Remote homology detection of proteins involved in insulin signaling
Next, we looked at the human proteins and their pdam homologues in three receptor activated signaling pathways related to insulin signaling. We extracted from the literature all the proteins involved in the signaling pathways activated by binding of insulin to the IR. In addition, we also extracted proteins from related pathways, glucagon and somatostatin, which are known to down-regulate insulin signaling. In Figure 3 , all of the proteins shown in black have a predicted pdam homologue, while those shown in red, do not. Crosstalk between these pathways is mediated by a number of proteins that are common to two or even all three pathways.
For three proteins, we were not able to identify suitable pdam homologues, somatostatin, glucagon and BAD, as judged by their poor e-values of 0.52, 15 and 5.6 and small percent alignments 16% of 116 amino acids, 7% of 180 and 11% of 168 amino acids, respectively. Thus, in the insulin receptor signaling pathway, only one protein, BAD, is missing, at the effector end of the pathway, indicating that the pathway is mostly functional. Importantly, there is a clear homologue of both insulin and the insulin receptor present. In contrast, we were not able to find pdam homologues for either the pathway initiating ligands glucagon or somatostatin. These are both pathways that suppress insulin signaling.