Affinage

NPR1

Atrial natriuretic peptide receptor 1 · UniProt P16066

Length
1061 aa
Mass
118.9 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

The NPR1 symbol in this corpus resolves to two mechanistically distinct, coherent proteins encoded at non-orthologous loci: the Arabidopsis master immune regulator NPR1 and the mammalian natriuretic peptide receptor NPR1/NPRA, a transmembrane guanylyl cyclase. In plants, NPR1 transduces the defense hormone salicylic acid (SA) into transcriptional reprogramming: it rests as a cytoplasmic disulfide-bonded oligomer that, upon SA-driven cellular reduction, releases monomers that enter the nucleus, with Cys82/Cys216 governing this redox switch (PMID:12837250). Nuclear NPR1 acts as a transcriptional cofactor by binding TGA-class bZIP transcription factors to activate PR-1 and other defense genes (PMID:10339621); structurally, an SA-bound NPR1 homodimer with BTB, BTB-Kelch, ankyrin-repeat and SA-binding domains bridges two TGA dimers into a TGA3₂–NPR1₂–TGA3₂ enhanceosome, with SA-induced folding of the SA-binding domain onto the ankyrin repeats required for cofactor activity (PMID:35545668). NPR1 is itself a bona fide SA receptor acting in opposition to the co-repressors NPR3/NPR4 (PMID:29656896). NPR1 abundance and activity are tuned by progressive ubiquitination (a Cullin-RING E3 promotes chromatin association, the E4 ligase UBE4 drives proteasomal turnover, and deubiquitinases UBP6/7 extend its lifetime) (PMID:31589140), by the SCF/CUL1 substrate receptor HOS15 that preferentially degrades phosphorylated active NPR1 (PMID:33199617), by sumoylation through its SIM3 motif required for antiviral immunity (PMID:37328517), and by antagonistic phosphorylation in which TOR inhibits NPR1 at Ser-55/59 while SnRK1 activates it at Ser-557 (PMID:40667109). Beyond canonical activation, NPR1 forms cytoplasmic SA-induced condensates (SINCs) that scaffold a Cullin 3 E3 ligase to ubiquitinate and degrade EDS1 and WRKY factors, restraining cell death during effector-triggered immunity (PMID:32810437), and it more broadly serves as a CULLIN3 substrate adaptor, targeting the photomorphogenesis regulator PIF4 for degradation under blue light (PMID:39700134). Plant NPR1 also branches into SA-dependent cell-death control and abiotic stress, partnering with HSFA1 to drive cold-acclimation genes independently of SA and TGA (PMID:30250280, PMID:11844114). In mammals, NPR1/NPRA is a guanylyl-cyclase receptor whose ANP-induced desensitization is driven by dephosphorylation of its kinase homology domain linked to tight receptor dimerization (PMID:11551207); its expression is positively controlled by an Ets-1/p300 acetyltransferase complex at the promoter (PMID:19487584) and repressed by angiotensin II acting through PKC and CREB/HSF-4a recruitment of HDAC1/2 to deacetylate promoter histones (PMID:16930545, PMID:32152395), with NPRA/cGMP/PKG signaling governing proliferation, senescence and self-renewal in multiple cell types (PMID:36016499).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 High

    Established how NPR1 reaches defense gene promoters despite lacking direct sequence-specific DNA binding, by showing it works through TGA transcription factors.

    Evidence Yeast two-hybrid, in vitro pulldown and EMSA with point mutants, in Arabidopsis

    PMID:10339621

    Open questions at the time
    • Did not resolve the stoichiometry or architecture of the NPR1-TGA complex
    • Did not establish how NPR1 reaches the nucleus
  2. 2001 Medium

    Defined the molecular basis of mammalian NPRA desensitization, showing dephosphorylation of the kinase homology domain rather than phosphatase activation drives loss of responsiveness.

    Evidence Radiolabeled phosphorylation assays with the C423S dimerization mutant in HEK293 cells

    PMID:11551207

    Open questions at the time
    • Did not identify the kinase responsible for basal receptor phosphorylation
    • Single expression system
  3. 2001 Medium

    Placed NPR1 in a specific branch of resistance signaling by showing RPP5-related resistance can be activated independently of NPR1 yet still requires SA and EDS1.

    Evidence Genetic suppressor screen and double-mutant epistasis with SA measurement in Arabidopsis

    PMID:11605952

    Open questions at the time
    • Did not define molecular mechanism of the NPR1-independent branch
  4. 2003 High

    Identified the redox switch controlling NPR1 activation, explaining how SAR signals are converted into nuclear NPR1 accumulation.

    Evidence Redox biochemistry, Cys82/Cys216 mutagenesis, subcellular fractionation and reporter assays in Arabidopsis

    PMID:12837250

    Open questions at the time
    • Did not identify the reductase or upstream redox sensors
    • Later work questioned whether disulfide oligomerization occurs in vivo (#28)
  5. 2003 Medium

    Showed mammalian NPRA transcription is hormonally repressed, linking the renin-angiotensin system to natriuretic receptor abundance.

    Evidence Promoter-luciferase mapping and receptor-antagonist pharmacology in mouse mesangial cells

    PMID:12623988

    Open questions at the time
    • Did not identify the trans-acting factors or chromatin mechanism
  6. 2009 Medium

    Defined a positive transcriptional control circuit for mammalian NPRA, identifying Ets-1/p300 cooperativity at its promoter.

