Affinage

MUC5AC

Mucin-5AC · UniProt P98088

Length
5654 aa
Mass
585.6 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MUC5AC is a large gel-forming secreted mucin built from pro-von Willebrand factor-like D domains, cysteine-rich subdomains, and serine/threonine/proline-rich tandem-repeat arrays whose copy-number polymorphism underlies extensive allelic variation (PMID:11535137). Its biosynthesis requires C-mannosylation at WXXW motifs within the Cys1 and Cys5 subdomains in the endoplasmic reticulum, a modification needed for proper folding and ER export (PMID:14718370). At mucosal surfaces MUC5AC performs distinct protective functions: it spatially coordinates mucociliary transport on airway epithelium, such that its loss produces discoordinated rather than reduced transport (PMID:36427316), and in the gut it limits bacterial contact with and translocation across the colonic epithelium, protecting against experimental colitis (PMID:32385500). MUC5AC transcription is a convergence point for many epithelial signaling cascades, dominated by EGFR activation triggered by TACE-mediated cleavage of pro-TGF-alpha downstream of DUOX1-generated ROS, microbial serine proteases, and muscarinic M3 receptor signaling (PMID:15640347, PMID:21685325, PMID:20525722), by NF-kappaB acting both directly and through HIF-1alpha (PMID:19841186, PMID:29031476), and by STAT6, Notch, and MAPK-dependent inputs from type 2 and IL-17 cytokines (PMID:21622856, PMID:27588910, PMID:24892823). In cancer, MUC5AC acts beyond a secreted barrier: it physically engages CD44 to activate Src and drives colorectal tumor invasion and chemoresistance (PMID:32098629), binds ANXA2 to activate matrix metalloproteases and promote brain metastasis (PMID:38825648), undergoes ST6GalNAc-I-mediated STn sialylation that supports migration and metastasis (PMID:33792183), and is required for KRAS-driven lung adenocarcinoma and for suppression of anti-tumor neutrophil immunity in pancreatic cancer (PMID:21249315, PMID:30089720).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 Low

    Establishing the domain architecture of MUC5AC defined it as a von Willebrand factor-type gel-forming mucin and explained the molecular basis of its length polymorphism.

    Evidence Full-length cDNA sequencing and Southern blot of allelic variants

    PMID:11535137

    Open questions at the time
    • No functional consequences assigned to individual domains
    • Tandem-repeat polymorphism not linked to phenotype
  2. 2004 High

    Identifying C-mannosylation of the Cys subdomains answered how MUC5AC achieves proper folding and ER export, linking a specific co-translational glycosylation to secretion competence.

    Evidence WXXW mutagenesis, pulse-chase, lectin binding, and C-mannosylation-defective CHO-Lec35.1 cells with GFP-tagged subdomains

    PMID:14718370

    Open questions at the time
    • Done on isolated Cys subdomains, not full-length mucin
    • Enzyme responsible for C-mannosylation not identified
  3. 2005 High

    The DUOX1/ROS → TACE → pro-TGF-alpha → EGFR cascade established a unifying oxidant-driven route by which airway stimuli converge on MUC5AC transcription.

    Evidence siRNA, ROS scavengers, NADPH oxidase and TACE inhibitors with PMA/neutrophil elastase in HBE and NCI-H292 cells

    PMID:15640347

    Open questions at the time
    • Transcription factors terminal to EGFR not defined here
    • Single airway context
  4. 2007 High

    Reporter and in vivo work showed SMAD4 and HIF-1alpha bind conserved Muc5ac promoter motifs required for activity, and that Muc5ac is the dominant induced mucin in allergic airways.

    Evidence OVA mouse model plus luciferase promoter mutagenesis in a Clara cell line

    PMID:17463395

    Open questions at the time
    • Upstream activators of SMAD4/HIF-1alpha at the promoter not resolved
  5. 2009 High

    ChIP and reporter assays mapped a specific NF-kappaB (p50) site in the MUC5AC promoter, establishing direct cytokine-driven transcriptional control by IL-1beta and IL-17A.

    Evidence Reporter assays, p65 siRNA, NF-kappaB inhibitor, and ChIP in primary NHBE and HBE1 cells

    PMID:19841186

    Open questions at the time
    • Cooperation with other promoter factors not addressed
  6. 2011 Medium

    Microbial serine proteases and EGFR-Notch crosstalk were shown to feed the EGFR axis, broadening the range of stimuli that activate MUC5AC via TACE and amplifying signaling through reciprocal Notch-EGFR loops.

    Evidence Protease and TACE inhibitors, siRNA, neutralizing antibodies (Aspergillus); gamma-secretase inhibitors, Notch1 siRNA, NICD overexpression (Notch) in NCI-H292 and primary HBE cells

    PMID:21622856 PMID:21685325

    Open questions at the time
    • Single-lab pathway dissections
    • Quantitative contribution relative to other inputs unclear
  7. 2016 Medium

    Defining the STAT6 → TMEM16A → ERK route and Lyn-mediated negative regulation of STAT6 clarified how type 2 cytokine signaling is tuned at the MUC5AC promoter.

    Evidence STAT6 inhibition and TMEM16A siRNA (IL-13); Lyn gain/loss-of-function with ChIP for STAT6 binding in 16HBE and OVA mice

    PMID:27588910 PMID:28205598

    Open questions at the time
    • Single cell lines/labs
    • Integration with NF-kappaB inputs not tested
  8. 2020 High

    Co-IP and CRISPR knockout established MUC5AC as an active cancer-promoting protein through physical CD44 engagement and Src activation, beyond its role as a secreted barrier.

