10-skipped isoform fails to assemble and is non-functional.

    Evidence Systematic TM2 mutagenesis, biochemical trimerization assays in HEK cells and oocytes

    PMID:17001079

    Open questions at the time
    • Structure of the assembled trimer not resolved at atomic level
    • Whether TM2 requirements differ for heteromeric assembly unknown
  7. 2008 High

    Electrophysiology of native cortical astrocytes demonstrated that the predominant P2X receptor is a P2X1/5 heteromer with nanomolar ATP sensitivity, establishing physiological relevance of this heteromeric combination in the CNS.

    Evidence Whole-cell patch clamp on acutely isolated astrocytes from GFAP-EGFP transgenic mice, qRT-PCR

    PMID:18495881

    Open questions at the time
    • Functional consequence of astrocytic P2X1/5 activation for gliotransmission or calcium signaling not tested
    • Selective genetic ablation of P2X5 in astrocytes not performed
  8. 2010 High

    A splice-site SNP at exon 10 was shown to determine whether human P2X5 is functional (surface-expressed, full-length) or non-functional (cytoplasmic, truncated), with most non-African humans homozygous for the non-functional allele, resolving long-standing discrepancies in human P2X5 pharmacology.

    Evidence Human genotyping, immunostaining, electrophysiology, and FLIPR calcium imaging in stably expressing cell lines

    PMID:20223879

    Open questions at the time
    • Phenotypic consequences of lacking functional homomeric P2X5 in the majority human population not characterized
    • Whether heteromeric channels containing the truncated isoform retain any function is unknown
  9. 2012 High

    Discovery that P2X5 also heteromerizes with P2X2 and that these channels exhibit P2X7-like pore dilation, membrane blebbing, and phosphatidylserine exposure broadened the functional impact of P2X5 heteromers beyond P2X1/5.

    Evidence BRET, bimolecular fluorescence complementation, co-immunoprecipitation, and colocalization in mouse neuronal tissue

    PMID:22442090

    Open questions at the time
    • Stoichiometry of P2X2/5 heteromers not resolved
    • In vivo neuronal function of P2X2/5 channels not tested with subunit-specific knockouts
  10. 2017 High

    P2rx5 knockout mice revealed that P2X5 is required for ATP-induced inflammasome activation and IL-1β release in osteoclasts, and for inflammatory bone loss in vivo, establishing an immune-regulatory function distinct from ion conduction.

    Evidence P2rx5 knockout mice, in vitro osteoclast differentiation, IL-1β rescue, in vivo inflammatory bone loss model

    PMID:28298636

    Open questions at the time
    • Mechanism by which P2X5 activates the inflammasome (direct ion flux versus signaling intermediate) not delineated
    • Whether the osteoclast phenotype is cell-autonomous not formally shown
  11. 2018 Medium

    Extension to periodontitis confirmed that P2X5 deficiency reduces alveolar bone loss and gingival inflammatory cytokine expression, placing P2X5 upstream of IL-1β, IL-6, IL-17a, and RANKL in oral inflammatory bone destruction.

    Evidence P2rx5−/− mice in ligature-induced periodontitis model, micro-CT, gene expression analysis

    PMID:30103845

    Open questions at the time
    • Cell-type-specific contribution (osteoclast versus immune cell) not dissected
    • Single disease model without conditional knockout

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for P2X5 homotrimer and heteromer gating, the molecular mechanism linking P2X5 to inflammasome assembly, the physiological consequences of widespread human P2X5 loss-of-function (exon 10 skipping), and the in vivo role of P2X5 in muscle regeneration remain unresolved.
  • No atomic-resolution structure of P2X5 homotrimer or any P2X5-containing heteromer
  • Mechanism of inflammasome coupling unknown
  • No conditional knockout studies to separate cell-autonomous functions in muscle, bone, or brain

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0005215 transporter activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2 R-HSA-382551 Transport of small molecules 2
Partners
P2RX1P2RX2P2RX4
Complex memberships
P2X1/P2X5 heteromeric channelP2X2/P2X5 heteromeric channelP2X5 homotrimer

