Affinage

MUC2

Mucin-2 · UniProt Q02817

Length
5289 aa
Mass
550.9 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MUC2 is the major gel-forming mucin that builds the colonic mucus barrier, structurally separating luminal bacteria from the epithelium: it forms a bacteria-free inner layer firmly attached to the epithelium and a proteolytically expanded outer layer, and its loss in knockout mice allows direct bacterial contact, spontaneous colitis, and tumorigenesis (PMID:18806221, PMID:16831596). Mucin packing and ordered release derive from the N-terminal VWD1-D2-D'D3 domains, which form calcium- and pH-dependent aggregates at low pH that dissolve upon Ca2+ removal and pH increase, with the D'D3 domain assembling into hexameric cage-like ring platforms that template the branched mucin network stored in goblet cell granules (PMID:22451922, PMID:24816392). Secretion is actively gated: a sentinel goblet cell at the crypt entrance endocytoses TLR2/1, TLR4, and TLR5 ligands and activates the Nlrp6 inflammasome downstream of TLR/MyD88-dependent Nox/Duox ROS, triggering calcium-dependent compound exocytosis of MUC2 and an intercellular gap-junction signal that recruits MUC2 secretion from neighboring cells to expel bacteria (PMID:27339979). Beyond its barrier role, MUC2 actively shapes innate defense through its O-glycans, promoting β-defensin 2 and cathelicidin (LL-37/Cramp) production in colonic epithelium (PMID:25921338, PMID:28069814). The high biosynthetic burden of MUC2 production drives ROS-dependent ER stress and apoptosis in goblet cells, with autophagy required for goblet cell survival under heavy mucin load (PMID:29545196, PMID:34494458). MUC2 transcription is controlled by multiple inputs, including direct activation by p53 in response to DNA damage and by VIP/cAMP/ERK/p38 signaling converging on a CREB/AP-1 promoter element, layered upon epigenetic regulation by promoter histone H3 modification and CpG methylation (PMID:12374798, PMID:16227528, PMID:16721789, PMID:20198318).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 Medium

    Established that MUC2 abundance is set at the transcriptional level, showing the gene is an actively regulated output rather than constitutively expressed.

    Evidence Nuclear run-on transcription assay in primary tracheobronchial epithelial cells treated with vitamin A

    PMID:8179918

    Open questions at the time
    • Performed in airway not colonic epithelium
    • No specific transcription factor identified
    • Single study
  2. 1997 High

    Dissected the proximal MUC2 promoter, identifying the cis-elements and Sp1-family factors required for basal activity and cell-type-specific expression, and showing mRNA stability is not a major regulator.

    Evidence Luciferase reporter deletion analysis, EMSA with antibody supershift, and actinomycin D mRNA stability assays across cell lines

    PMID:9224654

    Open questions at the time
    • Did not link promoter elements to physiological signals
    • Cell-type-specificity element factors not fully resolved
  3. 2002 High

    Connected MUC2 transcription to genotoxic stress by showing p53 directly binds and activates the MUC2 promoter, placing the gene downstream of DNA-damage signaling.

    Evidence Tetracycline-regulatable p53 in DLD-1 cells, promoter deletion/mutagenesis, EMSA, and DNA-damage induction in wild-type vs mutant p53 cells

    PMID:12374798

    Open questions at the time
    • Physiological context of p53-driven MUC2 in vivo unresolved
    • Relationship to barrier function not addressed
  4. 2006 High

    Demonstrated that MUC2 is the structural backbone of the colonic mucus barrier and is required to keep bacteria off the epithelium, defining its core protective function and linking its loss to colitis and cancer.

    Evidence Muc2 knockout mice with DSS colitis, mucus-layer proteomics, and bacterial localization microscopy across two studies

    PMID:16831596 PMID:18806221

    Open questions at the time
    • Mechanism of inner/outer layer proteolytic conversion not fully defined
    • Did not resolve which secreted proteases expand the outer layer
  5. 2008 High

    Showed that MUC2 barrier loss synergizes with Apc mutation to drive colonic tumorigenesis via deregulated Wnt signaling, establishing the mucin as a tumor-suppressive barrier whose breach is oncogenic.

    Evidence Muc2-/- × Apc double-mutant mouse crosses, tumor counting, and gene expression profiling of intestinal epithelium

    PMID:18794118

    Open questions at the time
    • Whether tumor promotion is purely barrier-dependent or also cell-intrinsic unresolved
    • Subclinical inflammation mechanism not detailed
  6. 2012 High

    Resolved the biophysical basis of mucin packing and release by showing the N-terminus aggregates reversibly under granule-like Ca2+/low-pH conditions, explaining storage and post-secretion expansion.

    Evidence Recombinant MUC2-N, gel filtration, density gradient centrifugation, and electron microscopy mimicking secretory-pathway conditions

    PMID:22451922

    Open questions at the time
    • In vitro reconstitution; in vivo granule dynamics inferred
    • Coupling to C-terminal polymerization not addressed
  7. 2014 High

    Defined the architectural unit of stored mucin by showing the D'D3 domain forms hexameric cage-like ring platforms, giving a structural model for the branched mucin network.

