Affinage

NCF1

Neutrophil cytosol factor 1 · UniProt P14598

Length
390 aa
Mass
44.7 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NCF1/p47phox is the cytosolic organizer subunit of the phagocyte NADPH oxidase, providing the regulated assembly step that gates superoxide generation by the membrane flavocytochrome b558/NOX complex (PMID:8439286, PMID:11156938). In resting cells p47phox is autoinhibited; cell activation triggers PKC-, ERK1/2-, and p38 MAPK-mediated phosphorylation of a cluster of C-terminal serines, with distinct kinases targeting distinct sites — PKC isoforms (including PKCζ at Ser303/304/315 and PKCδ) act on the PKC consensus serines while MAPKs act exclusively on the proline-directed Ser345/Ser348 (PMID:8089108, PMID:8626435, PMID:11145703, PMID:15494525). This phosphorylation induces a conformational change in the C-terminus that exposes binding surfaces required for assembly (PMID:9200696), and only PKC-phosphorylated p47phox supports oxidase activation in cell-free reconstitution, with Ser379 essential for activity (PMID:9110996). Once de-repressed, p47phox docks at the membrane through its PX domain, which binds PtdIns(3,4)P2 (PMID:11433300), and its tandem SH3 domains, which engage the proline-rich region of p22phox, nucleating complex assembly with p67phox and p40phox (PMID:7744754, PMID:15657040, PMID:15181005). Phosphorylation at sites such as Ser345 underlies cytokine priming (GM-CSF via ERK1/2, TNF-α via p38) of the oxidase (PMID:16778989), and upstream PI3K signaling and c-Src feed into p47phox phosphorylation and recruitment in non-phagocytic cells (PMID:12663375, PMID:8939574, PMID:18070887). Beyond the canonical oxidase, p47phox scaffolds PKC isoforms via its C-terminus (PMID:10585874), associates with the actin cytoskeleton through cortactin (PMID:15618548), directly binds RelA through its SH3 domains to facilitate NF-κB transactivation (PMID:12618429), and binds PCNA and Nrf2 to tune oxidative-stress responses (PMID:31492810, PMID:28939422). Disease-relevant variants illustrate its physiology: a PX-domain Arg-to-Gln mutation abolishing phosphoinositide binding underlies chronic granulomatous disease (PMID:11433300), and the R90H variant impairing endosomal phospholipid binding promotes TLR-driven lupus pathogenesis (PMID:35788118). p47phox-dependent ROS additionally regulate immune and tissue homeostasis, from Treg-mediated suppression of effector T cells (PMID:21253614) to platelet activation (PMID:32422541) and roles in fibrosis and MASH progression (PMID:31442911, PMID:38851189).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1993 High

    Established that p47phox membrane translocation, not merely its phosphorylation, is the obligate continuous step for oxidase activation, separating two regulatory events that had been conflated.

    Evidence Subcellular fractionation and immunoblotting in normal and Ca2+-depleted neutrophils with staurosporine

    PMID:8439286

    Open questions at the time
    • Did not define the membrane docking determinants
    • Mechanism coupling phosphorylation to translocation unresolved
  2. 1994 High

    Mapped the C-terminal multi-site serine phosphorylation of activated p47phox and assigned sites to PKC versus MAPK consensus motifs, defining the substrate landscape for oxidase regulation.

    Evidence 32Pi labeling, CNBr fragmentation, and phosphopeptide mapping of p47phox from PMA-stimulated neutrophils

    PMID:8089108

    Open questions at the time
    • Which kinases hit which sites in vivo not established
    • Functional consequence of individual sites untested here
  3. 1996 High

    Resolved that PKC, PKA, and MAPK phosphorylate distinct serine subsets, with MAPK restricted to the proline-directed Ser345/348, establishing p47phox as an integration node for multiple kinase cascades.

    Evidence 2D tryptic phosphopeptide mapping of Ser→Ala mutants in B lymphoblasts and in vitro kinase assays; comparative in vitro assays with p38, ERK, JNK

    PMID:8626435 PMID:8900416

    Open questions at the time
    • Did not test which sites drive activation versus priming
    • In-cell stoichiometry not quantified
  4. 1997 High

    Demonstrated that phosphorylation acts mechanistically by inducing a C-terminal conformational change and that only PKC-phosphorylated p47phox (with Ser379 intact) supports activation, providing the causal link between phosphorylation and assembly.

    Evidence N-ethylmaleimide reactivity assay and two-stage cell-free oxidase reconstitution with kinase-specific phosphorylated p47phox and S379A mutant

    PMID:9110996 PMID:9200696

    Open questions at the time
    • Atomic structure of the conformational change not resolved
    • Why PKA/MAPK phosphorylation is insufficient alone unexplained
  5. 1995 High

    Identified the SH3-mediated and proline-rich interactions linking p47phox to p67phox and p40phox, beginning the structural map of complex assembly.

    Evidence Far-Western overlay, deletion mutagenesis, and solution binding with cell-free oxidase assay

    PMID:7744754

    Open questions at the time
    • These interactions found dispensable in cell-free assay, leaving their in-cell role open
    • Did not define p22phox docking
  6. 2001 High

    Defined the PX domain as a PtdIns(3,4)P2-binding membrane-targeting module and tied a CGD patient mutation to loss of this binding, explaining how p47phox is recruited to membranes.

    Evidence Lipid-binding assays with PX-domain site-directed and disease-linked mutagenesis

    PMID:11433300

    Open questions at the time
    • Did not address SH3-mediated p22phox docking
    • In vivo lipid specificity in different cell types not tested
  7. 2001 High

    Placed PKCζ and membrane-targeted PI3K upstream of p47phox phosphorylation and translocation, extending the activating kinase network beyond conventional PKC.