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 P2RX5 (P2X5) encodes an ATP-gated ion channel with two transmembrane segments and a large extracellular loop; expressed in Xenopus oocytes/HEK cells, it produces slowly desensitizing currents that do not respond to alpha,beta-methylene-ATP and are not blocked by suramin or PPADS. cDNA cloning, heterologous expression, electrophysiology The Journal of neuroscience High 8786426
1998 P2X1 and P2X5 subunits co-assemble to form a novel heteromeric ATP-gated ion channel with distinct biphasic kinetics (fast desensitizing peak + sustained plateau) and a higher EC50 for alpha,beta-methylene-ATP than homomeric P2X1; co-immunoprecipitation of epitope-tagged subunits provided biochemical proof of heteromeric assembly. Heterologous co-expression in HEK293 cells, electrophysiology, co-immunoprecipitation Molecular pharmacology High 9855626
1999 P2X1 and P2X5 subunits form heteromeric channels with the pharmacology of P2X1 (sensitive to alpha,beta-methylene-ATP and TNP-ATP) but the slow-desensitization kinetics of P2X5; direct physical co-assembly was demonstrated by reciprocal subunit-specific co-purifications of epitope-tagged proteins in HEK-293A cells. Xenopus oocyte expression, electrophysiology, reciprocal co-purification The Journal of biological chemistry High 10336430
1999 P2X5 pharmacological properties characterised in more detail: plateau currents potentiated by low PPADS concentrations and raised extracellular Ca2+; agonist rank order and antagonist profile distinct from P2X1 homomers. Heterologous expression in HEK293, voltage-clamp electrophysiology Molecular pharmacology Medium 10496954
1999 P2X5 immunoreactivity is localized to the proliferating and differentiating cell layers (spinous and granular layers) of stratified squamous epithelia and growing hair follicles, suggesting a role in epithelial cell turnover. Immunohistochemistry on rat stratified squamous epithelial tissues Cell and tissue research Medium 10370147
2002 P2RX5 is expressed on skeletal muscle satellite cells; ATP activation of P2X5 receptors on satellite cells inhibits proliferation, stimulates myogenic differentiation markers (myogenin, p21, myosin heavy chain), accelerates myotube formation, and rapidly increases p38 MAPK phosphorylation; p38 inhibition blocks ATP's effect on cell number. Primary rat satellite cell culture, immunocytochemistry, RT-PCR, electrophysiology, Western blot, pharmacological inhibition of p38 The Journal of cell biology High 12135987
2002 Rat P2X5 homomeric receptor is sensitized by extracellular Ca2+; replacing Ca2+ with Ba2+ or Mg2+ prevents Ca2+-dependent rundown; Zn2+ first potentiates then inhibits ATP responses; reducing extracellular pH decreases agonist potency and efficacy; antagonist potency order: PPADS > TNP-ATP > suramin > RB-2 > Ip5I. Voltage-clamp in Xenopus oocytes expressing recombinant rat P2X5 Molecular pharmacology Medium 12237343
2003 Full-length human P2X5 (incorporating exon 10) forms functional ATP-gated channels; ATP (EC50 ~4 µM) evokes inward currents with slow desensitization; channel is permeable to Ca2+ (PCa/PNa=1.5), NMDG, and Cl-; inhibited by suramin, PPADS, and Brilliant Blue G; cells rapidly accumulate YO-PRO-1 dye indicating large-pore properties. Patch-clamp and fluorescence imaging of HEK293 cells expressing full-length human P2X5 Molecular pharmacology High 12761352