    Evidence Recombinant D'D3, gel filtration, electron microscopy with single-particle 3D reconstruction

    PMID:24816392

    Open questions at the time
    • High-resolution atomic structure not determined
    • How ring platforms integrate with full-length polymer in vivo unresolved
  8. 2016 High

    Identified the trigger and cellular circuit for MUC2 secretion, defining a sentinel goblet cell that senses bacterial ligands and orchestrates inflammasome-driven, calcium-dependent compound exocytosis and intercellular spreading of secretion.

    Evidence Multiple knockout mouse strains (Nlrp6, MyD88), live imaging, calcium signaling, and bacterial challenge

    PMID:27339979

    Open questions at the time
    • Identity of the gap-junction signal not defined
    • Human sentinel cell equivalence not demonstrated
  9. 2018 High

    Revealed a cost of high mucin output: MUC2 misfolding drives ROS-dependent ER stress and goblet cell apoptosis, linking biosynthetic burden to early colitis pathology.

    Evidence Isogenic high- vs MUC2-silenced HT29 cells, ROS inhibition rescue, and DSS colitis mouse model

    PMID:29545196

    Open questions at the time
    • Folding machinery handling MUC2 not identified
    • Threshold of biosynthesis triggering stress undefined
  10. 2021 Medium

    Showed autophagy is constitutively engaged to protect goblet cells producing high MUC2, and that IL-22 can correct MUC2 misfolding, defining a survival mechanism coupled to mucin synthesis.

    Evidence High vs silenced HT29 cells, CRISPR MUC2 KO LS174T, colonoids, autophagosome/pULK1 quantification, IL-22 rescue

    PMID:34494458

    Open questions at the time
    • Mechanistic link between MUC2 load and ULK1 activation unresolved
    • How IL-22 corrects folding not defined
  11. 2015 High

    Demonstrated MUC2 actively contributes to antimicrobial defense through its glycans, stimulating β-defensin 2 production beyond a passive physical barrier role.

    Evidence Purified MUC2 on goblet cells, shRNA silencing, Muc2-/- mice, and sodium metaperiodate glycan oxidation

    PMID:25921338

    Open questions at the time
    • Receptor sensing MUC2 glycans not identified
    • Specific glycan structures responsible undefined
  12. 2017 Medium

    Extended MUC2's immunomodulatory role by showing it promotes cathelicidin synthesis via cAMP/MAPK signaling, reinforcing its dual structural and signaling function.

    Evidence Purified MUC2 with shRNA silencing, pathway inhibitors, Muc2-/- mice, and E. histolytica infection

    PMID:28069814

    Open questions at the time
    • Direct receptor for MUC2 unresolved
    • Overlap with the β-defensin glycan mechanism not reconciled
  13. 2023 Medium

    Identified FCGBP as a coordinately produced, non-covalent glycan-mediated MUC2 partner that polarizes at wounds and influences epithelial wound closure, expanding the secreted-mucus interaction network.

    Evidence CRISPR MUC2 KO goblet-like cells, co-localization, co-IP, N-glycan inhibition, wound healing assays, DSS colitis

    PMID:37359538

    Open questions at the time
    • Direct vs glycan-bridged interaction not fully separated
    • Physiological significance of wound-margin polarization in vivo unclear
  14. 2021 Medium

    Mapped upstream differentiation control of MUC2, with DOCK4 driving the goblet cell program (Gfi1, Spdef) and MMP-9/Notch restraining it, contextualizing how MUC2-producing cells are specified.

    Evidence DOCK4 and MMP-9 knockout mice plus gain/loss-of-function in HT-29/Caco2 cells with differentiation marker readouts

    PMID:17484881 PMID:33559155

    Open questions at the time
    • Direct vs indirect effect of DOCK4 on MUC2 transcription unresolved
    • How GEF activity connects to differentiation factors undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the structurally defined N-terminal storage architecture, the sentinel-cell secretion circuit, the biosynthetic stress/autophagy program, and the multiple transcriptional/epigenetic inputs are integrated to set mucus barrier output in human disease remains unresolved.
  • No unified in vivo model connecting transcriptional control to secretion dynamics
  • Human (vs mouse) sentinel cell and Paneth-cell-coating functions incompletely resolved
  • Proteases driving outer-layer expansion not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
FCGBP

