Ramos Sonia, Khademi Farshad, Somesh Baggavalli P, Rivero Francisco
Institut für Biochemie I, Medizinische Fakultät, University of Cologne, Joseph-Stelzmann-Strasse 52, D-50931 Cologne, Germany.
Gene. 2002 Oct 2;298(2):147-57. doi: 10.1016/s0378-1119(02)00980-0.
Members of the RhoBTB subfamily of Rho GTPases are present in vertebrates, Drosophila and Dictyostelium. RhoBTB proteins are characterized by a modular organization, consisting of a GTPase (guanosine triphosphatase) domain, a proline rich region, a tandem of two BTB (Broad-Complex, Tramtrack, and Bric à brac) domains and a C-terminal region of unknown function and might act as docking points for multiple components participating in signal transduction cascades. We have determined the genomic organization and the expression pattern of the three RHOBTB genes of human and mouse. The exon-intron organization of each gene is conserved in three vertebrate species (human, mouse and Fugu). RHOBTB1 and RHOBTB2 have a similar exon-intron organization and are closely related to the single gene encoding the RhoBTB orthologs of two insect species. By contrast, the exon-intron organization of RHOBTB3 differed substantially from that of the two other genes, indicating that this gene arose by a duplication event independent of the one that gave rise to RHOBTB1 and RHOBTB2. RHOBTB1 (located on chromosome 10) and RHOBTB3 (located on chromosome 5) appear ubiquitously expressed. However, they display a differential pattern of expression: RHOBTB1 showed high levels in stomach, skeletal muscle, placenta, kidney and testis, whereas RHOBTB3 was highly expressed in neural and cardiac tissues, pancreas, placenta and testis. RHOBTB2 (located on chromosome 8) showed much lower levels of expression than the other two human RHOBTB genes and it was most abundant in neural tissues. The expression patterns of the human and mouse genes were roughly comparable. All three genes were also detected in fetal tissues, and in a number of cell lines RHOBTB3 predominates. RHOBTB genes are upregulated in some cancer cell lines, suggesting that these proteins might participate in tumorigenesis.
Rho GTPases的RhoBTB亚家族成员存在于脊椎动物、果蝇和盘基网柄菌中。RhoBTB蛋白的特点是模块化结构，由一个GTPase（鸟苷三磷酸酶）结构域、一个富含脯氨酸的区域、两个BTB（Broad-Complex、Tramtrack和Bric à brac）结构域串联以及一个功能未知的C末端区域组成，可能作为参与信号转导级联反应的多个组件的对接点。我们已经确定了人类和小鼠的三个RHOBTB基因的基因组结构和表达模式。每个基因的外显子-内含子结构在三种脊椎动物物种（人类、小鼠和河豚）中是保守的。RHOBTB1和RHOBTB2具有相似的外显子-内含子结构，并且与编码两种昆虫物种的RhoBTB直系同源物的单个基因密切相关。相比之下，RHOBTB3的外显子-内含子结构与其他两个基因有很大不同，表明该基因是通过独立于产生RHOBTB1和RHOBTB2的复制事件产生的。RHOBTB1（位于10号染色体上）和RHOBTB3（位于5号染色体上）似乎普遍表达。然而，它们表现出不同的表达模式：RHOBTB1在胃、骨骼肌、胎盘、肾脏和睾丸中表达水平较高，而RHOBTB3在神经和心脏组织、胰腺、胎盘和睾丸中高表达。RHOBTB2（位于8号染色体上）的表达水平比其他两个人类RHOBTB基因低得多，并且在神经组织中最为丰富。人类和小鼠基因的表达模式大致相当。在胎儿组织中也检测到了所有三个基因，并且在许多细胞系中RHOBTB3占主导地位。RHOBTB基因在一些癌细胞系中上调，表明这些蛋白质可能参与肿瘤发生。