    Evidence Reciprocal co-IP, CRISPR/Cas9 knockout, in vitro and orthotopic in vivo assays in colorectal cancer cells

    PMID:32098629

    Open questions at the time
    • Binding interface not mapped
    • Generalizability beyond CRC unestablished
  9. 2020 High

    Genetic knockout in the colon demonstrated that MUC5AC's barrier function operates by excluding bacteria, with antibiotics rescuing the colitis phenotype.

    Evidence Muc5ac-/- mice, DSS colitis, bacterial translocation assays, 16S sequencing, antibiotic rescue

    PMID:32385500

    Open questions at the time
    • Mechanism of bacterial exclusion at molecular level not defined
  10. 2022 High

    Separate CRISPR knockout of MUC5AC and MUC5B in human airway cultures showed MUC5AC uniquely coordinates the spatial alignment of mucociliary transport rather than its overall magnitude.

    Evidence CRISPR-deficient human airway ALI cultures with quantitative transport measurement

    PMID:36427316

    Open questions at the time
    • Biophysical basis of coordination not resolved
  11. 2024 Medium

    Identification of the MUC5AC-ANXA2 axis and ST6GalNAc-I-mediated STn sialylation extended MUC5AC's tumor-promoting mechanism to MMP activation/metastasis and glycan-driven progression.

    Evidence Co-IP/proteomics and peptide inhibitor in brain-metastasis models (ANXA2); MUC5AC STn immunoprecipitation and ST6GalNAc-I CRISPR knockout in metastasis models (sialylation)

    PMID:33792183 PMID:38825648

    Open questions at the time
    • Single-lab studies
    • Interaction interfaces and glycosite specificity incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many converging transcriptional inputs are integrated at the native MUC5AC locus, and whether VNTR allelic variants confer functionally distinct mucin properties, remains unresolved.
  • No combinatorial promoter logic established across the cited pathways
  • Functional consequences of the 16 allelic protein variants untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005576 extracellular region 2 GO:0005783 endoplasmic reticulum 1 GO:0005886 plasma membrane 1
Partners
ANXA2CD44

