MUC1
GeneName
MUC1
Summary
MUC1, also known as KL-6, EMA, or PEM, is a 122 kDa glycoprotein that is expressed on the apical surface of epithelial cells and is also found in various extracellular compartments, including exosomes. It plays a role in cell signalling and adhesion, as well as in the regulation of transcription and DNA damage response. MUC1 is involved in the negative regulation of cell adhesion mediated by integrins and participates in the transcriptional regulation of genes associated with the p53 pathway, influencing both cell survival and apoptosis in response to DNA damage.
Importance
MUC1 is relevant to: - Cancer research due to its overexpression in various malignancies, making it a potential target for immunotherapy - Studies of epithelial cell biology and tissue homeostasis, given its role in cell adhesion and signalling - Understanding the mechanisms of DNA damage response and repair, particularly in the context of p53-mediated pathways - Investigating its potential as a biomarker for diseases such as lung fibrosis and breast cancer, where its expression levels may correlate with disease progression.
Top Products
For researchers investigating MUC1, we highly recommend the top-selling recombinant antibody, Anti-MUC1 antibody [EPR1023] (ab109185). This antibody has been validated in knockout models, ensuring its reliability in various applications, including immunohistochemistry (IHC), western blotting (WB), flow cytometry (FC), immunocytochemistry (ICC), and immunoprecipitation (IP). With 70 citations, it is well-regarded in the research community, making it an excellent choice for those seeking dependable MUC1 detection in their studies.
Abcam Product Citation Summary
The data indicates that MUC1 is being extensively studied in various human cancer contexts, particularly prostate cancer and breast cancer. The use of Abcam antibodies in Western blotting and immunohistochemistry highlights the importance of MUC1 as a potential biomarker in cancer research. Additionally, studies involving mouse models suggest a broader interest in understanding MUC1's role in mammary gland development and mucin expression.
Abcam Product Citation Table
Developmental stage
During fetal development, expressed at low levels in the colonic epithelium from 13 weeks of gestation.
Function
The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.
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.
Involvement in disease
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Highly glycosylated (N- and O-linked carbohydrates and sialic acid). O-glycosylated to a varying degree on serine and threonine residues within each tandem repeat, ranging from mono- to penta-glycosylation. The average density ranges from about 50% in human milk to over 90% in T47D breast cancer cells. Further sialylation occurs during recycling. Membrane-shed glycoproteins from kidney and breast cancer cells have preferentially sialyated core 1 structures, while secreted forms from the same tissues display mainly core 2 structures. The O-glycosylated content is overlapping in both these tissues with terminal fucose and galactose, 2- and 3-linked galactose, 3- and 3,6-linked GalNAc-ol and 4-linked GlcNAc predominating. Differentially O-glycosylated in breast carcinomas with 3,4-linked GlcNAc. N-glycosylation consists of high-mannose, acidic complex-type and hybrid glycans in the secreted form MUC1/SEC, and neutral complex-type in the transmembrane form, MUC1/TM.
Proteolytic cleavage in the SEA domain occurs in the endoplasmic reticulum by an autoproteolytic mechanism and requires the full-length SEA domain as well as requiring a Ser, Thr or Cys residue at the P + 1 site. Cleavage at this site also occurs on isoform MUC1/X but not on isoform MUC1/Y. Ectodomain shedding is mediated by ADAM17.
Dual palmitoylation on cysteine residues in the CQC motif is required for recycling from endosomes back to the plasma membrane.
Phosphorylated on tyrosines and serine residues in the C-terminal. Phosphorylation on tyrosines in the C-terminal increases the nuclear location of MUC1 and beta-catenin. Phosphorylation by PKC delta induces binding of MUC1 to beta-catenin/CTNNB1 and thus decreases the formation of the beta-catenin/E-cadherin complex. Src-mediated phosphorylation inhibits interaction with GSK3B. Src- and EGFR-mediated phosphorylation on Tyr-1229 increases binding to beta-catenin/CTNNB1. GSK3B-mediated phosphorylation on Ser-1227 decreases this interaction but restores the formation of the beta-cadherin/E-cadherin complex. On T-cell receptor activation, phosphorylated by LCK. PDGFR-mediated phosphorylation increases nuclear colocalization of MUC1CT and CTNNB1.
The N-terminal sequence has been shown to begin at position 24 or 28.
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.
Cellular localization
- Apical cell membrane
- Single-pass type I membrane protein
- Exclusively located in the apical domain of the plasma membrane of highly polarized epithelial cells. After endocytosis, internalized and recycled to the cell membrane. Located to microvilli and to the tips of long filopodial protusions.
- Isoform 5
- Secreted
- Isoform Y
- Secreted
- Isoform 9
- Secreted
- Mucin-1 subunit beta
- Cell membrane
- Cytoplasm
- Nucleus
- On EGF and PDGFRB stimulation, transported to the nucleus through interaction with CTNNB1, a process which is stimulated by phosphorylation. On HRG stimulation, colocalizes with JUP/gamma-catenin at the nucleus.
Alternative names
CD227, PUM, MUC1, Mucin-1, MUC-1, Breast carcinoma-associated antigen DF3, Cancer antigen 15-3, Carcinoma-associated mucin, Episialin, H23AG, Krebs von den Lungen-6, PEMT, Peanut-reactive urinary mucin, Polymorphic epithelial mucin, Tumor-associated epithelial membrane antigen, Tumor-associated mucin, CA 15-3, KL-6, PEM, EMA
Database links
swissprot:P15941 entrezGene:4582 omim:158340
Other research areas
- Immuno-oncology