    Evidence In vitro kinase assays with recombinant PKCζ, antisense/peptide inhibition in HL-60 cells; membrane-targeted PI3K transfection with wortmannin

    PMID:11145703 PMID:8939574

    Open questions at the time
    • PKCζ vs conventional PKC site selectivity in vivo unresolved
    • PI3K-to-kinase connection indirect
  8. 2004 Medium

    Showed p47phox also activates Nox3 and binds the p22phox proline-rich region via tandem SH3 domains, and that PKCδ drives its phosphorylation/translocation in monocytes, broadening its NOX-organizing role.

    Evidence Cell-based oxidase assays with autoinhibitory deletion mutants; PKCδ antisense, rottlerin, and in vitro kinase assays in monocytes

    PMID:15181005 PMID:15494525

    Open questions at the time
    • NOX-isoform selectivity determinants not mapped
    • Single-lab cell-based data
  9. 2005 High

    Provided atomic detail of p40phox SH3 binding to canonical and non-canonical motifs of the p47phox C-terminus and showed Ser379 phosphorylation destabilizes these interactions, linking phosphorylation to release of intramolecular/intermolecular contacts.

    Evidence 1.46 Å crystal structure of SH3p40–p47phox peptide complex with tryptophan-fluorescence binding measurements

    PMID:15657040

    Open questions at the time
    • Full-length autoinhibited structure not solved
    • Dynamics of the phosphorylation switch not captured
  10. 2006 High

    Established Ser345 as the molecular basis of cytokine priming, with GM-CSF/ERK1/2 and TNF-α/p38 converging on this single residue, explaining how inflammatory signals amplify oxidase output.

    Evidence Tandem MS, MAPK inhibitors, S345A mutagenesis in HL-60, and TAT-peptide inhibition

    PMID:16778989

    Open questions at the time
    • How Ser345 phosphorylation primes without full activation not detailed
    • Proline isomerase involvement not addressed
  11. 2000 High

    Demonstrated genetic requirement for p47phox in oxidase function via knockout and cDNA rescue, formally establishing it as essential and non-redundant for superoxide production.

    Evidence p47phox-/- microglia with retroviral human p47phox cDNA complementation and superoxide assays

    PMID:11156938

    Open questions at the time
    • Did not address tissue-specific roles
    • ERK pathway contribution to fMLP response left to other work
  12. 2003 Medium

    Revealed moonlighting roles of p47phox beyond superoxide production: scaffolding cortactin/actin and directly binding RelA to facilitate NF-κB transactivation, connecting the oxidase organizer to cytoskeleton and transcription.

    Evidence Reciprocal co-IP and imaging in VSMCs; yeast two-hybrid, co-IP, in vitro binding, and reporter assays for RelA; c-Src KO/inhibitor studies

    PMID:12618429 PMID:12663375 PMID:15618548

    Open questions at the time
    • Whether scaffolding functions require oxidase activity unclear
    • RelA interaction effects on specific target genes incompletely mapped
  13. 2012 Medium

    Identified an SH3-region segment (Thr233/Tyr231/Val232) and an M153T hinge polymorphism as determinants of membrane translocation and ROS output, refining the structural map of activation control.

    Evidence Systematic mutagenesis in COS(PHOX) cells with ROS and translocation readouts; backcross genetics linking M153T to arthritis resistance

    PMID:21275845 PMID:23271700

    Open questions at the time
    • Mechanism by which M153T alters membrane-stage activity unresolved
    • Single reconstituted cell system
  14. 2017 Medium

    Extended p47phox into redox-homeostasis and stress signaling by showing it binds Nrf2 to block Keap1-mediated ubiquitination and scaffolds PKCδ in neurotoxicity, positioning it as a regulator of antioxidant transcription and PKC localization.

    Evidence Co-IP, ubiquitination assays, and p47phox genetic ablation for Nrf2; co-IP and PKCδ/p47phox double-KO epistasis in methamphetamine-treated brain

    PMID:28939422 PMID:29269308

    Open questions at the time
    • Direct Nrf2 binding interface not defined
    • Single-lab studies
  15. 2019 Medium

    Discovered direct PCNA binding to the p47phox PX domain and transcriptional control of NCF1 by SRF/KAT8, adding cytosolic-cofactor and epigenetic layers to oxidase regulation.

    Evidence SPR and crystallography with PCNA inhibitor in colitis model; conditional SRF-KO mice with ChIP and SRF-KAT8 co-IP

    PMID:31442911 PMID:31492810

    Open questions at the time
    • How PCNA binding integrates with phosphorylation switch unclear
    • SRF/KAT8 mechanism shown in single tissue context
  16. 2022 Medium

    Linked NCF1 sequence variants to autoimmune and metabolic disease mechanisms: R90H impairs endosomal phospholipid binding to promote TLR-driven lupus, while NCF1-derived ROS otherwise restrain pDC accumulation and IFN-α signaling.

    Evidence Human variant knockin and pDC-conditional KO mice with phospholipid binding, endosomal pH, and TLR/STING/IFN-α readouts

    PMID:35788118 PMID:36853827

    Open questions at the time
    • Cell-type-specific contributions of endosomal vs plasma-membrane ROS not fully separated
    • Single-lab disease models
  17. 2024 Medium

    Defined a pathogenic axis in which macrophage NCF1 oxidizes phospholipids to drive TLR4/hepcidin-dependent iron-mediated Kupffer cell ferroptosis in MASH, illustrating tissue-level consequences of NCF1-dependent ROS.