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Dual oxidase 1 (Duox1) generates reactive oxygen species that activate TACE (TNF-alpha-converting enzyme), leading to cleavage of pro-TGF-alpha and subsequent EGFR activation, resulting in MUC5AC expression in airway epithelial cells. PKCdelta/PKC lies upstream of Duox1 in this cascade. siRNA knockdown of Duox1, ROS scavengers, NADPH oxidase inhibitors, TACE inhibition; stimulation with PMA and neutrophil elastase in human bronchial epithelial cells and NCI-H292 cells Proceedings of the National Academy of Sciences of the United States of America High 15640347
2009 IL-1beta and IL-17A induce MUC5AC expression via NF-kappaB-dependent transcriptional activation. A critical NF-kappaB binding site at position -3594/-3582 in the MUC5AC promoter was identified, and chromatin immunoprecipitation confirmed enhanced binding of NF-kappaB subunit p50 to this region following cytokine stimulation. Reporter gene assay, siRNA knockdown of p65, NF-kappaB small molecule inhibitor, ChIP analysis in well-differentiated primary normal human bronchial epithelial cells and HBE1 cells Journal of immunology High 19841186
2007 In allergic mouse airways, Muc5ac is the predominant gel-forming mucin induced, localizing to bronchial Clara cells. SMAD4 and HIF-1alpha bind to evolutionarily conserved motifs in the Muc5ac promoter and are required for promoter function; mutation of their recognition motifs abolishes promoter activity. Murine OVA model, luciferase reporter gene assay with promoter mutations, transcription factor binding analysis in transformed Clara cell line American journal of respiratory cell and molecular biology High 17463395
2004 The Cys subdomains of MUC5AC (Cys1 and Cys5) undergo C-mannosylation at their WXXW motifs in the endoplasmic reticulum. Mutation of the first tryptophan in the WXXW motif or expression in C-mannosylation-defective CHO-Lec35.1 cells reduces secretion and causes ER retention, indicating C-mannosylation is required for proper folding and/or ER export of MUC5AC. Pulse-chase labeling, mutagenesis of WXXW motif, lectin binding assays, live cell imaging of GFP-tagged Cys subdomains, C-mannosylation-defective cell line (CHO-Lec35.1) Glycobiology High 14718370
2002 IL-1beta induces MUC5AC expression in NCI-H292 airway epithelial cells through a COX-2/PGE2 pathway, with ERK1/2 and p38 MAPK acting upstream of COX-2 induction. Selective COX-2 inhibitor (NS398), MAPK inhibitors (PD98059, SB203580), exogenous PGE2 addition; mRNA and protein quantification Molecular pharmacology Medium 12391274
2000 Neutrophil elastase induces MUC5AC gene expression through an oxidant-dependent mechanism involving reactive oxygen species (hydroxyl radical/peroxynitrite) in airway epithelial cells. ROS scavenger DMTU, intracellular redox indicator dichlorodihydrofluorescein in A549 and primary normal human bronchial epithelial cells Chest Medium 10843967
2007 NQO1 (NAD(P)H:quinone oxidoreductase 1) mediates neutrophil elastase-induced oxidant stress and MUC5AC mRNA expression in airway epithelial cells; siRNA knockdown of NQO1 abrogates MUC5AC expression and reduces NE-induced lipid peroxidation. Pharmacologic NQO1 inhibitor (dicumarol), siRNA knockdown of NQO1, lipid peroxidation assay in A549 cells and primary normal human bronchial epithelial cells Free radical biology & medicine Medium 17395013
2011 Aspergillus fumigatus serine protease activity activates TACE, which cleaves membrane-bound pro-TGF-alpha; this leads to EGFR activation and induction of MUC5AC expression in airway epithelial cells. Cysteine protease inhibition had no effect, only serine protease inhibition blocked TACE activation and MUC5AC induction. Serine/cysteine protease inhibitors, TACE inhibitors, TACE siRNA, EGFR/TGF-alpha neutralizing antibodies in NCI-H292 cells and primary airway epithelial cells Journal of immunology High 21685325
2009 Neuregulin 1beta1 (NRG1beta1) induces MUC5AC and MUC5B expression in primary human bronchial epithelial cells via ErbB2 and ErbB3 receptors (not ErbB4), with downstream involvement of p38 MAPK, ERK1/2, and PI3K, and induction of ErbB2, AKT, and ERK1/2 phosphorylation. ErbB receptor-specific inhibitors, kinase inhibitors (p38, ERK1/2, PI3K), Western blot for phosphorylation, time- and dose-response studies in primary HBECs and in vivo antigen-challenged mice American journal of respiratory cell and molecular biology Medium 19556605
2009 PGF2alpha induces MUC5AC overproduction in human tracheobronchial epithelial cells via a sequential signaling cascade: PKC → ERK → p90RSK → CREB. CREB directly interacts with the MUC5AC promoter via a cAMP response element, and suppression of each signaling molecule along this pathway abrogates MUC5AC expression. Pathway inhibitors, promoter reporter assay (CRE-dependent MUC5AC promoter activity), CREB-MUC5AC promoter interaction assay Journal of immunology Medium 19201889