    Evidence Sequential ChIP, reporter assays and acetyltransferase-dead/E1A constructs

    PMID:19487584

    Open questions at the time
    • Did not link transcriptional output to receptor signaling phenotypes
    • Single lab
  7. 2018 High

    Resolved the receptor identity question by showing NPR1 and NPR3/NPR4 are SA receptors with opposing transcriptional outputs, reframing SA signaling as a balance of activators and repressors.

    Evidence Genetic epistasis with gain-of-function alleles and SA-binding assays in Arabidopsis

    PMID:29656896

    Open questions at the time
    • Did not provide structural basis of SA binding by NPR1 at this stage
  8. 2018 Medium

    Extended NPR1 function beyond SA-defense by showing it relays cold signals through HSFA1 independently of TGA factors.

    Evidence npr1 genetics, Co-IP, nuclear localization and cold-acclimation phenotyping in Arabidopsis

    PMID:30250280

    Open questions at the time
    • Did not establish how cold triggers NPR1 monomerization
    • Single lab
  9. 2019 High

    Established that ubiquitination of NPR1 is not simply destructive but a progressive, fine-tuning code coupling chromatin association to controlled turnover.

    Evidence Ubiquitination assays, ChIP and genetic analysis of UBE4 and UBP6/7 in Arabidopsis

    PMID:31589140

    Open questions at the time
    • Did not identify the initiating Cullin-RING E3 ligase
    • Did not map ubiquitination sites
  10. 2020 High

    Revealed a non-transcriptional NPR1 function in cell-fate control, showing condensate formation scaffolds a Cullin 3 ligase to degrade pro-death substrates during ETI.

    Evidence Live condensate imaging, Co-IP, ubiquitination assays and genetics in Arabidopsis

    PMID:32810437

    Open questions at the time
    • Did not define what triggers SINC assembly versus enhanceosome formation
    • Substrate ubiquitination sites not mapped
  11. 2020 Medium

    Identified HOS15 as the substrate receptor that selectively destroys phosphorylated, transcriptionally active NPR1, coupling activation to turnover.

    Evidence Co-IP, ubiquitination assays and loss-of-function genetics in Arabidopsis

    PMID:33199617

    Open questions at the time
    • Did not identify the kinase generating the phospho-mark recognized by HOS15
    • Single lab
  12. 2020 Medium

    Defined the chromatin mechanism by which angiotensin II represses mammalian NPRA, implicating CREB/HSF-4a recruitment and Class I HDAC-mediated histone deacetylation.

    Evidence ChIP, reporter assays, HDAC activity assays and pathway inhibitors in cells

    PMID:32152395

    Open questions at the time
    • Did not reconcile with the parallel PKC-dependent repression mechanism
    • Single lab
  13. 2021 Medium

    Challenged the disulfide-oligomer model by showing NSAIDs reduce NPR1 via cytosolic redox changes and that in vitro Cys oxidation/oligomerization does not occur in vivo.

    Evidence Cysteine labeling, redox measurements and npr3/npr4 genetics in Arabidopsis

    PMID:34911942

    Open questions at the time
    • Did not reconcile the discrepancy with earlier in vivo oligomer evidence (#0)
    • Mechanism of NSAID action on redox not fully defined
  14. 2022 High

    Provided the atomic-resolution architecture explaining how SA-bound NPR1 dimers bridge TGA dimers into an enhanceosome, unifying redox, SA-sensing and cofactor activity.

    Evidence Cryo-EM, X-ray crystallography, DNA-binding assays and genetic complementation in Arabidopsis

    PMID:35545668

    Open questions at the time
    • Did not capture the full enhanceosome on native promoter DNA in vivo
    • Did not resolve dynamics of SA-binding domain folding
  15. 2023 Medium

    Linked NPR1 sumoylation to antiviral defense and revealed a viral counter-strategy in which the NIb polymerase blocks the SIM3 motif to suppress both sumoylation and phosphorylation.

    Evidence Co-IP, sumoylation and phosphorylation assays with mutational analysis

    PMID:37328517

    Open questions at the time
    • Did not define how sumoylation alters NPR1 activity mechanistically
    • Single lab
  16. 2023 Medium

    Connected an environmental variable to NPR1 regulation, showing high humidity lowers Cullin 3 ligase activity, NPR1 ubiquitination and promoter binding to dampen defense.

    Evidence Immunoblotting, ChIP and Cullin 3a/b genetics under controlled humidity in Arabidopsis

    PMID:37728254

    Open questions at the time
    • Did not define how humidity signals to Cullin 3 activity
    • Single lab
  17. 2024 Medium

    Expanded NPR1's role as a CULLIN3 substrate adaptor beyond immunity, showing it targets PIF4 for degradation to control blue-light photomorphogenesis.

    Evidence In vivo ubiquitination with Lys-to-Arg mapping, Co-IP and genetic epistasis in Arabidopsis

    PMID:39700134

    Open questions at the time
    • Did not establish how cryptochromes promote the NPR1-PIF4 interaction structurally
    • Single lab
  18. 2024 Medium

    Demonstrated mammalian NPRA can be pharmacologically activated allosterically, providing proof-of-concept for an agonist antibody with venous-selective blood-pressure effects.

    Evidence Structural analysis plus in vivo animal pharmacology and human Phase I study

    PMID:39261724

    Open questions at the time
    • Did not fully define the allosteric activation mechanism at residue level
    • Single group
  19. 2025 Medium

    Integrated metabolic signaling into NPR1 control, showing antagonistic TOR (inhibitory, Ser-55/59) and SnRK1 (activating, Ser-557) phosphorylation gate NPR1 activity.