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Muc2 mucin is the major structural component of both the inner and outer colonic mucus layers; the inner layer is devoid of bacteria and firmly attached to the epithelium, while the outer layer is expanded by proteolytic cleavages of Muc2. Muc2-/- mice have bacteria in direct contact with epithelial cells and develop colitis and cancer, demonstrating that Muc2 builds the mucus barrier separating bacteria from colonic epithelia. Proteomics of mucus layers, Muc2 knockout mouse model, microscopy/bacterial localization assays Proceedings of the National Academy of Sciences of the United States of America High 18806221
2006 Muc2 deficiency (Muc2-/- mice) leads to spontaneous colitis with mucosal thickening, increased proliferation, and superficial erosions, and accelerates DSS-induced colitis, establishing that MUC2 is critical for colonic epithelial protection. Muc2 knockout and heterozygous mouse models, DSS-induced colitis, histological analysis, protein/mRNA quantification Gastroenterology High 16831596
2012 MUC2 N-terminal VWD1-D2-D'D3 domains (MUC2-N) form large calcium- and pH-dependent aggregates at pH 6.2 that dissolve upon Ca2+ removal and pH increase; electron microscopy reveals ring-like structures matching secretory granule contents, establishing a mechanism for mucin packing in goblet cell granules and pH/Ca2+-driven release and expansion upon secretion. Recombinant MUC2-N expression, gel filtration, density gradient centrifugation, transmission electron microscopy, mimicry of secretory pathway pH/Ca2+ conditions Proceedings of the National Academy of Sciences of the United States of America High 22451922
2016 A sentinel goblet cell at the colonic crypt entrance endocytoses TLR2/1, TLR4, and TLR5 ligands and activates the Nlrp6 inflammasome downstream of TLR/MyD88-dependent Nox/Duox reactive oxygen species synthesis, triggering calcium-dependent compound exocytosis of Muc2 from the sentinel cell and an intercellular gap junction signal that induces Muc2 secretion from adjacent goblet cells, expelling bacteria from the crypt. Analysis of colonic tissues from multiple mouse strains, genetic knockout models (Nlrp6, MyD88), live imaging, calcium signaling assays, bacterial challenge experiments Science (New York, N.Y.) High 27339979
2014 The MUC2 N-terminal D'D3 domain forms hexamers under native conditions (as shown by gel filtration and electron microscopy) and assembles into cage-like structures with 2- and 3-fold symmetry, confirming that MUC2 mucin forms branched net-like structures. The model proposes that stored MUC2 has two N-terminal concatenated ring platforms turned 180° against each other. Recombinant D'D3 domain production, gel filtration, electron microscopy, single particle image processing, 3D reconstruction Journal of molecular biology High 24816392
2008 Genetic epistasis between Muc2 and Apc in intestinal tumorigenesis: introduction of Muc2 deficiency into Apc1638N/+ and ApcMin/+ mice greatly increases tumor burden and shifts tumor development toward the colon in a Muc2 gene dosage-dependent manner; in compound mutants, deregulated Wnt signaling is the dominant tumorigenesis mechanism. Gene expression profiling of Muc2-/- epithelial cells indicates low-level chronic subclinical inflammation. Double-mutant mouse crosses (Muc2-/- × Apc1638N/+ and ApcMin/+), tumor counting, gene expression profiling of intestinal epithelial cells Cancer research High 18794118
2015 Purified human colonic MUC2 mucin promotes β-defensin 2 production in colonic goblet cells in combination with IL-1β; MUC2 shRNA silencing impairs β-defensin expression. Sodium metaperiodate oxidation of MUC2 glycans abolishes both its ability to stimulate β-defensin production and its inhibition of defensin antimicrobial activity, demonstrating that MUC2 glycans mediate these functions. Muc2-/- mice show impaired β-defensin expression in colon. Purified MUC2 mucin treatment of goblet cells, shRNA silencing, Muc2-/- mouse model, sodium metaperiodate oxidation, antimicrobial activity assays Mucosal immunology High 25921338
2018 High MUC2 biosynthesis and protein misfolding in goblet cells triggers elevated reactive oxygen species, leading to ER stress and apoptosis. Correcting MUC2 folding or inhibiting ROS alleviates ER stress and rescues cells from apoptosis. During early DSS colitis, mucus hypersecretion causes goblet cell ER stress and apoptosis preceding absorptive cell damage. Comparison of high-MUC2-producing HT29-H vs. lentivirus shRNA MUC2-silenced HT29-L cells, ER stress induction assays, ROS measurement, apoptosis quantification, Math1M1GFP and C57BL/6 DSS colitis mouse model The American journal of pathology High 29545196
2007 MMP-9 negatively regulates goblet cell differentiation and MUC-2 expression: MMP-9-/- mice have increased goblet cell numbers and elevated MUC-2 expression, with upregulation of KLF-4 and Elf-3 (goblet cell differentiation transcription factors) and downregulation of activated Notch-1 (NICD). MMP-9 overexpression in vitro inhibits goblet cell differentiation, while MMP-9 silencing in Caco2-BBE cells shifts their phenotype toward goblet cells. MMP-9 knockout mice, goblet cell line HT29-cl.16E, enterocyte line Caco2-BBE, MMP-9 overexpression and gene silencing, immunohistochemistry, Western blot Gastroenterology High 17484881