2010 Muscarinic M3 receptor (not M2) mediates carbachol-induced MUC5AC expression in human airway epithelial cells via EGFR transactivation and p44/42 MAPK phosphorylation; aclidinium inhibits carbachol- and cigarette smoke-induced MUC5AC overexpression through this pathway. siRNA against muscarinic receptor subtypes (M2, M3), EGFR tyrosine kinase inhibitor AG1478, phospho-EGFR and phospho-MAPK Western blot, in human bronchial tissue and cultured epithelial cells The European respiratory journal Medium 20525722
2011 EGF-induced MUC5AC expression requires bidirectional signaling between EGFR and Notch pathways: EGFR induces Notch intracellular domain (NICD) generation in an RBP-Jkappa-dependent manner, and Notch signaling amplifies EGFR/ERK activation. Forced NICD expression alone is sufficient to induce MUC5AC via EGFR-ERK activation. gamma-secretase inhibitors, Notch1 siRNA, NICD overexpression, EGFR antagonist antibody, EGFR and ERK inhibitors in NCI-H292 cells and primary human bronchial epithelial cells Journal of immunology Medium 21622856
2013 Neutrophil elastase induces MUC5AC secretion via PAR2 (protease-activated receptor 2), which increases cytosolic calcium from ER stores and via store-operated calcium entry (SOCE) channels, subsequently activating PKC to stimulate secretion. PAR1/2/3 expression analysis, PAR2 expression measurement after NE, calcium measurement with thapsigargin (ER depletion) and 2-APB (SOCE inhibitor), PKC activation assay in Calu-3 cells Molecular and cellular biochemistry Medium 23392769
2016 IL-13 induces MUC5AC expression in human airway epithelial cells via STAT6-dependent upregulation of TMEM16A, whose chloride channel activity activates ERK1/2; TMEM16A knockdown or channel inhibition reduces ERK1/2 phosphorylation and MUC5AC expression. STAT6 inhibition, TMEM16A siRNA knockdown, chloride channel inhibitor T16Ainh-A01, ERK1/2 inhibitor PD98059, mRNA and protein quantification in HBE16 cells International immunopharmacology Medium 27588910
2014 IL-17A induces MUC5AC expression and goblet cell hyperplasia through the Act1-mediated signaling pathway involving MAPK (ERK, p38, JNK) activation; siRNA knockdown of IL-17RA, IL-17RC, and Act1 each block IL-17A-induced MUC5AC production. siRNA knockdown of IL-17RA, IL-17RC, Act1; MAPK Western blot; qPCR and Western blot in polyp epithelial cells and NCI-H292 cells PloS one Medium 24892823
2017 IL-1beta upregulates Muc5ac expression via NF-kappaB-induced HIF-1alpha: NF-kappaB activation induces HIF-1alpha, which directly binds the Muc5ac promoter and enhances its transcriptional activity. HIF-1alpha siRNA knockdown and NF-kappaB inhibition (Bay11-7082) each reduce IL-1beta-induced Muc5ac expression. siRNA knockdown of HIF-1alpha, NF-kappaB inhibitor, luciferase reporter assay with Muc5ac promoter, EMSA for HIF-1alpha binding to Muc5ac promoter in NHBECs Immunology letters Medium 29031476
2017 Lyn kinase negatively regulates MUC5AC expression by downregulating STAT6 and its binding to the Muc5ac promoter; Lyn overexpression decreases IL-4/IL-13-induced MUC5AC expression and STAT6 phosphorylation, while Lyn knockdown increases them. ChIP confirmed that Lyn overexpression decreases STAT6 binding to the Muc5ac promoter. Lyn overexpression and siRNA knockdown in 16HBE cells and OVA mouse model, ChIP analysis for STAT6 binding to Muc5ac promoter, STAT6 phosphorylation Western blot Scientific reports Medium 28205598
2021 Benzo(a)pyrene induces MUC5AC expression through an AhR/mitochondrial ROS/ERK pathway: AhR nuclear translocation activates CYP1s (CYP1A1/CYP1B1), increasing mitochondrial ROS, which activates ERK and CREB to drive MUC5AC promoter activity. AhR overexpression enhances and AhR/CREB siRNA knockdown reduces BaP-induced MUC5AC. AhR siRNA and overexpression lentivirus, CREB siRNA, CYP1 inhibitor, mitochondrial ROS inhibitor Mito-TEMP, ERK inhibitor U0126, luciferase MUC5AC promoter assay in NCI-H292 cells Ecotoxicology and environmental safety Medium 33421718
2009 dsRNA (poly(I:C)) synergistically amplifies TGF-alpha-induced MUC5AC expression via sustained ERK activation; this occurs through poly(I:C)-mediated inhibition of MKP3 (MAPK phosphatase 3) upregulation. Overexpression of MKP3 completely suppresses the poly(I:C)-enhanced MUC5AC induction. MEK1/2 inhibitor U0126, MKP3 overexpression, ERK phosphorylation Western blot, MUC5AC promoter activity assay in NCI-H292 cells and primary HBECs Journal of immunology Medium 19109160
2018 TGF-beta3 induces MUC5AC hyper-expression in airway epithelium through autophagy activation and subsequent AP-1 (activator protein-1) activation; Smad2/3 pathway mediates TGF-beta3-induced autophagy. Inhibition of autophagy reduces TGF-beta3-induced MUC5AC expression in vitro and in vivo. Autophagy inhibitors in OVA mouse model, autophagy induction by TGF-beta3 in human bronchial epithelial cells, AP-1 activation measurement, Smad2/3 pathway analysis EBioMedicine Medium 29997053