    Evidence In vitro kinase assays, phospho-site mutagenesis and tor/snrk1 epistasis in Arabidopsis (preprint)

    PMID:40667109

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Did not map how these phospho-marks intersect with ubiquitination and HOS15 recognition

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the in vivo redox-oligomer model is reconciled with evidence that disulfide oligomerization does not occur in planta, and how the layered ubiquitination, sumoylation and phospho-codes are integrated into a single decision between enhanceosome assembly and condensate-mediated degradation, remains unresolved.
  • Discrepancy between in vivo oligomer (#0) and no-oligomer (#28) models unresolved
  • No unified model linking phosphorylation, ubiquitination and sumoylation timing
  • Switch between transcriptional cofactor and SINC/E3-adaptor roles not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0009975 cyclase activity 2 GO:0060089 molecular transducer activity 2 GO:0140110 transcription regulator activity 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2
Partners
EDS1HOS15HSFA1PIF4PKS5PPARATGA3TGA6
Complex memberships
NPR1-Cullin 3 E3 ligase (SINC)NPRA/PGRMC1/EGFRSCF/CUL1-HOS15TGA3-NPR1 enhanceosome (TGA3₂-NPR1₂-TGA3₂)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 In uninduced plants, Arabidopsis NPR1 exists as an oligomer formed through intermolecular disulfide bonds. Upon SAR induction, a biphasic change in cellular redox potential reduces NPR1 to a monomeric form that accumulates in the nucleus and activates defense gene expression. Mutation of Cys82 or Cys216 leads to constitutive monomerization and constitutive nuclear localization and defense gene expression. Redox biochemistry, site-directed mutagenesis, subcellular fractionation, reporter gene assays Cell High 12837250
1999 Arabidopsis NPR1 interacts with a subclass of bZIP/TGA transcription factors (AHBP-1b and TGA6) in yeast two-hybrid and in vitro assays. Point mutations that abolish NPR1 function in plants also impair these interactions. The TGA factor AHBP-1b binds specifically to the SA-responsive promoter element of the PR-1 gene, suggesting NPR1 regulates PR-1 expression by interacting with TGA transcription factors. Yeast two-hybrid, in vitro pulldown, gel mobility shift assay (EMSA), point mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 10339621
2022 Cryo-EM and crystal structures of Arabidopsis NPR1 reveal a bird-shaped homodimer comprising a BTB domain, BTB-and-carboxyterminal Kelch helix bundle, four ankyrin repeats, and a disordered SA-binding domain. A unique zinc-finger motif in the BTB domain mediates ankyrin repeat interaction and NPR1 oligomerization. SA-induced folding and docking of the SA-binding domain onto ankyrin repeats is required for NPR1 transcriptional cofactor activity. Dimeric NPR1 bridges two fatty-acid-bound TGA3 dimers to form an enhanceosome (TGA3₂-NPR1₂-TGA3₂ complex). Cryo-electron microscopy, X-ray crystallography, DNA-binding assay, genetic complementation Nature High 35545668
2018 NPR3/NPR4 function as transcriptional co-repressors and SA inhibits their activities to promote expression of downstream immune regulators, functioning in parallel to NPR1. A gain-of-function npr4-4D allele unable to bind SA constitutively represses SA-induced immune responses. An equivalent mutation in NPR1 abolishes SA binding and SA-induced defense gene expression. Both NPR1 and NPR3/NPR4 are bona fide SA receptors playing opposite transcriptional roles. Genetic epistasis (double mutants), gain-of-function allele analysis, SA-binding assays Cell High 29656896
2020 NPR1 promotes cell survival during effector-triggered immunity by forming salicylic acid-induced NPR1 condensates (SINCs) enriched with stress response proteins. NPR1 condensate formation is required for assembly of an NPR1-Cullin 3 E3 ligase complex that ubiquitinates SINC-localized substrates including EDS1 and specific WRKY transcription factors, thereby modulating the cell death/survival decision. Fluorescence microscopy (condensate imaging), Co-IP, ubiquitination assays, genetic loss-of-function Cell High 32810437
2019 Ubiquitination of NPR1 is a progressive event: initial modification by a Cullin-RING E3 ligase promotes its chromatin association and target gene expression. Enhanced polyubiquitination by the E4 ligase UBE4 targets NPR1 for proteasomal degradation. Two proteasome-associated deubiquitinases UBP6/7 oppose ubiquitin ligase activities to enhance NPR1 longevity and fine-tune transcriptome reprogramming. Ubiquitination assays, ChIP, proteasome inhibitor treatments, genetic analysis eLife High 31589140
2010 PKS5, a SNF1-related kinase, interacts with NPR1 via NPR1's ankyrin repeat (AKR) motif and phosphorylates NPR1 at its C-terminal region. PKS5 loss-of-function reduces/delays expression of NPR1 target genes WRKY38 and WRKY62, and this effect requires NPR1, placing PKS5 upstream of NPR1 in this pathway. Co-IP, in vitro kinase assay, double mutant epistasis, qRT-PCR Journal of genetics and genomics Medium 20621018
