The phosphophoryn gene family: identical domain structures at the carboxyl end

Phosphophoryns (PPs), a family of aspartic acid and phosphoserine rich dentin proteins, are considered to be archetypal regulators of extracellular matrix biomineralization. Their very unusual composition, extensive phosphorylation, and tissue-specific heterogeneity have made their characterization a difficult task. We have recently cloned several rat incisor PP genes from our odontoblast cDNA library. The first clone, designated as DMP2, was 2.4 kb long, with an open reading frame of approximately 700 bp and an untranslated region of approximately 1.7 kb. Northern blot analysis of odontoblast mRNA showed a single message between 5 and 6 kb. When a 5' RACE technique was used to obtain the full length clone, a second approximately 2 kb DNA fragment (DMP3) was also found. Cloning and sequencing of DMP3 showed that the 3' end was highly homologous to the 3' end of DMP2, but the 5' end of this clone had 100% homology to dentin sialoprotein (DSP). DMP3 is not a typical Asp-rich phosphophoryn, but DMP2 contains a domain N-terminal to the common region which has the hallmark Asp- and Ser-rich composition of the phosphophoryns. Both DMP2 and DMP3 are closely localized on mouse chromosome 5q21, corresponding to human chromosome 4q21. The expression of these two genes is regulated differently. Thus, there may be a family of phosphophoryn-related genes coding for a common C-terminal peptide sequence domain, but involving different N-terminal domains with different functions.