Human salivary PRPs are determined by six closely linked genes on chromosome 12pl3.2. The many PRPs show complex electrophoretic patterns that differ between individuals and reflect numerous genetic polymorphisms. Frequent length and null polymorphisms are common among PRPs. Common themes emerge as a background for these PRP polymorphisms. First, posttranslational proteolysis occurs with double-banded patterns among acidic PRPs and the generation of numerous basic PRPs derived from precursor proteins. Specific mutations may interfere with proteolysis, preventing generation of double-banded acidic PRPs (as with the Pa protein) or of small basic PRPs from precursor proteins (as with Pm proteins). Second, single cysteine substitutions in PRPs (Pa from PRH1 and Gl 8 from PRB3) may lead to disulfide bonded homodimers as well as heterodimers with salivary peroxidase. Third, frequent homologous and unequal crossing-over within the PRP gene cluster leads to frequent protein size-variants (intragenic events as with the GI protein variants) and the generation of the PRB2/1 fusion gene (intergenic event) with deletion of the PRB1 coding region and absence of multiple PRB 1 coded proteins (Ps, Pm, Pe) in PRB2/1 homozygotes. Fourth, null mutations may also be produced (as with PsO and Gl 0) by single nucleotide changes.
References
1.
Azen, E.A.: Salivary Peroxidase (SAPX): Genetic Modification and Relationship to the Proline-Rich (Pr) and Acidic (Pa) Proteins, Biochem. Genet. 15:9-29 (1977).
2.
Azen, E.A.: Genetic Protein Polymorphisms in Human Saliva: An Interpretive Review. Biochem. Genet. 16:79-99 (1978).
3.
Azen, E.A.: Genetic Protein Polymorphisms of Human Saliva. In: Human Saliva: Clinical Chemistry and Microbiology, Vol. 1, pp. 161-195. ( J. O. Tenovuo, Ed.) CRC Press, Boca Raton, FL (1989).
4.
Azen, E.A. and C.L. Denniston: Genetic Polymorphism of Human Salivary Proline-Rich Proteins: Further Genetic Analysis. Biochem. Genet. 12:109-120 (1974).
5.
Azen, E.A. and C. Denniston: Polymorphism of Ps (Parotid Size Variant) and Detection of a Protein (PmS) Related to the Pm (Parotid Middle Band) System with Genetic Linkage of Ps and Pm to GI, Db and Pr Genetic Determinants. Biochem. Genet. 18:483-501 (1980).
6.
Azen, E.A. and C.L. Denniston: Genetic Polymorphisms of PIF (Parotid Isoelectric Focusing Variant) Proteins with Linkage to the PPP (Parotid Proline-Rich Protein) Gene Complex. Biochem. Genet. 19:475-485 (1981).
7.
Azen, E.A., C.K. Hurley, and C. Denniston: Genetic Polymorphism of the Major Parotid Salivary Glycoprotein (Gl) with Linkage to the Genes for Pr, Db, and Pa. Biochem. Genet. 17:257-279 (1979).
8.
Azen, E.A., H.-S. Kim, P. Goodman, S. Flynn, and N. Maeda: Alleles at the PRH1 Locus Coding for the Human Salivary Acidic Proline-rich Proteins (PRPs) Pa, Db and PIF, Am. J. Hum. Genet. 41:1035-1047 (1987).
9.
Azen, E.A., P. Latreille, and R.L. Niece: PRB1 Gene Variants Coding for Length and Null Polymorphisms Among Human Salivary Ps, PmF, PmS and Pe Proline-Rich Proteins (PRPs). Am. J. Hum. Genet., in press.
10.
Azen, E.A., K.M. Lyons, T. McGonigal, N.L. Barrett, L.S. Clements, N. Maeda, E.F. Vanin, D.M. Carlson, and O. Smithies: Clones from the Human Gene Complex Coding for Salivary Proline-Rich Protein. Proc. Natl. Acad. Sci. U.SA.81:5561-5565 (1984).