2020 HOS15, a substrate receptor for an SCF/CUL1 E3 ubiquitin ligase complex, negatively regulates plant immunity by destabilizing NPR1-containing transcriptional activation complexes. In unchallenged conditions HOS15 continuously eliminates NPR1 to prevent defense gene expression; upon defense activation, HOS15 preferentially associates with phosphorylated NPR1 to stimulate rapid degradation of transcriptionally active NPR1. Co-IP, ubiquitination assay, genetic loss-of-function, immunoblotting Proceedings of the National Academy of Sciences of the United States of America Medium 33199617
2023 NPR1 is sumoylated via its SUMO-interacting motif 3 (SIM3), which is required for its antiviral activity against turnip mosaic virus. The viral RNA-dependent RNA polymerase NIb binds to SIM3 of NPR1, preventing SUMO3 interaction and NPR1 sumoylation, and also impedes phosphorylation of NPR1 at Ser11/Ser15. Co-IP, sumoylation assay, mutational analysis, phosphorylation assay Nature communications Medium 37328517
2018 In response to low temperature, cytoplasmic NPR1 oligomers release monomers that translocate to the nucleus where they interact with heat shock transcription factor 1 (HSFA1) to promote induction of HSFA1-regulated cold-acclimation genes, independently of salicylic acid and TGA factors. Genetic analysis (npr1 mutants), Co-IP, nuclear localization assay, cold acclimation phenotype assays Nature plants Medium 30250280
2024 NPR1 acts as a substrate adaptor for a CULLIN3-based E3 ligase to ubiquitinate PIF4 at Lys129, Lys252, and Lys428, promoting PIF4 degradation via the 26S proteasome in response to blue light. Cryptochromes promote the NPR1-PIF4 interaction and PIF4 polyubiquitination. Genetic epistasis shows PIF4 acts downstream of NPR1 in blue-light-induced photomorphogenesis. In vivo ubiquitination assay, site-directed mutagenesis (Lys→Arg), Co-IP, genetic epistasis, transcriptome analysis Proceedings of the National Academy of Sciences of the United States of America Medium 39700134
2025 Under normal growth conditions, TOR kinase phosphorylates NPR1 at Ser-55/59, inhibiting its activity. During SA-induced defense, elevated SA enhances SnRK1 kinase activity, which inhibits TOR and phosphorylates NPR1 at Ser-557, activating NPR1 and facilitating subsequent post-translational modifications. In vitro kinase assay, phospho-specific mutagenesis, genetic epistasis (tor and snrk1 mutants), immunoblotting bioRxivpreprint Medium 40667109
2023 The fungal effector CfEC12 interacts with MdNIMIN2 (a NIM1-interacting protein that modulates NPR1 activity) at a region that overlaps with the MdNPR1-binding site on MdNIMIN2, competitively suppressing MdNIMIN2-MdNPR1 interaction and reducing defense gene expression. Yeast two-hybrid, Co-IP, bimolecular fluorescence complementation, transgenic overexpression Plant biotechnology journal Medium 37596985
2001 In the snc1 suppressor mutant, a RPP5-related resistance pathway is constitutively activated that confers resistance independently of NPR1 but requires the signal molecule SA and EDS1 function, placing NPR1 in a specific branch of disease resistance signaling that is bypassed in this genetic background. Genetic suppressor screen, double mutant analysis, SA measurement, pathogen inoculation assays Molecular plant-microbe interactions : MPMI Medium 11605952
2002 SA accumulation and NIM1/NPR1 are required for lsd1-mediated runaway cell death following pathogen infection, placing NPR1 downstream of SA in this cell death signaling pathway. Neither SA accumulation nor NPR1 is required for basal resistance in lsd1, indicating NPR1 regulates an SA-dependent branch of cell death control. Genetic double mutant analysis, SA measurement, pathogen inoculation The Plant journal : for cell and molecular biology Medium 11844114
2003 Angiotensin II negatively regulates Npr1 (NPRA) gene promoter activity and mRNA expression in mouse mesangial cells in a time- and dose-dependent manner. The repression maps to the promoter region ~916 bp upstream of the transcription start site and is partially blocked by angiotensin type 1 and type 2 receptor antagonists. Promoter-luciferase reporter assays, RT-PCR, receptor antagonist pharmacology Hypertension Medium 12623988
2001 ANP-induced desensitization of NPR-A (NPRA) is associated with dephosphorylation of the receptor's kinase homology domain. The C423S constitutively dimerized mutant of rNPR-A shows dramatically reduced phosphorylation (~24-fold less 32P incorporation and ~3.5% thiophosphate incorporation vs. WT), demonstrating a close relationship between tight receptor dimerization, dephosphorylation, and desensitization. Reduced NPR-A kinase activity (not merely phosphatase activation) drives this dephosphorylation. Radiolabeled phosphorylation assay ([32P] and [35S]ATPγS), site-directed mutagenesis (C423S), HEK293 cell expression system Biochemistry Medium 11551207
2006 Angiotensin II-mediated transcriptional repression of Npr1 (NPRA) gene promoter activity and downregulation of guanylyl cyclase activity is regulated by protein kinase C (PKC) pathways. PKC agonist (phorbol ester) enhanced Ang II repression; PKC antagonist staurosporine completely reversed the effects of Ang II and phorbol ester on NPRA mRNA and cGMP levels. Promoter-luciferase assays, RT-PCR, guanylyl cyclase (cGMP) activity assay, pharmacological PKC agonist/antagonist Biochemical and biophysical research communications Medium 16930545