2005 A frameshift polymorphism in the P2X5 gene creates the minor histocompatibility antigen LRH-1 presented by HLA-B7; differential protein expression (donor homozygous for frameshift → no protein) between donor and recipient generates an allogeneic CD8+ CTL response; LRH-1-specific CTL emergence correlates with CML remission after donor lymphocyte infusion. Genetic linkage analysis, tetramer analysis of CD8+ T cells, functional CTL assays The Journal of clinical investigation High 16322791
2006 The transmembrane domain 2 (TM2) of P2X5 is essential for homotrimerization; the C-terminal truncation caused by exon 10 skipping leaves a TM2 too short to span the membrane, causing subunit aggregation; mutagenesis identified Asp355 in TM2 as required for correct homotrimerization in a side-chain-specific manner. Systematic TM2 mutagenesis, biochemical trimerization assays, heterologous expression in Xenopus oocytes/HEK cells The Journal of biological chemistry High 17001079
2008 In mouse cortical astrocytes, the functional P2X receptor mediating ATP-evoked currents comprises P2X1 and P2X5 subunits; this heteromeric channel shows high ATP sensitivity (EC50 ~40 nM), biphasic kinetics, PPADS sensitivity, and ivermectin insensitivity, consistent with recombinant P2X1/5 heteromers. Whole-cell voltage clamp on acutely isolated cortical astrocytes from transgenic GFAP-EGFP mice, quantitative RT-PCR The Journal of neuroscience High 18495881
2010 A SNP at the 3' splice site of exon 10 of human P2X5 determines whether exon 10 is included; the exon-10-deleted isoform is retained in the cytoplasm and is non-functional (no ATP-evoked currents or Ca2+ signals); the full-length isoform is expressed at the cell surface and is functional; most non-African humans are homozygous for the non-functional G allele. Genotyping of human DNA, immunostaining of stably co-expressing cell lines, electrophysiology and FLIPR calcium imaging Molecular pharmacology High 20223879
2012 P2X5 subunits associate with P2X1, P2X2, and P2X4 subunits; P2X2/P2X5 heteromeric receptors form with alternate stoichiometries, are present at the plasma membrane, and display P2X7-like properties including pore dilatation, membrane blebbing, and phosphatidylserine exposure; P2X2 and P2X5 colocalize and physically interact in specific neuronal populations in mouse. BRET, bifunctional fluorescence complementation, co-immunoprecipitation, in vivo colocalization The Journal of neuroscience High 22442090
2014 P2RX5 protein is a cell-surface marker selectively expressed in classical brown and beige adipocytes in mice and humans, with little or no expression in white adipocytes; identified by in silico, in vitro, and in vivo methods. In silico analysis, in vitro adipocyte characterization, in vivo adipose tissue profiling, immunostaining Science translational medicine Medium 25080478
2017 P2X5 is required for ATP-mediated inflammasome activation and IL-1β production in osteoclasts; P2X5-deficient osteoclasts show hyper-multinucleation and impaired inflammatory bone loss in vivo; exogenous IL-1β rescues P2X5-deficient osteoclast maturation in vitro. P2rx5 knockout mice, in vitro osteoclast differentiation assays, IL-1β rescue experiments, in vivo inflammatory bone loss model Scientific reports High 28298636
2018 P2X5 deficiency reduces alveolar bone loss in a murine ligature-induced periodontitis model and decreases gingival expression of IL-1β, IL-6, IL-17a, and TNFSF11, placing P2X5 upstream of inflammatory cytokine production in periodontitis-associated bone destruction. P2rx5−/− mice, ligature-induced periodontitis model, micro-CT bone analysis, gene expression analysis BMB reports Medium 30103845

