SH2 Domain Origin 1 Identification of the Linker-SH2 Domain of STAT as the Origin of the SH2 Domain Using Two Dimensional Structural Alignment

2 Summary: The availability of large volumes of genomic sequences presents an unprecedented proteomic challenge to characterize the structure and function of various protein motifs. Primary sequence alignment is often unable to accurately identify a given motif due to sequence divergence; however, with the aid of secondary structural prediction for analysis, it becomes feasible to explore protein motifs on a proteome-wide scale. Here we report the use of secondary structural alignment to characterize the SH2 domains of both conventional and divergent sequences and divide them into two groups, Src-type and STAT-type. In addition to the basic “abbba ” structure (bB), the Src-type SH2 domain contains an extra b-strand (bE or bE-bF motif). Alternatively, th