Affinage

NR4A3

Nuclear receptor subfamily 4 group A member 3 · UniProt Q92570

Length
626 aa
Mass
68.2 kDa
Annotated
2026-04-29
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR4A3 (NOR-1) is an orphan nuclear receptor that functions as a ligand-independent transcription factor governing cell fate decisions across hematopoietic, vascular, metabolic, and immune lineages. It binds NBRE response elements in target gene promoters—including VCAM-1, VTN, SMPX, ALDOA, PFKL, and Cebpa—to regulate inflammation, proliferation, and metabolic programs (PMID:20558821, PMID:28666984, PMID:29343483, PMID:38629274). Beyond its nuclear transcriptional role, NR4A3 undergoes PKC-dependent translocation to mitochondria where it interacts with Bcl-2 to expose its BH3 domain and promote apoptosis, and it is itself transcriptionally regulated by p53, RUNX1, and NF-κB (PMID:20411565, PMID:30455429, PMID:21725049). Combined loss of NR4A3 and NR4A1 causes acute myeloid leukemia in mice through failure to maintain HSC quiescence and C/EBPα expression, while in the immune system NR4A3 is required for CD103+ dendritic cell migration via FOXO1/CCR7, monocyte-to-MoDC differentiation, and programming of CD8+ T cell effector versus memory fate (PMID:17515897, PMID:27820700, PMID:31285338, PMID:32913051).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Identification of NR4A3 as a recurrent fusion partner in extraskeletal myxoid chondrosarcoma established that its transcriptional domains are oncogenically relevant when dysregulated, motivating study of its normal transcriptional function.

    Evidence Molecular cloning and breakpoint analysis of t(9;17) and t(4;9) translocations in EMC patient tumors

    PMID:10602519

    Open questions at the time
    • Mechanism by which EWS-NR4A3 or TAF15-NR4A3 fusions drive sarcomagenesis not fully defined
    • Whether wild-type NR4A3 has any role in chondrocyte biology was unknown
  2. 2000 Medium

    Demonstration that NR4A3 binds NBRE promoter elements and activates steroidogenic gene transcription via PKA/PKC cascades established it as a functional transcription factor responsive to hormonal signaling.

    Evidence Reporter assays with NBRE sequences and PKA/PKC inhibitor pharmacology in adrenal fasciculata cells

    PMID:10875239

    Open questions at the time
    • Endogenous chromatin occupancy not confirmed
    • Whether NR4A3 has ligand-independent versus ligand-dependent activity was still debated
  3. 2001 High

    The EWS/NOR1 fusion was shown to gain a neomorphic splicing activity by interacting with U1C, demonstrating that the fusion creates functions absent from either partner alone.

    Evidence Yeast splicing complementation, mammalian splice-site assay, and co-immunoprecipitation with U1C

    PMID:11673470

    Open questions at the time
    • Relevance of splicing disruption to EMC tumorigenesis not established
    • Whether wild-type NR4A3 has any role in RNA processing is unknown
  4. 2005 Medium

    Prostaglandin A2 was identified as a ligand that activates NR4A3 through direct binding to its LBD, partially resolving whether this 'orphan' receptor has physiological ligands.

    Evidence GAL4-LBD reporter system and direct LBD binding assay

    PMID:16141523

    Open questions at the time
    • Physiological relevance of PGA2 as an endogenous NR4A3 ligand in vivo not confirmed
    • Structural basis of LBD-PGA2 interaction not resolved
  5. 2007 High

    Double knockout of NR4A3 and NR4A1 caused rapidly lethal AML with HSC expansion and defective extrinsic apoptosis, establishing NR4A3 as a bona fide tumor suppressor in myeloid leukemogenesis.

    Evidence Nr4a1/Nr4a3 double knockout mice with AML phenotype, validated against human AML samples

    PMID:17515897

    Open questions at the time
    • Individual contribution of NR4A3 versus NR4A1 to leukemia suppression not separated
    • Direct transcriptional targets mediating tumor suppression were unknown at this point
  6. 2010 High

    Two parallel discoveries defined NR4A3's mechanism in vascular inflammation and apoptosis: ChIP demonstrated direct VCAM-1 promoter binding in endothelial cells, while subcellular fractionation showed PKC-dependent nuclear-to-mitochondrial translocation where NR4A3 engages Bcl-2 to expose its BH3 domain.

    Evidence ChIP and NOR1-deficient apoE−/− atherosclerosis model (VCAM-1); PKC inhibitor pharmacology and Bcl-2 BH3 conformation assay in thymocytes (apoptosis)

    PMID:20411565 PMID:20558821

    Open questions at the time
    • Whether mitochondrial translocation and transcriptional function are coordinated or independent programs
    • Structural details of NR4A3-Bcl-2 interaction not resolved
  7. 2011 High

    Identification of NR4A3 as a direct RUNX1 transcriptional target linked familial platelet disorder/AML predisposition to NR4A3 downregulation, explaining how RUNX1 mutations expand myeloid progenitors.

    Evidence ChIP showing RUNX1 binding to NR4A3 promoter; lentiviral NR4A3 restoration partially rescued clonogenicity in FPD/AML patient CD34+ cells

    PMID:21725049

    Open questions at the time
    • Whether NR4A3 restoration alone is sufficient to prevent leukemic transformation in RUNX1-mutant settings
    • Other RUNX1 targets may contribute in parallel
  8. 2014 High

    NR4A3 was shown to be necessary and sufficient for Nkx6.1-driven β-cell proliferation, operating through E2F1/cyclin E1 upregulation and APC-mediated p21 degradation, revealing a cell cycle–promoting role distinct from its tumor-suppressive function in hematopoiesis.

