Affinage

DMBT1

Scavenger receptor cysteine-rich domain-containing protein DMBT1 · UniProt Q9UGM3

Length
2413 aa
Mass
260.7 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DMBT1 is a large, multi-domain scavenger receptor cysteine-rich (SRCR) glycoprotein that functions as a broad-spectrum pattern-recognition molecule at mucosal surfaces and, in an alternatively spliced/orthologous form (hensin/CRP-ductin/muclin), as an extracellular matrix regulator of epithelial differentiation (PMID:9288095, PMID:10485905, PMID:10444583, PMID:10749143). The protein — independently characterized as lung gp-340 and salivary agglutinin and shown by mass spectrometry to be identical — comprises 13–14 SRCR domains interspersed with SID and CUB domains and a terminal zona pellucida domain (PMID:10485905, PMID:11007786, PMID:11563989). Its bacteria-binding activity maps to a conserved SRCR motif: peptide and alanine-scanning studies narrowed the minimal site to an 11-residue sequence (GRVEVLYRGSW) within which the core VEVL and terminal tryptophan are critical, defining a common RVEVLYxxxSW recognition motif that binds a broad range of bacteria including S. mutans, group A streptococci, and S. aureus (PMID:12050164, PMID:15355985, PMID:18713006). Through these SRCR domains DMBT1 recognizes bacterial pili, antigen I/II polypeptides, leucine-rich-repeat surface proteins (Spy0843, LrrG, BspA), and the sialoadhesin SasA, agglutinating bacteria and reducing their epithelial adhesion (PMID:15784568, PMID:18452511, PMID:19465482, PMID:23439307, PMID:28489917). A dual cation-binding site within the SRCR fold provides the structural basis for this conserved ligand recognition (PMID:32098784). DMBT1 also binds surfactant protein D calcium-dependently and co-localizes with it in macrophage phagosomes, and it activates complement via the MBL/lectin pathway through its carbohydrate moieties (PMID:9153228, PMID:10485905, PMID:21920605). In innate immune signaling it is a NOD2/NF-κB and IL-22/STAT3 target gene that dampens LPS- and muramyl-dipeptide-induced NF-κB activation and confers mucosal protection: Dmbt1-deficient mice show enhanced DSS colitis and a reduced-SRCR deletion allele is associated with Crohn's disease risk (PMID:17548659, PMID:17983803, PMID:20824812). As hensin, DMBT1 polymerization and ECM deposition — requiring beta1-integrin activation — drives terminal differentiation of renal intercalated cells, and its loss causes complete distal renal tubular acidosis (PMID:21098262). It binds HIV-1 gp120 at the V3 loop in a calcium-dependent manner through its N-terminal SRCR domain, an interaction that inhibits infection in some contexts yet promotes viral capture, transcytosis, and infection of mucosal target cells in others (PMID:15242536, PMID:16796526, PMID:17709527, PMID:19553331).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1997 High

    Established DMBT1 as a candidate tumor-suppressor gene of the SRCR superfamily, defining its genomic locus and linking its loss to brain malignancy.

    Evidence Representational difference analysis, cloning, and deletion mapping in medulloblastoma/glioblastoma lines and tumors

    PMID:9288095

    Open questions at the time
    • No protein-level function defined at this stage
    • Causality of deletions in tumorigenesis not tested by rescue
  2. 1997 High

    Identified the secreted/macrophage-associated protein gp-340 and its calcium-dependent SP-D interaction, situating DMBT1 in respiratory innate defense before the gp-340/DMBT1 identity was formalized.

    Evidence Protein purification from lung washings, calcium-dependent maltose-insensitive SP-D binding, immunohistochemistry

    PMID:9153228

    Open questions at the time
    • Full primary structure and domain architecture not yet known
    • Physiological consequence of SP-D binding not established
  3. 1999 High

    Resolved the complete domain architecture (13+1 SRCR, SID, CUB, ZP domains) and unified gp-340 with the renal differentiation factor hensin as DMBT1 splice products, revealing dual immune and epithelial roles.

    Evidence cDNA cloning, domain mapping, genomic synteny mapping, immunoblotting

    PMID:10444583 PMID:10485905

    Open questions at the time
    • Which domains mediate which functions not yet mapped
    • Splice-isoform tissue distribution incompletely defined
  4. 2000 High

    Mass-spectrometric identity established that salivary agglutinin, lung gp-340, and DMBT1 are the same molecule with tissue-specific glycoforms, explaining its broad bacterial-binding reputation across mucosa.

    Evidence MALDI-TOF/Q-TOF peptide sequencing, immunoblot cross-reactivity, bacterial binding assays

    PMID:10749143 PMID:11007786 PMID:11563989

    Open questions at the time
    • Functional role of tissue-specific glycans not dissected
    • Binding domain not yet localized
  5. 2002 High

    Localized bacterial recognition to the SRCR domains and defined a minimal binding peptide, converting a multi-domain protein into a tractable molecular recognition unit.

    Evidence Proteolytic mapping plus synthetic SRCRP2 consensus peptide binding/agglutination assays

    PMID:12050164

    Open questions at the time
    • Individual critical residues not yet identified
    • Structural basis of peptide-ligand contact unknown
  6. 2004 High

    Mutagenesis pinpointed VEVL and the terminal Trp as essential and showed only DMBT1 orthologs use this motif, defining the chemistry of broad bacterial recognition.

