Many Protein Products from a Few Loci: Assignment of Human Salivary Proline-Rich Proteins to Specific Loci

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Earlier studies of protein polymorphisms led to the description of 13 linked loci thought to encode the human salivary proline-rich proteins (PRPs). However, more recent studies at the DNA level have shown that there are only six genes which encode PRPs. The present study was undertaken in order to reconcile these observations. Nucleotide and decoded amino acid sequences from each of the six genes were compared with the available protein sequence data for PRPs. This analysis allowed assignment of the PmF, PmS and Pe proteins to the PRB1 locus, the G1 protein to the PRB3 locus, the Po protein to the PRB4 locus, the Ps protein to the PRB2 locus, and the CON1 and CON2 proteins to the PRB4 locus. Correlations between insertion/deletion RFLPs and PRP protein phenotypes were observed for the PmF, PmS, Gl and CON2 proteins. Our overall analysis indicates that in many instances several proteins previously considered to be the products of separate loci are actually proteolytic cleavage products of a large precursor specified by one or other of the six genes identified at the DNA level. Our analysis also demonstrates that some of the ``null'' alleles proposed to occur at 11 of the 13 loci in the earlier genetic studies, are actually productive alleles having alterations at proteolytic cleavage sites within the relevant precursor protein. The absence of cleavage leads to the persistence of longer precursor peptides not resolved electrophoretically, concurrently with an absence of the smaller PRPs seen when cleavage occurs.

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