Vilmos P, Gaudenz K, Hegedus Z, Marsh J L
Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697, USA.
Mol Pathol. 2001 Oct;54(5):317-23. doi: 10.1136/mp.54.5.317.
To analyse the similarities between the Twisted gastrulation (TSG) proteins known to date; in addition, to determine phylogenetic relations among the TSG proteins, and between the TSGs and other protein families--the CCN (for example, CCN2 (CTGF), CCN1 (CYR61), and CCN3 (NOV)) and IGFBP (insulin-like growth factor binding protein) families.
TBLASTN and FASTA3 were used to identify new tsg genes and relatives of the TSG family. The sequences were aligned with ClustalW. The predictions of sites for signal peptide cleavage, post-translational modifications, and putative protein domains were carried out with software available at various databases. Unrooted phylogenetic trees were calculated using the UPGMA method.
Several tsg genes from vertebrates and invertebrates were compared. Alignment of protein sequences revealed a highly conserved family of TSG proteins present in both vertebrates and invertebrates, whereas the slightly less well conserved IGFBP and CCN proteins are apparently present only in vertebrates. The TSG proteins display strong homology among themselves and they are composed of a putative signal peptide at the N-terminus followed by a cysteine rich (CR) region, a conserved domain devoid of cysteines, a variable midregion, and a C-terminal CR region. The most striking similarity between the TSGs and the IGFBP and CCN proteins occurs in the N-terminal conserved cysteine rich domain and the characteristic 5' cysteine rich domain(s), spacer region, and 3' cysteine rich domain structure.
The family of highly conserved TSG proteins, together with the IGFBP and CCN families, constitute an emerging multigene superfamily of secreted cysteine rich factors. The TSG branch of the superfamily appears to pre-date the others because it is present in all species examined, whereas the CCN and IGFBP genes are found only in vertebrates.
分析迄今已知的扭曲原肠胚形成（TSG）蛋白之间的相似性；此外，确定TSG蛋白之间以及TSG与其他蛋白家族——CCN（例如CCN2（结缔组织生长因子）、CCN1（ Cyr61）和CCN3（肾母细胞瘤过度表达基因））和胰岛素样生长因子结合蛋白（IGFBP）家族之间的系统发育关系。
使用TBLASTN和FASTA3来鉴定新的tsg基因和TSG家族的相关基因。序列用ClustalW进行比对。利用各种数据库中可用的软件对信号肽切割位点、翻译后修饰位点和假定的蛋白质结构域进行预测。使用UPGMA方法计算无根系统发育树。
对来自脊椎动物和无脊椎动物的几个tsg基因进行了比较。蛋白质序列比对显示，在脊椎动物和无脊椎动物中均存在一个高度保守的TSG蛋白家族，而保守性稍差的IGFBP和CCN蛋白显然仅存在于脊椎动物中。TSG蛋白彼此之间显示出很强的同源性，它们在N端由一个假定的信号肽组成，其后是一个富含半胱氨酸（CR）的区域、一个不含半胱氨酸的保守结构域、一个可变的中间区域和一个C端CR区域。TSG与IGFBP和CCN蛋白之间最显著的相似性出现在N端保守的富含半胱氨酸结构域以及特征性的5'富含半胱氨酸结构域、间隔区和3'富含半胱氨酸结构域结构中。
高度保守的TSG蛋白家族，连同IGFBP和CCN家族，构成了一个新出现的分泌型富含半胱氨酸因子的多基因超家族。该超家族的TSG分支似乎比其他分支出现得更早，因为它存在于所有检测的物种中，而CCN和IGFBP基因仅在脊椎动物中发现。