    Evidence Adenoviral overexpression and siRNA knockdown in islets, global Nr4a1 KO mice

    PMID:24706823

    Open questions at the time
    • Whether NR4A3 directly binds E2F1 or cyclin E1 promoters not shown
    • Context-dependent switch between pro-proliferative and anti-proliferative roles not mechanistically explained
  9. 2015 High

    Discovery of a physical NR4A3–PARP-1 interaction that drives cardiac hypertrophy, with the C293Y mutation abolishing this interaction and hypertrophic response, established a non-transcriptional effector partnership for NR4A3.

    Evidence Co-immunoprecipitation, C293Y mutant analysis, PARP-1 activity assay, and hypertrophy markers in neonatal rat cardiomyocytes

    PMID:25625556

    Open questions at the time
    • Whether PARP-1 activation requires NR4A3 transcriptional activity or is purely protein-protein
    • In vivo cardiac phenotype of NR4A3 loss not reported
  10. 2016 High

    Multiple studies established NR4A3's immune roles: it is essential for CD103+ DC migration via maintenance of FOXO1/CCR7, and it regulates TLR-mediated DC activation through IKKβ and IRF4/IRF8.

    Evidence Nr4a3-deficient mice with mixed bone marrow chimeras (cell-intrinsic DC migration defect); siRNA in BMDCs with epistatic knockdown of IKKβ/IRF4/IRF8

    PMID:27820700 PMID:28893954

    Open questions at the time
    • Direct transcriptional targets of NR4A3 that maintain FOXO1 protein levels not identified
    • Whether NR4A3 directly binds IKKβ or IRF promoters unknown
  11. 2017 High

    Direct NBRE-dependent regulation of vitronectin by NR4A3 in vascular smooth muscle cells was rigorously confirmed by EMSA, ChIP, and site-directed mutagenesis, linking NR4A3 to VSMC migration.

    Evidence EMSA, ChIP, promoter deletion/mutagenesis with reporter assays, migration assay with anti-VTN blocking antibody in human VSMCs

    PMID:28666984

    Open questions at the time
    • In vivo relevance to neointimal formation or vascular remodeling not demonstrated
  12. 2018 High

    Two key advances resolved NR4A3's upstream regulation by p53 (direct promoter binding inducing apoptosis via PUMA/Bax) and its direct role in HSC quiescence through binding the Cebpa enhancer and antagonizing NF-κB at inflammatory gene loci.

    Evidence ChIP for p53 at NR4A3 promoter and NR4A3-Bcl-2 co-IP (p53 axis); ChIP-seq and conditional double KO in HSCs (Cebpa/NF-κB axis)

    PMID:29343483 PMID:30455429

    Open questions at the time
    • Whether p53-NR4A3 axis operates in leukemia suppression in vivo
    • Relative contributions of Cebpa activation versus NF-κB antagonism to HSC quiescence not quantified
  13. 2019 High

    NR4A3 was shown to direct monocyte-to-MoDC differentiation fate and to negatively regulate β-cell mass by inducing apoptosis under inflammatory conditions, illustrating its context-dependent pro-apoptotic versus differentiation functions.

    Evidence Nr4a3−/− mice with LPS challenge and bacterial infection (MoDC); Nr4a3 KO mice with β-cell mass quantification, overexpression/knockdown in INS cells and human islets

    PMID:30696767 PMID:31285338

    Open questions at the time
    • Direct transcriptional targets driving MoDC versus macrophage fate choice not identified
    • Whether β-cell apoptotic function involves mitochondrial translocation not tested
  14. 2020 High

    NR4A3 deficiency in CD8+ T cells revealed that NR4A3 normally programs effector differentiation at the expense of memory: its loss increased chromatin accessibility at bZIP/AP-1 motifs and enhanced memory precursor generation.

    Evidence NR4A3-deficient murine CD8+ T cells with ATAC-seq, transcriptional profiling, and cytokine assays

    PMID:32913051

    Open questions at the time
    • Whether NR4A3 directly binds and represses memory-associated loci or acts indirectly
    • Interaction with NR4A1 in T cell fate decisions not dissected
  15. 2022 High

    Dual PRDM1/NR4A3 CRISPR knockout in CAR T cells reduced exhaustion and improved antitumor efficacy, positioning NR4A3 as a targetable node in NFAT-driven T cell dysfunction.

    Evidence CRISPR KO in CAR T cells, scRNA-seq, in vivo tumor models

    PMID:36350986

    Open questions at the time
    • Whether NR4A3 deletion alone is sufficient for durable CAR T improvement
    • Mechanism of NFAT-NR4A3 transcriptional feedback not fully defined
  16. 2024 High

    NR4A3 was found to drive vascular calcification through a metabolic-epigenetic cascade: direct binding to ALDOA/PFKL promoters enhances glycolysis and lactate production, which promotes histone lactylation and downstream PHOSPHO1 activation.

