Affinage

CYBA

Cytochrome b-245 light chain · UniProt P13498

Length
195 aa
Mass
21.0 kDa
Annotated
2026-06-09
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CYBA encodes p22phox, the small membrane subunit that serves as the obligate stabilizing and assembly partner for the NADPH oxidase (Nox) catalytic flavocytochromes, where it underlies ROS production across phagocytic, vascular, and epithelial tissues (PMID:8527449, PMID:15994299, PMID:18292807). p22phox forms a 1:1 heterodimer with gp91phox (Nox2) in phagocyte cytochrome b558, and this association — together with heme incorporation — is required for maturation and stability of both subunits, including the Golgi-dependent terminal glycosylation of gp91phox (PMID:8527449, PMID:9341176, PMID:7919388). p22phox is essential for the activity of Nox1, Nox2, Nox3, and Nox4 but not Nox5, and uses structurally distinct interfaces for different catalytic partners: an N-terminal dual-tryptophan motif is required for Nox4 while a C-terminal proline-rich region (PRR) is required for Nox1/2/3 (PMID:15994299, PMID:18849343, PMID:27614387). The PRR functions as the docking site for the SH3 domain of the cytosolic organizer p47phox (or NOXO1), an interaction gated by phosphorylation that unmasks the p47phox SH3A domain and thereby triggers oxidase assembly (PMID:10391914, PMID:12056906). p22phox is itself phosphorylated on Thr147 by conventional PKC isoforms, which promotes p47phox recruitment and superoxide production (PMID:10593961, PMID:19948736). The dimer localizes to the endoplasmic reticulum or plasma membrane depending on cell type and partner, directing vectorial ROS/H2O2 generation (PMID:15477006, PMID:29278739, PMID:10938010). p22phox protein stability is controlled by PHD/pVHL-dependent ubiquitination, with hypoxia stabilizing the protein, and its transcription is regulated through an NF-κB site repressed by PPARγ and modulated by promoter and coding polymorphisms that tune oxidase output (PMID:30044141, PMID:26108185, PMID:15210651, PMID:19388116). Genetic loss of p22phox in mice abolishes both phagocyte oxidase function (a chronic granulomatous disease-like phenotype) and a distinct inner-ear Nox cytochrome required for vestibular organogenesis (PMID:18292807).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1994 High

    Establishing that p22phox supplies the docking interface for cytosolic oxidase components answered whether its role was structural assembly versus catalysis, by showing a single PRR mutation blocks assembly while leaving intrinsic electron transfer intact.

    Evidence Patient-derived P156Q neutrophils analyzed in cell-free translocation and oxygen-uptake assays; reconstitution of p22phox-deficient B-cell lines

    PMID:7919388 PMID:7964505

    Open questions at the time
    • Did not define the cytosolic partner domain binding the PRR
    • Structural basis of the PRR-SH3 interface unresolved
  2. 1995 High

    Direct biochemical determination of the gp91phox:p22phox stoichiometry settled the composition of cytochrome b558 as a defined 1:1 heterodimer.

    Evidence Affinity purification of cytochrome b558 with quantitative N-terminal peptide sequencing from human neutrophil membranes

    PMID:8527449

    Open questions at the time
    • Did not address assembly with non-Nox2 catalytic subunits
    • No structural model of the heterodimer
  3. 1997 High

    Linking heme incorporation and heterodimerization to mutual subunit maturation explained why p22phox is required for stable, glycosylated Nox2.

    Evidence Succinyl acetone heme-synthesis inhibition in PLB-985 cells plus heterologous co-expression in COS-7 and 3T3 cells

    PMID:9341176

    Open questions at the time
    • Did not localize the maturation steps along the secretory pathway in detail
    • Heme-binding residues on p22phox not mapped
  4. 2002 High

    Defining phosphorylation-gated unmasking of the p47phox SH3A domain answered how oxidase assembly is switched on, identifying p22phox PRR binding as the activation-controlled step.

    Evidence Peptide competition, phosphomimetic mutagenesis of p47phox, in vitro PKC phosphorylation, and cell-free oxidase reconstitution

    PMID:10391914 PMID:12056906

    Open questions at the time
    • Did not address how organizer identity (p47phox vs NOXO1) selects different Nox isoforms
    • Kinetics of assembly in intact cells not resolved
  5. 2000 High

    Demonstrating p22phox is itself phosphorylated on threonine by PA-activated and conventional PKC, coincident with oxidase activation, added a second regulatory input beyond p47phox.

    Evidence Cell-free and intact-neutrophil 32P-labeling, phosphoamino acid analysis, lipid specificity testing, and PLD inhibition across multiple agonists

    PMID:10593961 PMID:10893420

    Open questions at the time
    • Did not identify the specific phosphoacceptor residue at this stage
    • Functional consequence of p22phox phosphorylation not yet causally tested
  6. 2005 High

    Systematic dissection across the Nox family showed p22phox is a shared subunit for Nox1-4 but dispensable for Nox5, and that PRR requirements depend on organizer identity, broadening its role beyond the phagocyte oxidase.