    Evidence Macrophage-specific NCF1-KO mice with oxidized phospholipid, TLR4, hepcidin, and ferroptosis assays; platelet p47phox-/- studies of NOX1/NOX2 interaction

    PMID:32422541 PMID:38851189

    Open questions at the time
    • Whether oxidized-phospholipid signaling is direct or via secondary mediators unclear
    • Single-lab models

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multi-site phosphorylation code, PX/SH3 lipid and protein docking, and cytosolic cofactors (PCNA, PKC isoforms) are integrated into a unified quantitative activation switch in full-length p47phox remains unresolved.
  • No full-length structure of the autoinhibited or assembled complex
  • Site-by-site contribution to activation vs priming not quantitatively reconciled
  • NOX-isoform-selective regulation determinants undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0008289 lipid binding 3 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005768 endosome 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
CTTNCYBANCF2NCF4NFE2L2PCNAPRKCDRELA
Complex memberships
NADPH oxidase (NOX2) complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 The PX domain of p47phox binds specifically to phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2); an Arg-to-Gln mutation in the PX domain found in chronic granulomatous disease patients eliminates this phosphoinositide binding. Lipid-binding assays, site-directed mutagenesis of PX domain Nature cell biology High 11433300
1994 During neutrophil activation, p47phox is phosphorylated on multiple C-terminal serine residues (Ser-303, Ser-304, Ser-320, Ser-328, Ser-345, Ser-348, and at least one of Ser-359/370/379); Ser-303, Ser-304, Ser-320, and Ser-328 are in PKC consensus sequences, while Ser-345 and Ser-348 are in MAPK (-PXSP-) consensus sequences. 32Pi labeling of immunopurified p47phox from PMA-stimulated neutrophils, CNBr fragmentation, phosphopeptide mapping The Journal of biological chemistry High 8089108
1996 Both p38 MAPK and ERK1/2 phosphorylate p47phox at the same proline-directed site(s) in vitro; JNK does not phosphorylate p47phox. In vitro kinase assays with purified p38, ERK, and JNK using recombinant p47phox as substrate Archives of biochemistry and biophysics High 8900416
1996 Using 2D tryptic phosphopeptide mapping with p47phox Ser→Ala mutants expressed in B lymphoblasts: PKC phosphorylates peptides containing Ser303/304, Ser315, Ser320, Ser328, and Ser359/370; PKA phosphorylates Ser320 and Ser328/359/370; MAPK phosphorylates only Ser345/348. These three kinases thus phosphorylate distinct subsets of serines. Two-dimensional tryptic phosphopeptide mapping, site-directed mutagenesis (Ser→Ala), in vitro kinase assays with PKC, PKA, and MAPK The Journal of biological chemistry High 8626435
2006 GM-CSF and TNF-alpha prime NADPH oxidase activity by inducing phosphorylation of p47phox specifically at Ser345 via convergent MAPK pathways: ERK1/2 mediates GM-CSF-induced Ser345 phosphorylation, while p38 MAPK mediates TNF-alpha-induced Ser345 phosphorylation. A S345A mutant p47phox fails to support priming. Tandem mass spectrometry peptide sequencing, MAPK pathway inhibitors, S345A mutagenesis in HL-60 cells, cell-permeable TAT-peptide inhibition The Journal of clinical investigation High 16778989
2000 The ERK1/2 pathway participates in fMLP-induced p47phox phosphorylation in intact human neutrophils; ERK1/2 and PKC act additively on p47phox phosphorylation in fMLP-stimulated cells, identifying p47phox as a convergence point for these kinase cascades. ERK1/2 inhibitors (PD98059, U0126), PKC inhibitor (GF109203X), 2D phosphopeptide mapping in primary neutrophils Journal of immunology High 11046057
2001 PKC-zeta phosphorylates p47phox at Ser303/304 and Ser315 in vitro; PKC-zeta inhibition blocks fMLP-induced p47phox phosphorylation and membrane translocation as well as superoxide production in human neutrophils. In vitro kinase assay with recombinant PKC-zeta and p47phox, site-directed mutagenesis, cell-permeable peptide antagonist, antisense oligonucleotides in HL-60 cells Journal of immunology High 11145703
1999 p47phox directly interacts with PKC-beta(I), PKC-beta(II), and PKC-delta via its C-terminus; co-immunoprecipitation confirmed this interaction in intact cells; p47phox acts as a regulator of PKC localization and substrate phosphorylation in neutrophils. p47phox affinity chromatography to extract kinase, co-immunoprecipitation, subcellular fractionation in p47phox-deficient cells, in vitro reconstitution with rat brain cytosol The Biochemical journal High 10585874
2004 PKC-delta is required for p47phox phosphorylation and membrane translocation in activated human monocytes; p47phox serves as a direct substrate for PKC-delta in vitro. Pharmacological inhibitors (rottlerin), PKC-delta antisense oligonucleotides, in vitro kinase assay with recombinant p47phox-GST fusion protein Journal of immunology High 15494525
1997 PKC phosphorylation of p47phox induces a conformational change in the C-terminal region (detected by decreased reactivity of Cys378 to N-ethylmaleimide), revealing a binding site for interaction with cytochrome b558 during oxidase assembly. Chemical modification assay (N-ethylmaleimide reactivity) on PKC-phosphorylated vs. unphosphorylated p47phox, cell-free oxidase activation system Biochemistry High 9200696
1997 Kinase-dependent phosphorylation of p47phox is required for NADPH oxidase activation in a cell-free system; PKC-phosphorylated p47phox, but not PKA- or MAPK-phosphorylated p47phox, supports oxidase activation; the S379A mutant is inactive in both whole cells and in this cell-free system. Two-stage cell-free oxidase activation assay, kinase-phosphorylated p47phox preparations, S379A mutant analysis The Journal of biological chemistry High 9110996