2002 p53 directly activates MUC2 gene transcription: deletion and mutagenesis of the MUC2 promoter identified two p53-responsive elements, EMSA confirmed p53 binding to these elements, and MUC2 expression is induced by endogenous p53 in response to DNA damage (actinomycin D, UVC, X-ray) in cells with wild-type but not mutant p53. Tetracycline-regulatable p53 expression in DLD-1 cells, MUC2 promoter reporter (deletion and mutagenesis), EMSA, stress treatments in multiple cell lines The Journal of biological chemistry High 12374798
2005 VIP activates MUC2 transcription via cAMP → ERK and p38 signaling → CREB/ATF1 phosphorylation (via PKA/MSK1), and CREB/ATF1 and c-Jun bind to a distal conserved CREB/AP1 cis-element in the MUC2 5'-flanking region identified as a functional transcriptional activator. PKC, Ras, Raf, Src, calcium, and PI3K are not involved. MUC2 promoter reporter assays, CREB/ATF1 phosphorylation assays, EMSA showing CREB/ATF1 and c-Jun binding to MUC2 promoter element, pharmacological inhibitors (MEK, p38, PKA/MSK1 inhibitor H89, PKC inhibitor, etc.) American journal of physiology. Gastrointestinal and liver physiology High 16227528
1997 The MUC2 promoter basal activity requires a short segment (-91 to -73) containing a CACCC motif; EMSA showed nuclear protein binding to this region with both Sp1 and other Sp1 family members binding (confirmed by antibody supershift). A region (-228 to -171) confers cell-type specificity of expression. MUC2 mRNA is long-lived and its turnover does not differ between high- and low-expressing cell lines, indicating that MUC2 mRNA stability is not the major regulator of steady-state mRNA levels. Luciferase reporter constructs (promoter deletion analysis), EMSA, antibody supershift, actinomycin D mRNA stability assay, transfection of multiple cell lines The Biochemical journal High 9224654
2006 MUC2 expression is regulated by epigenetic mechanisms: histone H3 modification (H3-K4/K9 methylation and H3-K9/K27 acetylation) at the MUC2 promoter regulates MUC2 gene expression independently and in concert with DNA methylation. TSA (HDAC inhibitor) alone induces MUC2 mRNA in MUC2-negative PANC1 cells and converts histone H3 marks to those found in MUC2-positive BxPC3 cells; 5-aza alone causes only slight MUC2 induction. Treatment of pancreatic cancer cell lines (PANC1, BxPC3) with 5-azacytidine and/or TSA, ChIP for histone H3 modifications, MUC2 mRNA quantification International journal of cancer Medium 16721789
2005 Bile acids induce MUC2 transcription in human colon carcinoma cells through PKC-dependent (not MAP kinase-dependent) activation of AP-1; cotransfection with dominant-negative AP-1 vector decreased MUC2 transcription, and curcumin reduced both AP-1 activity and MUC2 transcription. MUC2 promoter reporter assay, AP-1 reporter assay, dominant-negative AP-1 cotransfection, Western blot for c-Jun/AP-1, pharmacological inhibitors (calphostin C, MAP kinase inhibitors) Cancer Medium 15754327
2018 MUC2 knockdown in breast cancer cell lines reduces proliferation, increases apoptosis in response to chemotherapy, and decreases metastatic burden in an experimental metastasis model. EGF induces MUC2 expression via the EGF receptor (abolished by Erlotinib), placing MUC2 downstream of EGFR signaling in breast cancer. Patient-derived xenograft cell lines with shRNA MUC2 knockdown, in vitro proliferation/apoptosis assays, in vivo experimental metastasis model (intravital imaging), EGF treatment ± Erlotinib Breast cancer research and treatment Medium 30317423
2023 FCGBP (IgGFc-binding protein) and MUC2 are coordinately biosynthesized in goblet-like cells; ~85% of MUC2 co-localizes with FCGBP in mucin granules. FCGBP and MUC2 interact non-covalently via N-linked glycans in secreted mucus. In MUC2 KO cells, cytoplasmic FCGBP is increased and wound healing occurs more rapidly (enhanced proliferation/migration within 2 days), whereas WT cells show MUC2/FCGBP polarization at the wound margin that impedes wound closure over 6 days. CRISPR-Cas9 MUC2 KO goblet-like cells, co-localization immunofluorescence, co-immunoprecipitation, N-linked glycan inhibition, wound healing assays, DSS colitis mouse model Frontiers in immunology Medium 37359538
2018 Muc2 coats murine Paneth cell granules (electron-lucent halo visible by EM); Muc2-/- Paneth cells contain larger, more densely packed granules and show defects in antimicrobial gene transcription and impaired lysozyme-containing granule release. This demonstrates Muc2 facilitates Paneth cell granule content release and dispersal. Human Paneth cells are Muc2-negative, highlighting a mouse-specific function. Immunostaining, electron microscopy, Muc2-/- mouse model, enteroids from WT and Muc2-/- small intestine, lysozyme release assays, antimicrobial gene expression American journal of physiology. Gastrointestinal and liver physiology Medium 29698056
2021 Autophagy is constitutively increased in high-MUC2-producing goblet cells (elevated pULK1S555 and increased autophagosomes) compared to MUC2-silenced or MUC2 KO cells, and is required for goblet cell survival during high mucin biosynthesis. IL-22 treatment corrects misfolded MUC2 and alleviates the autophagy process. High-MUC2 (HT29-H) vs. shRNA-silenced (HT29-L) cells, CRISPR/Cas9 MUC2 KO LS174T cells, colonoids from Muc2 WT and KO mice, autophagosome quantification, pULK1 Western blot, IL-22 treatment American journal of physiology. Gastrointestinal and liver physiology Medium 34494458
