A new proline-rich protein precursor expressed in the salivary glands of the rat is encoded by a gene homologous to the gene coding for the prohormone-like protein SMR1.

A gene encoding a prohormone-like protein (SMR1) has previously been characterized and shown to be expressed in the rat submandibular glands under androgenic control (Rosinski-Chupin, I., Tronik, D., and Rougeon, F. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 8553-8557). This gene, now named VCS-alpha 1, belongs to a multigene family (Rosinski-Chupin, I., and Rougeon, F. (1990) DNA Cell Biol. 9, 553-559). We now describe the structure and the expression of a second member (VCS-beta 1) of this family. The two genes differ principally in the protein-coding region, therefore we have named these related genes VCS (variable coding sequence). Genomic clones containing the VCS-beta 1 gene were obtained by screening a lambda EMBL3 library with a probe corresponding to the VCS-alpha 1 cDNA. The nucleotide sequence of VCS-beta 1 predicted a structure containing three exons. This structure, confirmed by sequencing a VCS-beta 1 cDNA obtained by reverse polymerase chain reaction, is identical to the organization of the VCS-alpha 1 gene. Comparison of the VCS-beta 1 and VCS-alpha 1 genomic sequences indicates regions of homology which are unevenly distributed, suggesting a differential evolution of some areas (particularly the third exon) of the VCS genes. The VCS-beta 1 cDNA codes for a proline-rich protein precursor named PR-V beta 1 (148 amino acids, 39.2% proline, 10.8% glycine) and characterized by a secretory signal-peptide and three repeats of a unit rich in proline residues surrounded by two clusters of potential endoprotease cleavage sites. mrNA coding for PR-V beta 1 was detected in the submandibular-sublingual gland complex of male and female rats. PR-V beta 1 is homologous to the proline-rich peptide B isolated from human saliva (Isemura, S., Saitoh, E., and Sanada, K. (1979) J. Biochem. (Tokyo) 86, 79-86) and to the submandibular proline-rich protein precursor MSG1 of the mouse (D. Tronik-Le Roux, M. Senorale-Pose, and F. Rougeon, manuscript in preparation). Our observations provide evidence that in addition to the known proline-rich protein genes, there is, in rodent and probably human genomes, another class of genes coding for salivary proline-rich proteins. The high conservation of various sites for bacterial collagenases localized in the repeat region of PR-V beta 1, MSG1, and PRP-B suggest a protective function of these proteins in the oral cavity.