Identification of two novel polycystic kidney disease-1-like genes in human and mouse genomes
Identification of two novel polycystic kidney disease-1-like genes in human and mouse genomes
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DOI：
10.1016/s0888-7543(03)00048-x
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发表时间：
2003-06-01
期刊：
影响因子：
4.4
通讯作者：
Somlo, S
中科院分区：
文献类型：
--
作者：
Li, AR;Tian, X;Somlo, S
由PKD1编码的多囊蛋白-1和由PKD2编码的多囊蛋白-2这两类多囊蛋白的典型成员的突变是常染色体显性多囊肾病的基础。在这里，我们报告了从人类和小鼠基因组中鉴定出一对与PKD1同源的基因。PKD1L2和PKD1L3分别位于人类16q22-q23染色体和小鼠8号染色体上，可选择性拼接。人类和小鼠的PKD1L2是高度保守的，每个PKD1L2由43个外显子和2460个密码子组成。PKD1L3显示区域序列分化，小鼠形式有两个额外的外显子和一个更大的外显子5。PKD1L2和PKD1L3的预测蛋白产物包含GPS和PLAT/LH2结构域的组合，这将它们独特地定义为多囊蛋白-1家族成员。预计它们具有11个跨膜区域，具有与该蛋白家族提出的受体功能一致的大细胞外结构域。PKD1L2和PKD1L3含有强离子通道特征基序，表明它们可能是阳离子通道孔的组成部分。多囊蛋白- 1相关蛋白可能不仅调节通道，而且实际上可能是孔隙形成单元的一部分。(C) 2003 Elsevier Science（美国）版权所有。
Mutations to the prototypical members of the two general classes of polycystins, polycystin-1 encoded by PKD1 and polycystin-2 encoded by PKD2, underlie autosomal-dominant polycystic kidney disease. Here we report the identification of a pair of genes homologous to PKD1 from both the human and mouse genomes. PKD1L2 and PKD1L3 are located on human chromosome 16q22-q23 and mouse chromosome 8 and are alternatively spliced. The human and mouse forms of PKD1L2 are highly conserved, with each one consisting of 43 exons and similar to2,460 codons. PKD1L3 shows regional sequence divergence, with the mouse form having two additional exons and a much larger exon 5. The predicted protein products of PKD1L2 and PKD1L3 contain the combination of GPS and PLAT/LH2 domains that uniquely define them as polycystin-1 family members. They are predicted to have 11 membrane-spanning regions with a large extracellular domain consistent with the proposed receptor function of this protein family. PKD1L2 and PKD1L3 contain strong ion channel signature motifs that suggest their possible function as components of cation channel pores. Polycystin-l-related proteins may not only regulate channels, but may actually be part of the pore-forming unit. (C) 2003 Elsevier Science (USA). All rights reserved.