PMC:3431878 / 10510-12315 JSONTXT

{"project":"2_test","denotations":[{"id":"22949880-12615972-50810680","span":{"begin":329,"end":331},"obj":"12615972"},{"id":"22949880-11125279-50810681","span":{"begin":592,"end":594},"obj":"11125279"},{"id":"22949880-11341784-50810682","span":{"begin":750,"end":752},"obj":"11341784"},{"id":"22949880-15943821-50810683","span":{"begin":753,"end":755},"obj":"15943821"},{"id":"22949880-14764598-50810684","span":{"begin":885,"end":887},"obj":"14764598"},{"id":"22949880-14764598-50810685","span":{"begin":1055,"end":1057},"obj":"14764598"},{"id":"22949880-14764598-50810686","span":{"begin":1285,"end":1287},"obj":"14764598"},{"id":"22949880-11786729-50810687","span":{"begin":1661,"end":1663},"obj":"11786729"},{"id":"T7728","span":{"begin":329,"end":331},"obj":"12615972"},{"id":"T85789","span":{"begin":592,"end":594},"obj":"11125279"},{"id":"T50797","span":{"begin":750,"end":752},"obj":"11341784"},{"id":"T23709","span":{"begin":753,"end":755},"obj":"15943821"},{"id":"T137","span":{"begin":885,"end":887},"obj":"14764598"},{"id":"T83000","span":{"begin":1055,"end":1057},"obj":"14764598"},{"id":"T25173","span":{"begin":1285,"end":1287},"obj":"14764598"},{"id":"T49369","span":{"begin":1661,"end":1663},"obj":"11786729"}],"text":"The elucidation of the almost complete CA125 nucleotide sequence represented a significant leap in understanding. It enabled clarification of known and/or suspected features such as glycosylation (amino domain), multivalent antibody binding (repeat domain) as well as anchorage to and release from the membrane (carboxy domain) [12,27]. The findings also raise questions regarding the generation of lower molecular weight isoforms. Only the existence of a CA125 precursor protein of approximately 400 kDa has been found to exist in the cytoplasm of OVCAR-3 cells prior to protein maturation [28]. CA125 variants are also thought to arise from proteolytic cleavage. Proteins such as MUC1 have a proteolytic cleavage motif, GSVVV, in their SEA domain [29,30], however the presence of a motif with a similar consensus sequence has only been confirmed in one SEA domain of CA125 thus far [22]. A cluster analysis of a human CA125 sequence, containing the first 12 tandem repeats and a murine homolog to the C-terminus of CA125, was performed by Maeda et al. [22]. Interestingly, a DSVLV sequence in the second SEA domain from the cytosolic side of CA125 was clustered with the GSVVV sequence. Therefore, it was concluded that proteolytic cleavage might also occur in this domain of CA125 [22]. However, the formation of further proteolytic fragments of CA125, by the mechanism of the DSVLV or GSVVV sequence, in additional SEA domains has not been reported. Furthermore, O’Brien et al. suggested that the formation of alternative splicing products of this protein seems unlikely, based on the inherent variation of the five exons encoding for each repeat sequence [18]. Therefore, a discrepancy exists between antibody findings of low molecular weight isoforms and the protein sequence data (discussed below)."}