1993 Translocation of p47phox (and p67phox) from cytosol to plasma membrane is an essential and continuous requirement for NADPH oxidase activation; phosphorylation of p47phox can be dissociated from translocation (staurosporine markedly inhibits phosphorylation but not translocation). Subcellular fractionation, immunoblotting of p47phox and p67phox in normal and Ca2+-depleted neutrophils with multiple agonists, staurosporine inhibition The Biochemical journal High 8439286
1995 The C-terminal proline-rich region of p47phox interacts with the second SH3 domain of p67phox; p47phox also interacts with p40phox; these interactions are not required for oxidase activity in the cell-free assay. Protein overlay (far Western), deletion mutagenesis of p47phox and p67phox, solution binding studies, cell-free oxidase assay The Journal of biological chemistry High 7744754
2005 Crystal structure of the SH3 domain of p40phox (SH3p40) alone and in complex with a 12-residue proline-rich region of p47phox revealed that SH3p40 interacts with both a canonical polyproline motif and a non-canonical motif of the p47phox C-terminus. Phosphorylation of Ser-379 (but not Ser-359/370) destabilizes binding to both SH3p40 and C-SH3p67. X-ray crystallography (1.46 Å resolution), intrinsic tryptophan fluorescence binding measurements, phosphorylation-state analysis The Journal of biological chemistry High 15657040
2012 The region of p47phox spanning residues 228-235 (specifically Thr233, and to a lesser degree Tyr231 and Val232) in the SH3 region is vital for NOX2 complex activation and for membrane translocation of p47phox upon stimulation. Site-directed mutagenesis of p47phox (deletion and single amino-acid substitutions), COS(PHOX) cell transfection, ROS assays, membrane translocation studies Journal of leukocyte biology High 23271700
2003 p47phox associates with the actin-binding protein cortactin and co-localizes with F-actin in Ang II-stimulated human VSMCs; disruption of the actin cytoskeleton prevents p47phox:actin interaction and attenuates ROS generation and p38MAPK/Akt signaling. Co-immunoprecipitation (p47phox with actin and cortactin), immunofluorescence confocal microscopy, cytochalasin disruption with functional readouts Arteriosclerosis, thrombosis, and vascular biology High 15618548
2003 c-Src regulates Ang II-mediated NADPH oxidase activity by stimulating p47phox serine phosphorylation and translocation from cytosol to membrane; c-Src knockout cells show decreased p47phox phosphorylation and blunted Ang II-induced oxidase activation. Co-immunoprecipitation with anti-phosphoserine antibody, immunofluorescence, c-Src-/- mouse cells, c-Src inhibitor PP2 Arteriosclerosis, thrombosis, and vascular biology Medium 12663375
2004 p47phox interacts with the tandem SH3 domains to bind the proline-rich region of p22phox, enabling NOX2 complex assembly; p47phox also activates Nox3 (in addition to gp91phox/NOX2), and deletion of the autoinhibitory region of p47phox renders it constitutively active toward both gp91phox and Nox3. Cell-based oxidase activation assays, autoinhibitory region deletion mutants, PMA stimulation experiments The Journal of biological chemistry Medium 15181005
2001 Membrane-targeted PI3-kinase induces wortmannin-sensitive continuous phosphorylation of p47phox in monoblastic cells, placing PI3K upstream of p47phox phosphorylation. Transfection of membrane-targeted PI3K construct in GM-1 cells, wortmannin inhibition, immunoblotting for p47phox phosphorylation Current biology Medium 8939574
2007 PI3K/p110alpha (but not p110beta) mediates PDGF-AA-dependent membrane recruitment of p47phox and Rac-1, leading to NOX activation and ROS production; p47phox-null cells fail to generate PDGF-dependent ROS; ROS are required for PDGF-dependent chemotaxis but not proliferation. p47phox-/- cells, dominant-negative Rac-1, mutant alphaPDGFR lacking specific signaling sites, PI3K isoform-specific inhibition, subcellular fractionation The Journal of biological chemistry High 18070887
2019 Cytosolic PCNA directly interacts with the PX domain of p47phox via its interdomain-connecting loop (demonstrated by surface plasmon resonance and crystallography), and this association regulates NADPH oxidase ROS production; PCNA inhibition decreases NADPH oxidase activation. Surface plasmon resonance, X-ray crystallography, competing peptides, PCNA inhibitor T2AA in vitro and in vivo (TNBS colitis model) The Journal of experimental medicine High 31492810
2003 p47phox directly interacts with RelA (NF-kappaB subunit) via its tandem SH3 domains binding to a proline-rich mid-region of RelA; this interaction facilitates IL-1beta-induced RelA phosphorylation and transactivation without affecting IkappaB degradation or RelA nuclear translocation. Yeast two-hybrid, co-immunoprecipitation, in vitro binding, co-localization by immunofluorescence, RelA-PR peptide competition, luciferase reporter assays The Journal of biological chemistry High 12618429
2017 p47phox physically binds to Nrf2 (but not p65phox or p40phox), suppresses Nrf2 ubiquitination by Keap1 (while p47phox itself becomes ubiquitinated by Keap1), and promotes Nrf2 nuclear translocation and target gene expression. Co-immunoprecipitation, ubiquitination assays, p47phox genetic ablation, selective p47phox overexpression in mouse lungs Free radical biology & medicine Medium 28939422
2011 Ncf1/p47phox expression in Tregs is required for NADPH oxidase-derived ROS-mediated direct suppression of CD4+ effector T cells; Ncf1-deficient Tregs suppress Ncf1-deficient Teffs very poorly; NADPH oxidase inhibitors and antioxidants block WT Treg-mediated suppression. Treg/Teff co-culture suppression assays with Ncf1-/- mice, NADPH oxidase inhibitors (DPI, VAS-2870), antioxidants (NAC, 2-ME), flow cytometry of CFSE dilution PloS one Medium 21253614
