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DMBT1 (Deleted in malignant brain tumors 1)

Written2007-08Jan Mollenhauer, Annemarie Poustka
Division of Molecular Genome Analysis, German Cancer Research Center, Im Neuenheimer, Feld 280, 69120 Heidelberg, Germany

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Alias (NCBI)gp-340 (glycoprotein-340; human)
SAG (salivary agglutinin; human)
apactin (mouse)
CRP-ductin (mouse)
gp300 (glycoprotein 300; mouse)
muclin (mouse)
vomeroglandin (mouse)
ebnerin (rat)
hensin (rabbit)
BGM (bovine gallbladder mucin, cattle)
H3 (rhesus monkey)
HGNC Alias symbGP340
HGNC Alias namesalivary agglutinin
 salivary scavenger and agglutinin
LocusID (NCBI) 1755
Atlas_Id 309
Location 10q26.13  [Link to chromosome band 10q26]
Location_base_pair Starts at 122560754 and ends at 122643736 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping DMBT1.png]
Local_order between D10S1421 and D10S1273E
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
DMBT1 (10q26.13)::SND1 (7q32.1)


  Genomic organization of DMBT1. Top line: scale in kb. Second line: exon-intron structure of DMBT1 drawn to scale. Exons have the color code of the domains they are coding for. Exon 55 marked in black represents an exon with homology to the mouse and rat homologues, in which it codes for a transmembrane domain. Exon 55 has not yet been identified in a human transcript. Arrows depict regions, in which exon and intron sequences share high homologies. Bottom line: domain organization of the DMBT1 protein predicted from assembly of the first 54 exons. Entries to color codes and abbreviations are depicted in the section describing the protein.
Description The gene consists of 55 exons distributed over about 80 kb. Scavenger receptor cysteine-rich (SRCR) domains are coded by single exons. Two small exons coding for serine-threonine-proline-rich stretches of 20-24 amino acids in length follow each SRCR exon. To these stretches it has been referred to as SRCR-interspersed domains (SIDs). The only exception is that there is only one of the two SID exons between SRCR4 and SRCR5.
Transcription Longest transcript identified so far: 7656 bp including 5'-utr, exons 1-16 and exons 18-54. Various alternative transcripts with variable numbers of SRCR and SID exons exist. Exon 55 has not yet been verified to be present in human transcripts.
Pseudogene No pseudogene known so far.


