{"gene":"DUOXA1","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2020,"finding":"Cryo-EM structures of the mouse DUOX1-DUOXA1 complex reveal atomic details of the DUOX1-DUOXA1 interaction interface, a lipid-mediated NADPH-binding pocket, and the electron transfer path. An unexpected dimer-of-dimers configuration was identified and biochemical analyses indicated this represents an inactive state, suggesting an oligomerization-dependent regulatory mechanism for DUOX1-DUOXA1.","method":"Cryo-EM structure determination (with and without NADPH substrate), biochemical analyses","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structures with substrate and apo states, plus biochemical validation of dimer-of-dimers inactive state, multiple orthogonal approaches in a single rigorous study","pmids":["32929281"],"is_preprint":false},{"year":2024,"finding":"DUOXA1 is required for correct apical plasma membrane targeting of DUOX1 in polarized epithelial (MDCK) cells. N-glycosylation of DUOXA1 is essential for apical sorting of DUOX1; impairment of DUOXA1 N-glycosylation causes mistargeting of DUOX1 to the basolateral membrane. DUOXA2 cannot substitute for DUOXA1 in directing DUOX1 to the apical membrane.","method":"Co-expression in MDCK epithelial cells, N-glycosylation mutants, immunofluorescence localization assays","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence using glycosylation-defective mutants and specificity controls in polarized epithelial cells, single lab but multiple orthogonal approaches","pmids":["39126279"],"is_preprint":false},{"year":2014,"finding":"DUOXA1 overexpression in murine primary myoblasts increases H2O2 production (via DUOX1), causes fusion defects, reduces expression of myogenin and myosin heavy chain differentiation markers, and elevates apoptosis. The phenotype is rescued by siRNA knockdown of DUOX1 or ASK1, placing DUOXA1 upstream of DUOX1 and ASK1 in a pathway that inhibits muscle satellite cell differentiation.","method":"Adenoviral overexpression, shRNA knockdown, siRNA rescue, H2O2 measurement, differentiation marker immunoblotting","journal":"Cell communication and signaling : CCS","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via double knockdown rescue, multiple differentiation readouts, and ROS measurement; single lab but multiple orthogonal methods","pmids":["24410844"],"is_preprint":false},{"year":2009,"finding":"DUOXA1/NIP1 overexpression in MDA-MB-231 breast cancer cells increases ROS production, inhibits cell proliferation (with upregulation of p21Cip1/WAF1), downregulates cell-surface integrin αVβ5 and CD9 (impairing cell spreading), and modulates actin cytoskeleton to affect cell-cell adhesion. These effects were not observed in DUOX1-depleted cells, indicating DUOXA1 acts through DUOX1-dependent ROS.","method":"Transient transfection overexpression, DUOX1 depletion, ROS measurement, immunoblotting for p21/integrin/CD9, cell spreading assay, actin cytoskeleton imaging","journal":"Breast cancer research and treatment","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — multiple cellular readouts and DUOX1-depletion control placing DUOXA1 upstream of DUOX1-ROS axis, single lab","pmids":["19322654"],"is_preprint":false},{"year":2011,"finding":"A single functional DUOXA1 allele (in the context of two functioning DUOX1 alleles but absent/defective DUOXA2) produces only mild transient hypothyroidism, demonstrating functional redundancy between DUOXA1 and DUOXA2 maturation factors. Heterodimerization with DUOXA1 or DUOXA2 is essential for maturation and function of the respective DUOX enzyme complexes.","method":"In vitro reconstitution of DUOX2/DUOXA2(C189R) loss-of-function; clinical genetic mapping of deletion; functional assay of mutant DUOXA2","journal":"The Journal of clinical endocrinology and metabolism","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro reconstitution of DUOXA2 mutant loss-of-function combined with clinical genetics establishing pathway redundancy; single lab, two orthogonal approaches","pmids":["21367925"],"is_preprint":false},{"year":2018,"finding":"DUOXA1 overexpression in platinum-resistant ovarian cancer cells drives elevated ROS production, which