2001 Fusion proteins linking truncated p47phox(1-286) N-terminally to truncated p67phox(1-210) reconstitute NADPH oxidase with 8-fold higher efficiency and greater stability than individual components, and show nearly full activation without anionic amphiphile, supporting a model of direct p47phox-p67phox-cytochrome b558 topology. Cell-free NADPH oxidase reconstitution with fusion protein constructs, superoxide production assays, Km determination for NADPH The Journal of biological chemistry Medium 11333262
2004 HBP1 transcriptional repressor directly binds six tandem HBP1 DNA-binding elements at positions -1243 to -1318 bp of the p47phox gene promoter, represses p47phox endogenous gene expression in a sequence-specific manner, and thereby reduces intracellular superoxide production to inhibit G1 cell cycle progression. Promoter-reporter assays, HBP1 dominant-negative mutant, electrophoretic mobility shift, chromatin immunoprecipitation (implied), intracellular superoxide measurement Molecular and cellular biology Medium 15024088
2019 SRF recruits the histone acetyltransferase KAT8 to epigenetically activate NCF1/NCF2 transcription during hepatic stellate cell activation, thereby increasing ROS production and promoting liver fibrosis; SRF conditional knockout reduces NCF1/NCF2 expression and ROS in HSCs. HSC-conditional SRF knockout mice, chromatin immunoprecipitation, co-immunoprecipitation of SRF with KAT8, siRNA knockdown, ROS measurement Redox biology Medium 31442911
2009 Aryl hydrocarbon receptor (AhR) directly binds a xenobiotic-responsive element (XRE) in the NCF1 promoter upon benzo(a)pyrene stimulation, inducing NCF1/p47phox transcription, protein translocation, and priming of macrophage superoxide production. AhR siRNA knockdown, chemical AhR inhibition, NCF1 promoter-luciferase assay, EMSA, chromatin immunoprecipitation, p47phox translocation and ROS assays Free radical biology & medicine Medium 19559082
2000 p47phox is genetically required for superoxide production by microglial cells: p47phox-deficient microglia fail to produce superoxide, and retroviral transduction of human p47phox cDNA restores superoxide generation with normal kinetics. p47phox-/- knockout mice, primary microglial cultures, retroviral transduction with human p47phox cDNA, superoxide assays FASEB journal High 11156938
2006 The PX domain of p47phox translocates to the plasma membrane in activated human neutrophils but does not associate with the membrane of mature phagosomes (unlike RhoB). Nucleofection of primary human neutrophils with GFP-tagged p47phox PX domain constructs, live-cell fluorescence microscopy BMC immunology Medium 17150107
2011 A single nucleotide polymorphism at position 153 of Ncf1 (M153T substitution, located in the hinge region between PX and SH3 domains) regulates ROS production and arthritis resistance; it does not affect p47phox/p67phox cytosolic complex assembly or membrane localization but likely affects downstream NOX2 complex activity at the membrane. COS(PHOX) cell transfection with mutated Ncf1 constructs, backcross genetics to DA strain, granulocyte ROS assays, p47phox/p67phox co-assembly and membrane localization assays Antioxidants & redox signaling Medium 21275845
2022 NCF1 p.R90H variant reduces p47phox affinity for phospholipids, impairing its endosomal localization; the resulting defect in NOX2-derived ROS at endosomes leads to acidified endosomal pH and facilitated TLR-dependent signaling in plasmacytoid dendritic cells, promoting lupus pathogenesis. Human NCF1 p.R90H knockin mice, pDC-conditional Cre knockout, phospholipid binding assays, endosomal pH measurement, TLR signaling assays, IFN-α measurement The Journal of clinical investigation Medium 35788118
2023 NCF1-dependent ROS production in plasmacytoid dendritic cells (pDCs) suppresses lupus by limiting pDC accumulation through inhibition of the AKT/mTOR pathway and CCR2-mediated tissue migration, and by dampening the STING/IFN-α/JAK1/STAT1 cascade. Cell-specific Cre-deleter knockout mice, NCF1-339 human variant knockin mice, transgenic reconstitution, AKT/mTOR pathway analysis, IFN-α and STING pathway measurements JCI insight Medium 36853827
2024 Macrophage NCF1 promotes Kupffer cell ferroptosis and MASH progression by oxidizing phospholipids; the oxidized phospholipids trigger TLR4-dependent hepcidin production in hepatocytes, leading to increased iron deposition and subsequent ferroptosis in Kupffer cells. Macrophage-specific NCF1 knockout mice, oxidized phospholipid measurements, TLR4 signaling assays, hepcidin measurement, iron deposition and ferroptosis assays Cell metabolism Medium 38851189
2020 p47phox translocates to the membrane in platelets after CRP or thrombin stimulation and interacts with both NOX1 and NOX2; p47phox deficiency impairs platelet ROS generation, aggregation, spreading, and clot retraction, and reduces phosphorylation of Syk and PLCγ2. p47phox-/- mice, platelet function assays, co-immunoprecipitation of p47phox with NOX1 and NOX2, phosphorylation analysis, in vivo thrombosis models Redox biology Medium 32422541
2020 Fragment-based drug discovery using fluorescence polarization and surface plasmon resonance identified small molecules binding to two distinct sites in the tandem SH3 domain of p47phox (p47phoxSH3A-B); a dimeric optimized compound inhibits the p47phoxSH3A-B–p22phox protein-protein interaction with Ki of 20 μM. Fragment screening by FP and thermal shift assay, SPR validation, structural studies, p22phox competition assay Journal of medicinal chemistry Medium 31922756
2017 PKCδ co-immunoprecipitates with p47phox in methamphetamine-treated mouse brain; PKCδ knockout or p47phox knockout each abolish methamphetamine-induced increases in NADPH oxidase activity and ROS, and rottlerin (PKCδ inhibitor) provides no additive protection over p47phox knockout, placing PKCδ upstream of p47phox in this pathway. Co-immunoprecipitation, PKCδ and p47phox knockout mice, PKCδ antisense oligonucleotides, NADPH oxidase activity and ROS assays Free radical biology & medicine Medium 29269308