    Evidence CUT&TAG chromatin occupancy, NR4A3−/− mice with medial arterial calcification models, glycolysis/lactate assays, RNA-seq

    PMID:38629274

    Open questions at the time
    • Whether this glycolysis–lactylation axis operates in other NR4A3-expressing tissues
    • Structural basis for NR4A3 selectivity at ALDOA versus other glycolytic gene promoters unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unifying mechanistic framework explaining how NR4A3 switches between pro-proliferative (β-cells, salivary gland), anti-proliferative (HSCs), and pro-apoptotic (thymocytes, cancer) outputs in different cellular contexts remains undefined.
  • No structural model of full-length NR4A3 exists
  • Endogenous physiological ligand(s) remain debated
  • How post-translational modifications (PKC phosphorylation, m6A on mRNA) are integrated to determine nuclear versus mitochondrial function is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 6 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 6 GO:0005739 mitochondrion 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-168256 Immune System 6 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2
Partners
BCL2FOXA1FOXO1KLF2KLF4NR4A1PARP1SIX3

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Abrogation of both NR4A3 (Nor-1) and NR4A1 (Nur77) in mice leads to rapidly lethal acute myeloid leukemia involving abnormal expansion of hematopoietic stem cells and myeloid progenitors, decreased expression of AP-1 transcription factors JunB and c-Jun, and defective extrinsic apoptotic (Fas-L and TRAIL) signaling, establishing NR4A3 as a tumor suppressor of myeloid leukemogenesis. Genetic knockout mouse model (double Nr4a1/Nr4a3 knockout) with phenotypic readout (AML development, HSC expansion, apoptotic signaling analysis) Nature medicine High 17515897
2000 NR4A3 (Nor1) is expressed in the pituitary gland and adrenal cortex; ACTH and angiotensin II treatment induces Nor1 expression in adrenal fasciculata cells; Nor1 activates steroidogenic enzyme genes (e.g., P450c21) through binding to NGFI-B response element (NBRE) promoter sequences; transcriptional regulation of Nor1 in adrenal cells depends on protein kinase A and protein kinase C cascades. Transactivation reporter assays, binding experiments with NBRE and NurRE sequences, pharmacological inhibition of PKA/PKC pathways Endocrinology Medium 10875239
2005 Prostaglandin A2 (PGA2) acts as a transactivator for NR4A3 (NOR1) by directly binding to the ligand-binding domain (LBD) of NOR1 and activating NOR1-dependent transcription; LBD-deleted NOR1 shows little transcriptional activation by PGA2. GAL4-based reporter system, direct LBD binding assay, transgenic mouse-derived spleen cell sensitivity assay Biological & pharmaceutical bulletin Medium 16141523
2001 The EWS/NOR1 fusion protein (arising from chromosomal translocation in extraskeletal myxoid chondrosarcoma) gains a novel activity affecting pre-mRNA splicing: it complements loss of function of yeast splicing factor Snu23p, causes increased usage of distal 5'-splice sites in mammalian cells, and interacts with the human splicing protein U1C—activities not possessed by EWS or NOR1 alone. Functional complementation screening in yeast, pre-mRNA splicing assay in mammalian cells, co-immunoprecipitation with U1C splicing protein The Journal of biological chemistry High 11673470
1999 In extraskeletal myxoid chondrosarcoma with t(9;17)(q22;q11), the NR4A3 (CHN/TEC) gene fuses with RBP56 (TAF15) to generate a chimeric RBP56/CHN oncogenic fusion, demonstrating that the N-terminal transactivation domains of EWS and RBP56 are pathogenetically equivalent when fused to NR4A3. Molecular cloning, RT-PCR, chromosomal translocation breakpoint analysis Oncogene High 10602519
2010 NR4A3 (Nor-1) in endothelial cells is rapidly induced by inflammatory stimuli through NF-κB-dependent transactivation of the NOR1 promoter; NOR1 induces VCAM-1 promoter activity by directly binding to a canonical NR4A response element in the VCAM-1 promoter (confirmed by ChIP and transient transfection); NOR1 deficiency in apoE-/- mice reduces atherosclerosis by decreasing macrophage content. ChIP assay, transient transfection with VCAM-1 promoter-reporter constructs, NOR1-deficient mouse atherosclerosis model, monocyte adhesion functional assay Circulation research High 20558821
2010 NR4A3 (Nor-1) translocates from the nucleus to mitochondria in thymocytes undergoing apoptosis; this translocation requires phosphorylation by PKC (both classical and novel isoforms); Nor-1 associates with Bcl-2 in the mitochondria, inducing a conformational change that exposes the Bcl-2 BH3 domain. PKC inhibitor pharmacology, phosphorylation analysis, subcellular fractionation/translocation assay, Bcl-2 BH3 conformation assay in thymocytes European journal of immunology Medium 20411565
