Recombinant Human Mucin-1 (MUC1), partial

Function

The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity

Subcellular Location

Cell membrane; Cytoplasm; Nucleus

Disease Association

[MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes] | Tubulointerstitial kidney disease, autosomal dominant 2 (ADTKD2) : A form of autosomal dominant tubulointerstitial kidney disease, a genetically heterogeneous disorder characterized by slowly progressive loss of kidney function, bland urinary sediment, hyperuricemia, absent or mildly increased albuminuria, lack of severe hypertension during the early stages, and normal or small kidneys on ultrasound. Renal histology shows variable abnormalities including interstitial fibrosis with tubular atrophy, microcystic dilatation of the tubules, thickening of tubular basement membranes, medullary cysts, and secondary glomerulosclerotic or glomerulocystic changes with abnormal glomerular tufting. There is significant variability, as well as incomplete penetrance. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed on the apical surface of epithelial cells, especially of airway passages, breast and uterus. Also expressed in activated and unactivated T-cells. Overexpressed in epithelial tumors, such as breast or ovarian cancer and also in non-epithelial tumor cells. Isoform Y is expressed in tumor cells only

Subunit

The alpha subunit forms a tight, non-covalent heterodimeric complex with the proteolytically-released beta-subunit. Interaction, via the tandem repeat region, with domain 1 of ICAM1 is implicated in cell migration and metastases. Isoform 1 binds directly the SH2 domain of GRB2, and forms a MUC1/GRB2/SOS1 complex involved in RAS signaling. The cytoplasmic tail (MUC1CT) interacts with several proteins such as SRC, CTNNB1 and ERBs. Interaction with the SH2 domain of CSK decreases interaction with GSK3B. Interacts with CTNNB1/beta-catenin and JUP/gamma-catenin and promotes cell adhesion. Interaction with JUP/gamma-catenin is induced by heregulin. Binds PRKCD, ERBB2, ERBB3 and ERBB4. Heregulin (HRG) stimulates the interaction with ERBB2 and, to a much lesser extent, the interaction with ERBB3 and ERBB4. Interacts with P53 in response to DNA damage. Interacts with KLF4. Interacts with estrogen receptor alpha/ESR1, through its DNA-binding domain, and stimulates its transcription activity. Binds ADAM17. Isoform ZD forms disulfide-linked oligomers

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• Ligtenberg M.J.L. et al. Episialin, a carcinoma-associated mucin, is generated by a polymorphic gene encoding splice variants with alternative amino termini. — J. Biol. Chem. (1990)
• Gendler S.J. et al. Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin. — J. Biol. Chem. (1990)
• Lancaster C.A. et al. Structure and expression of the human polymorphic epithelial mucin gene: an expressed VNTR unit. — Biochem. Biophys. Res. Commun. (1990)
• Wreschner D.H. et al. Human epithelial tumor antigen cDNA sequences. Differential splicing may generate multiple protein forms. — Eur. J. Biochem. (1990)
• Hareuveni M. et al. A transcribed gene, containing a variable number of tandem repeats, codes for a human epithelial tumor antigen. cDNA cloning, expression of the transfected gene and over-expression in breast cancer tissue. — Eur. J. Biochem. (1990)
• Tsarfaty I. et al. Isolation and characterization of an expressed hypervariable gene coding for a breast-cancer-associated antigen. — Gene (1990)
• Zrihan-Licht S. et al. Characterization and molecular cloning of a novel MUC1 protein, devoid of tandem repeats, expressed in human breast cancer tissue. — Eur. J. Biochem. (1994)