Kasper S, Matusik R J
Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-2765, USA.
Biochim Biophys Acta. 2000 Oct 18;1482(1-2):249-58. doi: 10.1016/s0167-4838(00)00170-9.
Probasin (PB) occurs both as a secreted and a nuclear protein that is abundantly expressed in the epithelial cells of the rat prostate. A genomic clone of 17.5 kb gene was isolated from a rat liver genomic library, determining that the probasin gene was comprised of seven exons where the splice donor/acceptor sites conformed to the GT/AG consensus sequence. The exon number and size are remarkably similar to those of aphrodisin, rat alpha(2)-urinary globulin and major urinary protein, outlier members of the lipocalin superfamily. In addition, alignment of the deduced amino acids determined that the probasin gene also contains the glycine-X-tryptophan (G-X-W) motif similar to that of human retinol serum binding protein which binds retinol, and the C-X-X-X-C motif also found in insect lipocalins that bind pheromones. The cysteine residues in exons 3 and 6 are conserved, predicting a secondary structure of eight beta-sheets and the alpha-helix commonly seen in the lipocalin superfamily. Unique PB characteristics include a large genomic fragment (17.5 kb compared to the 3-5 kb seen in other lipocalin genes) and an isoelectric point (pI) of 11.5 which is very basic compared to that of the other more acidic lipocalins. Functionally, PB gene expression is regulated by androgens and zinc in the epithelial cells of the rodent prostate. The 5'-flanking region of probasin contains two androgen receptor binding sites that allow androgen-specific gene expression as well as prostate-specific elements that target and maintain high levels of transgene expression in several PB transgenic mouse models.
前列腺素（PB）以分泌型和核蛋白形式存在，在大鼠前列腺上皮细胞中大量表达。从大鼠肝脏基因组文库中分离出一个17.5 kb基因的基因组克隆，确定前列腺素基因由7个外显子组成，其剪接供体/受体位点符合GT/AG共有序列。外显子数量和大小与黄体生成素、大鼠α(2)-尿球蛋白和主要尿蛋白（脂联素超家族的异常成员）非常相似。此外，推导氨基酸序列的比对确定，前列腺素基因还含有与结合视黄醇的人视黄醇血清结合蛋白相似的甘氨酸-X-色氨酸（G-X-W）基序，以及在结合信息素的昆虫脂联素中也发现的C-X-X-X-C基序。外显子3和6中的半胱氨酸残基是保守的，预测其二级结构为脂联素超家族中常见的8个β-折叠和α-螺旋。独特的PB特征包括一个大的基因组片段（17.5 kb，而其他脂联素基因中为3-5 kb）和11.5的等电点（pI），与其他酸性更强的脂联素相比，这个等电点非常碱性。在功能上，PB基因表达受啮齿动物前列腺上皮细胞中的雄激素和锌调节。前列腺素的5'-侧翼区域包含两个雄激素受体结合位点，允许雄激素特异性基因表达，以及在几个PB转基因小鼠模型中靶向并维持高水平转基因表达的前列腺特异性元件。