2014 Nkx6.1 induces expression of Nr4a3 (and Nr4a1) in pancreatic islets; Nr4a3 is both necessary and sufficient for Nkx6.1-mediated β-cell proliferation; Nr4a3 increases expression of cell cycle inducers E2F1 and cyclin E1, and induces components of the anaphase-promoting complex (including UBE2C), leading to degradation of the cell cycle inhibitor p21. Adenoviral overexpression, siRNA knockdown, global Nr4a1 knockout mice, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 24706823
2008 Retroviral overexpression of NR4A3 (NOR1) in 3T3-L1 or 3T3-F442A preadipocytes potently inhibits adipogenesis in a manner that cannot be rescued by PPARγ overexpression or activation; NR4A3 inhibits mitotic clonal expansion of preadipocytes; NOR1 (and family members Nur77 and Nurr1) upregulate gap-junction protein Gja1 and Tll1 as downstream mediators. Retroviral transduction, adipogenesis assays, transcriptional profiling, retroviral expression of target genes Molecular endocrinology (Baltimore, Md.) Medium 18945812
2011 NR4A3 is a direct transcriptional target of RUNX1; downregulation of NR4A3 in RUNX1-mutated hematopoietic progenitors increases clonogenic potential; restoration of NR4A3 expression partially reduces the clonogenic potential of patient progenitors from familial platelet disorder/AML pedigrees. ChIP demonstrating RUNX1 binding to NR4A3 promoter, lentiviral NR4A3 restoration in patient-derived CD34+ progenitors, clonogenic assays Blood High 21725049
2018 NR4A3 is a direct transcriptional target of p53: p53 binds the promoter of NR4A3 and induces its transcription; NR4A3 overexpression promotes apoptosis by augmenting pro-apoptotic genes PUMA and Bax; NR4A3 physically interacts with anti-apoptotic Bcl-2 protein, sequestering it from inhibiting apoptosis. ChIP assay for p53 binding to NR4A3 promoter, luciferase reporter assay, Co-immunoprecipitation (NR4A3-Bcl-2 interaction), overexpression/knockdown with apoptosis readout Oncogene High 30455429
2018 NR4A1 and NR4A3 (NR4A1/3) restrict HSC proliferation by directly binding to a hematopoietic-specific Cebpa enhancer to activate C/EBPα transcription; NR4A1/3 also occupy regulatory regions of NF-κB-regulated inflammatory cytokines, antagonizing NF-κB signaling; conditional knockout of NR4A1/3 in HSCs causes loss of quiescence, accumulation of oxidative stress, DNA damage, and upregulation of cell cycle and inflammation programs. Conditional double knockout mouse model, ChIP-seq/genomic occupancy studies, molecular profiling of HSCs, NF-κB signaling analysis Blood High 29343483
2016 NR4A3 (NOR-1) is essential for migration of CD103+ dendritic cells to lymph nodes; this defect is cell-intrinsic; NR4A3 deficiency causes marked loss of surface CCR7 expression specifically on CD103+ DCs (not T cells); NR4A3 maintains FOXO1 protein levels in CD103+ DCs through an AKT-dependent mechanism, and FOXO1 regulates CCR7 expression; NR4A3 is also required for homeostatic mitochondrial function in CD103+ DCs. Nr4a3-deficient mouse model, mixed bone marrow chimera (cell-intrinsic proof), flow cytometry for CCR7/FOXO1, AKT pathway inhibitor studies The Journal of clinical investigation High 27820700
2019 NR4A3 is required for differentiation of monocytes into monocyte-derived dendritic cells (MoDCs) but not other DC types; Nr4a3-/- mice show severely impaired generation of DC-SIGN+ MoDCs in response to LPS, resulting in inability to mount optimal CD8+ T cell responses to gram-negative bacteria; transcriptomics shows NR4A3 skews monocyte fate toward MoDCs over macrophages and enables acquisition of migratory characteristics. Nr4a3-/- mouse model, flow cytometry, transcriptomic analysis, in vivo bacterial infection challenge Proceedings of the National Academy of Sciences of the United States of America High 31285338
2020 NR4A3 deficiency in CD8+ T cells leads to preferential differentiation into memory precursor and central memory cells with increased cytokine production; NR4A3 deficiency early programs memory transcriptional programs and increases chromatin accessibility at bZIP transcription factor motifs, affecting Fos/Jun target gene transcription. NR4A3-deficient murine CD8+ T cells, ATAC-seq for chromatin accessibility, transcriptional profiling, cytokine production assays Proceedings of the National Academy of Sciences of the United States of America High 32913051
