Affinage

NAPA

Alpha-soluble NSF attachment protein · UniProt P54920

Length
295 aa
Mass
33.2 kDa
Annotated
2026-06-10
65 papers in source corpus 3 papers cited in narrative 3 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NAPA is an endoplasmic reticulum-localized protein that promotes cancer cell resistance to cisplatin-induced apoptosis through a p53-dependent mechanism (PMID:20653109). Mechanistically, NAPA maintains the stability of the E3 ubiquitin ligase synoviolin within the ER-associated degradation (ERAD) complex; by preserving synoviolin, NAPA drives p53 ubiquitination and degradation, keeping p53 levels low and suppressing apoptosis (PMID:21903092). Loss of NAPA activates ERK1/2 signaling, which promotes synoviolin ubiquitination and degradation, disrupts its association with the ERAD complex, and leads to p53 accumulation and apoptosis (PMID:21903092). NAPA expression is itself transcriptionally repressed: the Epstein-Barr virus oncoprotein LMP1 induces NF-κB p50, which binds the NAPA promoter as a homodimer to repress transcription, thereby sensitizing LMP1-expressing cells to cisplatin (PMID:21945668). Beyond this cisplatin-resistance axis, no further mechanistic detail for NAPA has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2010 Medium

    Established that NAPA functions in cancer cell survival rather than only housekeeping trafficking, by linking it to suppression of cisplatin-induced ER stress and apoptosis through p53.

    Evidence shRNA knockdown, overexpression, apoptosis/viability assays, xenograft tumor model, and p53 inhibitor/p53-null rescue in cancer cells

    PMID:20653109

    Open questions at the time
    • Did not define the molecular target through which NAPA controls p53
    • Mechanism connecting ER localization to p53 regulation unresolved
    • Single-lab phenotype without independent replication
  2. 2011 Medium

    Defined the molecular mechanism: NAPA stabilizes the ERAD E3 ligase synoviolin to drive p53 ubiquitination/degradation, with ERK1/2 acting as the destabilizing signal when NAPA is lost.

    Evidence co-immunoprecipitation, ubiquitination assays, ERK inhibitor rescue, and p53-null cell lines

    PMID:21903092

    Open questions at the time
    • How NAPA physically protects synoviolin from ubiquitination not structurally defined
    • Mechanism by which NAPA loss activates ERK1/2 unknown
    • Reciprocal validation of the synoviolin-ERAD interaction limited to one lab
  3. 2011 Medium

    Placed NAPA downstream of viral oncogenic signaling, showing it is transcriptionally repressed by LMP1-induced NF-κB p50 homodimers, which determines chemosensitivity.

    Evidence LMP1 expression/antisense knockdown, NAPA overexpression rescue, NF-κB p50 promoter binding, and cisplatin apoptosis assays

    PMID:21945668

    Open questions at the time
    • Promoter element and p50 binding site not finely mapped
    • Whether other stimuli regulate NAPA transcription unknown
    • Generality beyond LMP1-expressing cells untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether NAPA's canonical membrane-trafficking/SNARE function intersects with its role in synoviolin stability and p53 control remains unresolved.
  • No structural or biochemical mechanism linking NAPA to synoviolin protection
  • No characterization outside the cisplatin-resistance context in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-5357801 Programmed Cell Death 2 R-HSA-392499 Metabolism of proteins 1
Partners
SYVN1
Complex memberships
ERAD complex

