Ca125 gene and its use for diagnostic and therapeutic...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/12 (2006.01) C07K 14/705 (2006.01) C07K 16/30 (2006.01) C12N 15/00 (2006.01) C12P 21/02 (2006.01)

Patent

CA 2505919

The CA125 gene has been cloned and multiple repeat sequences as well as the carboxy terminus have been identified. The CA125 molecule comprises three major domains: an extracellular amino terminal domain (Domain 1); a large multiple repeat domain (Domain 2); and a carboxy terminal domain (Domain 3) which includes a transmembrane anchor with a short cytoplasmic domain. The amino terminal domain is assembled by combining five genomic exons, four very short amino terminal sequences and one extraordinarily large exon. This domain is dominated by its capacity for O-glycosylation and its resultant richness in serine and threonine residues. Additionally, an amino terminal extension is present, which comprises four genomic exons. The amino acid composition of the amino terminal extension was found to be consistent with the amino acid composition of the amino terminal domain. The molecular structure is dominated by a repeat domain comprising 156 amino acid repeat units, which encompass the epitope binding sites. More than 60 repeat units have been identified, sequenced, and contiguously placed in the CA125 domain structure. More specifically, this invention is directed to a CA125 cDNA sequence which can be introduced into animal or human cells to achieve transcription or expression of the cDNA.

L'invention concerne le clonage du gène CA125 et l'identification de plusieurs séquences de répétitions et du carboxy-terminal. La molécule CA125 comprend trois domaines principaux: un domaine extracellulaire N-terminal (Domaine 1); un domaine important de plusieurs répétitions (Domaine 2); et un domaine carboxy-terminal (Domaine 3) comprenant une ancre transmembranaire à court domaine cytoplasmique. Le domaine N-terminal est assemblé par combinaison de 5 exons génomiques, quatre séquences N-terminales très courtes et un exon très très important. Ce domaine est dominé par sa capacité de O-glycosylation et sa richesse découlante en sérine et résidus thréonine. De plus, une extension N-terminale est présente, laquelle comprend quatre exons génomiques. On a découvert que la composition d'acide aminé de l'extension N-terminale est compatible avec la composition d'acide aminé du domaine N-terminal. La structure moléculaire est dominée par un domaine de répétitions comprenant 156 unités de répétition d'acide aminé comprenant les sites de liaison de l'épitope. Plus de 60 unités de répétition ont été identifiées, séquencées et placées de manière contiguë dans la structure du domaine CA125. Plus précisément, l'invention concerne une séquence d'ADNc CA125 pouvant être introduite dans des cellules animales ou humaines de manière à exécuter la transcription ou l'expression de l'ADNc.

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