2020 MUC5AC physically interacts with CD44 (co-immunoprecipitation), and this interaction activates Src signaling. MUC5AC knockout (CRISPR/Cas9) reduces colorectal cancer invasion/migration, increases apoptosis, and sensitizes cells to 5-FU and oxaliplatin via modulation of p53/p21/beta-catenin/CD44/Lgr5 signaling. CRISPR/Cas9 knockout, siRNA knockdown, co-immunoprecipitation, in vitro functional assays, in vivo orthotopic mouse models in CRC cell lines Molecular cancer High 32098629
2011 MUC5AC expressed on the surface of pancreatic cancer cells enables escape from host immunosurveillance; MUC5AC knockdown (siRNA) suppresses in vivo tumor growth and allows neutrophil (Gr-1+) and B-cell (CD45R/B220+) infiltration. Tumor growth of MUC5AC-knockdown cells is restored upon neutrophil depletion, indicating MUC5AC specifically suppresses neutrophil anti-tumor activity. Stable siRNA knockdown in SW1990 and BxPC3 cells, xenograft studies, neutrophil depletion with anti-Gr-1 mAb, immunohistochemistry, serum antibody detection International journal of oncology Medium 21249315
2013 MUC5AC protects pancreatic cancer cells from TRAIL-induced apoptosis: MUC5AC-knockdown cells showed significantly increased active caspase-3 after TRAIL addition, while control cells did not, indicating MUC5AC inhibits TRAIL-mediated death pathways. Stable siRNA knockdown in SW1990 cells, TRAIL treatment, active caspase-3 measurement, immunocyte-depleted animal models International journal of oncology Medium 23292004
2021 ST6GalNAc-I catalyzes sialylation (STn modification) of MUC5AC; immunoprecipitation of MUC5AC in p53R175H-expressing cells showed higher affinity toward STn. ST6GalNAc-I knockout reduces MUC5AC glycosylation (less STn), decreases cell migration, and reduces liver metastasis in vivo. Immunoprecipitation of MUC5AC for STn, ST6GalNAc-I CRISPR knockout, in vivo metastasis models, ectopic p53 mutant expression Molecular oncology Medium 33792183
2022 MUC5B and MUC5AC play distinct roles in mucociliary transport: MUC5B deficiency impairs mucus transport (reduced overall transport), while MUC5AC deficiency results in discoordinated mucociliary transport, demonstrating that MUC5AC spatially aligns mucociliary transport on human airway epithelium. CRISPR-based generation of MUC5B- and MUC5AC-deficient human airway epithelial tissue cultures, mucociliary transport measurement Science advances High 36427316
2020 Muc5ac expression protects the colonic barrier during experimental colitis by limiting bacterial epithelial contact and translocation to mesenteric lymph nodes; Muc5ac-/- mice have worsened DSS colitis, and antibiotic treatment normalizes colitis severity in Muc5ac-/- mice, confirming that the protective effect is mediated by bacterial exclusion. Muc5ac-/- mouse model, DSS colitis, bacterial-epithelial contact quantification, bacterial translocation assay, 16S rRNA sequencing, antibiotic treatment Inflammatory bowel diseases High 32385500
2018 Muc5ac is required for KRAS-driven lung adenocarcinoma development: mice lacking Muc5ac have significantly reduced tumor development in both chemically-induced (urethane) and transgenic mutant-Kras lung adenocarcinoma models. Muc5ac-/- mice crossed with urethane-induced and transgenic Kras-mutant lung adenocarcinoma models, tumor burden quantification JCI insight Medium 30089720
2020 EGFR activation reduces claudin1 expression, and claudin1 knockdown induces MUC5AC overexpression in vitro and in vivo; restoring claudin1 expression by EGFR antagonism (erlotinib) reduces MUC5AC expression, placing claudin1 as a negative regulator of MUC5AC downstream of EGFR. claudin1 siRNA knockdown in 16HBE cells and HDM mouse model, erlotinib treatment, in vitro and in vivo MUC5AC measurement Mucosal immunology Medium 32132671
2020 MUC1-dependent EGFR activation mediates cigarette smoke-induced goblet cell metaplasia and Muc5ac overproduction; Muc1-knockout rats show no EGFR phosphorylation and are protected from GCM and Muc5ac overproduction after cigarette smoke exposure. MUC1 translocates from the apical surface to intracellular compartments in response to cigarette smoke. Muc1-knockout rat model, cigarette smoke exposure, EGFR phosphorylation Western blot, MUC1 localization immunostaining, siRNA knockdown in human lung cells and primary rat airway epithelial cells American journal of physiology. Lung cellular and molecular physiology Medium 32401676
2019 In neutrophil elastase (HNE)-induced MUC5AC overexpression in chronic rhinosinusitis, autophagy increases MUC5AC secretion by promoting JNK/c-Jun phosphorylation; siRNA knockdown of Beclin-1, Atg5, or c-Jun each block HNE-induced MUC5AC secretion in primary human nasal epithelial cells. Bafilomycin A1 (autophagy inhibitor), BECN1-siRNA, Atg5-siRNA, c-Jun-siRNA, SP600125 (JNK inhibitor), TEM for autophagosomes, in CRS patient mucosa and primary HNECs International immunopharmacology Medium 30909132
