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 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
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DOI：
10.1074/jbc.272.2.835
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发表时间：
1997-01-10
影响因子：
4.8
通讯作者：
Gu, TT
中科院分区：
文献类型：
--
作者：
MacDougall, M;Simmons, D;Gu, TT
牙本质是牙齿的主要矿化细胞外基质。牙本质的有机成分由 I 型胶原蛋白 (90%) 和 10% 非胶原蛋白组成，它们也是骨的成分。两种牙本质蛋白，牙本质唾液蛋白和牙本质磷蛋白，已被证明是牙齿特异性的，主要由成牙本质细胞表达。在本研究中，我们筛选了小鼠磨牙文库中的牙本质唾液蛋白和牙本质磷蛋白 cDNA 克隆。对克隆的分析得出了包含 940 个氨基酸开放阅读框的 4420 个核苷酸 cDNA 的特征。信号肽和NH2末端序列与大鼠牙本质唾液蛋白的cDNA序列有75%同源性。然而，连续的开放阅读框包含RGD序列，后面是重复的天冬氨酸和丝氨酸残基区域。这部分蛋白质编码的氨基酸序列与牙本质磷蛋白一致。非编码区包含三个潜在的聚腺苷酸化信号，其中两个被证明已被利用。 Northern 印迹分析表明成牙本质细胞中存在 4.4 和 2.2 kb 的两个主要转录本。染色体作图将该基因定位于人类 4 号染色体。这些数据表明，先前鉴定的牙本质细胞外基质蛋白、牙本质唾液蛋白和牙本质磷蛋白，表达为编码蛋白质的单个 cDNA 转录物，该蛋白质被特异性切割成具有独特物理化学特征的两个较小的多肽。因此，我们建议将该基因命名为牙本质唾液酸磷蛋白。人类牙本质唾液酸磷蛋白基因位于4号染色体上，表明该基因可能是II型牙本质发育不全遗传病的有力候选基因。
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 hu man 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.