    Evidence siRNA knockdown and PRR point mutagenesis with co-expression of all five Nox catalytic and regulatory subunits and ROS chemiluminescence

    PMID:15994299

    Open questions at the time
    • Did not map the distinct interfaces for each Nox isoform
    • Mechanism of Nox5 independence not addressed
  7. 2008 High

    Identifying separable N-terminal (Nox4) and C-terminal (Nox1/2/3) p22phox determinants explained how one subunit serves structurally distinct catalytic partners.

    Evidence Truncation and point mutagenesis (including Y121H) in p22phox-deficient cells with ROS assay and Nox4 co-IP; nmf333 Cyba-null mouse phenotyping

    PMID:18292807 PMID:18849343

    Open questions at the time
    • No atomic structure of the differential interfaces
    • Molecular basis of the inner-ear vestibular oxidase composition not fully defined
  8. 2009 High

    Pinpointing Thr147 as the functionally required PKC phosphosite causally connected p22phox phosphorylation to p47phox recruitment and superoxide output.

    Evidence T147A/T147D mutagenesis in CHO cells with in vivo p22phox-p47phox co-IP and in vitro PKC-alpha/delta phosphorylation

    PMID:19948736

    Open questions at the time
    • In vivo kinase responsible during physiological activation not definitively assigned
    • Temporal ordering relative to p47phox phosphorylation unresolved
  9. 2016 High

    Genomic CRISPR knockout with rescue confirmed the strict p22phox dependence of Nox1/Nox4 and the unique independence of Nox5, providing a definitive genetic test.

    Evidence CRISPR/Cas9 CYBA knockout with human/rat p22phox and DUOXA1/A2 rescue and mutagenesis panel

    PMID:27614387

    Open questions at the time
    • Did not resolve why DUOXA cannot substitute mechanistically
    • Structural distinction from DUOX maturation factors not addressed
  10. 2018 High

    Showing PHD/pVHL-dependent ubiquitination controls p22phox stability, with hypoxia stabilizing it, established a post-translational layer linking oxygen sensing to oxidase abundance.

    Evidence Ubiquitination and proteasome assays, PHD/pVHL siRNA, and a Y121H knock-in mouse pulmonary hypertension model

    PMID:30044141

    Open questions at the time
    • E3 ligase and hydroxylated residue not fully defined
    • Generalizability beyond vascular cells not established
  11. 2017 Medium

    Topology and localization studies refined where p22phox-dependent oxidases act, placing the Nox4 complex at the ER producing luminal H2O2 and reporting a NOX5-p22phox association at the mitochondrion.

    Evidence Rapamycin-induced FRB/FKBP dimerization topology assay, co-IP and immunofluorescence (Nox4/ER) plus co-IP in CGD patient cells (NOX5/mitochondria)

    PMID:28830888 PMID:29278739

    Open questions at the time
    • The NOX5-p22phox interaction conflicts with genetic data showing Nox5 is p22phox-independent and awaits independent replication
    • ER luminal H2O2 export route not defined
  12. 2024 Low

    How distinct organizer/cell-type contexts and post-translational controls combine to direct p22phox-dependent ROS to specific subcellular compartments and downstream signaling outcomes remains incompletely defined.