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Molecular cell 1606 11030332
1996 Cloning OF P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 768 8786426
2004 LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis. Trends in cell biology 348 15130581
2005 Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1. Cell 344 15707893
2004 Synergy between LRH-1 and beta-catenin induces G1 cyclin-mediated cell proliferation. Molecular cell 251 15327767
2005 Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development. Molecular and cellular biology 245 15831456
2002 Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. The Journal of biological chemistry 204 11927588
2005 Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP. Nature structural & molecular biology 173 15723037
2014 ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes. Science translational medicine 162 25080478
2010 GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXRbeta in the hepatic acute phase response. Genes & development 155 20159957
2003 Differential expression of steroidogenic factor-1 and FTF/LRH-1 in the rodent ovary. Endocrinology 148 12865342
2008 P2X1 and P2X5 subunits form the functional P2X receptor in mouse cortical astrocytes. The Journal of neuroscience : the official journal of the Society for Neuroscience 142 18495881
2003 Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1. Molecular cell 139 12820970
2007 LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease. Proceedings of the National Academy of Sciences of the United States of America 133 17670946
2003 Expression of LRH-1 and SF-1 in the mouse ovary: localization in different cell types correlates with differing function. Molecular and cellular endocrinology 130 12972182
2003 LXXLL-related motifs in Dax-1 have target specificity for the orphan nuclear receptors Ad4BP/SF-1 and LRH-1. Molecular and cellular biology 126 12482977
2003 Tumor necrosis factor alpha-dependent up-regulation of Lrh-1 and Mrp3(Abcc3) reduces liver injury in obstructive cholestasis. The Journal of biological chemistry 125 12837754
2001 The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor. The Journal of biological chemistry 120 11331284
2005 A frameshift polymorphism in P2X5 elicits an allogeneic cytotoxic T lymphocyte response associated with remission of chronic myeloid leukemia. The Journal of clinical investigation 117 16322791
2012 Nuclear receptors HNF4α and LRH-1 cooperate in regulating Cyp7a1 in vivo. The Journal of biological chemistry 113 23038264
1998 Co-expression of P2X1 and P2X5 receptor subunits reveals a novel ATP-gated ion channel. Molecular pharmacology 112 9855626
2006 The nuclear receptor LRH-1 critically regulates extra-adrenal glucocorticoid synthesis in the intestine. The Journal of experimental medicine 111 16923850
2003 Pharmacological and biophysical properties of the human P2X5 receptor. Molecular pharmacology 111 12761352
2002 ATP regulates the differentiation of mammalian skeletal muscle by activation of a P2X5 receptor on satellite cells. The Journal of cell biology 105 12135987
2011 Nuclear receptor liver receptor homologue 1 (LRH-1) regulates pancreatic cancer cell growth and proliferation. Proceedings of the National Academy of Sciences of the United States of America 97 21949357
2012 LRH-1-dependent glucose sensing determines intermediary metabolism in liver. The Journal of clinical investigation 94 22772466
1999 Localisation of P2X5 and P2X7 receptors by immunohistochemistry in rat stratified squamous epithelia. Cell and tissue research 94 10370147
2004 Differential expression of steroidogenic factor-1/adrenal 4 binding protein and liver receptor homolog-1 (LRH-1)/fetoprotein transcription factor in the rat testis: LRH-1 as a potential regulator of testicular aromatase expression. Endocrinology 90 14736734
2010 PPAR-gamma coactivator-1alpha regulates progesterone production in ovarian granulosa cells with SF-1 and LRH-1. Molecular endocrinology (Baltimore, Md.) 85 20133449
2008 The structure of corepressor Dax-1 bound to its target nuclear receptor LRH-1. Proceedings of the National Academy of Sciences of the United States of America 82 19015525
2013 Structure-based discovery of antagonists of nuclear receptor LRH-1. The Journal of biological chemistry 79 23667258
2011 LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function. Genes & development 79 21852532
2004 The orphan nuclear receptor LRH-1 activates the ABCG5/ABCG8 intergenic promoter. Journal of lipid research 79 15121760
2010 The orphan nuclear receptor LRH-1 promotes breast cancer motility and invasion. Endocrine-related cancer 78 20817789
2004 The role of alpha1-fetoprotein transcription factor/LRH-1 in bile acid biosynthesis: a known nuclear receptor activator that can act as a suppressor of bile acid biosynthesis. The Journal of biological chemistry 76 14766742
