Allelic variants of acidic proline-rich proteins observed in Japanese, Chinese, and Malays

Abstract

Three new variants of acidic proline-rich proteins (At, Au, Aw) were found in human parotid saliva by isoelectric focusing and basic gel electrophoresis. Electrophoretic comparison of the purified proteins and their tryptic peptides suggested minor charge and size differences from other acidic PRPs. Genetic and biochemical studies indicate that the At and Aw proteins are allelic products of the PRH1 locus. Gene frequencies of the At productive allele (PRH1(6)) in Japanese, Chinese, and Malays were 0.008, 0.012, and 0.004, respectively. The Au protein was also found in Japanese (2 in 746 samples), Chinese (1 in 215 samples), and Malays (1 in 220 samples), however, the Aw protein was found only in one Japanese (n = 746). These three proteins were not found in 106 Indian subjects.

Facts and artifacts in proteomics of body fluids. What proteomics of saliva is telling us?

“…Considering that a locus with two alleles may generate three different phenotypes (two homozygosis and one heterozygosis), a three-allelic locus six phenotypes (three homozygosis and three heterozygosis) and a locus with four alleles ten different phenotypes (four homozygosis and six heterozygosis), the number of potential PRPs phenotypes present in the Caucasian population is 64800 (366 3 610 2 ). It is worthwhile to mention that other uncommon allelic products of the PRH1 locus (At, Au, Aw) were found in Asiatic populations [32]. The variety of bPRP polymorphisms is further complicated by individual insertions/deletions, tandem repeats, alternative splicing and a complex post-translational maturation, comprehending different proteolytic processes and heterogeneous glycosylation [33].…”

Genetics of Salivary Protein Polymorphisms

“…From DNA analysis and comparisons of alleles coding for Db, Pa, and PIF proteins, amino acid substitutions occur in exon 3 (the major coding portion) that confer charge differences that adequately explain the separations by isoelectric focusing (Kim and Maeda, 1986;Azen et al, 1987 (Wong et al, 1983 (Shintani et al, 1990a). Because of the presence of this cysteine substitution, the Pal protein is also a disulfide-bonded dimer, whereas other acidic PRPs are monomers (Azen and Denniston, 1974;Azen, 1977Azen, , 1978.…”

“…Exon 3 encodes the N2 region, the proline-rich tandems repeats (H), and the C-terminal region (C Initially (prior to molecular-genetic analysis of PRP genes), it was assumed that the many PRP polymorphisms were coded by a closely linked gene complex with a gene corresponding to each polymorphism. The acidic protein polymorphisms include Pr (prolinerich proteins) (Azen and Oppenheim, 1973;Azen and Denniston, 1974), Pa (acidic protein) (Friedman et al, 1975), Db (double-band proteins) (Azen and Denniston, 1974), PIF (isoelectric focusing variant proteins) (Azen and Denniston, 1981), As (SDS electrophoretic variant protein) Minaguchi et al, 1990) and At, Au and Aw (Shintani et al, 1990a). Basic and glycosylated PRP polymorphisms include Pm/PmF (parotid middle band, fast) (Ikemoto et al, 1977), Gl (major parotid glycoproteins) (Azen et al, 1979), Ps (parotid size variant) (Azen and Denniston, 1980), PmS (parotid middle band, slow) (Azen and Denniston, 1980), CONI and CON2 (Concanavalin A-binding proteins) (Azen and Yu, 1984a), Pe and Po (Azen and Yu, 1984b), Pc (Karn et al, 1985), Pmo 1 and Pmo 2 (modified staining protein) (Minaguchi and Suzuki, 1988).…”

High‐resolution high‐performance liquid chromatography with electrospray ionization mass spectrometry and tandem mass spectrometry characterization of a new isoform of human salivary acidic proline‐rich proteins named Roma‐Boston Ser22(Phos) → Phe variant

“…Previous detection of aPRP polymorphisms was reported by Shintani et al in the Asian population and by Hay et al in the Western‐European population without characterization of the specific isoforms. It is entirely possible that the chromatographically characterized peaks of X‐s and X‐f by Hay et al correspond to the PRP1/PRP3 BR Ser 22 (phos)→Phe variants structurally characterized in this study.…”

“…Moreover, the Pa isoform displays a cysteine instead of an arginine at position 103. Further aPRP polymorphisms, although structurally not defined, have been previously described .…”