    Open questions at the time
    • No high-resolution structure of any Nox-p22phox heterodimer in the corpus
    • Integration of transcriptional, stability, and phosphorylation regulation in vivo not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
CYBBHSPA1BNCF1NOX1NOX3NOX4NOXO1RUBCN
Complex memberships
cytochrome b558 (NADPH oxidase)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 p22-phox and gp91-phox form a 1:1 stoichiometric heterodimer in phagocyte cytochrome b558, as determined by direct peptide sequencing of purified cytochrome b558 from human neutrophil membranes. Affinity purification of cytochrome b558 followed by direct N-terminal peptide sequencing and quantitative amino acid ratio analysis Biochemistry High 8527449
1997 Heme incorporation into cytochrome b558 is required for maturation and stability of both p22phox and the fully glycosylated gp91phox subunit; heterodimer formation with gp91phox stabilizes p22phox and promotes gp91phox carbohydrate maturation in the Golgi. Succinyl acetone inhibition of heme synthesis in PLB-985 cells; transgenic co-expression of gp91phox and p22phox in COS-7 and 3T3 cells lacking endogenous p22phox; Western blot for glycosylation state The Journal of biological chemistry High 9341176
1994 The Pro156Gln point mutation in the proline-rich region (PRR) of p22phox abolishes translocation of cytosolic p47phox and p67phox to the membrane in stimulated neutrophils, preventing NADPH oxidase activation, while electron flow within isolated cytochrome b558 membrane fractions is preserved under artificial activation conditions. Cell-free translocation assay using patient neutrophil membranes and cytosol; PMA-stimulated neutrophil fractionation; NADPH-dependent oxygen uptake assay with phospholipids The Journal of experimental medicine High 7964505
1994 Expression of p22phox in p22phox-deficient B-cell lines reconstitutes NADPH oxidase activity and is required for processing of the gp91phox precursor from the high-mannose (65 kDa) form to the terminally glycosylated mature form, demonstrating that p22phox–gp91phox association is a prerequisite for Golgi processing of gp91phox carbohydrate. Retroviral transduction of p22phox into patient B-cell lines; Western blot for glycosylation state of gp91phox; NADPH oxidase activity assay Blood High 7919388
1999 Phosphorylation of p47phox on serines in its C-terminal arginine/lysine-rich region disrupts an intramolecular interaction that normally masks the SH3A domain; phosphorylation unmasks SH3A, enabling it to bind the PRR of p22phox and activate NADPH oxidase. Phosphoserine-mimicking mutations (S310D, S328D) in full-length p47phox enable binding to p22phox proline-rich region, whereas wild-type p47phox does not bind. Peptide competition assays with p47phox SH3AB/p22phox C-terminal binding; NADPH oxidase cell-free activity assay; site-directed mutagenesis (S→D substitutions) of full-length p47phox The Journal of biological chemistry High 10391914
1999 p22phox is phosphorylated on a threonine residue by a phosphatidic acid (PA)-activated protein kinase and by conventional (but not novel or atypical) PKC isoforms; phosphorylation of p22phox correlates with NADPH oxidase activation in a cell-free system. Cell-free NADPH oxidase phosphorylation assay; lipid specificity testing (PA vs. other lipids); phosphoamino acid analysis; partial purification of PA-activated kinase; PKC isoform panel The Journal of biological chemistry High 10593961
2000 Multiple neutrophil agonists (PMA, opsonized zymosan, fMLP) induce phosphorylation of p22phox on threonine residue(s) in intact neutrophils; p22phox phosphorylation coincides temporally with NADPH oxidase activation and is PLD-dependent for fMLP/opsonized zymosan but PLD-independent for PMA stimulation. 32P-labeling of intact human neutrophils; phosphoamino acid analysis; ethanol-based PLD inhibition; GF109203X kinase inhibitor; coincidence analysis of p22phox phosphorylation and oxidase activity The Journal of biological chemistry High 10893420
2002 PKC isoforms alpha, beta II, delta, and zeta each phosphorylate p47phox and induce its association with the cytosolic fragment of p22phox, thereby activating NADPH oxidase in a cell-free system. Serine 328 is the most phosphorylated PKC site on p47phox. In vitro PKC phosphorylation assay with recombinant proteins; phosphopeptide mapping; p47phox serine-to-alanine mutants; overlay (p22phox cytosolic fragment binding) assay; cell-free NADPH oxidase reconstitution Biochemistry High 12056906
2005 The proline-rich region (PRR) of p22phox is essential for Nox1, Nox2, and Nox3 (but not Nox4 or Nox5) activity; P156Q mutation disrupting SH3 binding potently inhibits Nox1 and Nox2, and p22phox PRR mutations selectively depend on the organizer subunit identity (p47phox vs. NOXO1). p22phox is required for Nox1, Nox2, Nox3, and Nox4 but not Nox5 activity as shown by siRNA knockdown. siRNA knockdown of endogenous p22phox; coexpression of Nox catalytic and regulatory subunits; point mutagenesis of p22phox PRR (P156Q, P157Q, P160Q); ROS measurement (chemiluminescence) The Journal of biological chemistry High 15994299
2007 p22phox is essential for glycosylation/maturation, plasma membrane targeting, and activity of Nox3 in HEK-293 cells; p22phox co-precipitates with both Nox3 and the organizer NoxO1, indicating it physically associates with Nox3 and the regulatory complex. RNAi knockdown of endogenous p22phox; co-immunoprecipitation; in vitro translation with microsomes for glycosylation; HEK-293 reconstitution; Nox3 activity assay The Biochemical journal High 17140397