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 NAPA, localized to the endoplasmic reticulum (ER), protects cancer cells against cisplatin-induced apoptosis. Knockdown of NAPA using shRNA induced ER stress, apoptosis, and enhanced cisplatin cytotoxicity, while overexpression of NAPA reduced cisplatin-induced ER stress and apoptosis. The protective effect required p53, as it was abolished in p53-null H1299 cells and reduced by the p53 inhibitor PFT-alpha. Combined cisplatin/shNAPA treatment suppressed tumor growth in vivo in xenograft experiments. shRNA knockdown, overexpression, cell viability/apoptosis assays, in vivo xenograft tumor model, p53 inhibitor rescue experiments Biochemical pharmacology Medium 20653109
2011 NAPA promotes cisplatin resistance by maintaining stability of the E3 ubiquitin ligase synoviolin within the ER-associated degradation (ERAD) complex, thereby facilitating p53 ubiquitination and degradation. Knockdown of NAPA induced ubiquitination and degradation of synoviolin, disrupted the synoviolin-ERAD complex interaction, and caused p53 accumulation. Conversely, NAPA overexpression decreased synoviolin ubiquitination and reduced p53 levels. ERK1/2 activation upon NAPA knockdown was identified as an upstream mediator of synoviolin ubiquitination, as ERK inhibition reversed synoviolin ubiquitination and p53 accumulation. shRNA knockdown, overexpression, co-immunoprecipitation, ubiquitination assays, ERK inhibitor rescue, p53-null cell lines Biochemical pharmacology Medium 21903092
2011 The Epstein-Barr virus oncoprotein LMP1 downregulates NAPA expression by upregulating NF-κB p50, which forms p50 homodimers on the NAPA promoter to repress transcription. This NAPA repression sensitizes LMP1-expressing cells to cisplatin-induced apoptosis. Restoration of NAPA expression reversed LMP1-mediated cisplatin sensitization, and antisense knockdown of LMP1 restored NAPA protein levels and cisplatin resistance. LMP1 expression/knockdown (antisense oligonucleotides), NAPA overexpression rescue, NF-κB p50 chromatin binding on NAPA promoter, cisplatin apoptosis assays Biochemical pharmacology Medium 21945668