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The PX domains of p47phox and p40phox bind to lipid products of PI(3)K. Nature cell biology 525 11433300
2009 p47phox, the phagocyte NADPH oxidase/NOX2 organizer: structure, phosphorylation and implication in diseases. Experimental & molecular medicine 349 19372727
2003 Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases. The Journal of biological chemistry 316 12716910
2002 Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. Nature genetics 296 12461526
2004 Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proceedings of the National Academy of Sciences of the United States of America 291 15310853
1994 The phosphorylation of the respiratory burst oxidase component p47phox during neutrophil activation. Phosphorylation of sites recognized by protein kinase C and by proline-directed kinases. The Journal of biological chemistry 277 8089108
2008 Priming of the neutrophil NADPH oxidase activation: role of p47phox phosphorylation and NOX2 mobilization to the plasma membrane. Seminars in immunopathology 274 18536919
2006 A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites. The Journal of clinical investigation 255 16778989
2003 c-Src induces phosphorylation and translocation of p47phox: role in superoxide generation by angiotensin II in human vascular smooth muscle cells. Arteriosclerosis, thrombosis, and vascular biology 228 12663375
1996 Activation of p38 in stimulated human neutrophils: phosphorylation of the oxidase component p47phox by p38 and ERK but not by JNK. Archives of biochemistry and biophysics 206 8900416
1996 Phosphorylation of the respiratory burst oxidase subunit p47phox as determined by two-dimensional phosphopeptide mapping. Phosphorylation by protein kinase C, protein kinase A, and a mitogen-activated protein kinase. The Journal of biological chemistry 198 8626435
2001 Protein kinase C zeta phosphorylates a subset of selective sites of the NADPH oxidase component p47phox and participates in formyl peptide-mediated neutrophil respiratory burst. Journal of immunology (Baltimore, Md. : 1950) 187 11145703
2003 Translocation of glomerular p47phox and p67phox by protein kinase C-beta activation is required for oxidative stress in diabetic nephropathy. Diabetes 182 14514646
2006 Deletion of p47phox attenuates angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E-deficient mice. Circulation 176 16864727
2000 The mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 pathway is involved in formyl-methionyl-leucyl-phenylalanine-induced p47phox phosphorylation in human neutrophils. Journal of immunology (Baltimore, Md. : 1950) 161 11046057
2004 Protein kinase C delta is required for p47phox phosphorylation and translocation in activated human monocytes. Journal of immunology (Baltimore, Md. : 1950) 151 15494525
2008 Regulation of the phagocyte NADPH oxidase activity: phosphorylation of gp91phox/NOX2 by protein kinase C enhances its diaphorase activity and binding to Rac2, p67phox, and p47phox. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 139 19028840
2004 p47phox associates with the cytoskeleton through cortactin in human vascular smooth muscle cells: role in NAD(P)H oxidase regulation by angiotensin II. Arteriosclerosis, thrombosis, and vascular biology 134 15618548
2004 Nox3 regulation by NOXO1, p47phox, and p67phox. The Journal of biological chemistry 129 15181005
2007 ASK1-p38 MAPK-p47phox activation is essential for inflammatory responses during tuberculosis via TLR2-ROS signalling. Cellular microbiology 120 18028450
1996 Constitutive activation of protein kinase B and phosphorylation of p47phox by a membrane-targeted phosphoinositide 3-kinase. Current biology : CB 117 8939574
2017 A single nucleotide polymorphism in the NCF1 gene leading to reduced oxidative burst is associated with systemic lupus erythematosus. Annals of the rheumatic diseases 115 28606963
2012 The p47phox- and NADPH oxidase organiser 1 (NOXO1)-dependent activation of NADPH oxidase 1 (NOX1) mediates endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction in a streptozotocin-induced murine model of diabetes. Diabetologia 114 22549734
2008 Potent anti-inflammatory and neuroprotective effects of TGF-beta1 are mediated through the inhibition of ERK and p47phox-Ser345 phosphorylation and translocation in microglia. Journal of immunology (Baltimore, Md. : 1950) 112 18566433
1993 Relationship between phosphorylation and translocation to the plasma membrane of p47phox and p67phox and activation of the NADPH oxidase in normal and Ca(2+)-depleted human neutrophils. The Biochemical journal 111 8439286
2005 Angiotensin II induces MMP-2 in a p47phox-dependent manner. Biochemical and biophysical research communications 104 15670768
1997 Enhanced host defense after gene transfer in the murine p47phox-deficient model of chronic granulomatous disease. Blood 100 9116268
2016 Inhibition of autophagosome-lysosome fusion by ginsenoside Ro via the ESR2-NCF1-ROS pathway sensitizes esophageal cancer cells to 5-fluorouracil-induced cell death via the CHEK1-mediated DNA damage checkpoint. Autophagy 92 27310928
2013 Zinc oxide nanoparticles induce necrosis and apoptosis in macrophages in a p47phox- and Nrf2-independent manner. PloS one 91 23755271
2011 Ncf1 (p47phox) is essential for direct regulatory T cell mediated suppression of CD4+ effector T cells. PloS one 90 21253614
2004 Opposing roles of p47phox in basal versus angiotensin II-stimulated alterations in vascular O2- production, vascular tone, and mitogen-activated protein kinase activation. Circulation 84 14993144
2006 Homocysteine stimulates phosphorylation of NADPH oxidase p47phox and p67phox subunits in monocytes via protein kinase Cbeta activation. The Biochemical journal 81 16626305
2006 Hemizygosity at the NCF1 gene in patients with Williams-Beuren syndrome decreases their risk of hypertension. American journal of human genetics 78 16532385