2008 Deletion of p22phox in nmf333 mice inactivates both the phagocyte NADPH oxidase (producing a CGD-like immune phenotype) and a distinct Nox-containing cytochrome in inner ear epithelium required for vestibular organogenesis, demonstrating that p22phox is a shared, essential subunit of at least two biologically distinct superoxide-producing cytochromes. Genetic characterization of nmf333 mouse strain (Cyba deletion); immune function assays; vestibular phenotype analysis; comparative histology of inner ear The Journal of clinical investigation High 18292807
2008 The dual tryptophan motif in the N-terminal amino acids 6–11 of p22phox is essential for Nox4 activity, whereas the C-terminus (residues 130–195) is dispensable; substitution of Y121H preserves Nox4 activity but abolishes Nox2 and Nox3 function, revealing distinct structural requirements for p22phox interaction with different Nox isoforms. Truncation and point mutagenesis of p22phox; heterologous expression in p22phox-deficient lung carcinoma cells; ROS measurement; co-immunoprecipitation of Nox4–p22phox complex The Journal of biological chemistry High 18849343
2009 Phosphorylation of p22phox on threonine 147 is required for efficient NADPH oxidase complex formation and superoxide production; T147A mutation blocks p22phox–p47phox interaction in intact cells and inhibits superoxide production by >70%, while T147D (phosphomimetic) restores both p47phox binding and oxidase activity. PKC-alpha and PKC-delta phosphorylate T147 in vitro. Site-directed mutagenesis of p22phox (T147A, T147D) in CHO cell system; in vivo p22phox–p47phox co-immunoprecipitation; in vitro PKC phosphorylation assay; superoxide production measurement The Journal of biological chemistry High 19948736
2016 CRISPR/Cas9-mediated knockout of CYBA (p22phox) abolishes Nox1-dependent and Nox4-dependent ROS production but not Nox5-dependent superoxide production, confirming that Nox5 is the only Nox family member functionally independent of p22phox; activity is rescued by re-expression of human or rat p22phox but not by DUOXA1/A2. CRISPR/Cas9 knockout of CYBA; rescue experiments with human/rat p22phox and DUOXA1/A2; H2O2 and superoxide measurement; point mutants Q130* and Y121H tested for Nox4 maturation and activity Redox biology High 27614387
2004 Nox1 physically associates with p22phox in vascular smooth muscle cells, co-immunoprecipitating and co-localizing at the plasma membrane and submembrane areas; NADPH-driven superoxide production requires co-expression of both subunits. Co-immunoprecipitation of HA-tagged Nox1 with p22phox; confocal microscopy co-localization; electron spin resonance superoxide measurement in cells expressing Nox1 alone vs. with p22phox Free radical biology & medicine High 15477006
2017 p22phox and Nox4 interact in the endoplasmic reticulum; Nox4 expression is dependent on the presence of p22phox (asymmetric relationship), while p22phox levels are unaffected by Nox4; rapamycin-induced protein dimerization experiments indicate that the Nox4–p22phox complex produces H2O2 into the lumen of the ER. siRNA knockdown; co-immunoprecipitation; rapamycin-mediated FRB/FKBP heterodimerization topology assay; immunofluorescence; TGF-β1 stimulation of primary human/murine fibroblasts Free radical biology & medicine High 29278739
2017 NOX5 physically interacts with p22phox at the outer mitochondrial membrane in monocyte-derived dendritic cells; NOX5-p22phox complex drives monocyte-to-dendritic cell differentiation by regulating JAK/STAT/MAPK and NF-κB pathways, as shown by p22phox-deficient CGD patient cells and NOX5-specific siRNA. Co-immunoprecipitation of NOX5 and p22phox; immunofluorescence localization; siRNA knockdown of NOX5; differentiation assay using p22phox-deficient CGD patient monocytes; NOX5 selective inhibitors Blood Medium 28830888
2018 Hypoxia stabilizes p22phox by inhibiting its ubiquitination and proteasomal degradation via prolyl hydroxylase (PHD)- and pVHL-dependent pathways; stabilized p22phox promotes vascular cell proliferation/migration and increases HIF-1α levels under normoxia and hypoxia; mice with the Y121H p22phox point mutation (reduced p22phox stability) are protected from hypoxia-induced pulmonary hypertension. Ubiquitination assay; proteasome inhibitor experiments; siRNA knockdown of PHDs and pVHL; p22phox Y121H knock-in mouse model; hypoxia-induced PH model; HIF-1α measurement Antioxidants & redox signaling High 30044141
2016 N-terminal 8-amino acid peptide (N8) derived from p22phox is sufficient for interaction with the autophagy regulator Rubicon; this Rubicon–p22phox interaction facilitates phagosomal trafficking of the p22phox–gp91phox NOX complex to produce a ROS burst upon microbial infection. Peptide competition/blocking assay (Tat-N8 peptide); ROS measurement; co-immunoprecipitation of Rubicon and p22phox; cecal ligation and puncture mouse model of sepsis; survival analysis Biomaterials Medium 27267627
2010 p22phox-based NADPH oxidase activity is required for megakaryocytic differentiation; RNAi knockdown of p22phox abolishes ROS production and blocks differentiation of K562, HEL, and primary CD34+ cells, inhibiting downstream ERK, AKT, and JAK2 activation. RNAi knockdown of p22phox; antioxidant and DPI inhibition; flow cytometry for differentiation markers; Western blot for ERK/AKT/JAK2 phosphorylation Cell death and differentiation High 20523355