2009 Transcription factor Ets-1 and histone acetyltransferase p300 cooperatively activate Npr1 gene transcription. Sequential ChIP demonstrated direct physical association of p300 and Ets-1 on the Npr1 promoter. Mutant p300 lacking acetyltransferase activity failed to cooperate with Ets-1, and E1A (a p300 inhibitor) suppressed Npr1 promoter activity only when capable of binding p300. Sequential ChIP, promoter-reporter assay, siRNA knockdown, dominant-negative/mutant constructs Hypertension Medium 19487584
2010 GREBP (cGMP-response element-binding protein) binds specifically to a cGMP-response element (cGMP-RE) in the Npr1/GCA promoter, acts as a transcriptional repressor of NPR1/GCA, and is upregulated by ANP. Silencing GREBP with siRNA increased Npr1 promoter activity and GCA mRNA levels. Yeast one-hybrid, EMSA, ChIP, luciferase reporter assay, siRNA knockdown The Journal of biological chemistry Medium 20444705
2020 Angiotensin II represses Npr1 gene transcription by recruiting transcription factors CREB and HSF-4a and activating Class I HDACs (HDAC1/2), leading to decreased histone acetylation at H3K9/14ac and H4K8ac. This repression is transduced via tyrosine kinase and PI-3K pathways, as their inhibitors (genistein, wortmannin) reversed ANG II effects. ChIP, luciferase reporter, qRT-PCR, HDAC activity assay, pharmacological inhibitors, siRNA knockdown Scientific reports Medium 32152395
2020 In a mouse model of allergic contact dermatitis, NPRA in the spinal cord is required for histaminergic itch relay; Grpr+ neurons act downstream of Npr1+ (NPRA+) neurons in the spinal cord itch circuit. Genetic ablation of Npr1+ neurons or pharmacological blockade significantly attenuated chronic itch. Genetic cell-specific ablation, pharmacological receptor blockade, RNAscope in situ hybridization, mouse behavioral assays The Journal of investigative dermatology Medium 32032577
2011 NPR-A knockdown in mouse embryonic stem cells caused downregulation of pluripotency factors (Oct4, Nanog, Sox2), decreased phosphorylated Akt, G1 cell cycle arrest, and differentiation. ANP treatment upregulated Oct4, Nanog, and phosphorylated Akt in an NPR-A- and cGMP-dependent protein kinase-dependent manner, establishing NPR-A as a regulator of ES cell self-renewal via cGMP signaling. siRNA knockdown, flow cytometry, Western blot, pharmacological antagonist (NPR-A antagonist A71915, PKG inhibitor) Cell death & disease Medium 21390061
2017 ANP promotes proliferation and inhibits apoptosis of ovarian granulosa cells through formation of an NPRA/PGRMC1/EGFR complex, which activates MAPK/ERK signaling and transcription factor AP1. Co-immunoprecipitation, cell proliferation/apoptosis assays, Western blot for ERK phosphorylation, in vivo rat PCOS model Cell death & disease Medium 29072679
2015 ANP acting through NPRA inhibits cell cycle activity and reduces proliferation of embryonic cardiac progenitor cells (CPCs) but not differentiated cardiomyocytes, via NPRA/cGMP signaling; this effect is reversed by the NPRA-specific inhibitor A71915 and involves nuclear accumulation of p27. Pharmacological inhibition (A71915), cGMP measurement, DNA synthesis assay, immunofluorescence for p27, primary cell culture American journal of physiology. Cell physiology Medium 25631869
2022 Knockdown of NPRA in endothelial cells decreased expressions of PKG, SIRT1, eNOS, and phosphorylation of AMPK while increasing ROS production, promoting cellular senescence. This was rescued by cGMP analog (8-Br-cGMP) or AMPK activator (AICAR). Npr1+/- mice showed elevated blood pressure, vascular insensitivity to vasodilators, increased Cdkn1a and decreased eNos, reversed by viral overexpression of PKG, establishing an NPRA/PKG/AMPK signaling axis. siRNA knockdown, CRISPR/Cas9, Western blot, in vivo mouse model (Npr1+/-), viral gene delivery, pharmacological rescue Aging cell Medium 36016499
2023 NPRA binds to PPARα and prevents PPARα protein degradation; PPARα upregulation under NPRA protection activates CPT1B to promote fatty acid oxidation in gastric cancer cells. Co-immunoprecipitation, Western blot, in vitro and in vivo functional assays Translational oncology Low 37418841
2024 An agonist monoclonal antibody (REGN5381) targeting NPR1 induces an active-like receptor conformation as an allosteric agonist, resulting in preferential hemodynamic effects on venous vasculature and reductions in systolic and venous blood pressure in animal models and healthy human volunteers. Structural analysis, in vivo animal pharmacology, human Phase I clinical study Nature Medium 39261724
2021 Oxicam-type NSAIDs (tenoxicam, meloxicam, piroxicam) inhibit NPR1-mediated SA signaling by decreasing NPR1 protein levels independently of proposed SA receptors NPR3 and NPR4. TNX induces oxidation of cytosolic redox status, which regulates NPR1 homeostasis. In vitro, cysteine residues in NPR1 can be oxidized leading to disulfide-bridged oligomerization, but this does not occur in vivo regardless of SA or TNX treatment. Cysteine labeling assay, immunoblotting, genetic analysis (npr3/npr4 mutants), redox measurements Nature communications Medium 34911942
2023 High air humidity decreases Cullin 3-based E3 ubiquitin ligase activity, reducing NPR1 ubiquitination and NPR1 promoter-binding affinity, thereby dampening SA-mediated defense gene expression. Cullin 3a/b mutant plants phenocopy high-humidity disease susceptibility under low-humidity conditions. Immunoblotting, ChIP, genetic analysis (Cullin 3a/b mutants), humidity-controlled growth conditions The EMBO journal Medium 37728254