11.
Azen, E.A. and N. Maeda: Molecular Genetics of Human Salivary Proteins and their Polymorphisms. In: Advances in Human Genetics, pp. 141-199. ( H. Harris and K. Hirschhorn, Eds.) Plenum, New York ( 1988).
12.
Azen, E.A., K. Minaguchi, P. Latreille, and H.-S. Kim: Alleles at the PRB3 Locus Coding for a Disulfide-bonded Human Salivary Proline-Rich Glycoprotein (Gl 8) and a Null in an Ashkenazi Jew. Am. J. Hum. Genet.47:686-697 (1990).
13.
Azen, E.A., P. O'Connell and H.-S. Kim: PRB2/1 Fusion Gene: A Product of Unequal and Homologous Crossing-Over between Proline-Rich Protein (PRP) Genes PRB1 and PRB2. Am. J. Hum. Genet.50:842-851(1992).
14.
Azen, E.A. and F.G. Oppenheim: Genetic Polymorphism of Proline-Rich Human Salivary Proteins. Science180:1067-1069 (1973).
15.
Azen, E.A., A. Prakobphol, and S.L. Fisher: PRB3 Null Mutations Result in Absence of the Proline-Rich Glycoprotein G 1 (PRG) and Abolish Fusobacterium nucleatum Interactions with Saliva in vitro. Submitted.
16.
Azen, E.A. and P.L. Yu: Genetic Polymorphisms of CON1 and CON2 Salivary Proteins Detected by Immunologic and Concanavalin A Reactions on Nitrocellulose with Linkage of CON1 and CON2 Genes to the SPC (Salivary Protein Gene Complex). Biochem. Genet. 22:1-19 (1984a).
17.
Azen, E.A. and P.L. Yu: Genetic Polymorphism of Pe and Po Salivary Protein with Probable Linkage of their Genes to the Salivary Protein Gene Complex (SPC). Biochem. Genet. 22:1065-1080 (1984b).
18.
Friedman, R.D. and A.D. Merritt: Partial Purification and Characterization of a Polymorphic Protein (Pa) in Human Parotid Saliva. Am. J. Hum. Genet. 27:304-314 (1975).
19.
Hay, D.I., A. Bennick, D.H. Schlesinger, K. Minaguchi, G. Madapallimattam, and S.K. Schluckebier: The Primary Structures of Six Human Salivary Acidic Proline-Rich Proteins (PRP-1, PRP-2, PRP-3, PRP-4, PIF-s and PIF-f). Biochem. J.255:15-21 (1988).
20.
Ikemoto, S., K. Minaguchi, K. Suzuki, and K. Tomita: New Genetic Marker in Human Parotid Saliva (Pm). Science197:378-379 (1977).
21.
Isemura, S., E. Saitoh, and K. Sanada: The Amino Acid Sequence of a Salivary Proline-Rich Peptide, P-C, and its Relations to a Salivary Proline-Rich Phosphoprotein, Protein C. J. Biochem. 87:1071-1077 (1980).
22.
Kam, R.C., P.A. Goodman, and P.L. Yu: Description of a Genetic Polymorphism of a Human Proline-Rich Salivary Protein, Pc, and Its Relationship to Other Proteins in the Salivary Protein Complex (SPC). Biochem. Genet. 23:37-51 (1985).
23.
Kim, H.-S. and N. Maeda: Structure of Two HaeIII-type Genes in the Human Salivary Proline-Rich Protein Multigene Family. J. Biol. Chem. 261:6712-6718 (1986).
24.
Kim, H.-S., O. Smithies, and N. Maeda: A Physical Map of the Human Salivary Proline-Rich Protein Gene Cluster Covers over 700 kbp of DNA. Genomics6:260-267 (1990).
25.