2010 p22phox-dependent Nox oxidases maintain HIF-2alpha protein expression in VHL-deficient renal carcinoma cells through Akt-dependent phosphorylation and inactivation of the tumor suppressor tuberin, leading to mTORC1 pathway activation (S6K1 and 4E-BP1 phosphorylation). siRNA knockdown of p22phox; DPI (Nox inhibitor) treatment; Western blot for tuberin phosphorylation, S6K1, 4E-BP1, HIF-2alpha; human renal cell carcinoma tissue analysis The American journal of pathology Medium 20304964
2015 PPAR-γ suppresses p22phox transcription indirectly by inhibiting NF-κB nuclear translocation; the NF-κB binding site in the p22phox promoter is required for hypoxia-induced p22phox expression; postischemic p22phox siRNA reduces infarct volume and improves functional outcome in mice. PPAR-γ agonist/antagonist pharmacology; PPAR-γ siRNA and adenoviral overexpression; p22phox promoter-reporter assay; subcellular fractionation of NF-κB; p22phox siRNA in MCA occlusion model Molecular neurobiology Medium 26108185
2001 Thrombin activates the HIF-1 signaling pathway in vascular smooth muscle cells via p22phox-containing NADPH oxidase-derived ROS; p22phox antisense oligonucleotide transfection attenuates thrombin-induced HIF-1alpha, PAI-1, and VEGF expression, placing p22phox-dependent ROS upstream of p38 MAPK/PI3K in this pathway. p22phox antisense oligonucleotide transfection; p38 MAPK and PI3K inhibitors; HIF-1 DNA-binding assay; reporter gene assay; Western blot for HIF-1alpha Circulation research Medium 11440977
2004 The -930A/G polymorphism in the p22phox gene promoter functionally increases CYBA transcriptional activity; hypertensive subjects with the GG genotype exhibit increased p22phox mRNA and protein expression and enhanced NADPH oxidase activity in phagocytic cells compared to AA/AG carriers. Reporter gene transfection in vascular smooth muscle cells (A→G substitution); Northern and Western blotting of patient phagocytes; chemiluminescence NADPH oxidase activity assay Hypertension Medium 15210651
2009 Three common CYBA polymorphisms forming haplogroup C (c.214T>C, c.521T>C, c.*24G>A) result in significantly lower NOX2-dependent ROS generation; the *24A allele decreases CYBA 3'-UTR reporter gene activity, while the nonsynonymous coding SNPs contribute to reduced p22phox function as confirmed by lentiviral transduction into p22phox-deficient B-lymphocytes. EBV-transformed B-lymphocyte panel (50 donors); ROS measurement; lentiviral transduction of CYBA haplotype variants into p22phox-deficient cells; luciferase/3'-UTR reporter assay Human mutation High 19388116
2000 p22phox in endothelial cells localizes predominantly intracellularly, co-localizing with gp91phox in the vicinity of the endoplasmic reticulum, in contrast to the primarily plasma membrane localization in phagocytes; the endothelial gp91phox sequence differs from phagocytic gp91phox in a putative NADPH-binding domain and glycosylation sites. cDNA cloning and sequencing; subcellular fractionation; immunofluorescence co-localization with ER markers in rat coronary microvascular endothelial cells Arteriosclerosis, thrombosis, and vascular biology Medium 10938010
2005 Thrombin-induced upregulation of p22phox in endothelial cells occurs via a redox-sensitive positive feedback loop dependent on p38 MAPK and PI3K/Akt; H2O2 itself increases p22phox expression and ROS production, and p22phox is required for thrombin- or H2O2-stimulated cell proliferation. Antisense p22phox; antioxidant (vitamin C) and DPI treatment; p38 MAPK and PI3K/Akt inhibitors; two-photon confocal microscopy co-localization of p22phox and ROS; Northern/Western blotting Free radical biology & medicine Medium 15683718
2015 IL-1β upregulates p22phox and NOX4 expression in human articular chondrocytes, leading to increased ROS production; NOX4 inhibition decreases IL-1β-induced collagenase synthesis, and a redox-dependent loop sustains pro-catabolic IL-1β neosynthesis. IL-1β stimulation; NOX inhibitors (DPI, GKT136901, Tiron, HO-1); ROS detection; MMP expression assay; NOX4 mRNA comparison between OA and non-OA cartilage Osteoarthritis and cartilage Medium 26521743
2013 Hsp70/Hsp72 negatively regulates the Nox4/p22phox complex; losartan increases Hsp70 membrane translocation and its interaction/co-localization with Nox4/p22phox, decreasing Nox4/p22phox co-immunoprecipitation and NADPH oxidase activity; Hsp72 depletion by siRNA prevents losartan from reducing angiotensin II-enhanced NADPH oxidase activity and stress fiber formation. Co-immunoprecipitation; confocal immunofluorescence; siRNA knockdown of Hsp72; NADPH oxidase activity assay; actin cytoskeleton assessment in SHR VSMCs Cell stress & chaperones Medium 23761196
2015 p22phox overexpression in oral squamous cell carcinoma cells confers cisplatin resistance by sequestering cisplatin in the cytoplasm (perinuclear compartment), blocking its nuclear entry and DNA-adduct formation, delaying chk1-p53 signaling, and activating PI3K/Akt. p22phox stable overexpression and knockdown; cytoplasmic/nuclear cisplatin fractionation; platinum-DNA adduct assay; chk1/p53 Western blot; PI3K/Akt inhibition; IC50 determination Oncotarget Medium 25686830