2010 Genome-wide interrogation of hepatic FXR reveals an asymmetric IR-1 motif and synergy with LRH-1. Nucleic acids research 75 20483916
2006 Phosphorylation of the hinge domain of the nuclear hormone receptor LRH-1 stimulates transactivation. The Journal of biological chemistry 75 16439367
1999 Functional and biochemical evidence for heteromeric ATP-gated channels composed of P2X1 and P2X5 subunits. The Journal of biological chemistry 75 10336430
2005 SUMO-dependent compartmentalization in promyelocytic leukemia protein nuclear bodies prevents the access of LRH-1 to chromatin. Molecular and cellular biology 72 15923626
2010 Emerging actions of the nuclear receptor LRH-1 in the gut. Biochimica et biophysica acta 66 21194563
2014 SUMOylation-dependent LRH-1/PROX1 interaction promotes atherosclerosis by decreasing hepatic reverse cholesterol transport. Cell metabolism 65 25176150
2017 Impaired SUMOylation of nuclear receptor LRH-1 promotes nonalcoholic fatty liver disease. The Journal of clinical investigation 64 28094767
2018 LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival. Nature communications 62 30305617
2011 Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2). Journal of medicinal chemistry 61 21391689
2004 Regulation of aromatase expression by the nuclear receptor LRH-1 in adipose tissue. Molecular and cellular endocrinology 61 15026173
2012 P2X2 and P2X5 subunits define a new heteromeric receptor with P2X7-like properties. The Journal of neuroscience : the official journal of the Society for Neuroscience 60 22442090
1999 Properties of the novel ATP-gated ionotropic receptor composed of the P2X(1) and P2X(5) isoforms. Molecular pharmacology 60 10496954
2000 Evidence for P2X(3), P2X(4), P2X(5) but not for P2X(7) containing purinergic receptors in Müller cells of the rat retina. Brain research. Molecular brain research 59 10762695
2014 Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic reticulum stress resolution. eLife 57 24737860
2016 LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer. Genes & development 54 27298334
2015 Liver receptor homolog-1 (LRH-1): a potential therapeutic target for cancer. Cancer biology & therapy 54 25951367
2014 Molecular basis for the regulation of the nuclear receptor LRH-1. Current opinion in cell biology 54 25463843
2012 The orphan nuclear receptor LRH-1 and ERα activate GREB1 expression to induce breast cancer cell proliferation. PloS one 52 22359603
2011 Testosterone, not 5α-dihydrotestosterone, stimulates LRH-1 leading to FSH-independent expression of Cyp19 and P450scc in granulosa cells. Molecular endocrinology (Baltimore, Md.) 52 21273442
2017 The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts. Scientific reports 51 28298636
2005 Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity. Journal of molecular biology 51 16289203
2010 Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation. Nucleic acids research 49 20375098
2018 LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus. Nature communications 48 29662071
2015 LRH-1 drives colon cancer cell growth by repressing the expression of the CDKN1A gene in a p53-dependent manner. Nucleic acids research 48 26400164
2002 Sensitization by extracellular Ca(2+) of rat P2X(5) receptor and its pharmacological properties compared with rat P2X(1). Molecular pharmacology 48 12237343
2015 LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis. Nature communications 47 25873311
2006 P2X5 subunit assembly requires scaffolding by the second transmembrane domain and a conserved aspartate. The Journal of biological chemistry 47 17001079
1999 Expression of two ATP-gated ion channels, P2X5 and P2X6, in developing chick skeletal muscle. Developmental dynamics : an official publication of the American Association of Anatomists 47 10633863
2016 MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway. Oncology research 46 27983934
2001 Loss of purinergic P2X(3) and P2X(5) receptor innervation in human detrusor from adults with urge incontinence. The Journal of neuroscience : the official journal of the Society for Neuroscience 45 11549755
2018 miR-1275 controls granulosa cell apoptosis and estradiol synthesis by impairing LRH-1/CYP19A1 axis. Biochimica et biophysica acta. Gene regulatory mechanisms 44 29378329
2018 LRH-1 regulates hepatic lipid homeostasis and maintains arachidonoyl phospholipid pools critical for phospholipid diversity. JCI insight 44 29515023
2015 Down-regulation of MicroRNA-381 promotes cell proliferation and invasion in colon cancer through up-regulation of LRH-1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 44 26320367
2010 Dax1 up-regulates Oct4 expression in mouse embryonic stem cells via LRH-1 and SRA. Molecular endocrinology (Baltimore, Md.) 44 20943815