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Inducers of plant systemic acquired resistance regulate NPR1 function through redox changes. Cell 977 12837250
2002 Tobacco Rar1, EDS1 and NPR1/NIM1 like genes are required for N-mediated resistance to tobacco mosaic virus. The Plant journal : for cell and molecular biology 787 12028572
2018 Opposite Roles of Salicylic Acid Receptors NPR1 and NPR3/NPR4 in Transcriptional Regulation of Plant Immunity. Cell 525 29656896
2004 NPR1, all things considered. Current opinion in plant biology 485 15337097
1999 Interaction of NPR1 with basic leucine zipper protein transcription factors that bind sequences required for salicylic acid induction of the PR-1 gene. Proceedings of the National Academy of Sciences of the United States of America 480 10339621
2020 Formation of NPR1 Condensates Promotes Cell Survival during the Plant Immune Response. Cell 274 32810437
1998 The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease. The EMBO journal 271 9843498
2004 NPR1: the spider in the web of induced resistance signaling pathways. Current opinion in plant biology 262 15231270
2001 Activation of an EDS1-mediated R-gene pathway in the snc1 mutant leads to constitutive, NPR1-independent pathogen resistance. Molecular plant-microbe interactions : MPMI 207 11605952
2011 TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor. Cell 178 22118465
2019 The NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1) and Related Family: Mechanistic Insights in Plant Disease Resistance. Frontiers in plant science 162 30815005
2001 The Npr1 kinase controls biosynthetic and endocytic sorting of the yeast Gap1 permease. The Journal of biological chemistry 138 11500493
2020 Diverse Roles of the Salicylic Acid Receptors NPR1 and NPR3/NPR4 in Plant Immunity. The Plant cell 135 33037144
2004 Overexpression of (At)NPR1 in rice leads to a BTH- and environment-induced lesion-mimic/cell death phenotype. Molecular plant-microbe interactions : MPMI 132 14964528
2022 Structural basis of NPR1 in activating plant immunity. Nature 131 35545668
2018 NPR1 mediates a novel regulatory pathway in cold acclimation by interacting with HSFA1 factors. Nature plants 110 30250280
2023 NPR1, a key immune regulator for plant survival under biotic and abiotic stresses. Molecular cell 98 38103555
2008 Expression of callose synthase genes and its connection with Npr1 signaling pathway during pathogen infection. Planta 97 18807070
2013 TORC1-regulated protein kinase Npr1 phosphorylates Orm to stimulate complex sphingolipid synthesis. Molecular biology of the cell 86 23363605
2017 ANP promotes proliferation and inhibits apoptosis of ovarian granulosa cells by NPRA/PGRMC1/EGFR complex and improves ovary functions of PCOS rats. Cell death & disease 81 29072679
2002 Ventricular expression of natriuretic peptides in Npr1(-/-) mice with cardiac hypertrophy and fibrosis. American journal of physiology. Heart and circulatory physiology 81 12124219
2002 Runaway cell death, but not basal disease resistance, in lsd1 is SA- and NIM1/NPR1-dependent. The Plant journal : for cell and molecular biology 77 11844114
2000 Tobacco TGA factors differ with respect to interaction with NPR1, activation potential and DNA-binding properties. Plant molecular biology 73 10809449
2011 NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 (NPR1) and some NPR1-related proteins are sensitive to salicylic acid. Molecular plant pathology 71 21118350
2007 Npr1-regulated gene pathways contributing to cardiac hypertrophy and fibrosis. Journal of molecular endocrinology 65 17293444
2010 InhA1, NprA, and HlyII as candidates for markers to differentiate pathogenic from nonpathogenic Bacillus cereus strains. Journal of clinical microbiology 64 20129969
2014 The TORC1 effector kinase Npr1 fine tunes the inherent activity of the Mep2 ammonium transport protein. Nature communications 59 24476960
2019 Dynamic ubiquitination determines transcriptional activity of the plant immune coactivator NPR1. eLife 58 31589140
2017 A Conserved Puccinia striiformis Protein Interacts with Wheat NPR1 and Reduces Induction of Pathogenesis-Related Genes in Response to Pathogens. Molecular plant-microbe interactions : MPMI 54 27898286
2010 PKS5, a SNF1-related kinase, interacts with and phosphorylates NPR1, and modulates expression of WRKY38 and WRKY62. Journal of genetics and genomics = Yi chuan xue bao 50 20621018
2023 A fungal CFEM-containing effector targets NPR1 regulator NIMIN2 to suppress plant immunity. Plant biotechnology journal 45 37596985
2023 A plant RNA virus inhibits NPR1 sumoylation and subverts NPR1-mediated plant immunity. Nature communications 40 37328517
2004 NPR1 kinase and RSP5-BUL1/2 ubiquitin ligase control GLN3-dependent transcription in Saccharomyces cerevisiae. The Journal of biological chemistry 40 15247235
2008 Elicitor and Fusarium-induced expression of NPR1-like genes in banana. Plant physiology and biochemistry : PPB 37 18657982
2016 Retinoic acid and sodium butyrate suppress the cardiac expression of hypertrophic markers and proinflammatory mediators in Npr1 gene-disrupted haplotype mice. Physiological genomics 35 27199456
2003 Angiotensin II-mediated negative regulation of Npr1 promoter activity and gene transcription. Hypertension (Dallas, Tex. : 1979) 35 12623988
