MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism.

Toribara, Neil W.; Gum, James R.; Culhane, Patrick J.; Lagacé, Robert; Hicks, James W.; Petersen, Gloria M.; Kim, Young S.

doi:10.1172/jci115360

Cited by 172 publications

(114 citation statements)

References 25 publications

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“…(30). It seems that 11p15.5 human mucin genes are characterized by (i) a large exon encoding the repetitive domain as demonstrated for MUC5B and as suggested by Toribara et al for MUC2 (15), (ii) the presence of Cys subdomains with 10% Cys residues (30), and (iii) a unique sequence just downstream from the repetitive domain typical of the 11p15.5 mucin genes and a cysteine-rich region, which is divided in several subdomains similar to vWF-D4, vWF-B, vWF-C, and CK domains (Fig. 4).…”

Section: Methodsmentioning

confidence: 76%

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

Desseyn¹,

Aubert²,

Seuningen³

et al. 1997

Journal of Biological Chemistry

115

102

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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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Section: Methodsmentioning

confidence: 76%

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

Desseyn¹,

Aubert²,

Seuningen³

et al. 1997

Journal of Biological Chemistry

115

102

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“…MUC2 glycoprotein is a secretory mucin, containing two distinct regions with a high degree of internal homology. Region 1 consists mostly of 48-bp repeats and region 2 is composed of 69-bp tandem repeats (12). MUC2 apomucin is expressed by adenomas and mucinous carcinomas of the colorectum, but the expression of MUC2 may be associated with less aggressive biological properties in non-mucinous adenocarcinoma of the colorectum (13,14).…”

Section: Introductionmentioning

confidence: 99%

Coexpression of MUC1 with p53 or MUC2 correlates with Lymph Node Metastasis in Colorectal Carcinomas

et al. 2002

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The alteration of the mucin profile have been known to play a role in colorectal carcinogenesis. MUC1 is up-regulated and MUC2 is down-regulated in colorectal carcinomas. Overexpression of p53 is frequently noted in colorectal carcinomas with deep invasion or lymph node metastasis. However, there have been few reports about the association between MUC1, MUC2, and p53 expression with respect to the metastatic potential. This study was aimed to investigate the relationship of MUC1, MUC2, and protein p53 expressions with clinicopathological factors in colorectal carcinomas. Expressions of MUC1, MUC2, and p53 protein were examined immunohistochemically. Of total 97 cancers, 44 (45%) were MUC1 positive, 39 (40%) were MUC2 positive and 58 (59%) showed a p53 overexpression. Coexpression of MUC1 with p53 and dual expression of MUC1 with MUC2 were associated with a higher frequency of lymph node metastasis (p<0.05). The right colon showed a higher MUC1 positivity and frequent lymph node metastasis than the left colon (p<0.05). These results suggest that the coexpression of MUC 1 with p53 or MUC2 are involved in regional lymph node metastasis in colorectal carcinomas. The high expression of MUC1 in the right colon cancer was revealed to relate with lymph node metastasis.

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“…At present, at least nine human mucin gene products have been identified and the complete nucleotide sequences of MUC1 [12][13][14][15], MUC2 [16][17][18][19] and MUC7 [20] have been reported. In addition, partial sequences of MUC3 [21], MUC4 [22], MUC5 (now referred to as MUC5AC ; [23][24][25][26][27]), MUC5B [28], MUC6 [29], a novel tracheobronchial mucin (possibly MUC8 ; [30]) and a sublingual-gland mucin [31] have been described.…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning of a major human gall bladder mucin: complete C-terminal sequence and genomic organization of MUC5B

Keates

Nunes

Afdhal

et al. 1997

Biochemical Journal

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Gall bladder mucin has been shown to play a central role in the pathogenesis of cholesterol gallstone disease. While cloning and sequencing studies have provided a wealth of information on the structure of other gastrointestinal and respiratory mucins, nothing is known about the primary structure of human gall bladder mucin. In this study, we show that the tracheobronchial mucin MUC5B is a major mucin gene product expressed in the gall bladder. Antibodies directed against deglycosylated human gall bladder mucin were used to screen a gall bladder cDNA expression library, and most of the isolated clones contained repetitive sequences nearly identical with those in the tandem repeat region of MUC5B. An additional clone (hGBM2-3) contained an open reading frame coding for a 389 residue cysteine-rich sequence. The arrangement of cysteine residues in this sequence was very similar to that in the C-terminal regions of MUC2, MUC5AC and human von Willebrand factor. This cysteine-rich sequence was connected to a series of degenerate MUC5B tandem repeats in a 7.5 kb HincII genomic DNA fragment. This fragment, with ten exons and nine introns, contained MUC5B repeats in exon 1 and a 469 residue cysteine-rich sequence in exons 2–10 that provided a 152 nucleotide overlap with cDNA clone hGBM2-3. Interestingly, the exon–intron junctions in the MUC5B genomic fragment occurred at positions equivalent to those in the D4 domain of human von Willebrand factor, suggesting that these proteins evolved from a common evolutionary ancestor through addition or deletion of exons encoding functional domains.

show abstract

MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism.

Cited by 172 publications

References 25 publications

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

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

Coexpression of MUC1 with p53 or MUC2 correlates with Lymph Node Metastasis in Colorectal Carcinomas

Molecular cloning of a major human gall bladder mucin: complete C-terminal sequence and genomic organization of MUC5B

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