2003 Deficiency of NADPH oxidase components p47phox and gp91phox caused granulomatous synovitis and increased connective tissue destruction in experimental arthritis models. The American journal of pathology 78 14507659
2007 Phosphatidylinositol 3-kinase-dependent membrane recruitment of Rac-1 and p47phox is critical for alpha-platelet-derived growth factor receptor-induced production of reactive oxygen species. The Journal of biological chemistry 76 18070887
1997 Kinase-dependent activation of the leukocyte NADPH oxidase in a cell-free system. Phosphorylation of membranes and p47(PHOX) during oxidase activation. The Journal of biological chemistry 74 9110996
2011 Copy number variation of the gene NCF1 is associated with rheumatoid arthritis. Antioxidants & redox signaling 71 21728841
2006 Ascorbate inhibits NADPH oxidase subunit p47phox expression in microvascular endothelial cells. Free radical biology & medicine 69 17157199
1999 Direct interaction between p47phox and protein kinase C: evidence for targeting of protein kinase C by p47phox in neutrophils. The Biochemical journal 69 10585874
1995 Interactions between the cytosolic components p47phox and p67phox of the human neutrophil NADPH oxidase that are not required for activation in the cell-free system. The Journal of biological chemistry 67 7744754
2012 Zymosan induces NADPH oxidase activation in human neutrophils by inducing the phosphorylation of p47phox and the activation of Rac2: involvement of protein tyrosine kinases, PI3Kinase, PKC, ERK1/2 and p38MAPkinase. Biochemical pharmacology 66 23085266
2003 L-arginine reverses p47phox and gp91phox expression induced by high salt in Dahl rats. Hypertension (Dallas, Tex. : 1979) 66 14504257
2019 Serum response factor (SRF) promotes ROS generation and hepatic stellate cell activation by epigenetically stimulating NCF1/2 transcription. Redox biology 64 31442911
2007 Reactive oxygen species and p47phox activation are essential for the Mycobacterium tuberculosis-induced pro-inflammatory response in murine microglia. Journal of neuroinflammation 64 18036262
2005 Effects of p47phox C terminus phosphorylations on binding interactions with p40phox and p67phox. Structural and functional comparison of p40phox and p67phox SH3 domains. The Journal of biological chemistry 64 15657040
2002 Glutamine plays a role in superoxide production and the expression of p47phox, p22phox and gp91phox in rat neutrophils. Clinical science (London, England : 1979) 64 12241540
2022 A dual Keap1 and p47phox inhibitor Ginsenoside Rb1 ameliorates high glucose/ox-LDL-induced endothelial cell injury and atherosclerosis. Cell death & disease 63 36163178
2004 HBP1 repression of the p47phox gene: cell cycle regulation via the NADPH oxidase. Molecular and cellular biology 63 15024088
1997 Activation of the leukocyte NADPH oxidase subunit p47phox by protein kinase C. A phosphorylation-dependent change in the conformation of the C-terminal end of p47phox. Biochemistry 62 9200696
2015 Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats. Nutrients 60 26133972
2005 Immunohistochemical study of p47Phox and gp91Phox distributions in rat brain. Brain research 60 15804439
2024 Reactive oxygen species regulation by NCF1 governs ferroptosis susceptibility of Kupffer cells to MASH. Cell metabolism 58 38851189
2013 Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1. Hypertension (Dallas, Tex. : 1979) 56 24126171
2008 Heme oxygenase-1 protects against neutrophil-mediated intestinal damage by down-regulation of neutrophil p47phox and p67phox activity and O2- production in a two-hit model of alcohol intoxication and burn injury. Journal of immunology (Baltimore, Md. : 1950) 56 18453614
2012 Phosphorylation of smooth muscle 22α facilitates angiotensin II-induced ROS production via activation of the PKCδ-P47phox axis through release of PKCδ and actin dynamics and is associated with hypertrophy and hyperplasia of vascular smooth muscle cells in vitro and in vivo. Circulation research 55 22798525
2013 Increased reactive oxygen species production and p47phox phosphorylation in neutrophils from myeloproliferative disorders patients with JAK2 (V617F) mutation. Haematologica 54 23975181
2012 Identification of a region in p47phox/NCF1 crucial for phagocytic NADPH oxidase (NOX2) activation. Journal of leukocyte biology 54 23271700
2006 Chronic granulomatous disease caused by mutations other than the common GT deletion in NCF1, the gene encoding the p47phox component of the phagocyte NADPH oxidase. Human mutation 48 16972229
2015 p47(phox) contributes to albuminuria and kidney fibrosis in mice. Kidney international 47 25565313
2000 Genetic requirement of p47phox for superoxide production by murine microglia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 46 11156938
2016 Protective effect of resveratrol against chronic intermittent hypoxia-induced spatial memory deficits, hippocampal oxidative DNA damage and increased p47Phox NADPH oxidase expression in young rats. Behavioural brain research 44 26940604
1992 O2- production by B lymphocytes lacking the respiratory burst oxidase subunit p47phox after transfection with an expression vector containing a p47phox cDNA. Proceedings of the National Academy of Sciences of the United States of America 44 1332032
2019 NCF1-339 polymorphism is associated with altered formation of neutrophil extracellular traps, high serum interferon activity and antiphospholipid syndrome in systemic lupus erythematosus. Annals of the rheumatic diseases 43 31704719
2012 Deletion of p47phox attenuates the progression of diabetic nephropathy and reduces the severity of diabetes in the Akita mouse. Diabetologia 43 22653270
2006 Translocation of proteins homologous to human neutrophil p47phox and p67phox to the cell membrane in activated hemocytes of Galleria mellonella. Developmental and comparative immunology 41 16920193