    Evidence Overlapping peptides and alanine-substitution scanning with bacterial binding assays

    PMID:15355985

    Open questions at the time
    • Bacterial counter-ligands for many species still unknown
    • Whether motif binds protein or glycan ligands not resolved
  7. 2004 Medium

    Demonstrated DMBT1 binds the conserved HIV-1 gp120 V3 loop independently of the CD4 site and inhibits infection, extending its pattern recognition to a virus.

    Evidence V3 peptide binding, sCD4 competition, HIV infection inhibition assays

    PMID:15242536

    Open questions at the time
    • Context-dependence of inhibition versus enhancement unresolved
    • Domain responsible not yet mapped
  8. 2005 Medium

    Showed fluid-phase versus surface-adsorbed DMBT1 recognize bacteria via distinct adhesins, establishing that immobilization state dictates recognition outcome (aggregation versus adhesion).

    Evidence Aggregation/adhesion assays with isogenic adhesin mutants and surface adsorption

    PMID:15784568

    Open questions at the time
    • Structural change upon surface adsorption not defined
    • Single bacterial genus tested for the mechanism
  9. 2007 High

    Positioned DMBT1 within innate immune signaling as a NOD2/NF-κB target that feedback-suppresses NF-κB and limits bacterial invasion, and demonstrated in vivo mucosal protection with a human Crohn's disease association.

    Evidence NF-κB reporters, siRNA, Salmonella invasion assays; Dmbt1-/- DSS colitis model and genetic association

    PMID:17548659 PMID:17983803

    Open questions at the time
    • Mechanism by which DMBT1 dampens NF-κB signaling not defined
    • Causal SRCR-deletion variant biology in patients incomplete
  10. 2008 Medium

    Refined the universal bacterial-binding motif (RVEVLYxxxSW) with species-specific residue usage and linked DMBT1 deficiency to impaired pancreatic exocrine secretory trafficking, broadening its functional scope.

    Evidence Alanine scan across multiple species; Dmbt1-/- pancreatic amylase release and pulse-chase trafficking

    PMID:18202109 PMID:18452511 PMID:18713006

    Open questions at the time
    • How a secreted SRCR protein influences intracellular secretory trafficking unclear
    • Direct pili counter-receptor structure not solved
  11. 2009 Medium

    Resolved the dual HIV outcome by showing genital/macrophage DMBT1 concentrates virus, enhances fusion, and mediates apical-to-basolateral transcytosis, reframing it as a context-dependent infection facilitator.

    Evidence Macrophage/genital epithelial infection and fusion assays, transwell transcytosis with primary endocervical tissue, blocking reagents, heparan sulfate perturbation

    PMID:17709527 PMID:18641344 PMID:19553331

    Open questions at the time
    • What determines inhibition versus enhancement in vivo unknown
    • Relative contribution of SRCR versus heparan sulfate moieties unresolved
  12. 2009 Medium

    Identified bacterial leucine-rich-repeat surface proteins as a recurring class of DMBT1 ligands, implicating a core peptide distinct from the XXXXW motif.

    Evidence Mass spectrometry, bacterial gene inactivation, recombinant truncated protein and peptide inhibition assays

    PMID:19465482

    Open questions at the time
    • Structural mapping of the LRR-binding core peptide not done
    • Single lab
  13. 2010 High

    Defined the hensin/DMBT1 differentiation mechanism: beta1-integrin-dependent ECM polymerization converts beta- to alpha-intercalated cells, and its loss causes complete distal renal tubular acidosis.

    Evidence Conditional Dmbt1 and beta1-integrin knockout mice, V-ATPase/pendrin/kAE1 immunofluorescence, acid-feeding challenge

    PMID:21098262

    Open questions at the time
    • Molecular link between ECM polymerization and intracellular polarity reversal not defined
    • Receptor downstream of beta1 integrin not identified
  14. 2010 Medium

    Mapped IL-22/STAT3-NF-κB and CREB1/ATF-2 transcriptional control of DMBT1 and tied a non-coding risk SNP to reduced intestinal expression, connecting cytokine signaling to mucosal defense capacity.

    Evidence Microarray, STAT3 siRNA, pathway inhibitors, promoter deletion luciferase, EMSA

    PMID:20824812 PMID:24223725

    Open questions at the time
    • Quantitative effect of expression on host protection not measured
    • In vivo relevance of the SNP regulation not tested
  15. 2011 Medium

    Showed DMBT1 activates the lectin (MBL) complement pathway through its carbohydrate, linking pattern recognition to complement-mediated clearance.

    Evidence C4 deposition ELISA with MBL-blocking antibodies, MBL-deficient sera, periodate glycan oxidation

    PMID:21920605

    Open questions at the time
    • Identity of the MBL-engaging glycan not defined
    • Downstream opsonization/clearance not measured
  16. 2013 Medium

    Expanded the ligand repertoire with the S. aureus sialoadhesin SasA and dimeric TFF3, both engaged via defined carbohydrate or dimerization-dependent contacts.

    Evidence sasA inactivation, SPR with defined sialyl glycans; ELISA binding with TFF isoform controls

    PMID:23439307 PMID:23691218

    Open questions at the time
    • Functional consequence of TFF3 binding not established
    • In vivo relevance of SasA interaction untested
  17. 2017 Medium

    Demonstrated DMBT1 directly binds Pseudomonas aeruginosa pili to inhibit twitching motility and corneal traversal in vivo, showing motility/virulence suppression beyond simple agglutination.

    Evidence Mass spectrometry identification, dot-immunoblot pili binding, twitching and epithelial traversal assays, murine corneal infection model

    PMID:28489917

    Open questions at the time
    • Mechanism by which pili binding inhibits motility unresolved
    • PilA/cAMP shown unaffected, leaving signaling step unknown
  18. 2020 High

    Provided the structural basis for DMBT1 ligand recognition: a dual cation-binding site in SRCR domains 1 and 8 conserved across the SRCR superfamily.