  Domain organization of DMBT1. Prototype: protein assembled from the first 54 exons (corresponding transcripts not yet identified). DMBT1/8kb.2: secreted DMBT1 variant encoded by the largest known transcript. DMBT1/6kb.1: secreted DMBT1 variant encoded by the smallest known transcript. Pink triangle: signal peptide putatively required for secretion; blue box repetitive motif of unknown function; red circles: scavenger receptor cysteine-rich (SRCR) domains; orange circles: SRCR-interspersed domains (SIDs); orange circles with TTT and STP: threonine- and serine-threonine-proline-rich domains with limited similarity to SIDs; CUB: C1r/C1s-Uegf-Bmp1 domains; ZP: zona pellucida domain.
Description The largest known protein variant (DMBT1/8kb.2) comprises 2413 amino acids and has a calculated molecular weight of 265 kDa. Probably due to glycosylation the molecular weight of the purified protein is approximately 340 kDa. The smallest known variant (DMBT1/6kb.1), which lacks several SRCR domains and SIDs, comprises 1785 amino acids with a calculated molecular weight of 196 kDa. Various other protein variants lacking one or more SRCR domains may exist. The protein variants may arise due to genetic polymorphisms and/or alternative splicing.
The SRCR domains are involved in ligand interactions. An 11 amino acid motif (GRVEVLYRGSW) present in each of the repeated SRCR domains has been shown to be responsible for the binding of a broad spectrum of Gram-positive and Gram-negative bacteria. The N-terminal SRCR1/SD1 domain has been shown to interact with HIV gp120 and to suppress HIV infection. The functions of the CUB domains and of SRCR14, which shows only limited similarity to the other SRCR domains within DMBT1, have not yet been determined. In other proteins, ZP domains have been shown to function in oligomerization. DMBT1 is also secreted as high molecular weight oligomers.
SRCR, CUB, and ZP domains exclusively occur in multicellular animal organisms.
Expression Main sites of DMBT1 expression are surface epithelial cells and associated glands, in particular in the respiratory and gastrointestinal tract. In most tissues low to moderate DMBT1 levels are expressed under normal conditions. An upregulation has been observed in response to various pathophysiological conditions, such as bacterial infection, inflammation, tumor-flanking tissues, carcinogen exposure, etc. Expression has also been noted in other tissues such as the brain and in immune cells.
Localisation Extracellular. DMBT1 is either secreted to the mucus and other body fluids or to the extracellular matrix.
Function DMBT1 exerts at least two distinct functions. As extracellular matrix protein, DMBT1 triggers polarity and terminal differentiation of epithelial cells as well as differentiation of embryonic stem cells to monolayered epithelia, which has been demonstrated by in vitro studies with rodent orthologs of DMBT1. DMBT1 secreted to the luminal side of epithelial surfaces plays a role in defense against bacterial and viral pathogens. This mechanism includes pathogen recognition through a peptide motif present in the SRCR domains and mediation of pathogen aggregation. DMBT1 further has been shown to exert anti-inflammatory effects. In response to activation of the intracellular pattern recognition molecule NOD2 and consecutive NFkB-activation, upregulation of DMBT1 takes place, which in turn hinders bacterial invasion and LPS-induced TLR4-activation. Hindrance of bacterial invasion may abolish NOD2 activation. Thus DMBT1 may act anti-inflammatory via inhibiting both NOD2- and TLR4-mediated NF-kB-activation. As DMBT1 is NF-kB responsive, this presumably builds up an autoregulatory homeostatic loop, by which DMBT1 is able to regulate its own expression as extracellular sensory element. These data point to a function in anti-inflammatory immune exclusion similar to mucosal antibodies (sIgA).
Homology Homologies exist to other SRCR proteins such as CD5 and CD6, which function in immune defense. However, to date there is no SRCR protein known that additionally contains CUB and ZP domains. At the level of the SRCR domains, DMBT1 further shares some homologies with the sponge aggregation receptor (AR), which initiates the first steps in regeneration of a complete sponge body after dissociation.


Germinal Initial evidence has been gained that the SRCR- and SID-coding exons are subjected to copy number variations.
Somatic Few point mutations have been identified in cancer so far. There is no hard evidence for an inactivation by biallelic mutation in cancer. Copy number variations of the SRCR- and SID-coding exons have been noted in different cancer types, including brain, lung, breast, gastrointestinal tumors and melanoma. It has not yet been determined to which extent these represent de novo rearrangements or germline mutations/polymorphisms. Underexpression has been observed for lung, colon, gastric, esophageal, breast, and skin cancer. By contrast overexpression was observed for pancreatic and prostate cancer.

Implicated in

Entity Cancer
Disease Based on underexpression and on its role in triggering differentiation, a role in tumor suppression of different cancer types, mainly of epithelial origin, has been proposed. A genetic scan in mice identified DMBT1 as candidate genetic modifier, which may determine the penetrance of breast cancer in the presence of p53 mutations. Lower DMBT1 protein levels have been observed in the normal mammary gland epithelium of women, which developed breast cancer versus tissues obtained from healthy donors.
Entity Crohn's Disease
Disease Activation of DMBT1 was found to be impaired in the intestinal epithelium of Crohn's disease with predisposing NOD2 mutations.
Entity Infection
Disease Based on its broad bacterial binding specificity and inhibitory effects on bacterial and viral (HIV, influenza A viruses) infection in vitro, a role in infectious diseases has been proposed.
Entity Caries
Disease DMBT1 alias SAG (salivary agglutinin) has been studied for about two decades as the major caries bacteria agglutinating non-immunoglobulin in the saliva/oral cavity. Based on its capacity to aggregate caries bacteria (e. g. Streptococcus mutans), it was proposed to exert functions in preventing caries. Based on its capacity to mediate bacterial adhesion to enamel-like surfaces, it was proposed to exert functions in promoting caries by other groups.