2001 Reduced activity of the NPR-A kinase triggers dephosphorylation and homologous desensitization of the receptor. Biochemistry 35 11551207
2020 HOS15 is a transcriptional corepressor of NPR1-mediated gene activation of plant immunity. Proceedings of the National Academy of Sciences of the United States of America 34 33199617
2018 NPR1 as a transgenic crop protection strategy in horticultural species. Horticulture research 33 29581883
2009 NPR1 protein regulates pathogenic and symbiotic interactions between Rhizobium and legumes and non-legumes. PloS one 32 20027302
2023 Seeing is believing: Understanding functions of NPR1 and its paralogs in plant immunity through cellular and structural analyses. Current opinion in plant biology 31 36934653
2020 Spinal GRPR and NPRA Contribute to Chronic Itch in a Murine Model of Allergic Contact Dermatitis. The Journal of investigative dermatology 31 32032577
2021 Overexpressing a NPR1-like gene from Citrus paradisi enhanced Huanglongbing resistance in C. sinensis. Plant cell reports 30 33386424
2023 High air humidity dampens salicylic acid pathway and NPR1 function to promote plant disease. The EMBO journal 29 37728254
2011 NPR-A regulates self-renewal and pluripotency of embryonic stem cells. Cell death & disease 29 21390061
2023 MSC-NPRA loop drives fatty acid oxidation to promote stemness and chemoresistance of gastric cancer. Cancer letters 27 37209945
2006 Ammonia-specific regulation of Gln3 localization in Saccharomyces cerevisiae by protein kinase Npr1. The Journal of biological chemistry 26 16864577
2015 Phylogenetic and expression analysis of the NPR1-like gene family from Persea americana (Mill.). Frontiers in plant science 25 25972890
2024 Agonist antibody to guanylate cyclase receptor NPR1 regulates vascular tone. Nature 24 39261724
2020 A new mode of NPR1 action via an NB-ARC-NPR1 fusion protein negatively regulates the defence response in wheat to stem rust pathogen. The New phytologist 24 32544264
1997 Cloning of the nprA gene for neutral protease A of Bacillus thuringiensis and effect of in vivo deletion of nprA on insecticidal crystal protein. Applied and environmental microbiology 24 9172350
2021 Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway. Nature communications 23 34911942
2019 Structure of a Therapeutic Full-Length Anti-NPRA IgG4 Antibody: Dissecting Conformational Diversity. Biophysical journal 23 31023536
2022 Chronological attenuation of NPRA/PKG/AMPK signaling promotes vascular aging and elevates blood pressure. Aging cell 21 36016499
2006 Inhibition and down-regulation of gene transcription and guanylyl cyclase activity of NPRA by angiotensin II involving protein kinase C. Biochemical and biophysical research communications 21 16930545
2020 Identification and Characterization of NPR1 and PR1 Homologs in Cymbidium orchids in Response to Multiple Hormones, Salinity and Viral Stresses. International journal of molecular sciences 20 32183174
2020 GRPR/Extracellular Signal-Regulated Kinase and NPRA/Extracellular Signal-Regulated Kinase Signaling Pathways Play a Critical Role in Spinal Transmission of Chronic Itch. The Journal of investigative dermatology 18 33039402
2019 Genome-Wide Identification and Analysis of the NPR1-Like Gene Family in Bread Wheat and Its Relatives. International journal of molecular sciences 18 31783558
2018 InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From Macrophages. Frontiers in microbiology 18 29875760
2013 Interactive roles of NPR1 gene-dosage and salt diets on cardiac angiotensin II, aldosterone and pro-inflammatory cytokines levels in mutant mice. Journal of hypertension 18 23188418
2009 Cooperative activation of Npr1 gene transcription and expression by interaction of Ets-1 and p300. Hypertension (Dallas, Tex. : 1979) 18 19487584
2019 Pib2-Dependent Feedback Control of the TORC1 Signaling Network by the Npr1 Kinase. iScience 17 31622882
2016 Klf10 deficiency in mice exacerbates pulmonary inflammation by increasing expression of the proinflammatory molecule NPRA. The international journal of biochemistry & cell biology 17 27592451
2015 Atrial natriuretic peptide inhibits cell cycle activity of embryonic cardiac progenitor cells via its NPRA receptor signaling axis. American journal of physiology. Cell physiology 17 25631869
2011 Role of the Npr1 kinase in ammonium transport and signaling by the ammonium permease Mep2 in Candida albicans. Eukaryotic cell 17 21278231
2019 NPR1 and Redox Rhythmx: Connections, between Circadian Clock and Plant Immunity. International journal of molecular sciences 16 30857376
2003 TA repeat variation, Npr1 expression, and blood pressure: impact of the Ace locus. Hypertension (Dallas, Tex. : 1979) 16 12511524
2014 New proteomic insights on the role of NPR-A in regulating self-renewal of embryonic stem cells. Stem cell reviews and reports 15 24798243
2024 NPR1 promotes blue light-induced plant photomorphogenesis by ubiquitinating and degrading PIF4. Proceedings of the National Academy of Sciences of the United States of America 14 39700134
2023 Reactive Oxygen Species in Drought-Induced Stomatal Closure: The Potential Roles of NPR1. Plants (Basel, Switzerland) 14 37765358
