The CA 125 Gene: An Extracellular Superstructure Dominated by Repeat Sequences

@article{Obrien2001TheC1,
  title={The CA 125 Gene: An Extracellular Superstructure Dominated by Repeat Sequences},
  author={Timothy J O'brien and John B. Beard and Lowell J. Underwood and Richard A Dennis and Alessandro D. Santin and Lyndal York},
  journal={Tumor Biology},
  year={2001},
  volume={22},
  pages={348 - 366}
}
CA 125 has long presented problems to both clinicians and investigators because there was no definitive information on its structure and function. Here, we describe our work on cloning the CA 125 gene with the anticipation that such information will provide the basis for understanding its structure and its physiologic role in both normal and malignant tissues. The CA 125 protein core is composed of a short cytoplasmic tail, a transmembrane domain and an extraordinarily large glycosylated… 

Figures from this paper

The CA 125 Gene: A Newly Discovered Extension of the Glycosylated N-Terminal Domain Doubles the Size of This Extracellular Superstructure
TLDR
A further major extension to the glycosylated extracellular amino terminal domain of CA 125 is described, providing the basis for the ability to understand the physiologic function of this molecule in biologic development and pathologic transformation.
MUC16/CA125 in the Context of Modular Proteins with an Annotated Role in Adhesion-Related Processes: In Silico Analysis
TLDR
In silico analysis of corresponding mucin sequences, a homology to conserved domains from the family of herpesvirus major outer envelope protein (BLLF1) was found and the possible involvement of MUC16/CA125 in carbohydrate-binding interactions or cellular transport of protein/ion was suggested.
Expression and Epitope Characterization of a Recombinant CA 125 Repeat: Fourth Report from the ISOBM TD-1 Workshop
TLDR
The ability to ‘activate’ R11 epitopes indicates that some may not be displayed optimally on isolated repeats, suggesting that a number of epitopes are preferentially displayed only when contained within multiple repeat domains.
Crystal structure of a human MUC16 SEA domain reveals insight into the nature of the CA125 tumor marker
TLDR
The purification and the first X‐ray structure of a human MUC16 SEA domain is reported, confirming that the CA125 epitope is localized to the SEA domain and will serve to accelerate future work to understand the functional role of M UC16 SEA domains and antibody recognition of the CA 125 epitope.
Synthesis and structural characterization of the peptide epitope of the ovarian cancer biomarker CA125 (MUC16)
TLDR
Findings suggest that future structural characterization efforts of CA125 should be especially mindful of the amino acid sequence and oxidation state of the protein.
Solution Structure of the SEA Domain from the Murine Homologue of Ovarian Cancer Antigen CA125 (MUC16)*
TLDR
The sequence alignment of the SEA domain family was refined on the basis of the three-dimensional structure, which allowed us to classify the SEA domains into several subfamilies, suggesting that each subfamily has a different function.
MUC16: molecular analysis and its functional implications in benign and malignant conditions
TLDR
In this review, the various aspects of MUC16 are discussed, which include its discovery, structure, and biological significance both in benign and malignant conditions with an attempt to dissect its functional relevance.
A Binding Domain on Mesothelin for CA125/MUC16*
TLDR
The identified CA125-binding domain significantly inhibits cancer cell adhesion and merits evaluation as a new therapeutic agent for preventing or treating peritoneal malignant tumors.
The cancer antigen CA125 represents a novel counter receptor for galectin-1
TLDR
A functional link is established between CA125 and β-galactoside-binding, cell-surface lectins, which are components of the extracellular matrix implicated in the regulation of cell adhesion, apoptosis, cell proliferation and tumor progression, and finds that CA125 is a counter receptor for galectin-1.
...
...

References

SHOWING 1-10 OF 35 REFERENCES
More than 15 Years of CA 125: What is Known about the Antigen, Its Structure and Its Function
TLDR
A model of a theoretical CA 125 molecule is presented to stimulate discussion on the regulation of CA 125 synthesis, its secretion and its structural configuration and it will provide a focus of attention until the CA 125 gene is cloned and the real molecule is described.
Mucin genes and the proteins they encode: structure, diversity, and regulation.
  • J. Gum
  • Biology
    American journal of respiratory cell and molecular biology
  • 1992
TLDR
Much work remains before the authors gain an understanding of the mechanisms involved in the expression of mucin genes and their tissue-specific regulation, as well as in characterizing the genes that encode mucins.
Molecular Cloning of the CA125 Ovarian Cancer Antigen
TLDR
The isolation of a long, but partial, cDNA that corresponds to the CA125 antigen and the deduced amino acid sequence has many of the attributes of a mucin molecule and was designated CA125/MUC16 (gene MUC16).
Purification and characterization of the CA 125 tumor-associated antigen from human ascites.
TLDR
The results suggest that the affinity column is useful for the purification of CA 125, and the purified, immunoreactive CA 125 (IR-CA 125) was shown to be proteinaceous in nature.
Human Mucin Gene MUC5B, the 10.7-kb Large Central Exon Encodes Various Alternate Subdomains Resulting in a Super-repeat
TLDR
The super-repeat present in MUC5B is the largest ever determined in mucin genes and the central exon of this gene is, by far, the largest reported for a vertebrate gene.
New monoclonal antibodies identify the glycoprotein carrying the CA 125 epitope.
CA125 phosphorylation is associated with its secretion from the WISH human amnion cell line.
Evidence is presented suggesting that CA125 is a serine and/or threonine phosphoprotein and that its secretion from the human amnion WISH cell line is closely linked to its phosphorylation. It is
CA 125 - Epitopes and Molecular Size
TLDR
CA 125 has two main immunogenic areas reactive with mouse and rat monoclonal antibodies, defined by the antibodies OC 125 and M11, respectively, which are named OC 125-like and M 11-like antibodies.
MUC13, a Novel Human Cell Surface Mucin Expressed by Epithelial and Hemopoietic Cells*
TLDR
In situ hybridization in murine tissues revealed expression in intestinal epithelial and lymphoid cells, and Immunohistochemistry demonstrated the human MUC13 protein on the apical membrane of both columnar and goblet cells in the gastrointestinal tract, indicative of secretion in addition to presence on the cell surface.
The CA 125 tumour-associated antigen: a review of the literature.
TLDR
Serum CA 125 estimation is of clinical value in the pre-operative diagnosis and monitoring of ovarian malignancy and may be a prognostic indicator for this disease.
...
...