Dentin phosphoprotein and dentin sialoprotein are cleavage products expressed from a single transcript coded by a gene on human chromosome 4. Dentin phosphoprotein DNA sequence determination.
Dentin is the major mineralized extracellular matrix of the tooth. The organic components of dentin consist of type I collagen (90%) with 10% noncollagenous proteins, which are also components of bone. Two dentin proteins, dentin sialoprotein and dentin phosphoprotein, have been shown to be tooth-specific being expressed mostly by odontoblast cells. In this study, we screened a mouse molar tooth library for dentin sialoprotein and dentin phosphoprotein cDNA clones. Analysis of the clones resulted in characterization of a 4420-nucleotide cDNA that contained a 940-amino acid open reading frame. The signal peptide and NH2-terminal sequence was 75% homologous to the cDNA sequence of rat dentin sialoprotein. The continued open reading frame, however, contained a RGD sequence followed by a region of repeated aspartic acid and serine residues. This portion of the protein codes for amino acid sequence consistent with that of dentin phosphoprotein. The noncoding region contains three potential polyadenylation signals, two of which were shown to be utilized. Northern blot analysis indicated the presence of two major transcripts of 4.4 and 2.2 kilobases in odontoblasts. Chromosomal mapping localized the gene to human chromosome 4. These data suggest that the previously identified dentin extracellular matrix proteins, dentin sialoprotein and dentin phosphoprotein, are expressed as a single cDNA transcript coding for a protein that is specifically cleaved into two smaller polypeptides with unique physical-chemical characteristics. Therefore, we propose that the gene be named dentin sialophosphoprotein. The location of the human dentin sialophosphoprotein gene on chromosome 4 suggests that this gene may be a strong candidate gene for the genetic disease dentinogenesis imperfecta type II.
MacDougall
M
M
University of Texas Health Science Center at San Antonio, Dental School, Department of Pediatric Dentistry, 78284-7888, USA. MacDougall@UTHSCSA.edu
Simmons
D
D
Luan
X
X
Nydegger
J
J
Feng
J
J
Gu
T T
TT
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002894:Chromosomes, Human, Pair 4; D004247:DNA / Q000737:chemistry*; D016326:Extracellular Matrix Proteins; D016368:Frameshift Mutation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011498:Protein Precursors; D011499:Protein Processing, Post-Translational; D051381:Rats; D016415:Sequence Alignment; D012795:Sialoglycoproteins / Q000378:metabolism*; D013045:Species Specificity; D000099311:Dentin Sialophosphoprotein
D004247:DNA; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D011498:Protein Precursors; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C017630:phosphophoryn