2020 Genome-wide identification of the NPR1-like gene family in Brassica napus and functional characterization of BnaNPR1 in resistance to Sclerotinia sclerotiorum. Plant cell reports 14 32140767
2020 Angiotensin II represses Npr1 expression and receptor function by recruitment of transcription factors CREB and HSF-4a and activation of HDACs. Scientific reports 14 32152395
2020 Molecular Cloning and Functional Analysis of the NPR1 Homolog in Kiwifruit (Actinidia eriantha). Frontiers in plant science 14 33042179
2019 Genetic disruption of Npr1 depletes regulatory T cells and provokes high levels of proinflammatory cytokines and fibrosis in the kidneys of female mutant mice. American journal of physiology. Renal physiology 14 30943067
2019 Characterization of NPR1 and NPR4 genes from mulberry (Morus multicaulis) and their roles in development and stress resistance. Physiologia plantarum 13 30506684
2015 ANP/NPRA signaling preferentially mediates Th2 responses in favor of pathological processes during the course of acute allergic asthma. International journal of clinical and experimental medicine 13 26131085
2011 Npr1 Ser/Thr protein kinase links nitrogen source quality and carbon availability with the yeast nitrate transporter (Ynt1) levels. The Journal of biological chemistry 13 21652715
2008 The NprA nitroreductase required for 2,4-dinitrophenol reduction in Rhodobacter capsulatus is a dihydropteridine reductase. Environmental microbiology 13 18355323
2005 Regulation and characterization of two nitroreductase genes, nprA and nprB, of Rhodobacter capsulatus. Applied and environmental microbiology 13 16332736
2023 NPRA promotes fatty acid metabolism and proliferation of gastric cancer cells by binding to PPARα. Translational oncology 12 37418841
2015 NPR-A: A Therapeutic Target in Inflammation and Cancer. Critical reviews in eukaryotic gene expression 12 25955817
2001 Deletion of aprA and nprA genes for alkaline protease A and neutral protease A from bacillus thuringiensis: effect on insecticidal crystal proteins. Journal of biotechnology 12 11035189
2024 Genome-wide analysis of NPR1-like genes in citrus species and expression analysis in response to citrus canker (Xanthomonas axonopodis pv. citri). Frontiers in plant science 11 38606070
2016 Differential expression and regulation of anti-hypertrophic genes Npr1 and Npr2 during β-adrenergic receptor activation-induced hypertrophic growth in rats. Molecular and cellular endocrinology 11 27283501
2010 GREBP, a cGMP-response element-binding protein repressing the transcription of natriuretic peptide receptor 1 (NPR1/GCA). The Journal of biological chemistry 11 20444705
2018 Feedback regulation of TORC1 by its downstream effectors Npr1 and Par32. Molecular biology of the cell 10 30156471
2010 Identification of a novel NPR1-like gene from Nicotiana glutinosa and its role in resistance to fungal, bacterial and viral pathogens. Plant biology (Stuttgart, Germany) 10 20653885
2025 NPR1 Promotes Lipid Droplet Lipolysis to Enhance Mitochondrial Oxidative Phosphorylation and Fuel Gastric Cancer Metastasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 40539884
2020 Salicylic acid receptor NPR1 is involved in guard cell chitosan signaling. Bioscience, biotechnology, and biochemistry 9 31983298
2019 Plant chemical genetics reveals colistin sulphate as a SA and NPR1-independent PR1 inducer functioning via a p38-like kinase pathway. Scientific reports 9 31371749
2020 A new strategy to improve the water solubility of an organic fluorescent probe using silicon nanodots and fabricate two-photon SiND-ANPA-N3 for visualizing hydrogen sulfide in living cells and onion tissues. Journal of materials chemistry. B 8 31976510
2019 Genetic disruption of guanylyl cyclase/natriuretic peptide receptor-A upregulates renal (pro) renin receptor expression in Npr1 null mutant mice. Peptides 8 30965084
2012 Disruption of Npr1 gene differentially regulates the juxtaglomerular and distal tubular renin levels in null mutant mice. International journal of physiology, pathophysiology and pharmacology 8 23071870
2025 Salicylic Acid Engages Central Metabolic Regulators SnRK1 and TOR to Govern Immunity by Differential Phosphorylation of NPR1. bioRxiv : the preprint server for biology 7 40667109
2023 Role of NPR1 in Systemic Acquired Stomatal Immunity. Plants (Basel, Switzerland) 7 37299116
2017 Suppression of Npr1, not Npr2 gene function induces hypertrophic growth in H9c2 cells in vitro. Biochemical and biophysical research communications 7 28743500
2015 Brain Natriuretic Peptide Stimulates Lipid Metabolism through Its Receptor NPR1 and the Glycerolipid Metabolism Pathway in Chicken Adipocytes. Biochemistry 7 26463554
1994 Expression of mRNA for atrial natriuretic peptide receptor guanylate cyclase (ANPRA) in human retina. Cellular and molecular neurobiology 7 7954658
2024 Epigenetic mechanisms differentially regulate blood pressure and renal dysfunction in male and female Npr1 haplotype mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6 39109516
2023 Genome-Wide Identification of the NPR1-like Gene Family in Solanum tuberosum and Functional Characterization of StNPR1 in Resistance to Ralstonia solanacearum. Genes 6 37372350

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