HGNC Approved Gene Symbol: MUC13
Cytogenetic location: 3q21.2 Genomic coordinates (GRCh38): 3:124,905,442-124,934,751 (from NCBI)
Epithelial mucins, such as MUC13, are a family of secreted and cell surface glycoproteins expressed by ductal and glandular epithelial tissues (Williams et al., 2001).
By searching EST databases for sequences similar to rodent Muc13, followed by RT-PCR, Williams et al. (2001) cloned human MUC13. The rodent and human MUC13 cDNAs contain a series of CA dinucleotide repeats and an alternative polyadenylation signal. The deduced 512-amino acid human protein has a calculated molecular mass of 54.7 kD. Both human and rodent MUC13 have an N-terminal signal peptide, followed by a serine/threonine-rich mucin repeat domain, a cysteine-rich EGF (131530)-like domain, a SEA module, 2 more cysteine-rich EGF-like domains, a transmembrane region, and a cytoplasmic tail. The mucin repeat domain is predicted to be heavily O-glycosylated, and MUC13 also has sites for N-glycosylation and phosphorylation. Northern blot analysis detected highest expression of a 3.2-kb transcript in colon and trachea, with moderate levels in kidney, small intestine, appendix, and stomach, and low levels in several other tissues. In fetal tissues, expression was high in kidney and low in spleen, lung, thymus, and liver. In situ hybridization of mouse tissues revealed Muc13 in intestinal epithelial and lymphoid cells. Immunohistochemical analysis showed human MUC13 on the apical membrane of columnar and goblet cells in the gastrointestinal tract and in goblet cell thecae, suggesting that MUC13 is both secreted and expressed on the cell surface.
Using real-time RT-PCR, Moehle et al. (2006) detected highest MUC13 expression in fetal lung and in adult colon and small intestine. High MUC13 expression was also detected in kidney, trachea, and stomach, and expression was moderate in pancreas and low in prostate.
Williams et al. (2001) found that MUC13 was expressed on the cell surface and underwent N- and O-glycosylation. MUC13 was cleaved internally to produce an N-terminal mucin subunit, called the alpha subunit, and a C-terminal beta subunit that included the transmembrane region. Beta subunits appeared to undergo homodimerization that was dependent on intrachain disulfide bonds.
Using quantitative real-time RT-PCR and immunoblot analysis, Shimamura et al. (2005) showed that MUC13 was upregulated in gastric cancers. Immunohistochemical analysis showed MUC13 staining in 74 (64.9%) of 114 gastric cancers, predominantly in intestinal type, and in 9 of 10 intestinal metaplasias, but not in normal gastric mucosa. MUC13 localized to the apical side of tubular glands in intestinal-type cancers and to the cytoplasm in diffuse cancers.
By microarray analysis, Moehle et al. (2006) found coordinated downregulation of mucins, including MUC13, in ileum and colon of patients with inflammatory bowel disease (IBD; see 266600), including Crohn disease and ulcerative colitis, compared with controls. They identified an NF-kappa-B (see 164011)-binding site in the MUC13 promoter and showed that activation of the NF-kappa-B signaling pathway by the inflammatory cytokines TNF-alpha (TNF; 191160) and TGF-beta (TGFB1; 190180) upregulated MUC13 mRNA expression nearly 3-fold and 2-fold, respectively.
Using FISH, Williams et al. (2001) mapped the MUC13 gene to chromosome 3q13.3.
Moehle, C., Ackermann, N., Langmann, T., Aslanidis, C., Kel, A., Kel-Margoulis, O., Schmitz-Madry, A., Zahn, A., Stremmel, W., Schmitz, G. Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease. J. Molec. Med. 84: 1055-1066, 2006. [PubMed: 17058067] [Full Text: https://doi.org/10.1007/s00109-006-0100-2]
Shimamura, T., Ito, H., Shibahara, J., Watanabe, A., Hippo, Y., Taniguchi, H., Chen, Y., Kashima, T., Ohtomo, T., Tanioka, F., Iwanari, H., Kodama, T., Kazui, T., Sugimura, H., Fukayama, M., Aburatani, H. Overexpression of MUC13 is associated with intestinal-type gastric cancer. Cancer Sci. 96: 265-273, 2005. [PubMed: 15904467] [Full Text: https://doi.org/10.1111/j.1349-7006.2005.00043.x]
Williams, S. J., Wreschner, D. H., Tran, M., Eyre, H. J., Sutherland, G. R., McGuckin, M. A. MUC13, a novel human cell surface mucin expressed by epithelial and hemopoietic cells. J. Biol. Chem. 276: 18327-18336, 2001. [PubMed: 11278439] [Full Text: https://doi.org/10.1074/jbc.M008850200]