2017 MUC2 mucin (with butyrate and IL-1β) promotes cathelicidin LL-37 synthesis in colonic epithelial cells via activation of cyclic AMP and MAPK signaling pathways; MUC2-silenced cells show reduced LL-37 responses, and Muc2-/- mice show significantly reduced colonic cathelicidin (Cramp) expression in both basal conditions and during E. histolytica infection. Purified MUC2 treatment of goblet cells, lentivirus shRNA MUC2 silencing, cAMP and MAPK pathway inhibitors, Muc2-/- mouse model, E. histolytica colonic loop infection Infection and immunity Medium 28069814
2002 IL-1β induces MUC2 (and MUC5AC) expression in NCI-H292 airway epithelial cells via ERK1/2 and p38 MAPK activation of COX-2, leading to PGE2 synthesis; PGE2 directly induces MUC2 expression, and adding exogenous PGE2 overcomes MAPK inhibitor blockade, placing COX-2/PGE2 downstream of MAPK in this pathway. Pharmacological inhibitors (NS398/COX-2 inhibitor, PD98059/ERK inhibitor, SB203580/p38 inhibitor), exogenous PGE2 addition, RT-PCR and protein measurement in NCI-H292 cells Molecular pharmacology Medium 12391274
2010 DNA methylation at specific CpG sites in the MUC2 promoter (regions at -289, -274, and -193) inversely correlates with MUC2 expression: mucinous CRC shows significantly lower methylation and higher MUC2 expression than non-mucinous CRC, and methylation status in cell lines correlates with MUC2 mRNA presence in 100% of cases. Bisulfite sequencing and methylation-specific PCR (MSP) in CRC cell lines and tissue samples, correlation with MUC2 protein expression by IHC, 5-aza-2'-deoxycytidine treatment International journal of oncology Medium 20198318
1994 Vitamin A down-regulates MUC2 gene expression at the transcriptional level in primary tracheobronchial epithelial cells (human, monkey, hamster); nuclear run-on assay demonstrated decreased transcriptional rate of MUC2 in vitamin A-treated cultures, and the effect was time- and dose-dependent. Primary tracheobronchial epithelial cultures, Northern blot, nuclear run-on transcription assay, dose-response and time-course experiments American journal of respiratory cell and molecular biology Medium 8179918
2021 DOCK4 (a guanine nucleotide exchange factor) promotes goblet cell differentiation and MUC2 production: DOCK4 knockout mice show disordered intestinal epithelium, reduced goblet cells, and low MUC2 and differentiation factor (Gfi1, Spdef) expression; DOCK4 overexpression increases and siRNA knockdown decreases Gfi1, Spdef, and MUC2 in HT-29 cells. DOCK4 knockout mice, DOCK4 overexpression and siRNA knockdown in HT-29 cells, qRT-PCR and Western blot for MUC2/Gfi1/Spdef Journal of cellular physiology Medium 33559155
2019 Bile acids activate the FXR/NF-κB signaling pathway to upregulate CDX2 expression, which in turn transcriptionally activates MUC2; chromatin immunoprecipitation confirmed enhanced binding of p50 (but not p65) to the CDX2 promoter upon bile acid treatment; FXR agonist (GW4064) enhanced and antagonist (Z-guggulsterone) attenuated these effects. In vitro and in vivo bile acid treatment, FXR knockdown and agonist/antagonist experiments, NF-κB reporter assays, quantitative ChIP for p50/p65 at CDX2 promoter, CDX2 promoter activity assays International journal of oncology Medium 30747230
1996 MUC2 precursor biosynthesis and total MUC2 protein levels are significantly decreased in active ulcerative colitis compared to controls and return to normal during remission, but MUC2 mRNA levels are similar regardless of disease activity, indicating that regulation of MUC2 synthesis in UC is post-transcriptional. Metabolic labeling of colonic biopsies, SDS-PAGE quantification of MUC2 precursor, Western blot for total MUC2 protein, Northern blot for MUC2 mRNA Biochemical and biophysical research communications Medium 8702401
1999 The MUC2 tandem repeat presents trimeric Tn antigen (three or more consecutive O-GalNAc residues on serine/threonine) as a high-affinity receptor for a calcium-type lectin on histiocytic macrophages; the biosynthesis of trimeric Tn is strictly regulated by the acceptor specificity of pp-GalNAc-transferases. MUC2 tandem repeat peptide binding assays to macrophage lectin, pp-GalNAc-transferase specificity studies Journal of biochemistry Low 10578046
2014 Serum amyloid A3 (SAA3) up-regulates MUC2 mRNA expression in mouse colonic epithelial CMT-93 cells, while SAA1 does not; E. coli and LPS induce SAA3 expression but do not directly increase MUC2 mRNA, suggesting SAA3 acts as an intermediary in E. coli-stimulated MUC2 regulation. Treatment of CMT-93 cells with recombinant SAA1 and SAA3, pathogens (rotavirus, Toxoplasma, S. aureus, E. coli), LPS; qRT-PCR for SAA isoforms and MUC2 The Journal of veterinary medical science Low 24694941
2011 In male Muc2-deficient mice, gastric ulcer healing is significantly impaired and induction of COX-2 in response to indomethacin or acetic acid is significantly reduced compared to WT. This sex-specific defect is recapitulated in bone marrow-derived macrophages, linking Muc2 to COX-2-dependent gastric mucosal repair. Muc2-/- mouse model, indomethacin and acetic acid gastric ulcer induction, COX-2 expression measurement, bone marrow-derived macrophage stimulation with endotoxin The American journal of pathology Medium 21356364

