PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats
PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats
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DOI：
10.1086/340448
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发表时间：
2002-05-01
影响因子：
9.8
通讯作者：
Germino, GG
中科院分区：
文献类型：
--
作者：
Onuchic, LF;Furu, L;Germino, GG
常染色体隐性遗传性多囊肾病(ARPKD)是一种严重的多囊肾病，主要见于婴幼儿和儿童期，以肾脏增大和先天性肝纤维化为特征。我们已经鉴定出ARPKD中突变的基因PKHD1。PKHD1的长度大于或等于469kb，主要在人胎儿和成人肾脏中表达，包括至少86个外显子，这些外显子可变地组装成许多选择性剪接的转录本。最长的连续开放阅读框编码一个由4,074个氨基酸组成的蛋白质Polyductin，据预测在其羧基末端附近有一个跨膜(TM)结构域，免疫球蛋白样丛蛋白转录因子结构域，在其氨基末端有平行的β-螺旋1重复序列。几个转录本编码缺乏TM的截短产物，如果翻译可能会分泌。PKHD1基因产物是一类新的蛋白质的成员，这些蛋白质与肝细胞生长因子受体和丛状蛋白具有相同的结构特征，属于参与调节细胞增殖和细胞黏附和排斥的蛋白质超家族。
Autosomal recessive polycystic kidney disease (ARPKD) is a severe form of polycystic kidney disease that presents primarily in infancy and childhood and that is characterized by enlarged kidneys and congenital hepatic fibrosis. We have identified PKHD1, the gene mutated in ARPKD. PKHD1 extends over greater than or equal to469 kb, is primarily expressed in human fetal and adult kidney, and includes a minimum of 86 exons that are variably assembled into a number of alternatively spliced transcripts. The longest continuous open reading frame encodes a 4, 074-amino-acid protein, polyductin, that is predicted to have a single transmembrane (TM)-spanning domain near its carboxyl terminus, immunoglobulin-like plexin-transcription-factor domains, and parallel beta-helix 1 repeats in its amino terminus. Several transcripts encode truncated products that lack the TM and that may be secreted if translated. The PKHD1-gene products are members of a novel class of proteins that share structural features with hepatocyte growth-factor receptor and plexins and that belong to a superfamily of proteins involved in regulation of cell proliferation and of cellular adhesion and repulsion.