Alternative titles; symbols
HGNC Approved Gene Symbol: MUC3A
Cytogenetic location: 7q22.1 Genomic coordinates (GRCh38): 7:100,949,534-100,968,347 (from NCBI)
The mucin genes encode epithelial glycoproteins, some of which are secreted and some membrane bound. Each of the genes contains at least one large domain of tandemly repeated sequence that encodes the peptide sequence rich in serine and/or threonine residues, which carries most of the O-linked glycosylation (Gendler and Spicer, 1995).
Gum et al. (1990) screened a small intestinal cDNA library with antibodies to deglycosylated small intestinal mucin and identified 2 partial cDNA clones corresponding to a novel intestinal mucin gene, which they designated MUC3. RNA dot-blot analysis detected expression in small intestine, colon, and 2 colonic tumors.
Williams et al. (1999) revised previous information on the genome structure of the MUC3 gene, demonstrating that it encodes a transmembrane mucin and is subject to alternative splicing to a form lacking 1 EGF-like domain and the transmembrane domain. Structural homology of the human MUC3 sequence with that of rat and mouse Muc3 indicated that it is closely related to the rodent proteins and is likely to be involved in ligand binding and intracellular signaling.
Pratt et al. (2000) reported that a number of consistent single nucleotide changes were observed in different MUC3 cDNAs from a single individual, suggesting the presence of at least 3 different transcripts. They presented evidence that this transcript heterogeneity is due to the existence of allelic changes and to tandem duplication of the MUC3 gene, resulting in a second gene, MUC3B (605633). Pratt et al. (2000) found that both MUC3A and MUC3B contain tandem serine- and threonine-rich repeats, followed by 2 EGF (131530)-like domains, a transmembrane domain, and a cytoplasmic tail.
Kyo et al. (2001) reanalyzed the 3-prime terminal structure of 'MUC3' and demonstrated that 'MUC3' consists of 2 genes, MUC3A and MUC3B, each encoding membrane-bound mucins possessing 2 epidermal growth factor-like domains.
Pan et al. (2013) showed that synthetic peptide-mediated upregulation of MUC3 dramatically inhibited adherence of enteropathogenic E. coli or enterohemorrhage E. coli serotype O157:H7 to HT-29 human intestinal epithelial cells. Peptide stimulation altered expression of a number of transcription factors, including upregulation of SP1 (189906), CREB1 (123810), and CDX2 (600297). These transcription factors bound to consensus sites in the MUC3 promoter upon peptide stimulation and likely mediated MUC3 upregulation.
By human/rodent somatic cell hybrid analysis, Gum et al. (1990) mapped the MUC3 gene to chromosome 7. Fox et al. (1991, 1992) used a cDNA clone to map MUC3 to 7q22 by in situ hybridization. They also identified RFLPs related to the MUC3 gene and used these to map the gene in relation to MET (164860) and to CFTR (602421).
Pratt et al. (2000) presented evidence that the MUC3A and MUC3B genes resulted from tandem duplication on chromosome 7q22.
For discussion of an association between variation in the MUC3A gene and inflammatory bowel disease, see IBD11 (191390).
Fox, M., Lahbib, F., Pratt, W., Attwood, J., Gum, J., Kim, Y., Swallow, D. M. Regional localisation of MUC3 to chromosome 7q22. (Abstract) Cytogenet. Cell Genet. 58: 1920-1921, 1991.
Fox, M. F., Lahbib, F., Pratt, W., Attwood, J., Gum, J., Kim, Y., Swallow, D. M. Regional localization of the intestinal mucin gene MUC3 to chromosome 7q22. Ann. Hum. Genet. 56: 281-287, 1992. [PubMed: 1362870] [Full Text: https://doi.org/10.1111/j.1469-1809.1992.tb01154.x]
Gendler, S. J., Spicer, A. P. Epithelial mucin genes. Annu. Rev. Physiol. 57: 607-634, 1995. [PubMed: 7778880] [Full Text: https://doi.org/10.1146/annurev.ph.57.030195.003135]
Gum, J. R., Hicks, J. W., Swallow, D. M., Lagace, R. L., Byrd, J. C., Lamport, D. T. A., Siddiki, B., Kim, Y. S. Molecular cloning of cDNAs derived from a novel human intestinal mucin gene. Biochem. Biophys. Res. Commun. 171: 407-415, 1990. [PubMed: 2393399] [Full Text: https://doi.org/10.1016/0006-291x(90)91408-k]
Kyo, K., Muto, T., Nagawa, H., Lathrop, G. M., Nakamura, Y. Associations of distinct variants of the intestinal mucin gene MUC3A with ulcerative colitis and Crohn's disease. J. Hum. Genet. 46: 5-20, 2001. [PubMed: 11289722] [Full Text: https://doi.org/10.1007/s100380170118]
Pan, Q., Tian, Y., Li, X., Ye, J., Liu, Y., Song, L., Yang, Y., Zhu, R., He, Y., Chen, L., Chen, W., Mao, X., Peng, Z., Wang, R. Enhanced membrane-tethered mucin 3 (MUC3) expression by a tetrameric branched peptide with a conserved TFLK motif inhibits bacteria adherence. J. Biol. Chem. 288: 5407-5416, 2013. [PubMed: 23316049] [Full Text: https://doi.org/10.1074/jbc.M112.408245]
Pratt, W. S., Crawley, S., Hicks, J., Ho, J., Nash, M., Kim, Y. S., Gum, J. R., Swallow, D. M. Multiple transcripts of MUC3: evidence for two genes, MUC3A and MUC3B. Biochem. Biophys. Res. Commun. 275: 916-923, 2000. [PubMed: 10973822] [Full Text: https://doi.org/10.1006/bbrc.2000.3406]
Williams, S. J., Munster, D. J., Quin, R. J., Gotley, D. C., McGuckin, M. A. The MUC3 gene encodes a transmembrane mucin and is alternatively spliced. Biochem. Biophys. Res. Commun. 261: 83-89, 1999. [PubMed: 10405327] [Full Text: https://doi.org/10.1006/bbrc.1999.1001]