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proceedings of the National Academy of Sciences of the United States of America 1621 18806221
2006 Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 1282 16831596
2016 A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science (New York, N.Y.) 455 27339979
2012 Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin. Proceedings of the National Academy of Sciences of the United States of America 272 22451922
1998 Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria. Biochimica et biophysica acta 182 9630659
2020 The role of MUC2 mucin in intestinal homeostasis and the impact of dietary components on MUC2 expression. International journal of biological macromolecules 179 32707285
2004 Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. American journal of clinical pathology 177 15272531
1991 MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism. The Journal of clinical investigation 177 1885763
1998 The MUC2 gene product: a human intestinal mucin. The international journal of biochemistry & cell biology 168 9722984
2016 The Densely O-Glycosylated MUC2 Mucin Protects the Intestine and Provides Food for the Commensal Bacteria. Journal of molecular biology 163 26880333
1994 Altered expression of MUC2, MUC4, and MUC5 mucin genes in pancreas tissues and cancer cell lines. Gastroenterology 155 8143972
1996 Quantitative analysis of MUC2 synthesis in ulcerative colitis. Biochemical and biophysical research communications 136 8702401
1999 Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: its relationship with a new morphological classification of cholangiocarcinoma. Hepatology (Baltimore, Md.) 133 10573510
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
1994 Expression of MUC2-mucin in colorectal adenomas and carcinomas of different histological types. International journal of cancer 119 7927933
1996 Expression of MUC2 and MUC3 mRNA in human normal, malignant, and inflammatory intestinal tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 114 8813081
1996 Significance of MUC1 and MUC2 mucin expression in colorectal cancer. Journal of clinical pathology 111 8813954
2003 Immunohistochemical evaluation of PCNA, p53, HSP60, HSP10 and MUC-2 presence and expression in prostate carcinogenesis. Anticancer research 108 12820390
2004 MUC1 and MUC2 in pancreatic neoplasia. Journal of clinical pathology 106 15113850
2006 MUC1, MUC2, MUC4, MUC5AC and MUC6 expression in the progression of prostate cancer. Clinical & experimental metastasis 103 16475027
1997 Expression of MUC1 and MUC2 mucins in epithelial ovarian tumours. The Journal of pathology 103 9422987
2019 Bile acids promote gastric intestinal metaplasia by upregulating CDX2 and MUC2 expression via the FXR/NF-κB signalling pathway. International journal of oncology 91 30747230
2008 Interaction of Muc2 and Apc on Wnt signaling and in intestinal tumorigenesis: potential role of chronic inflammation. Cancer research 90 18794118
1994 Developmental expression of mucin genes MUC1 and MUC2. Journal of cell science 89 7515892
2002 Interleukin-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells. Molecular pharmacology 86 12391274
2015 Colonic MUC2 mucin regulates the expression and antimicrobial activity of β-defensin 2. Mucosal immunology 82 25921338
1997 Identification and characterization of the MUC2 (human intestinal mucin) gene 5'-flanking region: promoter activity in cultured cells. The Biochemical journal 79 9224654
2023 Orchestration of MUC2 - The key regulatory target of gut barrier and homeostasis: A review. International journal of biological macromolecules 78 36870625
2001 Mucins MUC1, MUC2, MUC5AC and MUC6 expression in the evaluation of differentiation and clinico-biological behaviour of gastric carcinoma. Virchows Archiv : an international journal of pathology 78 11889602
1999 Gastrointestinal expression and partial cDNA cloning of murine Muc2. The American journal of physiology 75 9886986
2014 The molecular background of mucinous carcinoma beyond MUC2. The journal of pathology. Clinical research 74 27499889
2004 Colonic expression of MUC2, MUC5AC, and TFF1 in inflammatory bowel disease in children. Journal of pediatric gastroenterology and nutrition 74 15097436
2017 MUC2 Mucin and Butyrate Contribute to the Synthesis of the Antimicrobial Peptide Cathelicidin in Response to Entamoeba histolytica- and Dextran Sodium Sulfate-Induced Colitis. Infection and immunity 72 28069814
2000 Differential expression of MUC2 and MUC5AC mucin genes in primary ovarian and metastatic colonic carcinoma. Human pathology 70 10872659