sustains activation of the ATR-Chk1 DNA damage response pathway leading to cisplatin resistance. Blocking DUOXA1, ROS, ATR, or Chk1 overcomes resistance in vitro and in vivo.","method":"qHTCS screen, RNA-seq, ROS measurement, RNAi/inhibitor knockdown of DUOXA1/ATR/Chk1, in vitro and in vivo cisplatin resistance assays","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple inhibition strategies (RNAi and small molecule) with in vitro and in vivo validation; single lab, multiple orthogonal methods placing DUOXA1 upstream of ROS-ATR-Chk1","pmids":["29704517"],"is_preprint":false},{"year":2019,"finding":"A heterozygous DUOXA1 missense mutation (p.R56W) decreases DUOX1 mRNA and protein expression and correspondingly impairs H2O2 generation. The results confirm that intact DUOXA1 is required for full DUOX1 activity and H2O2 generation, establishing DUOXA1 as an essential co-factor for DUOX1-dependent H2O2 production.","method":"Direct sequencing, site-directed mutagenesis, expression analysis (mRNA and protein), H2O2 generation functional assay","journal":"Frontiers in endocrinology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional mutagenesis with H2O2 assay and expression analysis; single lab, mechanistically informative but single mutation study","pmids":["31428054"],"is_preprint":false}],"current_model":"DUOXA1 is a transmembrane maturation factor that co-assembles with DUOX1 to form an active NADPH oxidase complex capable of producing H2O2; cryo-EM structures reveal the atomic details of the DUOX1-DUOXA1 interaction, a lipid-mediated NADPH-binding pocket, and an oligomerization-dependent (dimer-of-dimers) inactive state; DUOXA1's N-glycosylation is required for correct apical targeting of DUOX1 in polarized epithelial cells; and DUOXA1-driven ROS production regulates muscle satellite cell differentiation (via DUOX1/ASK1), cancer cell adhesion/proliferation, and cisplatin resistance (via ATR-Chk1 activation)."},"narrative":{"mechanistic_narrative":"DUOXA1 is a transmembrane maturation factor that co-assembles with the NADPH oxidase DUOX1 to form an active complex that generates H2O2 [PMID:32929281, PMID:31428054]. Cryo-EM structures of the DUOX1-DUOXA1 complex define the interaction interface, a lipid-mediated NADPH-binding pocket, and the electron transfer path, and reveal a dimer-of-dimers configuration that constitutes an inactive state, indicating oligomerization-dependent regulation of the oxidase [PMID:32929281]. Intact DUOXA1 is essential for full DUOX1 expression and H2O2 production: a missense mutation (p.R56W) lowers DUOX1 mRNA and protein and impairs H2O2 generation [PMID:31428054], while DUOXA1 and the paralog DUOXA2 are functionally redundant as DUOX maturation partners, with single-allele DUOXA1 sufficiency producing only mild transient hypothyroidism [PMID:21367925]. Beyond assembly, DUOXA1 controls DUOX1 trafficking — its N-glycosylation directs apical plasma membrane targeting of DUOX1 in polarized epithelial cells, a role DUOXA2 cannot substitute [PMID:39126279]. Through its DUOX1-dependent ROS output, DUOXA1 acts as an upstream signaling input: it inhibits muscle satellite cell differentiation via a DUOX1/ASK1 pathway [PMID:24410844], suppresses cancer cell proliferation and adhesion by modulating p21, integrin αVβ5, CD9, and the actin cytoskeleton [PMID:19322654], and sustains ATR-Chk1 DNA damage signaling to confer cisplatin resistance [PMID:29704517].","teleology":[{"year":2009,"claim":"Established that DUOXA1 (NIP1) exerts cellular effects through DUOX1-dependent ROS, linking a maturation factor to control of proliferation and adhesion rather than acting independently.","evidence":"Overexpression with DUOX1 depletion control plus ROS, p21/integrin/CD9 immunoblotting and cytoskeleton imaging in MDA-MB-231 breast cancer cells","pmids":["19322654"],"confidence":"Medium","gaps":["Single lab, correlative readouts","Direct biochemical demonstration of complex assembly not shown here","Physiological relevance of overexpression unclear"]},{"year":2011,"claim":"Defined DUOXA1 and DUOXA2 as functionally redundant maturation factors required for DUOX enzyme function, clarifying why loss of one paralog is partially tolerated.","evidence":"In