title: The intriguing heterogeneity of human salivary proline-rich proteins: Short title: Salivary proline-rich protein species.
abstract: The most heterogeneous family of human salivary proteins is represented by proline-rich proteins (PRPs) divided in acidic, basic, and basic glycosylated (aPRPs, bPRPs, gPRPs). They are encoded by six genes, clustered on chromosome 12p13.2: PRH1-2 encode aPRPs, PRB1-4 encode bPRPs and gPRPs. Each gene exists in different allelic forms: two for PRH2, three for PRH1, PRB2, and PRB4, four for PRB1, and PRB3. During granule maturation, PRP proproteins undergo proteolysis by the action of convertases and carboxypeptidases. Differently from bPRPs, proteolysis of aPRPs is not complete, and, besides fragments, entire protein species are also secreted. Maturation process generates ten aPRPs (PRP-1, PRP-2, PIF-s, Db-s, Pa, PRP-3, PRP-4, PIF-f, Db-f, P-C), and at least 18 bPRPs (II-2, P-E, IB-6, Ps-1, Ps-2, IB-1, P-J, IB-8a, P-F, P-H, P-D, II-1, protein glycosylated A, CD-IIg, and Gl1-4). In addition, single nucleotide and length polymorphisms, and differentially spliced transcripts originate several natural variants. Phosphorylation, N-pyroglutaminylation, dimerization, and N-/O-glycosylation also occur during maturation, enlarging the number of protein species, further increased by proteolytic events governed by carboxy- and endo-peptidases during and after secretion, and giving rise to a huge number of small peptides. The PRP functional role is still poorly understood.
  
  
  CONCLUSIONS
  The high polymorphism of PRPs gives an important contribution to the high heterogeneity and inter-individual variability of the human salivary proteome. The products of six genes clustered on chromosome 12p13.2 comprise a mixture of entire, truncated, phosphorylated, glycosylated and dimerized protein/peptide species, sharing large part of their sequences, and possibly involved in different biological activities. Whatever the role of PRP species is, it should be crucial, given that PRPs are the most conserved oral salivary proteins among mammals.
authors.affiliation: Department of Life and Environmental Sciences, Biomedical section, University of Cagliari, Cagliari Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Manconi
authors.affiliation: Biochemistry and Clinical Biochemistry Institute, Medicine Faculty, Catholic University of Rome, Roma Italy; Institute of Chemistry of the Molecular Recognition, CNR, Roma Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Castagnola
authors.affiliation: Department of Life and Environmental Sciences, Biomedical section, University of Cagliari, Cagliari Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cabras
authors.affiliation: Department of Life and Environmental Sciences, Biomedical section, University of Cagliari, Cagliari Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Olianas
authors.affiliation: Institute of Chemistry of the Molecular Recognition, CNR, Roma Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Vitali
authors.affiliation: Institute of Chemistry of the Molecular Recognition, CNR, Roma Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Desiderio
authors.affiliation: Department of Life and Environmental Sciences, Biomedical section, University of Cagliari, Cagliari Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sanna
authors.affiliation: Department of Life and Environmental Sciences, Biomedical section, University of Cagliari, Cagliari Italy. Electronic address: imessana@unica.it.
authors.forename: Irene
authors.initials: I
authors.lastname: Messana
mesh_terms: D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D059748:Proteolysis; D055273:Salivary Proline-Rich Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D010455:Peptides; D055273:Salivary Proline-Rich Proteins; D002268:Carboxypeptidases
keywords: Acidic proline-rich proteins; Basic proline-rich proteins; N-/O-glycosylated proline-rich proteins; N-pyroglutaminylation; Phosphorylation