    Evidence Structural determination of SALSA SRCR domains with cation-binding site identification and comparative analysis

    PMID:32098784

    Open questions at the time
    • Co-structures with specific bacterial/viral ligands not solved
    • How the cation site reconciles diverse ligand classes not shown
  19. 2022 Low

    Implicated DMBT1 in tumor suppression via galectin-3/PI3K-AKT and in exosome-delivered pro-angiogenic signaling, extending its activities to growth control and tissue repair.

    Evidence Overexpression and Co-IP in ovarian cancer cells; exosome proteomics and DMBT1 knockdown in stem-cell/MSC exosomes with angiogenesis and wound-healing readouts

    PMID:29556344 PMID:32424818 PMID:35726847

    Open questions at the time
    • Galectin-3 interaction rests on single Co-IP with pharmacological pathway inference, no reconstitution
    • Direct binding underlying exosomal angiogenesis not demonstrated
    • How a secreted SRCR protein engages intracellular PI3K/AKT/beta-catenin pathways unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single dual-cation SRCR fold reconciles recognition of structurally diverse ligands (bacterial pili, LRR proteins, sialoglycans, gp120 V3, SP-D, complement initiators), and how the secreted/ECM hensin form transmits differentiation signals through beta1 integrin, remain mechanistically open.
  • No co-crystal structures with physiological ligands
  • Signal transduction from hensin ECM to intracellular polarity reversal undefined
  • Determinants of HIV inhibition versus enhancement unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 3 GO:0008289 lipid binding 1 GO:0098631 cell adhesion mediator activity 1 GO:0098772 molecular function regulator activity 1
Localization
GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 2 GO:0005764 lysosome 1 GO:0031012 extracellular matrix 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
ITGB1LGALS3MBL2SFTPDTFF3