vitro reconstitution of DUOXA2(C189R) loss-of-function and clinical genetic mapping of a deletion","pmids":["21367925"],"confidence":"Medium","gaps":["Degree of redundancy may differ by tissue","Does not address trafficking specificity later found to differ between paralogs"]},{"year":2014,"claim":"Placed DUOXA1 upstream of a DUOX1/ASK1 ROS signaling cascade that inhibits myogenic differentiation, defining a developmental function for the maturation factor.","evidence":"Adenoviral overexpression in primary myoblasts with siRNA double-knockdown rescue, H2O2 measurement, and differentiation marker immunoblotting","pmids":["24410844"],"confidence":"High","gaps":["Direct ASK1 activation by DUOX1-derived H2O2 not biochemically resolved","In vivo relevance to satellite cell biology not tested"]},{"year":2018,"claim":"Connected DUOXA1-driven ROS to sustained ATR-Chk1 DNA damage signaling, providing a mechanism for platinum chemoresistance.","evidence":"qHTCS screen, RNA-seq, ROS measurement, RNAi/inhibitor knockdown of DUOXA1/ATR/Chk1, and in vitro/in vivo cisplatin resistance assays in ovarian cancer cells","pmids":["29704517"],"confidence":"Medium","gaps":["Single lab","Mechanism by which ROS sustains ATR-Chk1 not molecularly defined"]},{"year":2019,"claim":"Demonstrated through a patient missense mutation that intact DUOXA1 is required for DUOX1 expression and H2O2 output, cementing its role as an essential co-factor.","evidence":"Direct sequencing, site-directed mutagenesis (p.R56W), mRNA/protein expression analysis, and H2O2 generation assay","pmids":["31428054"],"confidence":"Medium","gaps":["Single mutation studied","How R56W destabilizes DUOX1 mechanistically not resolved"]},{"year":2020,"claim":"Resolved the atomic architecture of the DUOX1-DUOXA1 complex and identified an oligomerization-dependent inactive state, explaining how the oxidase is assembled and regulated.","evidence":"Cryo-EM structures of the mouse complex with and without NADPH plus biochemical analyses of the dimer-of-dimers state","pmids":["32929281"],"confidence":"High","gaps":["Mouse structure; human-specific features not addressed","Trigger that switches between active and inactive oligomeric states unknown"]},{"year":2024,"claim":"Identified DUOXA1 N-glycosylation as the determinant directing apical targeting of DUOX1, revealing a trafficking role distinct from DUOXA2.","evidence":"Co-expression in polarized MDCK cells with N-glycosylation mutants, specificity controls, and immunofluorescence localization","pmids":["39126279"],"confidence":"High","gaps":["Glycan-reading sorting machinery not identified","Tested in MDCK model only"]},{"year":null,"claim":"How the structurally defined inactive dimer-of-dimers state is dynamically regulated in cells, and how this couples to DUOXA1's trafficking and signaling roles, remains open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No human DUOX1-DUOXA1 structure in the corpus","Physiological signal controlling oligomeric switching unknown","Link between apical localization and downstream ROS signaling outputs untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,4,6]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[2,3,5]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[2,3,5]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,1,6]}],"complexes":["DUOX1-DUOXA1 NADPH oxidase complex"],"partners":["DUOX1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q1HG43","full_name":"Dual oxidase maturation factor 1","aliases":["Dual oxidase activator 1","Numb-interacting protein"],"length_aa":343,"mass_kda":37.8,"function":"Required for the maturation and transport of functional DUOX1 from the endoplasmic reticulum to the plasma membrane (PubMed:16651268). Recruits DUOX1 to the apical cell membrane (PubMed:39126279)","subcellular_location":"Apical cell membrane","url":"https://www.uniprot.org/uniprotkb/Q1HG43/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DUOXA1","classification":"Not Classified","n_dependent_lines":21,"n_total_lines":1208,"dependency_fraction":0.0173841059602649},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DUOXA1","total_profiled":1310},"omim":[{"mim_id":"612772","title":"DUAL OXIDASE