2018 High MUC2 Mucin Expression and Misfolding Induce Cellular Stress, Reactive Oxygen Production, and Apoptosis in Goblet Cells. The American journal of pathology 68 29545196
2012 Mucin Muc2 deficiency and weaning influences the expression of the innate defense genes Reg3β, Reg3γ and angiogenin-4. PloS one 67 22723890
2007 Matrix metalloproteinase-9 regulates MUC-2 expression through its effect on goblet cell differentiation. Gastroenterology 67 17484881
2005 Vasoactive intestinal peptide upregulates MUC2 intestinal mucin via CREB/ATF1. American journal of physiology. Gastrointestinal and liver physiology 66 16227528
2003 MUC1 and MUC2 expression in pancreatic ductal carcinoma obtained by fine-needle aspiration. Cancer 66 14681945
2002 Expression of MUC1 and MUC2 mucin gene products in human ovarian carcinomas. Japanese journal of clinical oncology 65 12578901
2010 Inflammation modulates the expression of the intestinal mucins MUC2 and MUC4 in gastric tumors. Oncogene 63 20062084
2012 Roles of the gel-forming MUC2 mucin and its O-glycosylation in the protection against colitis and colorectal cancer. Biological & pharmaceutical bulletin 60 23037153
2006 MUC2 expression is regulated by histone H3 modification and DNA methylation in pancreatic cancer. International journal of cancer 60 16721789
1991 Production of MUC1 and MUC2 mucins by human tumor cell lines. Biochemical and biophysical research communications 54 1713449
2003 MUC-2 mucin production in Hirschsprung's disease: possible association with enterocolitis development. Journal of pediatric surgery 53 12632359
1999 Diverse glycosylation of MUC1 and MUC2: potential significance in tumor immunity. Journal of biochemistry 52 10578046
2002 Transcriptional activation of the MUC2 gene by p53. The Journal of biological chemistry 51 12374798
1997 MUC1 and MUC2 mucins in flat and polypoid colorectal adenomas. Journal of clinical pathology 51 9215126
1993 Expression of MUC2 epithelial mucin in breast carcinoma. Journal of clinical pathology 50 8227409
2010 Altered expression of MUC2 and MUC5AC in progression of colorectal carcinoma. World journal of gastroenterology 49 20731025
2002 Alterations in Muc2 biosynthesis and secretion during dextran sulfate sodium-induced colitis. American journal of physiology. Gastrointestinal and liver physiology 49 11804861
2020 p-Cymene and Rosmarinic Acid Ameliorate TNBS-Induced Intestinal Inflammation Upkeeping ZO-1 and MUC-2: Role of Antioxidant System and Immunomodulation. International journal of molecular sciences 48 32824269
1997 Organization and regulatory aspects of the human intestinal mucin gene (MUC2) locus. The Journal of biological chemistry 48 9065467
1994 Distribution of lysozyme and mucin (MUC2 and MUC3) mRNA in human bronchus. Experimental lung research 48 7988497
2020 A Specific Mutation in Muc2 Determines Early Dysbiosis in Colitis-Prone Winnie Mice. Inflammatory bowel diseases 47 31748792
2017 MUC2 mucin deficiency alters inflammatory and metabolic pathways in the mouse intestinal mucosa. Oncotarget 46 29069719
2014 Intestinal MUC2 mucin supramolecular topology by packing and release resting on D3 domain assembly. Journal of molecular biology 42 24816392
2010 MUC2 gene promoter methylation in mucinous and non-mucinous colorectal cancer tissues. International journal of oncology 42 20198318
2013 Cloning, annotation and developmental expression of the chicken intestinal MUC2 gene. PloS one 41 23349743
2005 Bile acids induce MUC2 overexpression in human colon carcinoma cells. Cancer 41 15754327
2022 2'-Fucosyllactose Ameliorates Inflammatory Bowel Disease by Modulating Gut Microbiota and Promoting MUC2 Expression. Frontiers in nutrition 39 35252301
2021 Consequence of distinctive expression of MUC2 in colorectal cancers: How much is actually bad? Biochimica et biophysica acta. Reviews on cancer 39 34139275
2014 Bile acid induces MUC2 expression and inhibits tumor invasion in gastric carcinomas. Journal of cancer research and clinical oncology 39 25475007
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
1992 Expression of MUC1 and MUC2 mucins by human tumor cell lines. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 1283926
2019 Modulation of Mucin (MUC2, MUC5AC and MUC5B) mRNA Expression and Protein Production and Secretion in Caco-2/HT29-MTX Co-Cultures Following Exposure to Individual and Combined Aflatoxin M1 and Ochratoxin A. Toxins 35 30813459
2003 Methylation status of promoters and expression of MUC2 and MUC5AC mucins in pancreatic cancer cells. International journal of oncology 35 12527922
2000 Epidermal growth factor receptor, MUC-1 and MUC-2 in bladder cancer. Journal of experimental & clinical cancer research : CR 34 10965823