2017 PKCδ-dependent p47phox activation mediates methamphetamine-induced dopaminergic neurotoxicity. Free radical biology & medicine 40 29269308
2010 Homocysteine enhances cell proliferation in vascular smooth muscle cells: role of p38 MAPK and p47phox. Acta biochimica et biophysica Sinica 40 21068125
2005 Impaired NADPH oxidase activity in Rac2-deficient murine neutrophils does not result from defective translocation of p47phox and p67phox and can be rescued by exogenous arachidonic acid. Journal of leukocyte biology 40 16275890
2016 Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium. American journal of physiology. Lung cellular and molecular physiology 39 27343196
2005 Ncf1 (p47phox) polymorphism determines oxidative burst and the severity of arthritis in rats and mice. Cellular immunology 39 15936744
2002 NADPH oxidase priming and p47phox phosphorylation in neutrophils from synovial fluid of patients with rheumatoid arthritis and spondylarthropathy. Inflammation 39 12546136
2001 Fused p47phox and p67phox truncations efficiently reconstitute NADPH oxidase with higher activity and stability than the individual components. The Journal of biological chemistry 39 11333262
2005 Leukotriene B4 mediates p47phox phosphorylation and membrane translocation in polyunsaturated fatty acid-stimulated neutrophils. Journal of leukocyte biology 37 16006535
2017 The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice. Redox biology 35 29195137
2015 NAD(P)H oxidase subunit p47phox is elevated, and p47phox knockout prevents diaphragm contractile dysfunction in heart failure. American journal of physiology. Lung cellular and molecular physiology 35 26209274
1995 The fatty acid bimodal action on superoxide anion production by human adherent monocytes under phorbol 12-myristate 13-acetate or diacylglycerol activation can be explained by the modulation of protein kinase C and p47phox translocation. The Journal of biological chemistry 35 7797495
2014 P47phox-/- mice are compromised in expansion and activation of CD8+ T cells and susceptible to Trypanosoma cruzi infection. PLoS pathogens 34 25474113
2018 oxLDL-mediated cellular senescence is associated with increased NADPH oxidase p47phox recruitment to caveolae. Bioscience reports 32 29695496
2017 p47Phox/CDK5/DRP1-Mediated Mitochondrial Fission Evokes PV Cell Degeneration in the Rat Dentate Gyrus Following Status Epilepticus. Frontiers in cellular neuroscience 32 28919853
2001 Mutational analysis of patients with p47-phox-deficient chronic granulomatous disease: The significance of recombination events between the p47-phox gene (NCF1) and its highly homologous pseudogenes. Experimental hematology 32 11166463
2023 NCF1-dependent production of ROS protects against lupus by regulating plasmacytoid dendritic cell development and functions. JCI insight 31 36853827
2019 Cytosolic PCNA interacts with p47phox and controls NADPH oxidase NOX2 activation in neutrophils. The Journal of experimental medicine 31 31492810
2022 The NCF1 variant p.R90H aggravates autoimmunity by facilitating the activation of plasmacytoid dendritic cells. The Journal of clinical investigation 30 35788118
2020 Developing Inhibitors of the p47phox-p22phox Protein-Protein Interaction by Fragment-Based Drug Discovery. Journal of medicinal chemistry 30 31922756
2010 Lipopolysaccharide-induced cytokine expression in alveolar epithelial cells: role of PKCζ-mediated p47phox phosphorylation. Chemico-biological interactions 30 20920494
2012 p47(phox) directs murine macrophage cell fate decisions. The American journal of pathology 29 22222227
2011 Positioning of a polymorphic quantitative trait nucleotide in the Ncf1 gene controlling oxidative burst response and arthritis severity in rats. Antioxidants & redox signaling 29 21275845
2002 Genomic organization of the genes Gtf2ird1, Gtf2i, and Ncf1 at the mouse chromosome 5 region syntenic to the human chromosome 7q11.23 Williams syndrome critical region. Genomics 29 11827466
2006 Gene transfer and expression in human neutrophils. The phox homology domain of p47phox translocates to the plasma membrane but not to the membrane of mature phagosomes. BMC immunology 28 17150107
2005 Expression of NOX-I, gp91phox, p47phox and P67phox in the aorta segments above and below coarctation. Biochimica et biophysica acta 28 15814300
2017 Suppressed ubiquitination of Nrf2 by p47phox contributes to Nrf2 activation. Free radical biology & medicine 27 28939422
2014 Deficient production of reactive oxygen species leads to severe chronic DSS-induced colitis in Ncf1/p47phox-mutant mice. PloS one 27 24873968
2013 Different unequal cross-over events between NCF1 and its pseudogenes in autosomal p47(phox)-deficient chronic granulomatous disease. Biochimica et biophysica acta 27 23688784
2009 Aryl hydrocarbon receptor-dependent induction of the NADPH oxidase subunit NCF1/p47 phox expression leading to priming of human macrophage oxidative burst. Free radical biology & medicine 27 19559082
2009 Ncf1-associated reduced oxidative burst promotes IL-33R+ T cell-mediated adjuvant-free arthritis in mice. Journal of immunology (Baltimore, Md. : 1950) 26 19553535
2010 A copy number variation in human NCF1 and its pseudogenes. BMC genetics 25 20178640
2003 p47phox participates in activation of RelA in endothelial cells. The Journal of biological chemistry 25 12618429
2000 Genomic structure of the human p47-phox (NCF1) gene. Blood cells, molecules & diseases 24 10772875
2020 p47phox deficiency impairs platelet function and protects mice against arterial and venous thrombosis. Redox biology 23 32422541
2019 NCF1 (p47phox)-deficient chronic granulomatous disease: comprehensive genetic and flow cytometric analysis. Blood advances 23 30651282

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