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats. Circulation research 445 8978321
2001 Thrombin activates the hypoxia-inducible factor-1 signaling pathway in vascular smooth muscle cells: Role of the p22(phox)-containing NADPH oxidase. Circulation research 356 11440977
2002 Phosphorylation of p47phox sites by PKC alpha, beta II, delta, and zeta: effect on binding to p22phox and on NADPH oxidase activation. Biochemistry 336 12056906
2000 Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells. Life sciences 267 10946846
2001 The ligands/activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase Cu2+,Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells. Metabolism: clinical and experimental 247 11172467
1999 Expression of NADH/NADPH oxidase p22phox in human coronary arteries. Circulation 225 10510050
2003 Increased expression of NAD(P)H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment. Diabetologia 209 13680125
2000 Molecular characterization and localization of the NAD(P)H oxidase components gp91-phox and p22-phox in endothelial cells. Arteriosclerosis, thrombosis, and vascular biology 204 10938010
2005 Point mutations in the proline-rich region of p22phox are dominant inhibitors of Nox1- and Nox2-dependent reactive oxygen generation. The Journal of biological chemistry 195 15994299
2000 Differential activation of mitogen-activated protein kinases in smooth muscle cells by angiotensin II: involvement of p22phox and reactive oxygen species. Arteriosclerosis, thrombosis, and vascular biology 187 10764657
2006 Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression. Molecular pharmacology 181 16754784
1997 Biosynthesis of the phagocyte NADPH oxidase cytochrome b558. Role of heme incorporation and heterodimer formation in maturation and stability of gp91phox and p22phox subunits. The Journal of biological chemistry 130 9341176
2005 The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells. Free radical biology & medicine 116 15683718
2001 Expression of p22-phox and gp91-phox, essential components of NADPH oxidase, increases after myocardial infarction. Biochemical and biophysical research communications 100 11243862
2000 Oxidative stress and expression of p22phox are involved in the up-regulation of tissue factor in vascular smooth muscle cells in response to activated platelets. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 100 10928986
2008 Mutation of the Cyba gene encoding p22phox causes vestibular and immune defects in mice. The Journal of clinical investigation 99 18292807
2006 NADPH oxidase p22phox and catalase gene variants are associated with biomarkers of oxidative stress and adverse outcomes in acute renal failure. Journal of the American Society of Nephrology : JASN 94 17151330
1994 156Pro-->Gln substitution in the light chain of cytochrome b558 of the human NADPH oxidase (p22-phox) leads to defective translocation of the cytosolic proteins p47-phox and p67-phox. The Journal of experimental medicine 91 7964505
1999 The p22 phox A640G gene polymorphism but not the C242T gene variation is associated with coronary heart disease in younger individuals. Atherosclerosis 89 10488959
2008 Mutational analysis reveals distinct features of the Nox4-p22 phox complex. The Journal of biological chemistry 88 18849343
2000 C242T polymorphism of NADPH oxidase p22 PHOX gene and ischemic cerebrovascular disease in the Japanese population. Stroke 84 10754002
1999 Activation of the phagocyte NADPH oxidase protein p47(phox). Phosphorylation controls SH3 domain-dependent binding to p22(phox). The Journal of biological chemistry 82 10391914
2008 NADPH oxidase CYBA polymorphisms, oxidative stress and cardiovascular diseases. Clinical science (London, England : 1979) 77 18184111
2000 Phosphorylation of p22phox is mediated by phospholipase D-dependent and -independent mechanisms. Correlation of NADPH oxidase activity and p22phox phosphorylation. The Journal of biological chemistry 76 10893420
2010 p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation. Cell death and differentiation 75 20523355
2007 Role of the small GTPase Rac in p22phox-dependent NADPH oxidases. Biochimie 74 17583407
2005 NADPH oxidase-mediated oxidative stress: genetic studies of the p22(phox) gene in hypertension. Antioxidants & redox signaling 72 16115038
1998 Glucocorticoids inhibit superoxide anion production and p22 phox mRNA expression in human aortic smooth muscle cells. Hypertension (Dallas, Tex. : 1979) 72 9856978
2007 Critical roles for p22phox in the structural maturation and subcellular targeting of Nox3. The Biochemical journal 70 17140397
2004 Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice. American journal of physiology. Heart and circulatory physiology 69 15471976
2004 Functional effect of the p22phox -930A/G polymorphism on p22phox expression and NADPH oxidase activity in hypertension. Hypertension (Dallas, Tex. : 1979) 68 15210651
2004 Functional association of nox1 with p22phox in vascular smooth muscle cells. Free radical biology & medicine 65 15477006
1999 A phosphatidic acid-activated protein kinase and conventional protein kinase C isoforms phosphorylate p22(phox), an NADPH oxidase component. The Journal of biological chemistry 65 10593961
2015 PPAR-γ Ameliorates Neuronal Apoptosis and Ischemic Brain Injury via Suppressing NF-κB-Driven p22phox Transcription. Molecular neurobiology 64 26108185
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
