Disease	Score

Substances	Interaction	Organism	Category

Substances	Interaction	Organism	Category

The MUC1 gene provides instructions for making a protein called mucin 1. This protein is one of several mucin proteins that make up mucus, a slippery substance that lubricates and protects the lining of the airways, digestive system, reproductive system, and other organs and tissues. In addition to its role in mucus, mucin 1 is involved in cell signaling and kidney development. Although most mucin proteins are released from the cell, mucin 1 spans the cell membrane. It is found in epithelial cells, which are the cells that line the surfaces and cavities of the body. In particular, mucin 1 is found in the respiratory tract, female reproductive organs, and gastrointestinal tract. Like other mucins, mucin 1 has a region called the mucin domain that contains repeated stretches of protein building blocks (amino acids); the number of repeats can vary from 20 to 100. This protein is modified by the addition of numerous chains of sugar molecules, which are attached to certain amino acids in the mucin domain. The sugars spread out from the protein like branches on a tree and prevent access to the cell surface below, protecting the body from foreign invaders. The sugars also attract water molecules, helping lubricate and hydrate the tissues. The portion of mucin 1 that reaches inside the cell, called the cytoplasmic tail (or MUC1-CT), relays signals from outside the cell to the cell's nucleus; these signals instruct the cell to undergo certain changes. Through this process, mucin 1 is thought to be involved in cell growth and division (proliferation), helping cells stick to one another (cell adhesion), cell movement (motility), and cell survival. The cytoplasmic tail can also detach from the cell membrane and move to the nucleus, although the mechanism is unclear. Some researchers suggest that, in the nucleus, MUC1-CT helps control the activity of other genes. In addition, mucin 1 is present in cells that form the kidneys and is thought to play a role in the development of these organs.

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.

Medullary cystic kidney disease type 1 Mutations in the MUC1 gene cause medullary cystic kidney disease type 1 (MCKD1). This condition is characterized by impairment of kidney function that usually begins in adulthood and progressively worsens. Some affected individuals develop fluid-filled pockets in the kidneys called medullary cysts. This condition occurs when a single DNA building block (nucleotide) called cytosine is inserted into the MUC1 gene. These insertions occur in one particular region of the gene, the part that provides instructions for the repeating mucin domain. These mutations lead to the production of an altered mucin 1 protein, although it is unclear how this change causes kidney disease. Why the effects of MUC1 gene mutations are limited to the kidneys is also unknown.

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

The following transcription factors affect gene expression:

• NF-kappaB
• ER-alpha
• PPAR-gamma1
• PPAR-gamma2
• p53
• STAT3
• Sp1
• YY1
• AREB6
• GATA-3

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.

Developmental stage:

During fetal development, expressed at low levels in the colonic epithelium from 13 weeks of gestation.

Caution:

O-glycosylation sites are annotated in first sequence repeat only. Residues at similar position are probably glycosylated in all repeats. Experimental sites were determined in a synthetic peptide glycosylated in vitro (PubMed:7744025, PubMed:9597769).

Molecular Function:

• Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Dna Binding
• P53 Binding
• Transcription Cofactor Activity

Biological Processes:

• Dna Damage Response, Signal Transduction By P53 Class Mediator Resulting In Cell Cycle Arrest
• Dna Damage Response, Signal Transduction By P53 Class Mediator Resulting In Transcription Of P21 Class Mediator
• Negative Regulation Of Transcription By Competitive Promoter Binding
• O-Glycan Processing
• Negative Regulation Of Cell Adhesion Mediated By Integrin
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter In Response To Stress
• Regulation Of Transcription From Rna Polymerase Ii Promoter In Response To Stress
• Positive Regulation Of Histone H4 Acetylation
• Negative Regulation Of Intrinsic Apoptotic Signaling Pathway In Response To Dna Damage By P53 Class Mediator

*synonyms