Lyons, K.M., E.A. Azen, P.A. Goodman, and O. Smithies: Many Protein Products from a Few Loci: Assignment of Human Salivary Proline-Rich Proteins to Specific Loci. Genetics120:255-265 (1988a).
26.
Lyons, K.M., J.H. Stein, and O. Smithies: Length Polymorphisms in Human Proline-Rich Protein Genes Generated by Intragenic Unequal Crossing Over. Genetics120:267-278 (1988b).
27.
Maeda, N.: Inheritance of Human Salivary Proline-Rich Proteins: A Reinterpretation in Terms of Six Loci Forming Two Subfamilies. Biochem. Genet. 23:455-464 (1985).
28.
Maeda, N., H.-S. Kim, E.A. Azen, and O. Smithies: Differential RNA Splicing and Post Translational Cleavages in the Proline-Rich Protein Gene System. J. Biol. Chem.260:11123-. 11130 (1985).
29.
Mamula, P.W., D.J. Morley, S.H. Larsen, and R.C. Kam: Expression of Human Salivary Protein Genes. Biochem. Genet. 26:165-175 (1988).
30.
Minaguchi, K., Y. Takaesu, T. Tsutsumi, and K. Suzuki: Studies of Genetic Markers in Human Saliva. VII. Frequencies of the Major Parotid Salivary Glycoprotein (Gl) System in a Japanese Population. Bull. Tokyo Dent. Coll. 22:1-6 (1981).
31.
Minaguchi, K. and A. Bennick: Genetics of Human Salivary Proteins. J. Dent. Res. 68:2-15 (1989).
32.
Minaguchi, K., M. Shintani, and K. Suzuki: New Allelic Product of PRH1 Locus Coding for Salivary Acidic Proline-Rich Proteins. Hum. Hered. 40:221-230 (1990).
33.
Minaguchi, K. and K. Suzuki: Genetic Polymorphisms of the Pmo1 and Pmo2 Salivary Proteins Detected by the Modified Protein Staining Method. Ann. Hum. Genet. 52:177-187 (1988).
34.
O'Connell, P., M. Lathrop, M. Law, M. Leppert, Y. Nakamura, M. Hoff, E. Kumlin, W. Thomas, T. Elsner, L. Ballard, P. Goodman, E.A. Azen, J.E. Sadler, G.Y. Cai, J.M. Lalouel, and R. White: A Primary Genetic Linkage Map for Human Chromosome 12. Genomics1:93-102 (1987).
35.
Orkin, S.H.: The Mutation and Polymorphism of the Human β-globin Gene and Its Surrounding DNA. Annu. Rev. Genet. 18:131-171 (1984).
36.
Robinson, R. and A. Bennick: Posttranslational Processing of Salivary Proline-Rich Proteins. In: Canadian Federation of Biological Societies, 28th Annual Meeting, Proceedings 28:No. PA202. (1986).
37.
Shintani, M., K. Minaguchi, K. Suzuki, and K.-A. Lim: Allelic Variants of Acidic Proline-Rich Proteins Observed in Japanese, Chinese, and Malays. Biochem. Genet.28:173-184 (1990a).
38.
Shintani, M., K. Minaguchi, K.A. Lim, M. Hashimoto, and K. Suzuki: Salivary Proline-Rich Protein Polymorphisms in Chinese, Malays and Indians in Singapore. Hum. Hered.40:89-98 (1990b).
39.
Wong, R.S.C. and A. Bennick: The Primary Structure of a Salivary Calcium-Binding Proline-Rich Phosphoprotein (Protein C), a Possible Precursor of a Related Salivary Protein A. J. Biol. Chem. 255:5943-5948 (1980).
40.
Wong, R.S.C., G. Madapallimattam, and A. Bennick: The Role of Glandular Kallikrein in the Formation of a Salivary Proline-Rich Protein A by Cleavage of a Single Bond in Salivary Protein C. Biochem. J. 211:35-44 (1983).