2001 Genomic structure, developmental distribution and functional properties of the chicken P2X(5) receptor. Journal of neurochemistry 44 11389176
2024 Hepatic FXR-FGF4 is required for bile acid homeostasis via an FGFR4-LRH-1 signal node under cholestatic stress. Cell metabolism 43 39393353
2006 Immunolocalization of liver receptor homologue-1 (LRH-1) in human breast carcinoma: possible regulator of insitu steroidogenesis. Cancer letters 43 16427184
2004 The distribution of P2X5 purinergic receptors in the enteric nervous system of mouse. Cell and tissue research 42 15551155
2008 Myeloid leukemic progenitor cells can be specifically targeted by minor histocompatibility antigen LRH-1-reactive cytotoxic T cells. Blood 40 19074734
2005 Bile acids reduce SR-BI expression in hepatocytes by a pathway involving FXR/RXR, SHP, and LRH-1. Biochemical and biophysical research communications 40 16168958
2018 Nuclear Receptor LRH-1 Functions to Promote Castration-Resistant Growth of Prostate Cancer via Its Promotion of Intratumoral Androgen Biosynthesis. Cancer research 39 29438990
2009 Transcriptional activity of the murine retinol-binding protein gene is regulated by a multiprotein complex containing HMGA1, p54 nrb/NonO, protein-associated splicing factor (PSF) and steroidogenic factor 1 (SF1)/liver receptor homologue 1 (LRH-1). The international journal of biochemistry & cell biology 39 19389484
2015 A gene-expression screen identifies a non-toxic sumoylation inhibitor that mimics SUMO-less human LRH-1 in liver. eLife 38 26653140
2003 LRH-1/hB1F and HNF1 synergistically up-regulate hepatitis B virus gene transcription and DNA replication. Cell research 38 14728801
2014 LRH-1 governs vital transcriptional programs in endocrine-sensitive and -resistant breast cancer cells. Cancer research 37 24520076
2008 Expression of P2X5 receptors in the mouse CNS. Neuroscience 37 18773945
2014 Human FXR regulates SHP expression through direct binding to an LRH-1 binding site, independent of an IR-1 and LRH-1. PloS one 36 24498423
2012 Genome-wide analysis of hepatic LRH-1 reveals a promoter binding preference and suggests a role in regulating genes of lipid metabolism in concert with FXR. BMC genomics 36 22296850
2006 Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1. Biochemical and biophysical research communications 36 17204240
2021 Emerging functions of the nuclear receptor LRH-1 in liver physiology and pathology. Biochimica et biophysica acta. Molecular basis of disease 34 33862147
2008 Expression of P2X5 in lymphoid malignancies results in LRH-1-specific cytotoxic T-cell-mediated lysis. British journal of haematology 34 18410452
2017 MicroRNA-374b reduces the proliferation and invasion of colon cancer cells by regulation of LRH-1/Wnt signaling. Gene 32 29128635
2010 Genetic and functional analysis of human P2X5 reveals a distinct pattern of exon 10 polymorphism with predominant expression of the nonfunctional receptor isoform. Molecular pharmacology 32 20223879
2006 LRH-1/NR5A2 cooperates with GATA factors to regulate inhibin alpha-subunit promoter activity. Molecular and cellular endocrinology 30 16893604
2019 The Ovulatory Signal Precipitates LRH-1 Transcriptional Switching Mediated by Differential Chromatin Accessibility. Cell reports 29 31461657
2013 Nuclear receptor LRH-1 induces the reproductive neuropeptide kisspeptin in the hypothalamus. Molecular endocrinology (Baltimore, Md.) 29 23504956
2011 The liver receptor homolog-1 (LRH-1) is expressed in human islets and protects {beta}-cells against stress-induced apoptosis. Human molecular genetics 29 21536586
2021 NF-κB Regulation of LRH-1 and ABCG5/8 Potentiates Phytosterol Role in the Pathogenesis of Parenteral Nutrition-Associated Cholestasis. Hepatology (Baltimore, Md.) 28 34310734
2018 LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21. Cancer management and research 28 30122988
2020 Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function. Structure (London, England : 1993) 27 32433991
2011 Regulation of miR-200c by nuclear receptors PPARα, LRH-1 and SHP. Biochemical and biophysical research communications 27 22100809
2010 LRH-1 and Nanog regulate Dax1 transcription in mouse embryonic stem cells. Molecular and cellular endocrinology 27 20937355
2006 P2X5 receptors are expressed on neurons containing arginine vasopressin and nitric oxide synthase in the rat hypothalamus. Brain research 27 16765918
2016 MicroRNA-376c suppresses non-small-cell lung cancer cell growth and invasion by targeting LRH-1-mediated Wnt signaling pathway. Biochemical and biophysical research communications 26 27049310
2018 The purinergic receptor P2X5 contributes to bone loss in experimental periodontitis. BMB reports 25 30103845