MATURATION FACTOR 2; DUOXA2","url":"https://www.omim.org/entry/612772"},{"mim_id":"612771","title":"DUAL OXIDASE MATURATION FACTOR 1; DUOXA1","url":"https://www.omim.org/entry/612771"},{"mim_id":"606759","title":"DUAL OXIDASE 2; DUOX2","url":"https://www.omim.org/entry/606759"},{"mim_id":"606758","title":"DUAL OXIDASE 1; DUOX1","url":"https://www.omim.org/entry/606758"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"esophagus","ntpm":137.2},{"tissue":"skin 1","ntpm":65.3},{"tissue":"thyroid gland","ntpm":78.9}],"url":"https://www.proteinatlas.org/search/DUOXA1"},"hgnc":{"alias_symbol":["FLJ32334","NUMBIP","NIP","mol"],"prev_symbol":[]},"alphafold":{"accession":"Q1HG43","domains":[{"cath_id":"-","chopping":"76-168_234-247","consensus_level":"medium","plddt":93.9675,"start":76,"end":247},{"cath_id":"1.20.5","chopping":"22-71","consensus_level":"medium","plddt":92.5332,"start":22,"end":71}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q1HG43","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q1HG43-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q1HG43-F1-predicted_aligned_error_v6.png","plddt_mean":82.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DUOXA1","jax_strain_url":"https://www.jax.org/strain/search?query=DUOXA1"},"sequence":{"accession":"Q1HG43","fasta_url":"https://rest.uniprot.org/uniprotkb/Q1HG43.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q1HG43/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q1HG43"}},"corpus_meta":[{"pmid":"33956157","id":"PMC_33956157","title":"Mol* Viewer: modern web app for 3D visualization and analysis of large biomolecular structures.","date":"2021","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/33956157","citation_count":851,"is_preprint":false},{"pmid":"12460286","id":"PMC_12460286","title":"A fluorimetric method for the estimation of G+C mol% content in microorganisms by thermal denaturation temperature.","date":"2002","source":"Environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/12460286","citation_count":633,"is_preprint":false},{"pmid":"2839545","id":"PMC_2839545","title":"Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart.","date":"1988","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/2839545","citation_count":568,"is_preprint":false},{"pmid":"6874946","id":"PMC_6874946","title":"Inhibition of phagocytosis of complement C3- or immunoglobulin G-coated particles and of C3bi binding by monoclonal antibodies to a monocyte-granulocyte membrane glycoprotein (Mol).","date":"1983","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/6874946","citation_count":355,"is_preprint":false},{"pmid":"3155749","id":"PMC_3155749","title":"Interaction of the 70,000-mol-wt amino-terminal fragment of fibronectin with the matrix-assembly receptor of fibroblasts.","date":"1985","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/3155749","citation_count":326,"is_preprint":false},{"pmid":"6795304","id":"PMC_6795304","title":"B cell helper factors. 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Production and Stabilization of Specific Upregulated Long Noncoding RNA HOXD-AS2 in Glioblastomas Are Mediated by TFE3 and miR-661, Respectively. Int. J. Mol. Sci. 2022, 23, 2828.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39796287","citation_count":18,"is_preprint":false},{"pmid":"6645981","id":"PMC_6645981","title":"Possible heterogeneity of Streptococcus milleri determined by DNA mol % (guanine plus cytosine) measurement and physiological characterization.","date":"1983","source":"Microbios","url":"https://pubmed.ncbi.nlm.nih.gov/6645981","citation_count":18,"is_preprint":false},{"pmid":"34958660","id":"PMC_34958660","title":"Molecular persistent spectral image (Mol-PSI) representation for machine learning models in drug design.","date":"2022","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/34958660","citation_count":17,"is_preprint":false},{"pmid":"31428054","id":"PMC_31428054","title":"Identification of Two Missense Mutations in DUOX1 (p.R1307Q) and DUOXA1 (p.R56W) That Can Cause Congenital Hypothyroidism Through Impairing H2O2 Generation.","date":"2019","source":"Frontiers in endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/31428054","citation_count":16,"is_preprint":false},{"pmid":"23604909","id":"PMC_23604909","title":"Gene-trap mutagenesis using Mol/MSM-1 embryonic stem cells from MSM/Ms mice.","date":"2013","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/23604909","citation_count":16,"is_preprint":false},{"pmid":"27941179","id":"PMC_27941179","title":"Flaxseed oil supplementation manipulates correlations between serum individual mol % free fatty acid levels and insulin resistance in type 2 diabetics. 