2018 IL-13 induces MUC5AC expression in nasal epithelial cells through ERK1/2 activation and C-JUN upregulation mediated by IL-13Ralpha2, and this can be attenuated by ERK1/2 inhibitor or dexamethasone. ERK1/2 inhibitor, siRNA, MUC5AC mRNA/protein quantification, ERK phosphorylation Western blot in primary hNECs and ALI cultures Allergy Low 29405354
2014 IL-13 induces MUC5AC expression in mouse tracheal epithelial cells via a PI3K-NFAT3 pathway: IL-13 promotes NFAT3 dephosphorylation/activation, and both PI3K inhibitor (LY294002) and NFAT inhibitor (Cyclosporin A) block IL-13-induced MUC5AC production without affecting Foxa2 or mClca3 expression. PI3K inhibitor LY294002, NFAT inhibitor Cyclosporin A, phosphorylation assay for NFAT3, MUC5AC mRNA and protein measurement in ALI cultures of mouse tracheal epithelial cells Biochemical and biophysical research communications Low 24583134
2013 PGE2 induces MUC5AC expression in human intrahepatic biliary epithelial cells via EP4 receptor-p38 MAPK signaling; EP4 agonist increases and EP4 antagonist decreases MUC5AC expression, and p38 MAPK inhibitor reduces PGE2-induced MUC5AC expression. EP4 agonist/antagonist, p38 MAPK inhibitor, LPS stimulation with TLR4 antagonist and NF-kappaB inhibitor in HIBECs; bile samples from hepatolithiasis patients Annals of hepatology Low 23619266
2022 ITGB4 deficiency in airway epithelial cells induces MUC5AC overexpression through the EGFR/ERK/c-Jun pathway; EGFR inhibitors prevent mucus hypersecretion and MUC5AC overexpression in ITGB4-deficient mice after RSV infection. ITGB4 siRNA knockdown in HBE cells, ITGB4-deficient mice, RSV infection, EGFR inhibitor treatment, ERK/c-Jun pathway Western blot International journal of biological sciences Medium 34975337
2016 Spleen tyrosine kinase (SYK) induces MUC5AC expression in human airway epithelial cells via ERK2 and p38 MAPK signaling pathways; ERK2 siRNA and p38 MAPK siRNA each block SYK-induced MUC5AC expression. ERK1/2 inhibitor U0126, p38 inhibitor SB203580, ERK2 siRNA, p38 MAPK siRNA, SYK stimulation in NCI-H292 and primary human nasal epithelial cells American journal of rhinology & allergy Low 26980390
2023 Oxidative stress induces MUC5AC expression in airway epithelial cells via a mitochondrial damage-dependent STING (stimulator of interferon genes) pathway; STING knockout suppresses H2O2-induced MUC5AC expression, while cGAS knockout does not. STING and cGAS CRISPR knockout cells, hydrogen peroxide treatment, mitochondrial antioxidants, cytosolic mitochondrial DNA measurement in NCI-H292 and primary NHBECs FASEB bioAdvances Medium 37020748
2024 MUC5AC interacts with Annexin A2 (ANXA2) in lung adenocarcinoma cells (identified by immunoprecipitation and proteomic analysis); this MUC5AC/ANXA2 signaling axis activates downstream matrix metalloproteases and facilitates ECM degradation to promote brain metastasis. A peptide inhibitor disrupting MUC5AC-ANXA2 interaction abrogates metastasis. Immunoprecipitation, proteomic analysis, MUC5AC depletion in brain-tropic cell lines, intracardiac injection brain metastasis models, peptide inhibitor Experimental & molecular medicine Medium 38825648
2022 NOTCH3 intracellular domain (NICD3) regulates MUC5AC (and MUC2) expression by directly recruiting SMARCA4 (BRG1/transcription activator); NOTCH3 controls MUC5AC transcription in a SMARCA4-dependent manner in colorectal cancer cells. Co-immunoprecipitation of NICD3 and SMARCA4, RNA sequencing for target gene identification, functional assays in CRC cells Molecular oncology Medium 35900231
2024 MUC5AC contains polymorphic variable number tandem repeats (VNTRs) with cysteine-rich domain and VNTR copy-number variation defining 30 allelic variants encoding 16 distinct proteins (5,249-6,325 aa). Long-read sequencing and haplotype analysis reveal three phylogenetic clades (H1, H2, H3) with signatures of positive selection in East Asians and balancing selection in Europeans. Long-read sequencing and assembly of 206 human and 20 NHP haplotypes, Locityper genotyping of 2,600 samples from 1000 Genomes Project, Tajima's D and linkage disequilibrium analysis American journal of human genetics Low 38991590
2001 MUC5AC gene organization was fully elucidated: the 5' region encodes a signal peptide, four pro-von Willebrand factor-like D domains (D1, D2, D', D3), and the central region contains 9 cysteine-rich domains interspersed with serine/threonine/proline-rich domains and four tandem repeat arrays (TR1-TR4). Length polymorphism is due to variable numbers of tandem repeats in TR1 and TR4. Full-length cDNA sequencing, Southern blot analysis for allelic variations The Biochemical journal Low 11535137