2015 IL-1beta mediates MMP secretion and IL-1beta neosynthesis via upregulation of p22(phox) and NOX4 activity in human articular chondrocytes. Osteoarthritis and cartilage 63 26521743
2009 Three common polymorphisms in the CYBA gene form a haplotype associated with decreased ROS generation. Human mutation 59 19388116
2016 CYBA encoding p22(phox), the cytochrome b558 alpha polypeptide: gene structure, expression, role and physiopathology. Gene 57 27048830
1994 p22-phox-deficient chronic granulomatous disease: reconstitution by retrovirus-mediated expression and identification of a biosynthetic intermediate of gp91-phox. Blood 57 7919388
2004 Relation between development of nephropathy and the p22phox C242T and receptor for advanced glycation end product G1704T gene polymorphisms in type 2 diabetic patients. Diabetes care 56 14747204
2000 Statistical and mutational analysis of chronic granulomatous disease in Japan with special reference to gp91-phox and p22-phox deficiency. Human genetics 52 10914676
2017 NOX5 and p22phox are 2 novel regulators of human monocytic differentiation into dendritic cells. Blood 51 28830888
2006 NADPH oxidase (CYBA) and FcgammaR polymorphisms as risk factors for aggressive periodontitis: a case-control association study. Journal of clinical periodontology 47 16899095
2013 Increased p22(phox)/Nox4 expression is involved in remodeling through hydrogen peroxide signaling in experimental persistent pulmonary hypertension of the newborn. Antioxidants & redox signaling 46 23244636
1995 Stoichiometry of p22-phox and gp91-phox in phagocyte cytochrome b558. Biochemistry 45 8527449
2001 NADH/NADPH oxidase p22 phox gene polymorphism is associated with improved coronary endothelial vasodilator function. European heart journal 44 11133215
2014 Identification of NoxD/Pro41 as the homologue of the p22phox NADPH oxidase subunit in fungi. Molecular microbiology 43 25424886
2004 Genistein inhibits expressions of NADPH oxidase p22phox and angiotensin II type 1 receptor in aortic endothelial cells from stroke-prone spontaneously hypertensive rats. Hypertension research : official journal of the Japanese Society of Hypertension 43 15750262
2001 Polymorphisms and promoter overactivity of the p22(phox) gene in vascular smooth muscle cells from spontaneously hypertensive rats. Circulation research 43 11157675
2010 CYP1A1, CYP1A2 and CYBA gene polymorphisms associated with oxidative stress in COPD. Clinica chimica acta; international journal of clinical chemistry 42 20080081
2011 Augmented NADPH oxidase activity and p22phox expression in monocytes underlie oxidative stress of patients with type 2 diabetes mellitus. Diabetes research and clinical practice 40 21237524
2008 Influence of glucosamine sulphate on oxidative stress in human osteoarthritic chondrocytes: effects on HO-1, p22(Phox) and iNOS expression. Rheumatology (Oxford, England) 40 18077487
2016 CRISPR/Cas9-mediated knockout of p22phox leads to loss of Nox1 and Nox4, but not Nox5 activity. Redox biology 38 27614387
2016 Subcellular localization of the FLT3-ITD oncogene plays a significant role in the production of NOX- and p22phox-derived reactive oxygen species in acute myeloid leukemia. Leukemia research 38 27870947
2010 The NADPH oxidase subunit p22phox inhibits the function of the tumor suppressor protein tuberin. The American journal of pathology 38 20304964
2006 NADPH oxidase subunits (NOX-1, p22phox, Rac-1) and tacrolimus-induced nephrotoxicity in a rat renal transplant model. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 38 17085464
2020 ROS production and mitochondrial dysfunction driven by PU.1-regulated NOX4-p22phox activation in Aβ-induced retinal pigment epithelial cell injury. Theranostics 35 33052238
2016 Human cellular CYBA UTR sequences increase mRNA translation without affecting the half-life of recombinant RNA transcripts. Scientific reports 35 27974853
2017 Interaction between p22phox and Nox4 in the endoplasmic reticulum suggests a unique mechanism of NADPH oxidase complex formation. Free radical biology & medicine 33 29278739
2010 Association of the CYBA, PPARGC1A, PPARG3, and PPARD gene variants with coronary artery disease and metabolic risk factors of coronary atherosclerosis in a Russian population. Heart and vessels 33 20512451
2009 Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. The Journal of biological chemistry 32 19948736
2006 C242T polymorphism in CYBA gene (p22phox) and risk of coronary artery disease in a population of Caucasian Italians. Disease markers 31 16788250
2020 Developing Inhibitors of the p47phox-p22phox Protein-Protein Interaction by Fragment-Based Drug Discovery. Journal of medicinal chemistry 30 31922756
2014 Polymorphisms of C242T and A640G in CYBA gene and the risk of coronary artery disease: a meta-analysis. PloS one 29 24392120
2009 Exercise training, NADPH oxidase p22phox gene polymorphisms, and hypertension. Medicine and science in sports and exercise 29 19516159
2014 Enhanced p22phox expression impairs vascular function through p38 and ERK1/2 MAP kinase-dependent mechanisms in type 2 diabetic mice. American journal of physiology. Heart and circulatory physiology 28 24486509
2010 The effect of p22-PHOX (CYBA) polymorphisms on premature coronary artery disease (≤ 40 years of age). Thrombosis and haemostasis 28 21136016
2009 Six different CYBA mutations including three novel mutations in ten families from Turkey, resulting in autosomal recessive chronic granulomatous disease. European journal of clinical investigation 28 19292887