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Sci. 2017, 18, 500.","date":"2020","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33374891","citation_count":6,"is_preprint":false},{"pmid":"30632747","id":"PMC_30632747","title":"DCA-MOL: A PyMOL Plugin To Analyze Direct Evolutionary Couplings.","date":"2019","source":"Journal of chemical information and modeling","url":"https://pubmed.ncbi.nlm.nih.gov/30632747","citation_count":5,"is_preprint":false},{"pmid":"39518907","id":"PMC_39518907","title":"The Detailed Analysis of Polish Patients with Non-Small Cell Lung Cancer Through Insights from Molecular Testing (POL-MOL Study).","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39518907","citation_count":5,"is_preprint":false},{"pmid":"39000609","id":"PMC_39000609","title":"Correction: Gabryś et al. 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Sci. 2024, 25, 3262.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39000609","citation_count":5,"is_preprint":false},{"pmid":"15066198","id":"PMC_15066198","title":"Functional role of a high mol mass protein complex in the sea urchin yolk granule.","date":"2004","source":"Development, growth & differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/15066198","citation_count":5,"is_preprint":false},{"pmid":"11048586","id":"PMC_11048586","title":"[Use of mesquite cotyledon (Prosopis chilensis (Mol) Shuntz) in the manufacturing of cereal bars].","date":"2000","source":"Archivos latinoamericanos de nutricion","url":"https://pubmed.ncbi.nlm.nih.gov/11048586","citation_count":5,"is_preprint":false},{"pmid":"30096877","id":"PMC_30096877","title":"Correction: Chang, C.-H.; et al. 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Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers. Int. J. Mol. Sci. 2014, 15, 18117-18130.","date":"2016","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/27213350","citation_count":3,"is_preprint":false},{"pmid":"6984489","id":"PMC_6984489","title":"Characterization of a 75,000 mol. wt glycoprotein synthesized by guinea-pig T-lymphocytes: a possible homologue of Lyt-1 antigen.","date":"1982","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/6984489","citation_count":3,"is_preprint":false},{"pmid":"32290108","id":"PMC_32290108","title":"Correction: Wang, Y.T., et al. Selenium Nanoparticle Synthesized by Proteus mirabilis YC801: An Efficacious Pathway for Selenite Biotransformation and Detoxification. Int. J. Mol. 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Sci. 2022, 23, 9368.","date":"2025","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41312664","citation_count":2,"is_preprint":false},{"pmid":"25559406","id":"PMC_25559406","title":"Polygenic expression of teratozoospermia and normal fertility in B10.MOL-TEN1 mouse strain.","date":"2015","source":"Congenital anomalies","url":"https://pubmed.ncbi.nlm.nih.gov/25559406","citation_count":2,"is_preprint":false},{"pmid":"40099807","id":"PMC_40099807","title":"Visualizing and analyzing 3D biomolecular structures using Mol* at RCSB.org: Influenza A H5N1 virus proteome case study.","date":"2025","source":"Protein science : a publication of the Protein Society","url":"https://pubmed.ncbi.nlm.nih.gov/40099807","citation_count":2,"is_preprint":false},{"pmid":"40448617","id":"PMC_40448617","title":"Intramolecular Electrochemiluminescence Resonant Energy Transfer Biosensor Utilizing Ir-Grafted 2D Hf-MOL and Circular DNA Walker for Ultrasensitive Detection of microRNA-21 in Non-Small-Cell Lung Cancer Diagnostics.","date":"2025","source":"Analytical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/40448617","citation_count":2,"is_preprint":false},{"pmid":"37288461","id":"PMC_37288461","title":"2-[3-(1H-Benzimidazol-2-yl)prop-yl]-1H-benzimidazol-3-ium 3,4,5-tri-hydroxy-benzoate-1,3-bis-(1H-benzimidazol-2-yl)propane-ethyl acetate (2/1/2.94): co-crystallization between a salt, a neutral mol-ecule and a solvent.","date":"2023","source":"Acta crystallographica. 