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 DMBT1 was identified as a novel gene on chromosome 10q25.3-26.1 encoding a member of the scavenger receptor cysteine-rich (SRCR) superfamily, with homozygous intragenic deletions detected in medulloblastoma and glioblastoma multiforme cell lines and primary tumors, and lack of expression demonstrated in brain-tumor cell lines. Representational difference analysis, molecular cloning, PCR-based deletion analysis, expression analysis Nature genetics High 9288095
1997 gp-340 (DMBT1) was purified from human bronchioalveolar lung washings and shown to bind surfactant protein D (SP-D) in a calcium-dependent, maltose-independent manner (protein-protein interaction via the CRD of SP-D), and was localized to the surface of and within alveolar macrophages. Protein purification, calcium-dependent binding assay, inhibition with maltose, immunohistochemistry, N-glycosidase F digestion, SDS-PAGE The Journal of biological chemistry High 9153228
1999 The primary structure of gp-340 (DMBT1) was established by molecular cloning, revealing a polypeptide of 2,413 amino acids with 13 SRCR domains, SRCR-interspersed domains, two CUB domains, a 14th SRCR domain, and a zona pellucida domain. gp-340 was confirmed to bind SP-D calcium-dependently. The protein is found in a soluble form and membrane-associated on alveolar macrophages, with SP-D and gp-340 co-localizing in the same phagosome/phagolysosome compartments. Molecular cloning (7,686-bp cDNA), RT-PCR, immunohistochemistry, co-localization Proceedings of the National Academy of Sciences of the United States of America High 10485905
1999 Hensin, the polarity-reversal extracellular matrix protein that converts beta-intercalated cells to alpha-intercalated cell phenotype, is an alternatively spliced product of the DMBT1 gene. Mouse genomic hensin maps to chromosome 7F4, syntenic to human 10q25-26. cDNA cloning, genomic Southern hybridization, chromosomal synteny mapping, immunoblotting with domain-specific antibodies The American journal of physiology High 10444583
2000 DMBT1 protein isoforms are identical to the collectin-binding protein gp-340 involved in respiratory immune defense; DMBT1 is expressed throughout the immune system; its orthologs CRP-ductin (mouse) and hensin (rabbit) are implicated in epithelial differentiation, indicating DMBT1 has dual functions in immune defense and epithelial development. Western blot, immunohistochemistry, RT-PCR expression analysis Cancer research Medium 10749143
2000 Salivary agglutinin is identical to lung gp-340 (DMBT1) as confirmed by MALDI-TOF mass spectrometry peptide sequencing and immunoblotting. Salivary agglutinin/gp-340 binds Streptococcus mutans, Helicobacter pylori, Streptococcus agalactiae, and oral commensal streptococci. The salivary form carries sialyl Le(x) carbohydrate not present on lung gp-340, indicating tissue-specific glycoforms. Protein purification, MALDI-TOF MS, HPLC peptide sequencing, immunoblotting with cross-reactive antibodies, bacterial binding assay The Journal of biological chemistry High 11007786
2001 Salivary agglutinin is identical to gp-340/DMBT1, confirmed by Q-TOF tandem MS peptide sequencing showing 100% identity to SRCR domain sequences of gp-340. Agglutinin and gp-340 bind S. mutans and surfactant protein D in a similar manner, and share histochemical distribution in submandibular salivary glands. Q-TOF tandem MS, Western blotting with cross-reactive monoclonal antibodies, bacterial binding assay, SP-D binding assay, immunohistochemistry The Biochemical journal High 11563989
2002 The bacteria-binding domain of salivary agglutinin/DMBT1 was localized to the SRCR domains. A 16-amino-acid consensus peptide (SRCRP2: QGRVEVLYRGSWGTVC) derived from the SRCR domain was identified as the minimal bacteria-binding site, capable of binding and agglutinating S. mutans and other bacteria. Endoproteinase Lys-C digestion, synthetic consensus peptides, bacterial adhesion and agglutination assays The Journal of biological chemistry High 12050164
2003 Mouse CRP-ductin (the DMBT1 ortholog) binds human SP-D in a calcium-dependent, maltose-insensitive manner and shows calcium-dependent binding to both gram-positive and gram-negative bacteria, supporting a conserved role in mucosal immune defense. Protein purification, calcium-dependent binding assay, bacterial binding assay, immunoblotting, RT-PCR European journal of immunology Medium 12884308
2004 The minimal bacteria-binding motif on DMBT1 was narrowed to an 11-amino-acid sequence (DMBT1pbs1: GRVEVLYRGSW) within the SRCR domains. Alanine substitution scanning revealed that VEVL and the terminal Trp are critical residues. Only DMBT1 orthologs, not other SRCR proteins, bound bacteria via this motif. Overlapping synthetic peptides, alanine substitution scanning, bacterial binding assays The Journal of biological chemistry High 15355985
2004 gp340 (DMBT1) binds to the V3 loop region of HIV-1 gp120 (a linear, conserved sequence near the V3 stem critical for chemokine receptor interaction). This binding is distinct from the CD4-binding site, is enhanced by prebinding of sCD4 to gp120, and mediates inhibition of HIV-1 infection. V3 peptide binding assays, HIV-1 infection inhibition assays, sCD4 competition assay AIDS research and human retroviruses Medium 15242536