2004 Angiotensin-converting enzyme and p22(phox) polymorphisms and the risk of coronary heart disease in a low-risk Spanish population. International journal of cardiology 28 15193812
2012 CYBA and GSTP1 variants associate with oxidative stress under hypobaric hypoxia as observed in high-altitude pulmonary oedema. Clinical science (London, England : 1979) 27 21973220
2013 Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: functional implications. Molecular biology and evolution 26 23821607
2008 Insight into the role of CYBA A640G and C242T gene variants and coronary heart disease risk. A case-control study. Free radical research 26 18324526
2001 NADH/NADPH oxidase p22 phox C242T polymorphism and lipid peroxidation in coronary artery disease. Clinical physiology (Oxford, England) 26 11722480
2007 The 242T variant of the CYBA gene polymorphism increases the risk of coronary artery disease associated with cigarette smoking and hypercholesterolemia. Coronary artery disease 25 17627182
2010 Association of p22phox gene C242T polymorphism with coronary artery disease: a meta-analysis. Thrombosis research 24 20100625
2003 Polymorphisms of the NADPH oxidase P22PHOX gene in a Caucasian population with intracranial aneurysms. Cerebrovascular diseases (Basel, Switzerland) 24 13130177
2014 The role of CYBA (p22phox) and catalase genetic polymorphisms and their possible epistatic interaction in cervical cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 25307973
2011 Association of genetic variants in the promoter region of genes encoding p22phox (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease in patients with type 1 diabetes mellitus. BMC medical genetics 23 21962117
2002 A novel and unusual case of chronic granulomatous disease in a child with a homozygous 36-bp deletion in the CYBA gene (A22(0)) leading to the activation of a cryptic splice site in intron 4. Human genetics 23 12073015
2019 Protective effects of gliclazide on high glucose and AGEs-induced damage of glomerular mesangial cells and renal tubular epithelial cells via inhibiting RAGE-p22phox-NF-kB pathway. European review for medical and pharmacological sciences 22 31696501
2013 Relationship of the p22phox (CYBA) gene polymorphism C242T with risk of coronary artery disease: a meta-analysis. PloS one 22 24039708
2013 Safflor yellow B suppresses angiotensin II-mediated human umbilical vein cell injury via regulation of Bcl-2/p22(phox) expression. Toxicology and applied pharmacology 21 23994555
2022 Germline Variants of CYBA and TRPM4 Predispose to Familial Colorectal Cancer. Cancers 19 35158942
2020 Decorin inhibits glucose-induced lens epithelial cell apoptosis via suppressing p22phox-p38 MAPK signaling pathway. PloS one 19 32339204
2018 Stabilization of p22phox by Hypoxia Promotes Pulmonary Hypertension. Antioxidants & redox signaling 19 30044141
2017 Association analysis of rs1049255 and rs4673 transitions in p22phox gene with coronary artery disease: A case-control study and a computational analysis. Irish journal of medical science 19 28474233
2014 The -930A>G polymorphism of the CYBA gene is associated with premature coronary artery disease. A case-control study and gene-risk factors interactions. Molecular biology reports 19 24477591
2007 Associations of polymorphism of P22(phox) C242T, plasma levels of vitamin E, and smoking with coronary heart disease in China. American heart journal 19 17383305
2000 Genetic studies of three Japanese patients with p22-phox-deficient chronic granulomatous disease: detection of a possible common mutant CYBA allele in Japan and a genotype-phenotype correlation in these patients. British journal of haematology 19 10759707
2018 Association between the CYBA and NOX4 genes of NADPH oxidase and its relationship with metabolic syndrome in non-alcoholic fatty liver disease in Brazilian population. Hepatobiliary & pancreatic diseases international : HBPD INT 18 30087027
2017 Is the C242T Polymorphism of the CYBA Gene Linked with Oxidative Stress-Associated Complications of Prematurity? Antioxidants & redox signaling 18 28375031
2017 Hypoxic vascular response and ventilation/perfusion matching in end-stage COPD may depend on p22phox. The European respiratory journal 18 28729471
2016 Peptide inhibition of p22phox and Rubicon interaction as a therapeutic strategy for septic shock. Biomaterials 18 27267627
2015 Allelic variations in the CYBA gene of NADPH oxidase and risk of kidney complications in patients with type 1 diabetes. Free radical biology & medicine 18 25862415
2005 Coronary microvascular endothelial cell growth regulates expression of the gene encoding p22-phox. Free radical biology & medicine 18 16257643
2017 Differential resistance to platinum-based drugs and 5-fluorouracil in p22phox-overexpressing oral squamous cell carcinoma: Implications of alternative treatment strategies. Head & neck 17 28498554
2015 p22phox confers resistance to cisplatin, by blocking its entry into the nucleus. Oncotarget 17 25686830
2013 Hsp70 regulation on Nox4/p22phox and cytoskeletal integrity as an effect of losartan in vascular smooth muscle cells. Cell stress & chaperones 17 23761196
2011 NADPH oxidase p22phox polymorphisms and oxidative stress in patients with obstructive sleep apnoea. Respiratory medicine 17 21872458
2008 The C242T polymorphism of the p22phox component of NAD(P)H oxidase and vascular risk. Two case-control studies and a meta-analysis. Thrombosis and haemostasis 17 18327409

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