The FuncPatch Server

Example 1: the case study of MAPK1 genes

Vertebrate MAPK1 (ERK2) genes encode protein kinases important to signal transduction. We applied FuncPatch to 17 MAPK1 orthologous proteins downloaded from the NCBI HomoloGene database (HomoloGene ID: 37670 [1]) and the rat MAPK1 protein tertiary structure (PDB ID: 1ERK) downloaded from the Protein Data Bank [2]. As shown in Figure 1, the 10% of sites with lowest estimated substitution rates are clustered together and form a conserved patch in the protein tertiary structure. The catalytic base of MAPK1, Asp-147, is located in the core region of the predicted conserved patch. Therefore, the conserved region predicted by MAPK1 corresponds to the catalytic site. Detailed results can be found here.


Figure 1. The 3D locations of the most conserved sites predicted by FuncPatch in the case study of MAPK1 genes. The blue sites are the 10% of sites with the lowest estimated substitution rates. The space-filled site corresponds to the catalytic base (Asp-147). The figure was prepared with Jmol [3].

Example 2: the case study of SMAD genes

SMAD genes are also critical components in signal transduction networks. We downloaded 11 SMAD1 genes (HomoloGene ID: 21194), 9 SMAD5 genes (HomoloGene ID: 4313), and 10 SMAD8 genes (HomoloGene ID: 21198) from the NCBI HomoloGene database. Then, we applied FuncPatch to find conserved patches in the SMAD dataset. The protein tertiary structure of the MH1 domain in the mouse SMAD protein was used as the representative structure (PDB ID: 3KMP). As shown in Figure 2, the 10% of sites with lowest estimated substitution rates are clustered together and form a conserved patch. The predicted conserved patch corresponds to a binding site which may contribute to the crosstalk between the calmodulin pathway and the SMAD pathway. Detailed results can be found here.


Figure 2. The 3D locations of the most conserved sites predicted by FuncPatch in the case study of SMAD genes. The blue sites are the 10% of sites with the lowest estimated substitution rates. The space-filled site corresponds to the binding site which may interact with calmodulin and may contribute to the crosstalk between the calmodulin pathway and the SMAD pathway. The figure was prepared with Jmol [3].

References

[1] http://www.ncbi.nlm.nih.gov/homologene

[2] http://www.rcsb.org

[3] http://www.jmol.org/

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