2022 Dual knockout of PRDM1 and NR4A3 in CAR T cells skews phenotypes away from TIM-3+CD8+ toward TCF1+CD8+, countering exhaustion and improving antitumor responses; NR4A3 is identified as part of an NFAT-driven T cell dysfunction program that is upregulated as negative epigenetic feedback when PRDM1 is deleted. CRISPR knockout (single and dual) in CAR T cells, scRNA-seq, in vivo tumor models Science translational medicine High 36350986
2015 NR4A3 (NOR1) physically interacts with PARP-1 (confirmed by co-immunoprecipitation); NOR1 overexpression enhances PARP-1 activity and promotes cardiac hypertrophy; a NOR1 mutant (C293Y) lacking PARP-1 binding activity fails to induce hypertrophy; PARP-1 inhibition or siRNA blocks NOR1-driven hypertrophic effects. Co-immunoprecipitation (NOR1-PARP-1), NOR1 overexpression/knockdown in neonatal rat cardiomyocytes, C293Y mutant analysis, PARP-1 activity assay, hypertrophy markers British journal of pharmacology High 25625556
2019 NR4A3 (Nor1) negatively regulates β-cell mass: Nor1 knockout mice display increased β-cell mass and improved glucose tolerance; Nor1 expression is induced by pro-inflammatory cytokines and elevated glucose; Nor1 overexpression in INS and human islet cells causes apoptosis, while siRNA-mediated Nor1 knockdown prevents cytokine-induced β-cell death. Nor1 knockout mouse histological analysis, lentiviral overexpression, siRNA knockdown in INS cells and human islets, apoptosis assays The Journal of biological chemistry High 30696767
2017 NR4A3 (NOR-1) directly regulates vitronectin (VTN) expression in human vascular smooth muscle cells by binding to an NBRE(-202/-195) site in the VTN promoter; NOR-1-driven VTN secretion promotes VSMC migration; this was confirmed by EMSA, ChIP, deletion and site-directed mutagenesis studies. Lentiviral NOR-1 overexpression/silencing, EMSA, ChIP, promoter deletion/mutagenesis with reporter assays, cell migration assay with anti-VTN blocking antibody FASEB journal High 28666984
2016 NR4A3 (NOR-1) expression is induced by exercise via calcium/calcineurin signaling in skeletal muscle; transgenic Nor-1 expression in skeletal muscle induces muscle hypertrophy, vascularization, and increased autophagy (elevated LC3A-II, autophagy protein 5 and 12, decreased p62, decreased mTORC1 activity). Transgenic Nor-1 mouse model, calcineurin inhibitor pharmacology, autophagy marker analysis (LC3A-GFP-RFP chimera), exercise studies Molecular endocrinology (Baltimore, Md.) Medium 27144290
2016 NR4A3 (NOR-1) regulates the small muscle protein X-linked (SMPX) in human vascular smooth muscle cells and skeletal muscle cells by binding to a non-consensus NBRE site in the human SMPX promoter; NOR-1 silencing prevents SMPX expression and differentiation of human skeletal muscle myoblasts to myotubes. Lentiviral NOR-1 overexpression/silencing, transcriptional reporter assays, EMSA (DNA-protein binding), NOR-1 siRNA knockdown in HSMM differentiation Scientific reports Medium 27181368
2013 6-Mercaptopurine (6-MP) activates NR4A3 (NOR-1) and enhances glucose transport activity in L6 skeletal muscle cells via increased GLUT4 translocation in an NR4A3-dependent manner; 6-MP also increases phospho-AS160 through NR4A3-independent mechanisms. NR4A3 overexpression/knockdown in L6 cells, glucose transport assay, GLUT4 translocation assay, 6-MP pharmacology American journal of physiology. Endocrinology and metabolism Medium 24022864
2019 NR4A3 overexpression in mouse salivary gland cells increases expression of known NR4A3 target genes and stimulates cell proliferation; recurrent t(4;9)(q13;q31) chromosomal rearrangements in acinic cell carcinoma translocate active SCPP enhancer regions upstream of NR4A3, driving its ectopic overexpression (enhancer hijacking); active chromatin regions and gene expression signatures in AciCCs correlate with NR4A3 transcription factor binding motifs. Whole genome sequencing, RNA-seq, ATAC-seq/chromatin profiling, NR4A3 overexpression in salivary gland cells with proliferation assay Nature communications High 30664630
2015 NR4A3 (Nor1) and NR4A1 (Nur77) increase thrombomodulin expression in endothelial cells through distinct mechanisms: Nur77 increases thrombomodulin mRNA stability (not promoter activity), whereas Nor1 enhances thrombomodulin expression primarily through induction of Krüppel-like factors 2 and 4 (KLF2/4); both receptors increase protein C activity and inhibit prothrombotic effects. Adenovirus-mediated transduction of Nur77 and Nor1 cDNAs, mRNA stability assays, promoter activity assays, KLF2/4 expression analysis, protein C activity assay, Nur77-deficient mouse thrombosis model Arteriosclerosis, thrombosis, and vascular biology Medium 26634653