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Diversity and abundance of nitrate reductase genes (narG and napA), nitrite reductase genes (nirS and nrfA), and their transcripts in estuarine sediments. Applied and environmental microbiology 173 17400770
1996 Disruption of an overlapping E-box/ABRE motif abolished high transcription of the napA storage-protein promoter in transgenic Brassica napus seeds. Planta 118 8818291
1999 Interaction between composite elements in the napA promoter: both the B-box ABA-responsive complex and the RY/G complex are necessary for seed-specific expression. Plant molecular biology 117 10480393
2009 Reduction of nitrate in Shewanella oneidensis depends on atypical NAP and NRF systems with NapB as a preferred electron transport protein from CymA to NapA. The ISME journal 106 19387485
2007 Growth of Campylobacter jejuni on nitrate and nitrite: electron transport to NapA and NrfA via NrfH and distinct roles for NrfA and the globin Cgb in protection against nitrosative stress. Molecular microbiology 99 17241202
2003 NapA protects Helicobacter pylori from oxidative stress damage, and its production is influenced by the ferric uptake regulator. Journal of medical microbiology 86 12748264
2008 Borrelia burgdorferi NapA-driven Th17 cell inflammation in lyme arthritis. Arthritis and rheumatism 81 18975343
2006 Dual Roles of Helicobacter pylori NapA in inducing and combating oxidative stress. Infection and immunity 72 17030577
1986 A novel intermediate filament-associated protein, NAPA-73, that binds to different filament types at different stages of nervous system development. The Journal of cell biology 72 3510220
2014 Redox metabolites signal polymicrobial biofilm development via the NapA oxidative stress cascade in Aspergillus. Current biology : CB 68 25532893
2003 Electron transport to periplasmic nitrate reductase (NapA) of Wolinella succinogenes is independent of a NapC protein. Molecular microbiology 60 12823811
2018 Production and delivery of Helicobacter pylori NapA in Lactococcus lactis and its protective efficacy and immune modulatory activity. Scientific reports 53 29691472
2019 Establishment Limitation Constrains the Abundance of Lactic Acid Bacteria in the Napa Cabbage Phyllosphere. Applied and environmental microbiology 40 31003989
2021 SpoT-mediated NapA upregulation promotes oxidative stress-induced Helicobacter pylori biofilm formation and confers multidrug resistance. Antimicrobial agents and chemotherapy 38 33649116
2006 The NapF protein of the Escherichia coli periplasmic nitrate reductase system: demonstration of a cytoplasmic location and interaction with the catalytic subunit, NapA. Microbiology (Reading, England) 38 17074894
2017 NapA Mediates a Redox Regulation of the Antioxidant Response, Carbon Utilization and Development in Aspergillus nidulans. Frontiers in microbiology 37 28424666
2005 Up-expression of NapA and other oxidative stress proteins is a compensatory response to loss of major Helicobacter pylori stress resistance factors. Free radical research 30 16298743
2009 Periplasmic nitrate reduction in Wolinella succinogenes: cytoplasmic NapF facilitates NapA maturation and requires the menaquinol dehydrogenase NapH for membrane attachment. Microbiology (Reading, England) 27 19477904
1995 Cloning and characterization of the NapA acid phosphatase/phosphotransferase of Morganella morganii: identification of a new family of bacterial acid-phosphatase-encoding genes. Microbiology (Reading, England) 25 7894706
2014 Illumina identification of RsrA, a conserved C2H2 transcription factor coordinating the NapA mediated oxidative stress signaling pathway in Aspergillus. BMC genomics 23 25416206
2005 Human peripheral and gastric lymphocyte responses to Helicobacter pylori NapA and AphC differ in infected and uninfected individuals. Gut 22 15591500
2021 The peptidoglycan-associated protein NapA plays an important role in the envelope integrity and in the pathogenesis of the lyme disease spirochete. PLoS pathogens 21 33984073
2011 Silencing of the SNARE protein NAPA sensitizes cancer cells to cisplatin by inducing ERK1/2 signaling, synoviolin ubiquitination and p53 accumulation. Biochemical pharmacology 21 21903092
2010 Knockdown of NAPA using short-hairpin RNA sensitizes cancer cells to cisplatin: implications to overcome chemoresistance. Biochemical pharmacology 21 20653109
2021 Reduction in Biogenic Amine Content in Baechu (Napa Cabbage) Kimchi by Biogenic Amine-Degrading Lactic Acid Bacteria. Microorganisms 19 34946171
2009 Density functional theory study of model complexes for the revised nitrate reductase active site in Desulfovibrio desulfuricans NapA. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 19 19484273
2005 Halotolerant cyanobacterium Aphanothece halophytica contains NapA-type Na+/H+ antiporters with novel ion specificity that are involved in salt tolerance at alkaline pH. Applied and environmental microbiology 19 16085800
2001 Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules. British journal of cancer 19 11259095
2007 Functional characterization of a NapA Na(+)/H(+) antiporter from Thermus thermophilus. FEBS letters 17 17254570
2019 NapA (Rv0430), a Novel Nucleoid-Associated Protein that Regulates a Virulence Operon in Mycobacterium tuberculosis in a Supercoiling-Dependent Manner. Journal of molecular biology 16 30872139
1999 Sodium phenylacetate (NaPa) induces modifications of the proliferation, the adhesion and the cell cycle of tumoral epithelial breast cells. Anticancer research 16 10470159
2022 The Contribution of Nitrate Dissimilation to Nitrate Consumption in narG- and napA-Containing Nitrate Reducers with Various Oxygen and Nitrate Supplies. Microbiology spectrum 13 36453888
2021 ESR1 NAPA Assay: Development and Analytical Validation of a Highly Sensitive and Specific Blood-Based Assay for the Detection of ESR1 Mutations in Liquid Biopsies. Cancers 13 33535614