2005 Fluid-phase gp340 and surface-adsorbed gp340 display differential bacterial recognition: fluid-phase gp340 aggregates bacteria via antigen I/II (SspA/SspB) polypeptides of S. gordonii, while surface-bound gp340 mediates adhesion via the sialic acid-binding adhesin Hsa. Mga virulence regulator deletion in S. pyogenes increases aggregation by gp340. Bacterial aggregation and adhesion assays with purified proteins, isogenic mutants lacking specific adhesins, hydroxylapatite surface-adsorption Infection and immunity Medium 15784568
2005 DMBT1 expression in gastric epithelial cells (AGS) is regulated by ERK and PKC signaling: high ERK activity suppresses DMBT1, while ERK inhibition or high cell density (causing G0/G1 arrest) induces DMBT1. DMBT1 knockdown by siRNA reduced PMA-induced trefoil factor 1 (TFF1) induction, suggesting DMBT1 acts at an early stage of gastric epithelial differentiation. RT-PCR, siRNA knockdown, ERK inhibitor (PD98059), CFSE labeling for cell growth, flow cytometry (G0/G1 arrest analysis) Carcinogenesis Medium 15760920
2006 The N-terminal SRCR domain of gp-340 (a 35-kDa truncated recombinant protein comprising the first SRCR and half of the first SID) is sufficient to bind HIV-1 gp120 V3 sequences in a Ca2+-dependent manner and inhibits both CCR5- and CXCR4-tropic HIV-1 isolates, similar to the full-length protein. Recombinant protein expression in 293 cells, Ca2+-dependent binding assay, HIV-1 infection inhibition assay AIDS research and human retroviruses Medium 16796526
2007 gp340 expressed on human genital epithelial cells binds HIV-1 envelope via a specific protein-protein interaction, allowing otherwise subinfectious amounts of HIV to efficiently infect target cells and extending the duration of viral infectivity. Cell surface expression analysis, HIV binding assays, HIV infection assays with blocking antibodies/peptides Journal of immunology Medium 17709527
2007 DMBT1 is a target gene of the intracellular pathogen receptor NOD2 via NF-κB activation in intestinal epithelial cells. TNF-α and LPS up-regulate DMBT1 expression. DMBT1 inhibits Salmonella enterica cytoinvasion and suppresses LPS- and muramyl dipeptide-induced NF-κB activation and cytokine secretion in vitro. In vitro stimulation, NF-κB reporter assay, siRNA knockdown, bacterial invasion assay, cytokine ELISA Journal of immunology High 17548659
2007 Dmbt1-deficient mice display enhanced susceptibility to dextran sulfate sodium-induced colitis with elevated Tnf, Il6, and Nod2 expression, demonstrating that DMBT1 confers mucosal protection in vivo. A deletion allele of DMBT1 with reduced SRCR domain-coding exons is associated with increased Crohn's disease risk. Dmbt1-/- knockout mice, DSS-induced colitis model, qRT-PCR, immunohistochemistry, genetic association study Gastroenterology High 17983803
2007 gp340 aggregates Group A streptococci by binding GAS pili. Pilus-defective GAS mutants fail to aggregate in saliva and show reduced gp340 binding. Heterologous expression of GAS pili on Lactococcus lactis confers gp340-mediated aggregation. gp340-mediated aggregation reduces bacterial adhesion to human epithelial cells. Pilus-defective GAS mutants, heterologous pilus expression, purified gp340 aggregation assay, bacterial adhesion assay Molecular microbiology High 18452511
2008 A common bacteria-binding motif RVEVLYxxxSW within DMBT1 SRCR domains mediates binding of a broad range of bacteria. Alanine substitution scanning of SRCRP2 showed that 8 residues are involved in binding with species-specific variation, but the core VxVxY and W residues are always required. Alanine substitution peptide scan, bacterial adhesion and agglutination assays with multiple species Biological chemistry Medium 18713006
2008 Monocyte-derived macrophages express gp340, and HIV-1 infection of macrophages is decreased when the viral envelope cannot bind gp340. Inhibition occurred at the level of membrane fusion for M-, T-, and dual-tropic envelopes, suggesting gp340 enhances HIV-1 infection of macrophages by concentrating virus locally. Macrophage expression analysis, HIV infection inhibition with anti-gp340 antibodies/peptides blocking envelope binding, fusion assay Journal of immunology Medium 18641344
2008 Muclin (Dmbt1 product) deficiency in mice impairs exocrine pancreatic function: attenuated neurohormonal-stimulated amylase release from acinar cells and retarded trafficking of newly synthesized secretory proteins to the stimulus-releasable pool, as shown by pulse-chase analysis. Dmbt1-/- knockout mice, amylase release assay, [35S]Met/Cys pulse-chase protein trafficking analysis American journal of physiology. Gastrointestinal and liver physiology Medium 18202109
2009 gp340 mediates transcytosis of HIV-1 across genital tract-derived cell lines and primary endocervical tissue from apical to basolateral surfaces. This transcytosis is blocked by antibodies or peptides that disrupt gp340-HIV envelope interaction. Heparan sulfate moieties on gp340 also participate in mediating transcytosis. Transwell transcytosis assay with primary endocervical tissue, blocking antibodies/peptides, heparan sulfate perturbation Journal of virology Medium 19553331
2009 Leucine-rich repeat (Lrr) motifs on bacterial surface proteins (S. pyogenes Spy0843, S. agalactiae LrrG, T. forsythia BspA) serve as recognition motifs for human gp340/DMBT1. The Lrr region mediates binding to gp340, and VEVLXXXXW-containing peptides inhibit this binding, implicating a gp340 core peptide distinct from the XXXXW motif. Mass spectrometry sequencing, gene inactivation (bacterial mutants), recombinant truncated protein binding assay, peptide inhibition assay The Journal of biological chemistry Medium 19465482
