Database of Supergene Family

(1)对参与细胞粘附的3个蛋白质家族、参与信号转导的6个蛋白质家族、ras相关GTP结合蛋白家族和其他6个蛋白质家族中的每一个进行氨基酸序列比对，并根据比对结果确定高度保守片段的共有序列和加权基序。系统发育树也反映了家族成员在进化中的分支顺序。这些数据已纳入我们的表观基因家族数据库。(2)提出了一种在数据库中搜索与已知家族成员的基序具有显著相似性的序列的新方法：在该方法中引入了一个评分系统，该评分系统代表基序的每个氨基酸位置上氨基酸的出现频率。在评分系统的基础上，对观察到的序列相似性进行统计检验。(3)将上述方法应用于参与细胞粘附的三个蛋白质家族，我们发现trk和免疫球蛋白家族成员之间，ret和钙粘蛋白家族成员之间，以及几种酪氨酸激酶和纤连蛋白III型家族成员之间的序列相似性。(4)从以上结果，我们表明，已知的受体型蛋白酪氨酸激酶根据胞外结构域的结构差异分为至少四组。这种分类几乎与基于从激酶结构域的序列比较推断的系统发育树的分类平行。

(1) For each of three protein families involved in cell adhesion, six protein families involved in signal transduction, ras-related GTP binding protein family, and other six protein families, the amino acid sequences were aligned among members, and the consensus sequence and weighted motifs of highly conserved segments were determined based on the alignment. phylogenetic trees representing branching orders of family members in evolution were also inferred. These data were included in our database of supergene family.(2) A new method was developed to search sequences in database that show significant similarities with motifs of known family members : In this method a score system was introduced representing the frequency of occurrence of an amino acid on each amino acid position of the motif. On the basis of the score system, a statistical test was carried out for the observed sequence similarity.(3) Applying the above method to three protein families involved in cell adhesion, we found sequence similarities between trk and immunoglobulin family members, between ret and cadherin family members, and between several tyrosine kinases and fibronectin type III family members.(4) From the above results, we showed that known receptor type protein tyrosine kinases are classified into at least four groups, based on the structural differences of the extracellular domains. This classification in almost parallel to that based on a phylogenetic tree inferred from a sequence comparison of the kinase domains.