2024 NR4A3 promotes vascular calcification via histone lactylation: NR4A3 directly binds to promoters of glycolysis genes ALDOA and PFKL to drive their transcription, thereby enhancing glycolysis and lactate production; elevated lactate promotes histone lactylation, which in turn activates transcription of Phospho1 (PHOSPHO1), promoting calcium deposition; NR4A3 deficiency inhibits this cascade and reduces calcification. NR4A3-/- mouse models of medial arterial calcification, RNA-seq, CUT&TAG chromatin occupancy analysis, glycolysis/lactate assays, Phospho1 pharmacological inhibition and overexpression Circulation research High 38629274
2016 Muscle contraction induces acute hydroxymethylation followed by demethylation of the NR4A3 promoter: electrical pulse stimulation causes early hydroxymethylation at the NR4A3 promoter (highest immediately post-EPS), followed by demethylation at 60 min and re-methylation at 120 min, accompanying transcriptional induction of NR4A3. Targeted bisulfite sequencing, hydroxymethylcytosine analysis, electrical pulse stimulation of C2C12 myotubes, acute exercise study in humans Frontiers in endocrinology Medium 28066330
2017 NR4A3 knockdown in bone marrow-derived dendritic cells suppresses TLR-mediated upregulation of CD80, CD86, IL-10, IL-6, and IL-12; NR4A3 knockdown decreases expression of IKKβ, IRF4, and IRF8; IKKβ mediates IL-10 and IL-6 induction while IRF4/IRF8 mediate IL-12 induction downstream of NR4A3. siRNA knockdown in bone marrow-derived DCs, cytokine and surface marker expression analysis, secondary siRNA knockdown of IKKβ/IRF4/IRF8 Journal of immunology (Baltimore, Md. : 1950) Medium 28893954
2018 NR4A3 knockdown in BeWo trophoblast cells increases FSK-induced cell fusion and expression of syncytialization markers (CGB, syncytin2), indicating that cAMP-PKA-upregulated NR4A3 acts as a negative regulator of syncytialization; NR4A3 counterbalances the positive regulator STAT5B in controlling the degree of trophoblast cell fusion. siRNA knockdown of NR4A3 in BeWo cells, microarray analysis, syncytialization assay (cell fusion), RT-PCR for syncytialization markers Journal of cellular biochemistry Medium 29377304
2004 NR4A3 (NOR1) physically interacts with the homeodomain transcription factor SIX3 and stimulates its transcriptional activity; the SIX3 holoprosencephaly mutation p.R257P abolishes the interaction with NOR1 in vivo, while p.L226V does not alter this interaction, demonstrating that different HPE2 SIX3 mutations affect distinct signaling pathways. GST fusion protein pull-down assays, transient co-transfection with expression and reporter vectors in Neuro-2a cells Human mutation Medium 15523651
2019 NR4A3 plays a pro-inflammatory role in osteoarthritis chondrocytes by enhancing IL-1β-stimulated expression of matrix-degrading enzymes (MMP-3, MMP-9, iNOS, COX-2) and enhancing NF-κB activation; NR4A3 overexpression also enhances EBSS-induced chondrocyte apoptosis. Lentiviral overexpression and siRNA knockdown in chondrocytes, NF-κB signaling analysis, MMP/iNOS/COX-2 expression, apoptosis assay Journal of cellular and molecular medicine Medium 31701670
2020 miR-106b-5p targets the 3' UTR of NR4A3 mRNA and negatively regulates NR4A3 expression, thereby inducing Treg/Th17 immune imbalance in immune thrombocytopenic purpura; NR4A3 regulates Treg differentiation via Foxp3; sh-NR4A3 decreases Foxp3 and TGF-β expression. Dual-luciferase reporter assay (miR-106b-5p/NR4A3 3'UTR), qRT-PCR, western blot, sh-NR4A3 knockdown, in vivo silencing of miR-106b-5p Cell cycle (Georgetown, Tex.) Medium 32323598
2024 NR4A3 protects against diabetes-induced atrial remodeling by preserving mitochondrial energy metabolism and reducing oxidative stress; NR4A3 maintains transcriptional expression of Sdha (succinate dehydrogenase subunit A); NR4A3 deficiency exacerbates atrial fibrosis and increases AF susceptibility, while AAV9-mediated NR4A3 overexpression alleviates atrial remodeling in db/db mice. Nr4a3-/- mouse model, AAV9-Nr4a3 overexpression in db/db mice, RNA-seq, metabolomics, electrophysiological analysis, histological analysis EBioMedicine Medium 39098108
2016 NOR1 (NR4A3) cooperates with a FOXA1-HDAC2 complex to repress Slug transcription, inhibiting epithelial-mesenchymal transition in nasopharyngeal carcinoma; FOXA1 and HDAC2 bind the slug promoter and directly repress its transcription. Data mining of gene expression profiles, ectopic expression, RNA interference, chromatin-related functional assays Oncotarget Medium 26934447
2022 FTO (fat mass and obesity-associated protein) demethylates NR4A3 mRNA (m6A modification); FTO knockdown increases methylation of NR4A3 mRNA; DHA (dihydroartemisinin) suppresses AngII-induced VSMC proliferation and inflammation by inhibiting the FTO/NR4A3 axis. m6A-RIP assay (MeRIP), FTO knockdown/overexpression with mutant FTO control, CCK-8 proliferation assay, immunofluorescence Inflammation research Medium 35059772