2010 Deletion of hensin/DMBT1 from intercalated cells blocks conversion of beta- to alpha-intercalated cells in the renal collecting tubule, causing complete distal renal tubular acidosis (dRTA). Polymerization and ECM deposition of hensin requires beta1 integrin activation; conditional deletion of beta1 integrin from intercalated cells produces an identical phenotype. Conditional Dmbt1 knockout and beta1-integrin knockout mice, immunofluorescence localization of V-ATPase/pendrin/kAE1, acid-feeding challenge, electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 21098262
2010 DMBT1 expression in intestinal epithelial cells is induced by IL-22 through STAT3 tyrosine phosphorylation and NF-κB activation. The IL-22-responsive element was mapped to positions -187 to -179 in the DMBT1 promoter by deletion analysis and EMSA. Microarray, siRNA knockdown of STAT3, MEK/PI3K/NF-κB inhibitors, promoter deletion luciferase assay, EMSA Inflammatory bowel diseases Medium 20824812
2011 Salivary agglutinin (DMBT1) activates complement via the lectin pathway (MBL pathway): antibodies against mannose-binding lectin (MBL) block C4 deposition on SAG-coated plates, SAG induces no C4 deposition in MBL-deficient sera, and periodate treatment of SAG (removing carbohydrate) abolishes MBL pathway activation. C4 deposition ELISA on SAG-coated microplates, MBL-blocking antibodies, MBL-deficient sera, periodate carbohydrate oxidation Molecular immunology Medium 21920605
2013 Staphylococcus aureus surface protein SasA is responsible for binding to gp340/DMBT1. Inactivation of the sasA gene reduces S. aureus binding to gp340-coated surfaces. Recombinant SasA binds gp340, inhibited by N-acetylneuraminic acid; surface plasmon resonance shows rSasA binds NeuAcα(2-3)Galβ(1-4)GlcNAc structures on gp340. Gene inactivation (sasA mutant), recombinant protein binding assay, sialic acid inhibition, surface plasmon resonance Infection and immunity High 23439307
2013 DMBT1(gp340) binds to solid-phase dimeric TFF3 in a calcium-dependent manner but does not bind monomeric TFF3, TFF2, or glycosylated TFF2, establishing a specific interaction requiring TFF3 dimerization. ELISA-based binding assay with recombinant TFF isoforms, calcium dependency analysis PloS one Medium 23691218
2013 The non-coding DMBT1 SNP rs2981804 modifies DNA binding sites for transcription factors CREB1 and ATF-2, and the genomic region comprising rs2981804 acts as a transcriptional regulator in vitro; the CD risk allele is associated with decreased intestinal DMBT1 expression. IL-22 induces DMBT1 expression in intestinal epithelial cells via STAT3, ATF-2, and CREB1. Electrophoretic mobility shift assay (EMSA), luciferase reporter assay, siRNA knockdown, quantitative PCR, Western blot PloS one Medium 24223725
2017 DMBT1 purified from human saliva inhibits twitching motility of Pseudomonas aeruginosa and prevents bacterial traversal of human corneal epithelial cells in vitro and reduces disease in a murine corneal infection model. DMBT1 does not affect PilA expression or intracellular cAMP levels, but dot-immunoblot assays show purified DMBT1 directly binds P. aeruginosa pili, suggesting inhibition involves a direct pili interaction. Protein fractionation and mass spectrometry identification, immunoprecipitation, purified DMBT1 twitching assay, dot-immunoblot pili binding assay, epithelial cell traversal assay, murine corneal infection model PLoS pathogens Medium 28489917
2018 DMBT1 protein is enriched in exosomes from human urine-derived stem cells (USC-Exos) and is required for USC-Exos-induced promotion of angiogenic responses of endothelial cells in vitro and for angiogenesis and wound healing in diabetic mice in vivo. Exosome proteomics, DMBT1 knockdown in USC-Exos, in vitro angiogenesis assays, streptozotocin-induced diabetic mouse wound healing model Theranostics Medium 29556344
2020 Crystal/structural analysis of DMBT1 (SALSA) SRCR domains 1 and 8 revealed a novel universal ligand-binding mechanism: the binding interface incorporates a dual cation-binding site that is highly conserved across the SRCR superfamily, suggesting this mechanism is applicable to all SRCR domains. Structural determination (crystallography implied), cation-binding site identification, comparative analysis across SRCR superfamily Life science alliance High 32098784
2020 DMBT1 overexpression in ovarian cancer cells inhibits proliferation, migration, and invasion, and immunoprecipitation reveals a direct interaction between DMBT1 and galectin-3. DMBT1 decreases galectin-3 expression and inhibits PI3K/AKT phosphorylation; overexpression of galectin-3 reverses DMBT1-mediated tumor suppression. Overexpression, CCK-8 proliferation assay, wound healing/transwell invasion assay, immunoprecipitation, Western blot for PI3K/AKT phosphorylation Cell biochemistry and function Low 32424818
2022 Exosomes derived from MSCs pretreated with ischemic heart extracts contain elevated DMBT1; silencing DMBT1 in MSCs reduces DMBT1 in exosomes and impairs HUVEC proliferation and migration, along with decreased p-Akt, beta-catenin, and VEGF, suggesting DMBT1 delivery via exosomes promotes angiogenesis through Akt/beta-catenin/VEGF signaling. Proteomics, DMBT1 siRNA knockdown, MTT and wound healing assays, Western blot for pathway components Cell transplantation Low 35726847

