Human Mucin Gene MUC5B, the 10.7-kb Large Central Exon Encodes Various Alternate Subdomains Resulting in a Super-repeat

Desseyn, Jean‐Luc; Guyonnet‐Duperat, Véronique; Porchet, Nicole; Aubert, Jean‐Pierre; Laine, Anne

doi:10.1074/jbc.272.6.3168

Cited by 157 publications

(161 citation statements)

References 43 publications

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“…The MUC5B mucin gene, mapped to chromosome 11p15 (Dufosse et al 1993), contains a 10.7-kb large central exon that encodes various alternate subdomains (Desseyn et al 1997), including imperfectly conserved repetitive tandem repeat units with sequences of 29 amino acids (SSTPGTAHTHTEQTTT-ATTPTATGTTATP) (Desseyn et al 1997;Dufosse et al 1993). MUC5B mucin tandem repeat units contain abundant T residues (14 out of 29 residues, potential sites for glycosylation) followed by P residues (potential recognition sites of glycosyltransferase).…”

Section: Discussionmentioning

confidence: 99%

Expression of Mucins in Mucoid Otitis Media

Lin

Tsuboi

Rimell

et al. 2003

JARO - Journal of the Association for Research in Otolaryngolog

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A hallmark of mucoid otitis media (MOM, i.e., chronic otitis media with mucoid effusion) is mucus accumulation in the middle ear cavity, a condition that impairs transduction of sounds in the ear and causes hearing loss. The mucin identities of mucus and the underlying mechanism for the production of mucins in MOM are poorly understood. In this study, we demonstrated that the MUC5B and MUC4 were major mucins in MOM that formed distinct treelike polymers (mucus strands). The MUC5B and MUC4 mRNAs in the middle ear mucosa with MOM were up regulated 5-fold and 6-fold, compared with the controls. This upregulation was accompanied by the extensive proliferation of the MUC5B-and MUC4-producing cells in the middle ear epithelium. Further study indicated that the mucin hyperproduction was significantly linked to CD4 + and CD8 + T cells and/or CD68 + monocyte macrophages. It suggests that MUC5B and MUC4 expression may be regulated by the products of these cells.

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Section: Discussionmentioning

confidence: 99%

Expression of Mucins in Mucoid Otitis Media

Lin

Tsuboi

Rimell

et al. 2003

JARO - Journal of the Association for Research in Otolaryngolog

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“…Recently, we have determined that the order of the four clustered 11p15.5 human mucin genes is tel-MUC6/MUC2/MUC5AC/MUC5B-cen (29). We have also established that MUC2, MUC5AC, and MUC5B have a consensus cysteine-rich domain found twice in MUC2 (16), at least four times in MUC5AC (21,22,24), and seven times in MUC5B (30).…”

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confidence: 96%

Genomic Organization of the 3′ Region of the Human Mucin GeneMUC5B

Desseyn¹,

Aubert²,

Seuningen³

et al. 1997

Journal of Biological Chemistry

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MUC5B, mapped clustered with MUC6, MUC2, and MUC5AC to chromosome 11p15.5, is a human mucin gene of which the genomic organization is being elucidated. We have recently published the sequence and the peptide organization of its huge central exon, 10,713 base pairs (bp) in length. We present here the genomic organization of its 3 region, which encompasses 10,690 bp. The genomic sequence has been completely determined. The 3 region of MUC5B is composed of 18 exons ranging in size from 32 to 781 bp, contrasting thus with the very large central exon. The sizes of the 18 introns range from 114 to 1118 bp. Some repetitive sequences were identified in four introns. The peptide deduced from the sequence of the 18 exons consists of an 808-amino acid peptide. This carboxyl-terminal region exhibits extensive sequence similarity to MUC2, MUC5AC, and von Willebrand factor, particularly the number and the positions of the cysteine residues, suggesting that this domain may be derived from a common ancestral gene. The presence in these components of a cystine knot also found in growth factors such as transforming growth factor-␤ is of particular interest. Moreover, one part of this peptide is identical to the 196-amino acid sequence deduced from the cDNA clone pSM2-1, which codes for a part of the high molecular weight mucin MG1 isolated from human sublingual gland. Considering the expression pattern of MUC5B and the origin of MG1, we can thus conclude that MUC5B encodes MG1.Mucus is the layer that covers, protects, and lubricates the luminal surfaces of epithelial respiratory, gastrointestinal, and reproductive tracts. These basic properties are due to the viscous and viscoelastic properties of mucins, the major glycoprotein components of mucus. Mucins constitute a family of high molecular mass glycoproteins synthesized by the goblet cells of the epithelia and in some cases by submucosal glands (for more complete reviews, see Refs. 1-3).Alterations of the biosynthesis of mucins affecting the protein core and/or the carbohydrate content linked to the peptide have been observed in numerous pathological situations such as various adenomas and carcinomas, inflammatory diseases such as cystic fibrosis, asthma, chronic bronchitis, or inflammatory bowel diseases (4 -7). Moreover, the hypersecretion of mucins and the presence of alternating hydrophobic and hydrophilic domains in mucins have been shown to play a central role in the pathogenesis of cholesterol gallstones (8, 9).All apomucins contain tandemly repeated sequences rich in threonine and/or serine. Due to the high carbohydrate content, the peptide moiety of mucins has been difficult to characterize. cDNA cloning has enabled researchers to approach the study of the mucins over the past decade. Today, the membrane-associated mucin MUC1 and the secreted MUC7 are the only mucins for which the full-length cDNA and the genomic organization have been reported (10 -13). Both were revealed to be, in fact, small mucins. A complete cDNA of the large secreted mucin MUC2 (14 -17) has been...

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“…This mucin-type region is interrupted four times by sequences that are repeated and distinct from the RI-RV tandems (40). MUC5B also contains four von Willebrand factor type D (VWD) domains (Fig.…”

Section: Muc1-cd Emerged From Tandem Repeat Regions In Muc5bmentioning

confidence: 99%

Evolution of the human MUC1 oncoprotein

Duraisamy¹,

Kufe²,

Ramasamy³

et al. 2007

Int J Oncol

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Abstract. The mucin (MUC) family consists of secreted and membrane-bound forms. The transmembrane mucin 1 (MUC1) is a heterodimer that is aberrantly overexpressed by diverse human carcinomas and certain hematologic malignancies. The MUC1 N-terminal (MUC1-N) and C-terminal (MUC1-C) subunits are generated by autocleavage within a SEA domain. The MUC1 cytoplasmic domain (MUC1-CD) located downstream of the SEA domain is sufficient for the induction of anchorage-independent growth and tumorigenicity; however, no information is available regarding the origin of these transforming sequences. Previous work demonstrated that, except for the SEA domain, MUC1 has no sequence homology with other membrane-bound mucins. The present results demonstrate that MUC1-CD evolved from repeat regions in the MUC5B secreted mucin. We also show that MUC1 sequences upstream to the SEA domain emerged from MUC5B. These findings indicate that both the MUC1-N and MUC1-C subunits evolved from secreted gel-forming mucins and that the MUC1-CD oncogenic function emerged by diversification after evolution from MUC5B.

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Human Mucin Gene MUC5B, the 10.7-kb Large Central Exon Encodes Various Alternate Subdomains Resulting in a Super-repeat

Cited by 157 publications

References 43 publications

Expression of Mucins in Mucoid Otitis Media

Expression of Mucins in Mucoid Otitis Media

Genomic Organization of the 3′ Region of the Human Mucin GeneMUC5B

Evolution of the human MUC1 oncoprotein

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