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An unexpected dimer-of-dimers configuration was identified and biochemical analyses indicated this represents an inactive state, suggesting an oligomerization-dependent regulatory mechanism for DUOX1-DUOXA1.\",\n      \"method\": \"Cryo-EM structure determination (with and without NADPH substrate), biochemical analyses\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structures with substrate and apo states, plus biochemical validation of dimer-of-dimers inactive state, multiple orthogonal approaches in a single rigorous study\",\n      \"pmids\": [\"32929281\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DUOXA1 is required for correct apical plasma membrane targeting of DUOX1 in polarized epithelial (MDCK) cells. N-glycosylation of DUOXA1 is essential for apical sorting of DUOX1; impairment of DUOXA1 N-glycosylation causes mistargeting of DUOX1 to the basolateral membrane. DUOXA2 cannot substitute for DUOXA1 in directing DUOX1 to the apical membrane.\",\n      \"method\": \"Co-expression in MDCK epithelial cells, N-glycosylation mutants, immunofluorescence localization assays\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence using glycosylation-defective mutants and specificity controls in polarized epithelial cells, single lab but multiple orthogonal approaches\",\n      \"pmids\": [\"39126279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DUOXA1 overexpression in murine primary myoblasts increases H2O2 production (via DUOX1), causes fusion defects, reduces expression of myogenin and myosin heavy chain differentiation markers, and elevates apoptosis. The phenotype is rescued by siRNA knockdown of DUOX1 or ASK1, placing DUOXA1 upstream of DUOX1 and ASK1 in a pathway that inhibits muscle satellite cell differentiation.\",\n      \"method\": \"Adenoviral overexpression, shRNA knockdown, siRNA rescue, H2O2 measurement, differentiation marker immunoblotting\",\n      \"journal\": \"Cell communication and signaling : CCS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via double knockdown rescue, multiple differentiation readouts, and ROS measurement; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"24410844\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"DUOXA1/NIP1 overexpression in MDA-MB-231 breast cancer cells increases ROS production, inhibits cell proliferation (with upregulation of p21Cip1/WAF1), downregulates cell-surface integrin αVβ5 and CD9 (impairing cell spreading), and modulates actin cytoskeleton to affect cell-cell adhesion. These effects were not observed in DUOX1-depleted cells, indicating DUOXA1 acts through DUOX1-dependent ROS.\",\n      \"method\": \"Transient transfection overexpression, DUOX1 depletion, ROS measurement, immunoblotting for p21/integrin/CD9, cell spreading assay, actin cytoskeleton imaging\",\n      \"journal\": \"Breast cancer research and treatment\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — multiple cellular readouts and DUOX1-depletion control placing DUOXA1 upstream of DUOX1-ROS axis, single lab\",\n      \"pmids\": [\"19322654\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"A single functional DUOXA1 allele (in the context of two functioning DUOX1 alleles but absent/defective DUOXA2) produces only mild transient hypothyroidism, demonstrating functional redundancy between DUOXA1 and DUOXA2 maturation factors. Heterodimerization with DUOXA1 or DUOXA2 is essential for maturation and function of the respective DUOX enzyme complexes.\",\n      \"method\": \"In vitro reconstitution of DUOX2/DUOXA2(C189R) loss-of-function; clinical genetic mapping of deletion; functional assay of mutant DUOXA2\",\n      \"journal\": \"The Journal of clinical endocrinology and metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro reconstitution of DUOXA2 mutant loss-of-function combined with clinical genetics establishing pathway redundancy; single lab, two orthogonal approaches\",\n      \"pmids\": [\"21367925\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"DUOXA1 overexpression in platinum-resistant ovarian cancer cells drives elevated ROS production, which sustains activation of the ATR-Chk1 DNA damage response pathway leading to cisplatin resistance. Blocking DUOXA1, ROS, ATR, or Chk1 overcomes resistance in vitro and in vivo.