Terminal differentiation of epithelia.
Al-Awqati Q, Vijayakumar S, Takito J
Biological chemistry. 2003 ; 384 (9) : 1255-1258.
PMID 14515985
Bacteria binding by DMBT1/SAG/gp-340 is confined to the VEVLXXXXW motif in its scavenger receptor cysteine-rich domains.
Bikker FJ, Ligtenberg AJ, End C, Renner M, Blaich S, Lyer S, Wittig R, van't Hof W, Veerman EC, Nazmi K, de Blieck-Hogervorst JM, Kioschis P, Nieuw Amerongen AV, Poustka A, Mollenhauer J
The Journal of biological chemistry. 2004 ; 279 (46) : 47699-47703.
PMID 15355985
Heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of deleted in malignant brain tumor 1.
Bisgaard HC, Holmskov U, Santoni-Rugiu E, Nagy P, Nielsen O, Ott P, Hage E, Dalhoff K, Rasmussen LJ, Tygstrup N
The American journal of pathology. 2002 ; 161 (4) : 1187-1198.
PMID 12368192
Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk.
Blackburn AC, Hill LZ, Roberts AL, Wang J, Aud D, Jung J, Nikolcheva T, Allard J, Peltz G, Otis CN, Cao QJ, Ricketts RS, Naber SP, Mollenhauer J, Poustka A, Malamud D, Jerry DJ
The American journal of pathology. 2007 ; 170 (6) : 2030-2041.
PMID 17525270
Processing of pro-Muclin and divergent trafficking of its products to zymogen granules and the apical plasma membrane of pancreatic acinar cells.
De Lisle RC, Ziemer D
European journal of cell biology. 2000 ; 79 (12) : 892-904.
PMID 11152281
Lung and salivary scavenger receptor glycoprotein-340 contribute to the host defense against influenza A viruses.
Hartshorn KL, White MR, Mogues T, Ligtenberg T, Crouch E, Holmskov U
American journal of physiology. Lung cellular and molecular physiology. 2003 ; 285 (5) : L1066-L1076.
PMID 12871854
Only multimeric hensin located in the extracellular matrix can induce apical endocytosis and reverse the polarity of intercalated cells.
Hikita C, Takito J, Vijayakumar S, Al-Awqati Q
The Journal of biological chemistry. 1999 ; 274 (25) : 17671-17676.
PMID 10364206
Induction of terminal differentiation in epithelial cells requires polymerization of hensin by galectin 3.
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The Journal of cell biology. 2000 ; 151 (6) : 1235-1246.
PMID 11121438
Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D.
Holmskov U, Mollenhauer J, Madsen J, Vitved L, Gronlund J, Tornoe I, Kliem A, Reid KB, Poustka A, Skjodt K
Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (19) : 10794-10799.
PMID 10485905
Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression.
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Cancer biology & therapy. 2004 ; 3 (12) : 1254-1261.
PMID 15477757
Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries.
Jonasson A, Eriksson C, Jenkinson HF, Källestå C, Johansson I, Strömberg N
BMC infectious diseases. 2007 ; 7 : page 57.
PMID 17562017
Induction of DMBT1 expression by reduced ERK activity during a gastric mucosa differentiation-like process and its association with human gastric cancer.
Kang W, Nielsen O, Fenger C, Leslie G, Holmskov U, Reid KB
Carcinogenesis. 2005 ; 26 (6) : 1129-1137.
PMID 15760920
DMBT1, a regulator of mucosal homeostasis through the linking of mucosal defense and regeneration?
Kang W, Reid KB
FEBS letters. 2003 ; 540 (1-3) : 21-25.
PMID 12681477
Prostatic intraepithelial neoplasia and adenocarcinoma in mice expressing a probasin-Neu oncogenic transgene.
Li Z, Szabolcs M, Terwilliger JD, Efstratiadis A
Carcinogenesis. 2006 ; 27 (5) : 1054-1067.
PMID 16401639
Human salivary agglutinin binds to lung surfactant protein-D and is identical with scavenger receptor protein gp-340.
Ligtenberg TJ, Bikker FJ, Groenink J, Tornoe I, Leth-Larsen R, Veerman EC, Nieuw Amerongen AV, Holmskov U
The Biochemical journal. 2001 ; 359 (Pt 1) : 243-248.
PMID 11563989
Allelic deletion analyses of MMAC/PTEN and DMBT1 loci in gliomas: relationship to prognostic significance.
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Clinical cancer research : an official journal of the American Association for Cancer Research. 1998 ; 4 (10) : 2447-2454.
PMID 9796977
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.
Madsen J, Torn&oring;e I, Nielsen O, Lausen M, Krebs I, Mollenhauer J, Kollender G, Poustka A, Skj&oring;dt K, Holmskov U
European journal of immunology. 2003 ; 33 (8) : 2327-2336.
PMID 12884308
Carcinogen inducibility in vivo and down-regulation of DMBT1 during breast carcinogenesis.
Mollenhauer J, Helmke B, Medina D, Bergmann G, Gassler N, Müller H, Lyer S, Diedrichs L, Renner M, Wittig R, Blaich S, Hamann U, Madsen J, Holmskov U, Bikker F, Ligtenberg A, Carlén A, Olsson J, Otto HF, O'Malley B, Poustka A
Genes, chromosomes & cancer. 2004 ; 39 (3) : 185-194.
PMID 14732920
Lack of DMBT1 expression in oesophageal, gastric and colon cancers.
Mori M, Shiraishi T, Tanaka S, Yamagata M, Mafune K, Tanaka Y, Ueo H, Barnard GF, Sugimachi K