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours. Nature genetics 403 9288095
2018 Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics 315 29556344
2000 Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is the lung scavenger receptor cysteine-rich protein gp-340. The Journal of biological chemistry 181 11007786
1999 Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D. Proceedings of the National Academy of Sciences of the United States of America 177 10485905
1997 Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule. The Journal of biological chemistry 177 9153228
2000 DMBT1 encodes a protein involved in the immune defense and in epithelial differentiation and is highly unstable in cancer. Cancer research 160 10749143
2023 Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 147 35235656
2007 Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates bacterial recognition and invasion. Journal of immunology (Baltimore, Md. : 1950) 135 17548659
2010 Review: Gp-340/DMBT1 in mucosal innate immunity. Innate immunity 132 20418254
2002 Identification of the bacteria-binding peptide domain on salivary agglutinin (gp-340/DMBT1), a member of the scavenger receptor cysteine-rich superfamily. The Journal of biological chemistry 128 12050164
2004 Bacteria binding by DMBT1/SAG/gp-340 is confined to the VEVLXXXXW motif in its scavenger receptor cysteine-rich domains. The Journal of biological chemistry 107 15355985
2005 Fluid- or surface-phase human salivary scavenger protein gp340 exposes different bacterial recognition properties. Infection and immunity 96 15784568
1999 Expression of DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer. Cancer research 96 10213490
1999 Lack of DMBT1 expression in oesophageal, gastric and colon cancers. British journal of cancer 95 9888459
2007 Salivary agglutinin/glycoprotein-340/DMBT1: a single molecule with variable composition and with different functions in infection, inflammation and cancer. Biological chemistry 93 18020944
2007 DMBT1 confers mucosal protection in vivo and a deletion variant is associated with Crohn's disease. Gastroenterology 91 17983803
2003 DMBT1, a regulator of mucosal homeostasis through the linking of mucosal defense and regeneration? FEBS letters 80 12681477
1988 Recombinant vaccinia virus expressing Epstein-Barr virus glycoprotein gp340 protects cottontop tamarins against EB virus-induced malignant lymphomas. Journal of medical virology 79 2839612
2010 Deletion of hensin/DMBT1 blocks conversion of beta- to alpha-intercalated cells and induces distal renal tubular acidosis. Proceedings of the National Academy of Sciences of the United States of America 71 21098262
1999 The genomic structure of the DMBT1 gene: evidence for a region with susceptibility to genomic instability. Oncogene 70 10597221
2010 Deleted in malignant brain tumors-1 protein (DMBT1): a pattern recognition receptor with multiple binding sites. International journal of molecular sciences 69 21614203
2001 Human salivary agglutinin binds to lung surfactant protein-D and is identical with scavenger receptor protein gp-340. The Biochemical journal 68 11563989
2007 gp340 expressed on human genital epithelia binds HIV-1 envelope protein and facilitates viral transmission. Journal of immunology (Baltimore, Md. : 1950) 66 17709527
1985 Recombinant vaccinia virus induces neutralising antibodies in rabbits against Epstein-Barr virus membrane antigen gp340. The EMBO journal 65 3004944
2003 CRP-ductin, the mouse homologue of gp-340/deleted in malignant brain tumors 1 (DMBT1), binds gram-positive and gram-negative bacteria and interacts with lung surfactant protein D. European journal of immunology 63 12884308
2002 Peptidomics-based approach reveals the secretion of the 29-residue COOH-terminal fragment of the putative tumor suppressor protein DMBT1 from pancreatic adenocarcinoma cell lines. Cancer research 57 12208737
2020 Soil bacterial diversity, structure, and function of Suaeda salsa in rhizosphere and non-rhizosphere soils in various habitats in the Yellow River Delta, China. The Science of the total environment 56 32562999
2016 Long non-coding RNA CRNDE promotes gallbladder carcinoma carcinogenesis and as a scaffold of DMBT1 and C-IAP1 complexes to activating PI3K-AKT pathway. Oncotarget 52 27637083
1999 Hensin, the polarity reversal protein, is encoded by DMBT1, a gene frequently deleted in malignant gliomas. The American journal of physiology 51 10444583
2010 DMBT1 is a novel gene induced by IL-22 in ulcerative colitis. Inflammatory bowel diseases 48 20824812
2002 Sequential changes of the DMBT1 expression and location in normal lung tissue and lung carcinomas. Genes, chromosomes & cancer 48 12203780
1999 Expression of the DMBT1 gene is frequently suppressed in human lung cancer. Japanese journal of cancer research : Gann 46 10551316
1992 Protective immunization against Epstein-Barr virus-induced disease in cottontop tamarins using the virus envelope glycoprotein gp340 produced from a bovine papillomavirus expression vector. The Journal of general virology 46 1311367
2013 A variant form of the human deleted in malignant brain tumor 1 (DMBT1) gene shows increased expression in inflammatory bowel diseases and interacts with dimeric trefoil factor 3 (TFF3). PloS one 45 23691218
2008 Scavenger receptor gp340 aggregates group A streptococci by binding pili. Molecular microbiology 45 18452511
2009 Leucine-rich repeats of bacterial surface proteins serve as common pattern recognition motifs of human scavenger receptor gp340. The Journal of biological chemistry 44 19465482
2011 The bacteria binding glycoprotein salivary agglutinin (SAG/gp340) activates complement via the lectin pathway. Molecular immunology 43 21920605
2001 Expressed sequence tags from a NaCl-treated Suaeda salsa cDNA library. Gene 43 11313146
1991 Identification of two T-cell epitopes on the candidate Epstein-Barr virus vaccine glycoprotein gp340 recognized by CD4+ T-cell clones. Journal of virology 43 1710291
2009 gp340 promotes transcytosis of human immunodeficiency virus type 1 in genital tract-derived cell lines and primary endocervical tissue. Journal of virology 42 19553331
2004 Homozygous deletion and expression of PTEN and DMBT1 in human primary neuroblastoma and cell lines. International journal of cancer 42 14999773
2004 DMBT1 expression is down-regulated in breast cancer. BMC cancer 41 15301691
2003 Frequent downregulation of DMBT1 and galectin-3 in epithelial skin cancer. International journal of cancer 41 12673672
1991 Salivary and serum IgA antibodies to the Epstein-Barr virus glycoprotein gp340: incidence and potential for virus neutralization. International journal of cancer 41 1850382
2019 Bioaugmentation-assisted phytoremediation of lead and salinity co-contaminated soil by Suaeda salsa and Trichoderma asperellum. Chemosphere 38 30851523
2017 SALSA-A dance on a slippery floor with changing partners. Molecular immunology 38 28668353
2017 Functional characterization of a type 2 metallothionein gene, SsMT2, from alkaline-tolerant Suaeda salsa. Scientific reports 37 29263347
2002 Immunohistochemical detection of salivary agglutinin/gp-340 in human parotid, submandibular, and labial salivary glands. Journal of dental research 37 11829014
2002 DMBT1 polymorphisms: relationship to malignant glioma tumorigenesis. Cancer research 37 11912156
2002 The SRCR/SID region of DMBT1 defines a complex multi-allele system representing the major basis for its variability in cancer. Genes, chromosomes & cancer 37 12353266
2007 Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries. BMC infectious diseases 36 17562017