\",\n      \"method\": \"qHTCS screen, RNA-seq, ROS measurement, RNAi/inhibitor knockdown of DUOXA1/ATR/Chk1, in vitro and in vivo cisplatin resistance assays\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple inhibition strategies (RNAi and small molecule) with in vitro and in vivo validation; single lab, multiple orthogonal methods placing DUOXA1 upstream of ROS-ATR-Chk1\",\n      \"pmids\": [\"29704517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"A heterozygous DUOXA1 missense mutation (p.R56W) decreases DUOX1 mRNA and protein expression and correspondingly impairs H2O2 generation. The results confirm that intact DUOXA1 is required for full DUOX1 activity and H2O2 generation, establishing DUOXA1 as an essential co-factor for DUOX1-dependent H2O2 production.\",\n      \"method\": \"Direct sequencing, site-directed mutagenesis, expression analysis (mRNA and protein), H2O2 generation functional assay\",\n      \"journal\": \"Frontiers in endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional mutagenesis with H2O2 assay and expression analysis; single lab, mechanistically informative but single mutation study\",\n      \"pmids\": [\"31428054\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DUOXA1 is a transmembrane maturation factor that co-assembles with DUOX1 to form an active NADPH oxidase complex capable of producing H2O2; cryo-EM structures reveal the atomic details of the DUOX1-DUOXA1 interaction, a lipid-mediated NADPH-binding pocket, and an oligomerization-dependent (dimer-of-dimers) inactive state; DUOXA1's N-glycosylation is required for correct apical targeting of DUOX1 in polarized epithelial cells; and DUOXA1-driven ROS production regulates muscle satellite cell differentiation (via DUOX1/ASK1), cancer cell adhesion/proliferation, and cisplatin resistance (via ATR-Chk1 activation).\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DUOXA1 is a transmembrane maturation factor that co-assembles with the NADPH oxidase DUOX1 to form an active complex that generates H2O2 [#0, #6]. Cryo-EM structures of the DUOX1-DUOXA1 complex define the interaction interface, a lipid-mediated NADPH-binding pocket, and the electron transfer path, and reveal a dimer-of-dimers configuration that constitutes an inactive state, indicating oligomerization-dependent regulation of the oxidase [#0]. Intact DUOXA1 is essential for full DUOX1 expression and H2O2 production: a missense mutation (p.R56W) lowers DUOX1 mRNA and protein and impairs H2O2 generation [#6], while DUOXA1 and the paralog DUOXA2 are functionally redundant as DUOX maturation partners, with single-allele DUOXA1 sufficiency producing only mild transient hypothyroidism [#4]. Beyond assembly, DUOXA1 controls DUOX1 trafficking — its N-glycosylation directs apical plasma membrane targeting of DUOX1 in polarized epithelial cells, a role DUOXA2 cannot substitute [#1]. Through its DUOX1-dependent ROS output, DUOXA1 acts as an upstream signaling input: it inhibits muscle satellite cell differentiation via a DUOX1/ASK1 pathway [#2], suppresses cancer cell proliferation and adhesion by modulating p21, integrin \\u03b1V\\u03b25, CD9, and the actin cytoskeleton [#3], and sustains ATR-Chk1 DNA damage signaling to confer cisplatin resistance [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established that DUOXA1 (NIP1) exerts cellular effects through DUOX1-dependent ROS, linking a maturation factor to control of proliferation and adhesion rather than acting independently.\",\n      \"evidence\": \"Overexpression with DUOX1 depletion control plus ROS, p21/integrin/CD9 immunoblotting and cytoskeleton imaging in MDA-MB-231 breast cancer cells\",\n      \"pmids\": [\"19322654\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single lab, correlative readouts\", \"Direct biochemical demonstration of complex assembly not shown here\", \"Physiological relevance of overexpression unclear\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined DUOXA1 and DUOXA2 as functionally redundant maturation factors required for DUOX enzyme function, clarifying why loss of one paralog is partially tolerated.