British journal of cancer. 1999 ; 79 (2) : 211-213.
PMID 9888459
Rare mutations of the DMBT1 gene in human astrocytic gliomas.
Mueller W, Mollenhauer J, Stockhammer F, Poustka A, von Deimling A
Oncogene. 2002 ; 21 (38) : 5956-5959.
PMID 12185598
Inflammation of the cystic fibrosis mouse small intestine.
Norkina O, Kaur S, Ziemer D, De Lisle RC
American journal of physiology. Gastrointestinal and liver physiology. 2004 ; 286 (6) : G1032-G1041.
PMID 14739145
Mutation analysis of DMBT1 in glioblastoma, medulloblastoma and oligodendroglial tumors.
Pang JC, Dong Z, Zhang R, Liu Y, Zhou LF, Chan BW, Poon WS, Ng HK
International journal of cancer. Journal international du cancer. 2003 ; 105 (1) : 76-81.
PMID 12672033
Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is the lung scavenger receptor cysteine-rich protein gp-340.
Prakobphol A, Xu F, Hoang VM, Larsson T, Bergstrom J, Johansson I, Frängsmyr L, Holmskov U, Leffler H, Nilsson C, Borén T, Wright JR, Strömberg N, Fisher SJ
The Journal of biological chemistry. 2000 ; 275 (51) : 39860-39866.
PMID 11007786
Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates bacterial recognition and invasion.
Rosenstiel P, Sina C, End C, Renner M, Lyer S, Till A, Hellmig S, Nikolaus S, Fölsch UR, Helmke B, Autschbach F, Schirmacher P, Kioschis P, Hafner M, Poustka A, Mollenhauer J, Schreiber S
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PMID 17548659
The Scavenger Receptor Cysteine-Rich (SRCR) domain: an ancient and highly conserved protein module of the innate immune system.
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Critical reviews in immunology. 2004 ; 24 (1) : 1-37.
PMID 14995912
DMBT1 polymorphisms: relationship to malignant glioma tumorigenesis.
Sasaki H, Betensky RA, Cairncross JG, Louis DN
Cancer research. 2002 ; 62 (6) : 1790-1796.
PMID 11912156
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.
Sasaki K, Sato K, Akiyama Y, Yanagihara K, Oka M, Yamaguchi K
Cancer research. 2002 ; 62 (17) : 4894-4898.
PMID 12208737
Decrease of deleted in malignant brain tumour-1 (DMBT-1) expression is a crucial late event in intrahepatic cholangiocarcinoma.
Sasaki M, Huang SF, Chen MF, Jan YY, Yeh TS, Ishikawa A, Mollenhauer J, Poustka A, Tsuneyama K, Nimura Y, Oda K, Nakanuma Y
Histopathology. 2003 ; 43 (4) : 340-346.
PMID 14511252
Molecular analysis of two putative tumour suppressor genes, PTEN and DMBT, which have been implicated in glioblastoma multiforme disease progression.
Somerville RP, Shoshan Y, Eng C, Barnett G, Miller D, Cowell JK
Oncogene. 1998 ; 17 (13) : 1755-1757.
PMID 9796706
Expression of the DMBT1 gene is frequently suppressed in human lung cancer.
Takeshita H, Sato M, Shiwaku HO, Semba S, Sakurada A, Hoshi M, Hayashi Y, Tagawa Y, Ayabe H, Horii A
Japanese journal of cancer research : Gann. 1999 ; 90 (9) : 903-908.
PMID 10551316
Conversion of ES cells to columnar epithelia by hensin and to squamous epithelia by laminin.
Takito J, Al-Awqati Q
The Journal of cell biology. 2004 ; 166 (7) : 1093-1102.
PMID 15452149
Hensin, the polarity reversal protein, is encoded by DMBT1, a gene frequently deleted in malignant gliomas.
Takito J, Yan L, Ma J, Hikita C, Vijayakumar S, Warburton D, Al-Awqati Q
The American journal of physiology. 1999 ; 277 (2 Pt 2) : F277-F289.
PMID 10444583
Hensin remodels the apical cytoskeleton and induces columnarization of intercalated epithelial cells: processes that resemble terminal differentiation.
Vijayakumar S, Takito J, Hikita C, Al-Awqati Q
The Journal of cell biology. 1999 ; 144 (5) : 1057-1067.
PMID 10085301
Respiratory innate immune proteins differentially modulate the neutrophil respiratory burst response to influenza A virus.
White MR, Crouch E, Vesona J, Tacken PJ, Batenburg JJ, Leth-Larsen R, Holmskov U, Hartshorn KL
American journal of physiology. Lung cellular and molecular physiology. 2005 ; 289 (4) : L606-L616.
PMID 15951332
Expression of DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer.
Wu W, Kemp BL, Proctor ML, Gazdar AF, Minna JD, Hong WK, Mao L
Cancer research. 1999 ; 59 (8) : 1846-1851.
PMID 10213490
gp340 (SAG) binds to the V3 sequence of gp120 important for chemokine receptor interaction.
Wu Z, Golub E, Abrams WR, Malamud D
AIDS research and human retroviruses. 2004 ; 20 (6) : 600-607.
PMID 15242536
The N-terminal SRCR-SID domain of gp-340 interacts with HIV type 1 gp120 sequences and inhibits viral infection.
Wu Z, Lee S, Abrams W, Weissman D, Malamud D
AIDS research and human retroviruses. 2006 ; 22 (6) : 508-515.
PMID 16796526
Salivary agglutinin inhibits HIV type 1 infectivity through interaction with viral glycoprotein 120.
Wu Z, Van Ryk D, Davis C, Abrams WR, Chaiken I, Magnani J, Malamud D
AIDS research and human retroviruses. 2003 ; 19 (3) : 201-209.
PMID 12689412