2011 Latent membrane protein 1 of Epstein-Barr virus sensitizes cancer cells to cisplatin by enhancing NF-κB p50 homodimer formation and downregulating NAPA expression. Biochemical pharmacology 13 21945668
2014 Serum Helicobacter pylori NapA antibody as a potential biomarker for gastric cancer. Scientific reports 12 24553293
2010 Resolution of two native monomeric 90kDa nitrate reductase active proteins from Shewanella gelidimarina and the sequence of two napA genes. Biochemical and biophysical research communications 11 20547139
2010 Structure and immunomodulatory property relationship in NapA of Borrelia burgdorferi. Biochimica et biophysica acta 11 20851780
2007 NapA and NapB are the Aspergillus nidulans Nap/SET family members and NapB is a nuclear protein specifically interacting with importin alpha. Fungal genetics and biology : FG & B 10 17890114
2010 Solid-phase synthesis and screening of N-acylated polyamine (NAPA) combinatorial libraries for protein binding. Bioorganic & medicinal chemistry letters 9 20932761
2017 The role of scientific self-regulation for the control of genome editing in the human germline: The lessons from the Asilomar and the Napa meetings show how self-regulation and public deliberation can lead to regulation of new biotechnologies. EMBO reports 8 28219901
2018 Understanding Comprehensive Transcriptional Response of Salmonella enterica spp. in Contact with Cabbage and Napa Cabbage. Journal of microbiology and biotechnology 7 30270599
1987 The expression of the intermediate filament-associated protein (NAPA-73) is associated with the stage of terminal differentiation of chick brain neurons. Brain research 7 3121130
2021 Study on the bZIP-Type Transcription Factors NapA and RsmA in the Regulation of Intracellular Reactive Species Levels and Sterigmatocystin Production of Aspergillus nidulans. International journal of molecular sciences 6 34769008
2019 The Glucosamine-derivative NAPA Suppresses MAPK Activation and Restores Collagen Deposition in Human Diploid Fibroblasts Challenged with Environmental Levels of UVB. Photochemistry and photobiology 6 31769510
2021 Biochemical and Computational Studies of the Interaction between a Glucosamine Derivative, NAPA, and the IKKα Kinase. International journal of molecular sciences 5 33562013
2017 Buried shallow fault slip from the South Napa earthquake revealed by near-field geodesy. Science advances 5 28782026
2015 Comparison of Iron-Binding Ability Between Thr70-NapA and Ser70-NapA of Helicobacter pylori. Helicobacter 5 26347349
2013 Cerebrospinal fluid T-regulatory cells recognize Borrelia burgdorferi NAPA in chronic Lyme borreliosis. International journal of immunopathology and pharmacology 5 24355226
2022 Investigating N-arylpyrimidinamine (NAPA) compounds as early-stage inhibitors against human cytomegalovirus. Antiviral research 4 36511318
2007 Sodium phenylacetate (NaPa) improves the TAM effect on glioblastoma experimental tumors by inducing cell growth arrest and apoptosis. Anticancer research 4 17465226
2002 Growth inhibition of human melanoma tumor cells by the combination of sodium phenylacetate (NaPA) and substituted dextrans and one NaPA-dextran conjugate. Anti-cancer drugs 4 11914639
2001 Crystallization and preliminary X-ray analysis of the periplasmic nitrate reductase (NapA-NapB complex) from Rhodobacter sphaeroides f. sp. denitrificans. Acta crystallographica. Section D, Biological crystallography 4 11717511
2025 Peroxiredoxin PrxA and thioredoxin TrxA mediate the redox signal to the transcription factor NapA in the fungus Aspergillus nidulans. International journal of biological macromolecules 3 40274147
2024 Assessing the effects of NapA gene overexpression on denitrification and denitrogenation in magnetospirillum gryphiswaldense MSR-1. Archives of microbiology 3 39425777
2020 Agrobacterium fabrum C58 involved nitrate reductase NapA and antisense RNA NorR to denitrify. FEMS microbiology ecology 2 33206969
2018 Designing a novel ELISA method based on CagA, NapA recombinant antigens to increase sensitivity and specificity of Helicobacter pylori whole cell antigen detection. Gastroenterology and hepatology from bed to bench 2 30425813
1990 Precocious expression of NAPA-73, an intermediate filament-associated protein, during nervous system and heart development in the chicken embryo. Annals of the New York Academy of Sciences 2 1694066
2023 The bZIP-type transcription factors NapA and RsmA modulate the volumetric ratio and the relative superoxide ratio of mitochondria in Aspergillus nidulans. Biologia futura 1 37814124
2021 Transient recombinant expression of highly immunogenic CagA, VacA and NapA in Nicotiana benthamiana. Biotechnology reports (Amsterdam, Netherlands) 1 35028298
2007 [Clone, expression and immunoreaction of napA gene of Helicobacter pylori]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 17488595
2026 Expression, purification and biochemical characterization of the periplasmic nitrate reductase NapA from Magnetospirillum gryphiswaldense MSR-1. Protein expression and purification 0 41771431
2026 In vitro exposure to non-antipseudomonal antibiotics (NAPA) induces Pseudomonas aeruginosa resistance to antipseudomonal antibiotics (APA). The Journal of antimicrobial chemotherapy 0 42219900
2025 Structural Studies on the M. tuberculosis Nucleoid-associated-Protein, NapA, Indicates DNA Bridging Mechanism. Journal of molecular biology 0 41106805
2024 Membrane Physiology Symposium April 22nd-23rd, 2024, Napa California, USA. Bioelectricity 0 39372087
2023 Complete genome sequence of Pectobacterium brasiliense strain 21PCA_AGRO2 with antimicrobial resistance isolated from napa cabbage. Microbiology resource announcements 0 37676017

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