MUC1: a large cell surface glycoprotein expressed by most glandular and ductal epithelial cells and some hematopoietic cell lineages. Plays a role in adhesion and cell-cell interactions, metastasis and signaling. May provide a protective layer on epithelial surfaces. Direct or indirect interaction with actin cytoskeleton. Its cytoplasmic tail (MUC1CT) is involved in several signaling pathways, including those involving Ras, beta-catenin, p120 catenin, p53 and estrogen receptor alpha. MUC1CT also forms complexes with transcription factors, and then translocates to the nucleus by an unknown mechanism, where it is believed to influence the transcription of their target genes. MUC1CT has also been proposed to localize to mitochondrial membranes under conditions of genotoxic stress, where it attenuates the apoptotic pathway in response and confers resistance to apoptosis-inducing drugs. Aberrantly glycosylated forms expressed in human epithelial tumors, such as breast or ovarian cancer and also in non-epithelial tumor cells. Nine alternatively spliced isoforms have been described. Isoforms 5 and 9 are secreted. Isoform 7, expressed only in tumor cells, is a receptor and binds the secreted isoform 5. The binding induces the phosphorylation of the isoform 7, alters cellular morphology and initiates cell signaling. Can bind to GRB2 adapter protein.
Protein type: Motility/polarity/chemotaxis; Membrane protein, integral; Nuclear receptor co-regulator; Tumor suppressor; Cell adhesion; Actin-binding
Chromosomal Location of Human Ortholog: 1q21
Cellular Component: extracellular space; cell surface; integral to plasma membrane; Golgi lumen; apical plasma membrane; nuclear chromatin; cytoplasm; vesicle
Molecular Function: protein binding; p53 binding; transcription cofactor activity
Biological Process: protein amino acid O-linked glycosylation; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; regulation of transcription from RNA polymerase II promoter in response to stress; cellular protein metabolic process; O-glycan processing; post-translational protein modification; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
Disease: Medullary Cystic Kidney Disease 1
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