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Abrogation of nuclear receptors Nr4a3 and Nr4a1 leads to development of acute myeloid leukemia. Nature medicine 274 17515897
2012 The significant other: splicing by the minor spliceosome. Wiley interdisciplinary reviews. RNA 253 23074130
2013 L2, the minor capsid protein of papillomavirus. Virology 179 23689062
2006 Significance of the minor cytochrome P450 3A isoforms. Clinical pharmacokinetics 176 16430309
2019 Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands. Nature communications 163 30664630
1997 Targeting the minor groove of DNA. Current opinion in structural biology 160 9204277
2006 What drives proteins into the major or minor grooves of DNA? Journal of molecular biology 146 17055530
1995 Complexes of the minor groove of DNA. Annual review of biophysics and biomolecular structure 145 7663124
2022 BLIMP1 and NR4A3 transcription factors reciprocally regulate antitumor CAR T cell stemness and exhaustion. Science translational medicine 111 36350986
2012 Thermospermine is not a minor polyamine in the plant kingdom. Plant & cell physiology 99 22366038
2019 Nuclear NR4A3 Immunostaining Is a Specific and Sensitive Novel Marker for Acinic Cell Carcinoma of the Salivary Glands. The American journal of surgical pathology 96 31094928
2022 Transsulfuration, minor player or crucial for cysteine homeostasis in cancer. Trends in cell biology 93 35365367
1984 Proximate biochemical composition and caloric content calculated from elemental CHN analysis: a stoichiometric concept. Oecologia 92 28310880
2002 The immunogenomics of minor histocompatibility antigens. Immunological reviews 90 12493008
2020 Nutritional and antinutritional composition of fava bean (Vicia faba L., var. minor) cultivars. Food research international (Ottawa, Ont.) 88 33648264
2014 Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors. Proceedings of the National Academy of Sciences of the United States of America 84 24706823
2008 Inhibition of adipocyte differentiation by Nur77, Nurr1, and Nor1. Molecular endocrinology (Baltimore, Md.) 83 18945812
2013 The Merkel cell polyomavirus minor capsid protein. PLoS pathogens 80 23990782
2014 Extraskeletal myxoid chondrosarcoma with non-EWSR1-NR4A3 variant fusions correlate with rhabdoid phenotype and high-grade morphology. Human pathology 77 24746215
2010 Deficiency of the NR4A orphan nuclear receptor NOR1 decreases monocyte adhesion and atherosclerosis. Circulation research 77 20558821
2024 Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation. Circulation research 76 38629274
2014 Role of PRMTs in cancer: Could minor isoforms be leaving a mark? World journal of biological chemistry 76 24921003
2000 Nuclear receptors Nor1 and NGFI-B/Nur77 play similar, albeit distinct, roles in the hypothalamo-pituitary-adrenal axis. Endocrinology 75 10875239
2021 Structure of the activated human minor spliceosome. Science (New York, N.Y.) 71 33509932
1999 Fusion of the RBP56 and CHN genes in extraskeletal myxoid chondrosarcomas with translocation t(9;17)(q22;q11). Oncogene 64 10602519
2005 Prostaglandin A2 acts as a transactivator for NOR1 (NR4A3) within the nuclear receptor superfamily. Biological & pharmaceutical bulletin 61 16141523
2017 Atomic Structures of Minor Proteins VI and VII in Human Adenovirus. Journal of virology 60 28978703
2002 Minor H antigens: genes and peptides. Transplant immunology 60 12216941
2015 The nuclear orphan receptor NR4A1 and NR4A3 as tumor suppressors in hematologic neoplasms. Current drug targets 58 25410408
2018 NR4A1 and NR4A3 restrict HSC proliferation via reciprocal regulation of C/EBPα and inflammatory signaling. Blood 57 29343483
2011 The nuclear receptors NUR77, NURR1 and NOR1 in obesity and during fat loss. International journal of obesity (2005) 54 22143616
2000 Differential patterns of induction of NGFI-B, Nor1 and c-fos mRNAs in striatal subregions by haloperidol and clozapine. Brain research 52 10773199
1997 Minor histocompatibility antigens. Current opinion in immunology 52 9368774
2011 Down-regulation of the RUNX1-target gene NR4A3 contributes to hematopoiesis deregulation in familial platelet disorder/acute myelogenous leukemia. Blood 51 21725049
2018 Orphan receptor NR4A3 is a novel target of p53 that contributes to apoptosis. Oncogene 47 30455429
2002 Subcellular localization of chlorosome proteins in Chlorobium tepidum and characterization of three new chlorosome proteins: CsmF, CsmH, and CsmX. Biochemistry 47 11914082
2019 The orphan nuclear receptor NR4A3 controls the differentiation of monocyte-derived dendritic cells following microbial stimulation. Proceedings of the National Academy of Sciences of the United States of America 43 31285338
2003 Thalassemia minor, the Gilbert mutation, and the risk of gallstones. Haematologica 42 14555305
2018 Dengue virus NS2 and NS4: Minor proteins, mammoth roles. Biochemical pharmacology 40 29674002
2010 Protein kinase C regulates mitochondrial targeting of Nur77 and its family member Nor-1 in thymocytes undergoing apoptosis. European journal of immunology 40 20411565
2001 The EWS/NOR1 fusion gene product gains a novel activity affecting pre-mRNA splicing. The Journal of biological chemistry 39 11673470
2011 NOR1 is an HSF1- and NRF1-regulated putative tumor suppressor inactivated by promoter hypermethylation in nasopharyngeal carcinoma. Carcinogenesis 38 21803736
2019 The pro-inflammatory effect of NR4A3 in osteoarthritis. Journal of cellular and molecular medicine 37 31701670
2021 NR4A3: A Key Nuclear Receptor in Vascular Biology, Cardiovascular Remodeling, and Beyond. International journal of molecular sciences 36 34768801
2020 NR4A3 Immunohistochemistry Reliably Discriminates Acinic Cell Carcinoma from Mimics. Head and neck pathology 36 32910350
2020 Early programming of CD8+ T cell response by the orphan nuclear receptor NR4A3. Proceedings of the National Academy of Sciences of the United States of America 36 32913051
2016 Muscle Contraction Induces Acute Hydroxymethylation of the Exercise-Responsive Gene Nr4a3. Frontiers in endocrinology 36 28066330
2008 Oligodendroglial cells and neurotrophins: a polyphonic cantata in major and minor. Journal of molecular neuroscience : MN 36 18327658
2018 Regulation of human trophoblast cell syncytialization by transcription factors STAT5B and NR4A3. Journal of cellular biochemistry 35 29377304
2018 MicroRNA-638 inhibits human airway smooth muscle cell proliferation and migration through targeting cyclin D1 and NOR1. Journal of cellular physiology 35 30076719
2015 The orphan receptor NOR1 participates in isoprenaline-induced cardiac hypertrophy by regulating PARP-1. British journal of pharmacology 35 25625556
2001 Minor H antigens: genes and peptides. European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 35 11881817
2020 Pharmacological potential of varinic-, minor-, and acidic phytocannabinoids. Pharmacological research 33 32416215
