ORP3 splice variants and their expression in human tissues and hematopoietic cells
ORP3 splice variants and their expression in human tissues and hematopoietic cells
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DOI：
10.1089/104454903321112442
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发表时间：
2003-01-01
影响因子：
3.1
通讯作者：
Kirkland, MA
中科院分区：
文献类型：
--
作者：
Collier, FM;Gregorio-King, CC;Kirkland, MA
ORP 3是新描述的氧化固醇结合蛋白（OSBP）相关蛋白（ORPs）家族的成员。我们先前证明该基因在CD 34（+）造血祖细胞中高度表达，并推断“全长”ORP 3基因包含23个外显子，编码887个氨基酸的预测蛋白，具有C-末端OSBP结构域和N-末端pleckstrin同源结构域。为了进一步表征该基因，我们从PCR产物中克隆了ORP 3 cDNA，并鉴定了多种剪接变体。共有8个异构体被证明与外显子9，12和15的选择性剪接。具有至外显子15的延伸的同种型截短预测蛋白质序列的OSBP结构域。在人体组织中有特定的亚型分布，大多数组织表达不同水平的具有完整OSBP结构域的亚型;而只有全脑、肾、脾、胸腺和甲状腺表达高水平的与截短的OSBP结构域相关的亚型。有趣的是，大多数亚型在小脑、心脏和肝脏中的表达可以忽略不计。这些数据表明，差异，mRNA剪接可能导致在功能上不同形式的ORP 3基因。
ORP3 is a member of the newly described family of oxysterol-binding protein (OSBP)-related proteins (ORPs). We previously demonstrated that this gene is highly expressed in CD34(+) hematopoietic progenitor cells, and deduced that the "full-length" ORP3 gene comprises 23 exons and encodes a predicted protein of 887 amino acids with a C-terminal OSBP domain and an N-terminal pleckstrin homology domain. To further characterize the gene, we cloned ORP3 cDNA from PCR products and identified multiple splice variants. A total of eight isoforms were demonstrated with alternative splicing of exons 9, 12, and 15. Isoforms with an extension to exon 15 truncate the OSBP domain of the predicted protein sequence. In human tissues there was specific isoform distribution, with most tissues expressing varied levels of isoforms with the complete OSBP domain; while only whole brain, kidney, spleen, thymus, and thyroid expressed high levels of the isoforms associated with the truncated OSBP domain. Interestingly, the expression in cerebellum, heart, and liver of most isoforms was negligible. These data suggest that differential, mRNA splicing may have resulted in functionally distinct forms of the ORP3 gene.