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Airway Mucus and Asthma: The Role of MUC5AC and MUC5B. Journal of clinical medicine 282 29186064
2019 Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways. American journal of respiratory and critical care medicine 233 30352166
2009 Regulation of airway MUC5AC expression by IL-1beta and IL-17A; the NF-kappaB paradigm. Journal of immunology (Baltimore, Md. : 1950) 221 19841186
2005 Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 217 15640347
2004 Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. American journal of clinical pathology 177 15272531
2007 Central role of Muc5ac expression in mucous metaplasia and its regulation by conserved 5' elements. American journal of respiratory cell and molecular biology 147 17463395
2002 Expression of MUC5AC and MUC5B mucins in normal and cystic fibrosis lung. Respiratory medicine 137 11860173
2013 Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 128 23807779
2020 Molecular implications of MUC5AC-CD44 axis in colorectal cancer progression and chemoresistance. Molecular cancer 116 32098629
2011 IL-13-induced MUC5AC production and goblet cell differentiation is steroid resistant in human airway cells. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 108 22092504
2006 MUC1, MUC2, MUC4, MUC5AC and MUC6 expression in the progression of prostate cancer. Clinical & experimental metastasis 103 16475027
1999 Aberrant expression of MUC5AC and MUC6 gastric mucin genes in colorectal polyps. International journal of cancer 103 9935202
1996 Aberrant expression of a human mucin gene (MUC5AC) in rectosigmoid villous adenoma. Gastroenterology 97 8536891
2002 Interleukin-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells. Molecular pharmacology 86 12391274
2004 C-Mannosylation of MUC5AC and MUC5B Cys subdomains. Glycobiology 81 14718370
2008 Mycoplasma pneumoniae induces airway epithelial cell expression of MUC5AC in asthma. The European respiratory journal 75 18166592
2004 Colonic expression of MUC2, MUC5AC, and TFF1 in inflammatory bowel disease in children. Journal of pediatric gastroenterology and nutrition 74 15097436
2004 Up-regulation of MUC5AC and MUC5B mucin genes in chronic rhinosinusitis. Archives of otolaryngology--head & neck surgery 72 15210557
2010 Aclidinium inhibits cholinergic and tobacco smoke-induced MUC5AC in human airways. The European respiratory journal 66 20525722
1998 Acrolein-induced MUC5ac expression in rat airways. The American journal of physiology 63 9575876
2005 Differential regulation of MUC5AC/Muc5ac and hCLCA-1/mGob-5 expression in airway epithelium. American journal of respiratory cell and molecular biology 59 16151054
2018 Role of IL-13Rα2 in modulating IL-13-induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa. Allergy 56 29405354
2021 Benzo(a)pyrene induces MUC5AC expression through the AhR/mitochondrial ROS/ERK pathway in airway epithelial cells. Ecotoxicology and environmental safety 55 33421718
2007 The expression of MUC5AC and MUC5B mucin genes in the mucosa of chronic rhinosinusitis and nasal polyposis. American journal of rhinology 54 17621824
2020 The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease. Molecules (Basel, Switzerland) 52 32992527
2016 Interleukin-13 stimulates MUC5AC expression via a STAT6-TMEM16A-ERK1/2 pathway in human airway epithelial cells. International immunopharmacology 52 27588910
2014 Interleukin-17A promotes MUC5AC expression and goblet cell hyperplasia in nasal polyps via the Act1-mediated pathway. PloS one 52 24892823
2011 Induction of mucin and MUC5AC expression by the protease activity of Aspergillus fumigatus in airway epithelial cells. Journal of immunology (Baltimore, Md. : 1950) 52 21685325
2000 Neutrophil elastase induces MUC5AC messenger RNA expression by an oxidant-dependent mechanism. Chest 52 10843967
2020 EGFR activation-induced decreases in claudin1 promote MUC5AC expression and exacerbate asthma in mice. Mucosal immunology 50 32132671
2018 Ramifications of secreted mucin MUC5AC in malignant journey: a holistic view. Carcinogenesis 49 29415129
2017 IL-1β upregulates Muc5ac expression via NF-κB-induced HIF-1α in asthma. Immunology letters 49 29031476
2011 Tumor-associated MUC5AC stimulates in vivo tumorigenicity of human pancreatic cancer. International journal of oncology 49 21249315
2010 Altered expression of MUC2 and MUC5AC in progression of colorectal carcinoma. World journal of gastroenterology 49 20731025
2012 Genes associated with MUC5AC expression in small airway epithelium of human smokers and non-smokers. BMC medical genomics 48 22676183
2005 MUC1 and MUC5AC mucin expression in liver fluke-associated intrahepatic cholangiocarcinoma. World journal of gastroenterology 48 16124042
2001 Human mucin gene MUC5AC: organization of its 5'-region and central repetitive region. The Biochemical journal 48 11535137
2011 Expression of MUC5AC in ocular surface epithelial cells using cationized gelatin nanoparticles. Molecular pharmaceutics 47 21770384
2019 Natural inhibitors on airway mucin: Molecular insight into the therapeutic potential targeting MUC5AC expression and production. Life sciences 45 31116959
2022 MUC5B mobilizes and MUC5AC spatially aligns mucociliary transport on human airway epithelium. Science advances 44 36427316
2017 Lyn regulates mucus secretion and MUC5AC via the STAT6 signaling pathway during allergic airway inflammation. Scientific reports 44 28205598
2000 Differential expression of MUC2 and MUC5AC in benign and malignant glandular lesions of the cervix uteri. Virchows Archiv : an international journal of pathology 38 11097361
2015 Immunohistochemical study of MUC1, MUC2 and MUC5AC in colorectal carcinoma and review of literature. Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology 37 25731647
2013 MUC5AC protects pancreatic cancer cells from TRAIL-induced death pathways. International journal of oncology 37 23292004
2020 Muc5ac Expression Protects the Colonic Barrier in Experimental Colitis. Inflammatory bowel diseases 36 32385500
2009 Regulation of neuregulin 1beta1-induced MUC5AC and MUC5B expression in human airway epithelium. American journal of respiratory cell and molecular biology 36 19556605
2021 ST6GalNAc-I promotes lung cancer metastasis by altering MUC5AC sialylation. Molecular oncology 35 33792183
2003 Methylation status of promoters and expression of MUC2 and MUC5AC mucins in pancreatic cancer cells. International journal of oncology 35 12527922
2018 Requirement for MUC5AC in KRAS-dependent lung carcinogenesis. JCI insight 33 30089720
2011 MUC5AC expression through bidirectional communication of Notch and epidermal growth factor receptor pathways. Journal of immunology (Baltimore, Md. : 1950) 33 21622856
2004 Expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen in pancreatic tumors. International journal of oncology 33 14654947
2013 Neutrophil elastase induces MUC5AC secretion via protease-activated receptor 2. Molecular and cellular biochemistry 32 23392769
2012 MUC5AC, cytokeratin 20 and HER2 expression and K-RAS mutations within mucinogenic growth in congenital pulmonary airway malformations. Histopathology 32 22348416
2007 Regulation of MUC5AC expression by NAD(P)H:quinone oxidoreductase 1. Free radical biology & medicine 32 17395013