\",\n      \"evidence\": \"In vitro reconstitution of DUOXA2(C189R) loss-of-function and clinical genetic mapping of a deletion\",\n      \"pmids\": [\"21367925\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Degree of redundancy may differ by tissue\", \"Does not address trafficking specificity later found to differ between paralogs\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Placed DUOXA1 upstream of a DUOX1/ASK1 ROS signaling cascade that inhibits myogenic differentiation, defining a developmental function for the maturation factor.\",\n      \"evidence\": \"Adenoviral overexpression in primary myoblasts with siRNA double-knockdown rescue, H2O2 measurement, and differentiation marker immunoblotting\",\n      \"pmids\": [\"24410844\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct ASK1 activation by DUOX1-derived H2O2 not biochemically resolved\", \"In vivo relevance to satellite cell biology not tested\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Connected DUOXA1-driven ROS to sustained ATR-Chk1 DNA damage signaling, providing a mechanism for platinum chemoresistance.\",\n      \"evidence\": \"qHTCS screen, RNA-seq, ROS measurement, RNAi/inhibitor knockdown of DUOXA1/ATR/Chk1, and in vitro/in vivo cisplatin resistance assays in ovarian cancer cells\",\n      \"pmids\": [\"29704517\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single lab\", \"Mechanism by which ROS sustains ATR-Chk1 not molecularly defined\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Demonstrated through a patient missense mutation that intact DUOXA1 is required for DUOX1 expression and H2O2 output, cementing its role as an essential co-factor.\",\n      \"evidence\": \"Direct sequencing, site-directed mutagenesis (p.R56W), mRNA/protein expression analysis, and H2O2 generation assay\",\n      \"pmids\": [\"31428054\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single mutation studied\", \"How R56W destabilizes DUOX1 mechanistically not resolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolved the atomic architecture of the DUOX1-DUOXA1 complex and identified an oligomerization-dependent inactive state, explaining how the oxidase is assembled and regulated.\",\n      \"evidence\": \"Cryo-EM structures of the mouse complex with and without NADPH plus biochemical analyses of the dimer-of-dimers state\",\n      \"pmids\": [\"32929281\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Mouse structure; human-specific features not addressed\", \"Trigger that switches between active and inactive oligomeric states unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified DUOXA1 N-glycosylation as the determinant directing apical targeting of DUOX1, revealing a trafficking role distinct from DUOXA2.\",\n      \"evidence\": \"Co-expression in polarized MDCK cells with N-glycosylation mutants, specificity controls, and immunofluorescence localization\",\n      \"pmids\": [\"39126279\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Glycan-reading sorting machinery not identified\", \"Tested in MDCK model only\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the structurally defined inactive dimer-of-dimers state is dynamically regulated in cells, and how this couples to DUOXA1's trafficking and signaling roles, remains open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No human DUOX1-DUOXA1 structure in the corpus\", \"Physiological signal controlling oligomeric switching unknown\", \"Link between apical localization and downstream ROS signaling outputs untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 4, 6]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [2, 3, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [2, 3, 5]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1, 6]}\n    ],\n    \"complexes\": [\"DUOX1-DUOXA1 NADPH oxidase complex\"],\n    \"partners\": [\"DUOX1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}