2017 Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of the opportunistic pathogen Pseudomonas aeruginosa. PLoS pathogens 35 28489917
2008 A common binding motif for various bacteria of the bacteria-binding peptide SRCRP2 of DMBT1/gp-340/salivary agglutinin. Biological chemistry 35 18713006
2005 Induction of DMBT1 expression by reduced ERK activity during a gastric mucosa differentiation-like process and its association with human gastric cancer. Carcinogenesis 34 15760920
1988 In vitro T cell responses to a candidate Epstein-Barr virus vaccine: human CD4+ T cell clones specific for the major envelope glycoprotein gp340. European journal of immunology 33 2904885
2015 Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and population subsistence strategy. Proceedings of the National Academy of Sciences of the United States of America 32 25848046
2007 Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk. The American journal of pathology 32 17525270
2013 Staphylococcus aureus SasA is responsible for binding to the salivary agglutinin gp340, derived from human saliva. Infection and immunity 31 23439307
2004 gp340 (SAG) binds to the V3 sequence of gp120 important for chemokine receptor interaction. AIDS research and human retroviruses 31 15242536
2004 Carcinogen inducibility in vivo and down-regulation of DMBT1 during breast carcinogenesis. Genes, chromosomes & cancer 30 14732920
2017 Human DMBT1-Derived Cell-Penetrating Peptides for Intracellular siRNA Delivery. Molecular therapy. Nucleic acids 28 28918028
2002 The scavenger receptor, cysteine-rich domain-containing molecule gp-340 is differentially regulated in epithelial cell lines by phorbol ester. Clinical and experimental immunology 28 12452835
2008 Effects of Muclin (Dmbt1) deficiency on the gastrointestinal system. American journal of physiology. Gastrointestinal and liver physiology 27 18202109
2007 Variant size- and glycoforms of the scavenger receptor cysteine-rich protein gp-340 with differential bacterial aggregation. Glycoconjugate journal 27 17243023
2002 Analysis of loss of chromosome 10q, DMBT1 homozygous deletions, and PTEN mutations in oligodendrogliomas. Journal of neurosurgery 26 12507139
2022 Suaeda salsa Root-Associated Microorganisms Could Effectively Improve Maize Growth and Resistance under Salt Stress. Microbiology spectrum 25 35950864
2003 Mutation analysis of DMBT1 in glioblastoma, medulloblastoma and oligodendroglial tumors. International journal of cancer 25 12672033
1983 Purification and properties of the gp340 component of Epstein-Barr virus membrane antigen in an immunogenic form. The Journal of general virology 25 6300296
2005 Generation of a vector system facilitating cloning of DMBT1 variants and recombinant expression of functional full-length DMBT1. Protein expression and purification 24 15866713
2015 Deleted in malignant brain tumors 1 (DMBT1) elicits increased VEGF and decreased IL-6 production in type II lung epithelial cells. BMC pulmonary medicine 23 25885541
2020 Structures of SALSA/DMBT1 SRCR domains reveal the conserved ligand-binding mechanism of the ancient SRCR fold. Life science alliance 22 32098784
2016 SALSA: A Regulator of the Early Steps of Complement Activation on Mucosal Surfaces. Frontiers in immunology 22 27014265
2006 The N-terminal SRCR-SID domain of gp-340 interacts with HIV type 1 gp120 sequences and inhibits viral infection. AIDS research and human retroviruses 22 16796526
2002 PTEN, DMBT1, and p16 alterations in diffusely infiltrating astrocytomas. International journal of oncology 22 12168116
1999 The major Epstein-Barr virus (EBV) envelope glycoprotein gp340 when incorporated into Iscoms primes cytotoxic T-cell responses directed against EBV lymphoblastoid cell lines. Vaccine 22 10195641
2022 Evaluation of CSTB and DMBT1 expression in saliva of gastric cancer patients and controls. BMC cancer 21 35488257
2020 Transcriptomic analysis identifies novel genes and pathways for salt stress responses in Suaeda salsa leaves. Scientific reports 21 32144380
2017 Ectopic expression of SsPETE2, a plastocyanin from Suaeda salsa, improves plant tolerance to oxidative stress. Plant science : an international journal of experimental plant biology 21 29362078
2013 Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2. PloS one 21 24223725
2012 Toxicological responses in halophyte Suaeda salsa to mercury under environmentally relevant salinity. Ecotoxicology and environmental safety 21 22947507
2008 HIV envelope binding by macrophage-expressed gp340 promotes HIV-1 infection. Journal of immunology (Baltimore, Md. : 1950) 21 18641344
2002 Determination of capsaicinoids in salsa by liquid chromatography and enzyme immunoassay. Journal of AOAC International 21 11878623
2002 Rare mutations of the DMBT1 gene in human astrocytic gliomas. Oncogene 21 12185598
2000 Analysis of the DMBT1 gene in carcinomas of the respiratory tract. International journal of cancer 21 10962442
2019 Adaptation of euhalophyte Suaeda salsa to nitrogen starvation under salinity. Plant physiology and biochemistry : PPB 20 31783204
2007 Respiratory Deleted in Malignant Brain Tumours 1 (DMBT1) levels increase during lung maturation and infection. Clinical and experimental immunology 20 17991292
2019 Transcriptome sequencing revealed molecular mechanisms underlying tolerance of Suaeda salsa to saline stress. PloS one 19 31335886
2022 Exosomes Derived From Mesenchymal Stem Cells Pretreated With Ischemic Rat Heart Extracts Promote Angiogenesis via the Delivery of DMBT1. Cell transplantation 18 35726847
2020 Flavobacterium alkalisoli sp. nov., isolated from rhizosphere soil of Suaeda salsa. International journal of systematic and evolutionary microbiology 18 32496180
2012 Expression of deleted in malignant brain tumours 1 (DMBT1) relates to the proliferation and malignant transformation of hepatic progenitor cells in hepatitis B virus-related liver diseases. Histopathology 17 22211283
2004 PTEN and DMBT1 homozygous deletion and expression in medulloblastomas and supratentorial primitive neuroectodermal tumors. Oncology reports 17 15547761
2002 An integrative model on the role of DMBT1 in epithelial cancer. Cancer detection and prevention 17 12430631
1992 Purification and characterization of Epstein-Barr virus gp340/220 produced by a bovine papillomavirus virus expression vector system. Vaccine 17 1332270
2010 Loss of DMBT1 expression in human prostate cancer and its correlation with clinical progressive features. Urology 16 21167560
2007 DMBT1 is frequently downregulated in well-differentiated gastric carcinoma but more frequently upregulated across various gastric cancer types. International journal of oncology 16 17487364
2017 Increased expression of deleted in malignant brain tumors (DMBT1) gene in precancerous gastric lesions: Findings from human and animal studies. Oncotarget 15 28423364
2012 DMBT1 homozygous deletion in diffuse astrocytomas is associated with unfavorable clinical outcome. Journal of neuropathology and experimental neurology 15 22805772
2010 Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity. Human mutation 15 19830809
1993 MHC class II-restricted presentation of endogenously synthesized antigen: Epstein-Barr virus transformed B cell lines can present the viral glycoprotein gp340 by two distinct pathways. International immunology 15 8391306
2020 DMBT1 suppresses cell proliferation, migration and invasion in ovarian cancer and enhances sensitivity to cisplatin through galectin-3/PI3k/Akt pathway. Cell biochemistry and function 14 32424818

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