2004 Expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen in pancreatic tumors. International journal of oncology 33 14654947
2017 Expression of survivin, MUC2 and MUC5 in colorectal cancer and their association with clinicopathological characteristics. Oncology letters 32 28693267
2018 Mucin 2 (MUC2) promoter characterization: an overview. Cell and tissue research 31 30218241
2018 Mucin 2 (MUC2) modulates the aggressiveness of breast cancer. Breast cancer research and treatment 31 30317423
2016 KLF4 deletion alters gastric cell lineage and induces MUC2 expression. Cell death & disease 31 27277677
2010 Toll-like receptor 2 and Muc2 expression on human intestinal epithelial cells by Gymnophalloides seoi adult antigen. The Journal of parasitology 30 19737027
2005 Expression of CDX2 and MUC2 in Barrett's mucosa. Pathology, research and practice 29 16259110
2001 Expression of MUC1 and MUC2 and carbohydrate antigen Tn change during malignant transformation of biliary papillomatosis. Histopathology 28 11422499
2010 Butyrate enemas do not affect human colonic MUC2 and TFF3 expression. European journal of gastroenterology & hepatology 27 20461009
2008 Expression of Pla2g2a prevents carcinogenesis in Muc2-deficient mice. Cancer science 27 19037975
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
2012 Loss of MUC2 expression predicts disease recurrence and poor outcome in colorectal carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 23179399
2009 Increased K-ras mutation and expression of S100A4 and MUC2 protein in the malignant intraductal papillary mucinous tumor of the pancreas. Journal of hepato-biliary-pancreatic surgery 24 19412570
1994 Expression of MUC2 gene is down-regulated by vitamin A at the transcriptional level in vitro in tracheobronchial epithelial cells. American journal of respiratory cell and molecular biology 24 8179918
2023 IgGFc-binding protein and MUC2 mucin produced by colonic goblet-like cells spatially interact non-covalently and regulate wound healing. Frontiers in immunology 23 37359538
2014 Up-regulation of MUC2 mucin expression by serum amyloid A3 protein in mouse colonic epithelial cells. The Journal of veterinary medical science 23 24694941
2006 Relationships between mucinous gastric carcinoma, MUC2 expression and survival. World journal of gastroenterology 23 16733847
2022 Endotoxins Induced ECM-Receptor Interaction Pathway Signal Effect on the Function of MUC2 in Caco2/HT29 Co-Culture Cells. Frontiers in immunology 22 35757703
2021 Autophagy is required during high MUC2 mucin biosynthesis in colonic goblet cells to contend metabolic stress. American journal of physiology. Gastrointestinal and liver physiology 22 34494458
2003 MUC1 and MUC2 expression in salivary gland tumors and in non-neoplastic salivary gland tissue. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 22 14616551
2021 DOCK4 stimulates MUC2 production through its effect on goblet cell differentiation. Journal of cellular physiology 21 33559155
2008 MUC2 expression in human middle ear epithelium of patients with otitis media. Archives of otolaryngology--head & neck surgery 21 18209134
2018 The Muc2 mucin coats murine Paneth cell granules and facilitates their content release and dispersion. American journal of physiology. Gastrointestinal and liver physiology 20 29698056
2013 PGE(2) induces MUC2 and MUC5AC expression in human intrahepatic biliary epithelial cells via EP4/p38MAPK activation. Annals of hepatology 20 23619266
1994 Alteration in expression of MUC2 and MUC3 mRNA levels in HT29 colonic carcinoma cells. Biochemical and biophysical research communications 20 8135773
1998 Immunohistochemical detection of MUC2 mucin core protein in ulcerative colitis. Journal of clinical laboratory analysis 19 9591701
2018 Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in ALK-positive lung cancer: Comparison with EGFR-mutated lung cancer. Pathology, research and practice 18 30580903
2011 Expression of MUC1 and MUC2 in ampullary cancer. International journal of surgical pathology 18 21700631
2011 Muc-2-deficient mice display a sex-specific, COX-2-related impairment of gastric mucosal repair. The American journal of pathology 17 21356364
2023 The Milk Active Ingredient, 2'-Fucosyllactose, Inhibits Inflammation and Promotes MUC2 Secretion in LS174T Goblet Cells In Vitro. Foods (Basel, Switzerland) 16 36613400
2007 Altered expression of MUC2 and MUC5AC in response to Shigella infection, an in vivo study. Biochimica et biophysica acta 15 17395379

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