2017 The Orphan Nuclear Receptor NR4A3 Is Involved in the Function of Dendritic Cells. Journal of immunology (Baltimore, Md. : 1950) 33 28893954
2016 The transcription factor NR4A3 controls CD103+ dendritic cell migration. The Journal of clinical investigation 31 27820700
2014 Chemical characterisation and analysis of the cell wall polysaccharides of duckweed (Lemna minor). Carbohydrate polymers 29 25037369
2019 The orphan nuclear receptor Nor1/Nr4a3 is a negative regulator of β-cell mass. The Journal of biological chemistry 28 30696767
2019 NR4A3 fusion proteins trigger an axon guidance switch that marks the difference between EWSR1 and TAF15 translocated extraskeletal myxoid chondrosarcomas. The Journal of pathology 28 31020999
2017 Minor collagens of the skin with not so minor functions. Journal of anatomy 27 31318053
2016 Significance of the NOR1-FOXA1/HDAC2-Slug regulatory network in epithelial-mesenchymal transition of tumor cells. Oncotarget 27 26934447
2021 Disruption of exon-bridging interactions between the minor and major spliceosomes results in alternative splicing around minor introns. Nucleic acids research 26 33660780
2020 miR-106b-5p induces immune imbalance of Treg/Th17 in immune thrombocytopenic purpura through NR4A3/Foxp3 pathway. Cell cycle (Georgetown, Tex.) 26 32323598
2016 The Nuclear Receptor, Nor-1, Induces the Physiological Responses Associated With Exercise. Molecular endocrinology (Baltimore, Md.) 26 27144290
2007 A mutation in CHN-1/CHIP suppresses muscle degeneration in Caenorhabditis elegans. Developmental biology 26 17961535
2020 Resveratrol prevented experimental pulmonary vascular remodeling via miR-638 regulating NR4A3/cyclin D1 pathway. Microvascular research 25 32057731
2018 Abberent expression of NOR1 protein in tumor associated macrophages contributes to the development of DEN-induced hepatocellular carcinoma. Journal of cellular physiology 25 29227538
2014 Deficiency of the NR4A orphan nuclear receptor NOR1 in hematopoietic stem cells accelerates atherosclerosis. Stem cells (Dayton, Ohio) 25 24806827
2022 Dihydroartemisinin alleviates AngII-induced vascular smooth muscle cell proliferation and inflammatory response by blocking the FTO/NR4A3 axis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 24 35059772
2015 Antithrombotic Effects of Nur77 and Nor1 Are Mediated Through Upregulating Thrombomodulin Expression in Endothelial Cells. Arteriosclerosis, thrombosis, and vascular biology 24 26634653
2021 SMARCA2-NR4A3 is a novel fusion gene of extraskeletal myxoid chondrosarcoma identified by RNA next-generation sequencing. Genes, chromosomes & cancer 23 34124809
1991 Minor histocompatibility antigens. Immunology letters 23 1916933
2021 MiR-20a-5p Negatively Regulates NR4A3 to Promote Metastasis in Bladder Cancer. Journal of oncology 22 34925506
2020 Long non-coding RNA LINC00467 drives hepatocellular carcinoma progression via inhibiting NR4A3. Journal of cellular and molecular medicine 22 32125766
2019 Radiotherapy in combination with hyperthermia suppresses lung cancer progression via increased NR4A3 and KLF11 expression. International journal of radiation biology 22 31498019
2018 The emerging role of minor intron splicing in neurological disorders. Cell stress 22 31225466
1991 Minor histocompatibility antigens. Trends in genetics : TIG 22 1887503
2019 An Integrated Model of Minor Intron Emergence and Conservation. Frontiers in genetics 21 31798628
2010 Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder. Genes, brain, and behavior 21 20659174
2020 miR‑106b‑5p modulates acute pulmonary embolism via NOR1 in pulmonary artery smooth muscle cells. International journal of molecular medicine 20 32323756
2021 Transcriptional Profiling of Monocytes Deficient in Nuclear Orphan Receptors NR4A2 and NR4A3 Reveals Distinct Signalling Roles Related to Antigen Presentation and Viral Response. Frontiers in immunology 19 34248958
2009 Common polymorphisms within the NR4A3 locus, encoding the orphan nuclear receptor Nor-1, are associated with enhanced beta-cell function in non-diabetic subjects. BMC medical genetics 19 19682370
2004 Coexpression of NOR1 and SIX3 proteins in extraskeletal myxoid chondrosarcomas without detectable NR4A3 fusion genes. Cancer genetics and cytogenetics 19 15262426
2017 The nuclear receptor NOR-1/NR4A3 regulates the multifunctional glycoprotein vitronectin in human vascular smooth muscle cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 28666984
2024 NR4A3 prevents diabetes induced atrial cardiomyopathy by maintaining mitochondrial energy metabolism and reducing oxidative stress. EBioMedicine 17 39098108
2021 Circ_0030586 inhibits cell proliferation and stemness in bladder cancer by inactivating the ERK signaling via miR-665/NR4A3 axis. Acta histochemica 17 34175686
2013 6-Mercaptopurine augments glucose transport activity in skeletal muscle cells in part via a mechanism dependent upon orphan nuclear receptor NR4A3. American journal of physiology. Endocrinology and metabolism 17 24022864
2010 Histopathology of the minor duodenal papilla. Digestive surgery 17 20551659
2016 The nuclear receptor NOR-1 regulates the small muscle protein, X-linked (SMPX) and myotube differentiation. Scientific reports 16 27181368
2010 Cytotoxicity of Vinca minor. Pharmaceutical biology 15 20645762
1979 Stress and Protein Turnover in Lemna minor. Plant physiology 15 16661102
2023 NR4A3 Expression Is Consistently Absent in Acinic Cell Carcinomas of the Breast: A Potential Nosologic Shift. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 14 36828363
2019 Skeletal muscle Nur77 and NOR1 insulin responsiveness is blunted in obesity and type 2 diabetes but improved after exercise training. Physiological reports 14 30912283
2017 Deletion of the NR4A nuclear receptor NOR1 in hematopoietic stem cells reduces inflammation but not abdominal aortic aneurysm formation. BMC cardiovascular disorders 14 29047330
2016 Selective anti-malarial minor groove binders. Bioorganic & medicinal chemistry letters 14 27212070
2024 Expanding the Spectrum of NR4A3 Fusion-Positive Gynecologic Leiomyosarcomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 13 38508521
2012 Minor withanolides of Physalis longifolia: structure and cytotoxicity. Chemical & pharmaceutical bulletin 13 23036966
2002 Intergenic mRNAs. Minor gene products or tools of diversity? Histology and histopathology 13 11962767
2022 Stress-induced immunosuppression affecting avian influenza virus vaccine immune response through miR-20a-5p/NR4A3 pathway in chicken. Veterinary microbiology 12 35994844
2020 NR4A3 induces endothelial dysfunction through up-regulation of endothelial 1 expression in adipose tissue-derived stromal cells. Life sciences 12 33221345
2004 Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1. Human mutation 12 15523651