2020 Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer. Medical oncology (Northwood, London, England) 29 32219571
2020 MUC1 contributes to goblet cell metaplasia and MUC5AC expression in response to cigarette smoke in vivo. American journal of physiology. Lung cellular and molecular physiology 28 32401676
2015 Resveratrol inhibits mucus overproduction and MUC5AC expression in a murine model of asthma. Molecular medicine reports 28 26549244
2009 CREB mediates prostaglandin F2alpha-induced MUC5AC overexpression. Journal of immunology (Baltimore, Md. : 1950) 28 19201889
2021 MUC5AC Expression in Various Tumor Types and Nonneoplastic Tissue: A Tissue Microarray Study on 10 399 Tissue Samples. Technology in cancer research & treatment 27 34547930
2018 TGF-β3 Promotes MUC5AC Hyper-Expression by Modulating Autophagy Pathway in Airway Epithelium. EBioMedicine 27 29997053
2015 6-Mercaptopurine reduces cytokine and Muc5ac expression involving inhibition of NFκB activation in airway epithelial cells. Respiratory research 27 26084512
2007 Mucin genes (MUC2, MUC4, MUC5AC, and MUC6) detection in normal and pathological endometrial tissues. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 27 17197898
2021 Pathophysiological relevance of sputum MUC5AC and MUC5B levels in patients with mild asthma. Allergology international : official journal of the Japanese Society of Allergology 26 34656442
2017 Concentrations of MUC16 and MUC5AC using three tear collection methods. Molecular vision 25 28761326
2012 Relationships between IL-17A and macrophages or MUC5AC in eosinophilic chronic rhinosinusitis and proposed pathological significance. Allergy & rhinology (Providence, R.I.) 24 23342289
2021 Understanding the Clinical Impact of MUC5AC Expression on Pancreatic Ductal Adenocarcinoma. Cancers 23 34205412
2015 Increased expression of MUC5AC and MUC5B promoting bacterial biofilm formation in chronic rhinosinusitis patients. Auris, nasus, larynx 23 25638393
2024 Increased Muc5AC and Decreased Ciliated Cells in Severe Asthma Partially Restored by Inhibition of IL-4Rα Receptor. American journal of respiratory and critical care medicine 22 38935626
2013 MUC5AC expression correlates with invasiveness and progression of extramammary Paget's disease. Journal of the European Academy of Dermatology and Venereology : JEADV 22 23581859
2021 Inducible expression quantitative trait locus analysis of the MUC5AC gene in asthma in urban populations of children. The Journal of allergy and clinical immunology 21 34019912
2018 Eucalyptol protects lungs against bacterial invasion through attenuating ciliated cell damage and suppressing MUC5AC expression. Journal of cellular physiology 21 29215731
2010 Dietary polyphenols affect MUC5AC expression and ciliary movement in respiratory cells and nasal mucosa. American journal of rhinology & allergy 21 20338103
2013 PGE(2) induces MUC2 and MUC5AC expression in human intrahepatic biliary epithelial cells via EP4/p38MAPK activation. Annals of hepatology 20 23619266
2024 Structural and genetic diversity in the secreted mucins MUC5AC and MUC5B. American journal of human genetics 19 38991590
2019 The role of autophagy in the overexpression of MUC5AC in patients with chronic rhinosinusitis. International immunopharmacology 19 30909132
2021 Resveratrol inhibits MUC5AC expression by regulating SPDEF in lung cancer cells. Phytomedicine : international journal of phytotherapy and phytopharmacology 18 34139546
2021 Muc5ac Production Inhibited by Decreased lncRNA H19 via PI3K/Akt/NF-kB in Asthma. Journal of asthma and allergy 18 34421304
2023 The association between MUC5AC and MUC5B genes expression and remodeling progression in severe neutrophilic asthma: A direct relationship. Respiratory medicine 17 37146737
2022 Autocrine TGF-alpha is associated with Benzo(a)pyrene-induced mucus production and MUC5AC expression during allergic asthma. Ecotoxicology and environmental safety 17 36068759
2014 Interleukin-13-induced MUC5AC expression is regulated by a PI3K-NFAT3 pathway in mouse tracheal epithelial cells. Biochemical and biophysical research communications 17 24583134
2000 Lack of mucin MUC5AC field change expression associated with tubulovillous and villous colorectal adenomas. Journal of clinical pathology 16 10767823
2024 Dissecting the MUC5AC/ANXA2 signaling axis: implications for brain metastasis in lung adenocarcinoma. Experimental & molecular medicine 15 38825648
2020 The effect of Notch signal pathway on PM2.5-induced Muc5ac in Beas-2B cells. Ecotoxicology and environmental safety 15 32678753
2007 Altered expression of MUC2 and MUC5AC in response to Shigella infection, an in vivo study. Biochimica et biophysica acta 15 17395379
2007 Histamine induces MUC5AC expression via a hCLCA1 pathway. Pharmacology 15 17622767
2022 ITGB4 deficiency induces mucus hypersecretion by upregulating MUC5AC in RSV-infected airway epithelial cells. International journal of biological sciences 14 34975337
2016 Increased expression of hCLCA1 in chronic rhinosinusitis and its contribution to produce MUC5AC. The Laryngoscope 14 27296651
2015 Middle Ear Response of Muc5ac and Muc5b Mucins to Nontypeable Haemophilus influenzae. JAMA otolaryngology-- head & neck surgery 14 26512766
2004 MUC1, MUC2 and MUC5AC expressions in cardiac myxoma. Virchows Archiv : an international journal of pathology 14 15568157
2023 Oxidative stress induces MUC5AC expression through mitochondrial damage-dependent STING signaling in human bronchial epithelial cells. FASEB bioAdvances 13 37020748
2019 Expression and Serum Levels of Mucin 5AC (MUC5AC) as a Biomarker for Cholangiocarcinoma: a Meta-analysis. Journal of gastrointestinal cancer 12 29139058
2018 Allethrin and prallethrin stimulates MUC5AC expression through oxidative stress in human airway epithelial cells. Biochemical and biophysical research communications 12 29885834
2018 Conjunctival MUC5AC+ goblet cell index: relationship with corneal nerves and dry eye. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 12 30043267
2017 Immunohistochemical Study of MUC1, MUC2 and MUC5AC Expression in Primary Breast Carcinoma. Journal of clinical and diagnostic research : JCDR 12 28571146
2016 The diagnostic performance of serum MUC5AC for cholangiocarcinoma: A systematic review and meta-analysis. Medicine 12 27310944
2013 The changes in MUC5AC expression in gastric cancer before and after Helicobacter pylori eradication. Clinics and research in hepatology and gastroenterology 12 23910060
2018 Endoplasmic Reticulum Stress Induces MUC5AC and MUC5B Expression in Human Nasal Airway Epithelial Cells. Clinical and experimental otorhinolaryngology 11 30336657
2022 NICD3 regulates the expression of MUC5AC and MUC2 by recruiting SMARCA4 and is involved in the differentiation of mucinous colorectal adenocarcinoma. Molecular oncology 10 35900231
2016 Spleen tyrosine kinase induces MUC5AC expression in human airway epithelial cell. American journal of rhinology & allergy 10 26980390
2009 Double-stranded RNA and TGF-alpha promote MUC5AC induction in respiratory cells. Journal of immunology (Baltimore, Md. : 1950) 10 19109160

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