This paper should be referenced as such :
Mollenhauer, J ; Poustka, A
DMBT1 (deleted in malignant brain tumors 1)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2):91-95.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)DMBT1   2926
Entrez_Gene (NCBI)DMBT1    deleted in malignant brain tumors 1
AliasesGP340; SAG; SALSA; muclin
GeneCards (Weizmann)DMBT1
Ensembl hg19 (Hinxton)ENSG00000187908 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000187908 [Gene_View]  ENSG00000187908 [Sequence]  chr10:122560754-122643736 [Contig_View]  DMBT1 [Vega]
ICGC DataPortalENSG00000187908
TCGA cBioPortalDMBT1
Genatlas (Paris)DMBT1
SOURCE (Princeton)DMBT1
Genetics Home Reference (NIH)DMBT1
Genomic and cartography
GoldenPath hg38 (UCSC)DMBT1  -     chr10:122560754-122643736 +  10q26.13   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)DMBT1  -     10q26.13   [Description]    (hg19-Feb_2009)
GoldenPathDMBT1 - 10q26.13 [CytoView hg19]  DMBT1 - 10q26.13 [CytoView hg38]
Genome Data Viewer NCBIDMBT1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB209691 AF159456 AJ000342 AJ243212 AJ243224
RefSeq transcript (Entrez)NM_001320644 NM_001377530 NM_004406 NM_007329 NM_017579
Consensus coding sequences : CCDS (NCBI)DMBT1
Gene ExpressionDMBT1 [ NCBI-GEO ]   DMBT1 [ EBI - ARRAY_EXPRESS ]   DMBT1 [ SEEK ]   DMBT1 [ MEM ]
Gene Expression Viewer (FireBrowse)DMBT1 [ Firebrowse - Broad ]
GenevisibleExpression of DMBT1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1755
GTEX Portal (Tissue expression)DMBT1
Human Protein AtlasENSG00000187908-DMBT1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)DMBT1
Human Protein Atlas [tissue]ENSG00000187908-DMBT1 [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed131 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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