More specifically, we defined the interaction based on a measure of gene functional similarity introduced in [ 34] as follows: Two protein complexes are functionally interacted with each other if they share at least one annotating GO term, where annotating GO terms include direct annotating GO terms and their ancestors in the GO directed acyclic graph.
Therefore, as we did in our previous study [ 21], we defined a functional similarity interaction between two protein complexes based on their shared protein elements as follows: Two protein complexes are functionally interacted with each other if they share at least one protein element.
In previous works, we have also investigated the prevalence on HPV virus in oral and oropharyngeal cancers [ 53], the golden standard method of HPV detection [ 54], and the prognostic role of other important proteins that are functionally interacting with beta-catenin [ 55– 55].
Although we trained our method to identify physical interactions, the lowest-scoring predicted partners are likely to be proteins that are at least functionally interacting with the protein of interest.
This domain is not conserved among other steroid receptors, but ER has been found to functionally interact with c-Src via MNAR (1, 26), and the transactivation activity of GR has been reported to be opposed by MNAR expression (5).
Spt16-C is an acidic domain that is essential for viability whose most 3′ end has recently been shown to functionally interact with histone H3 (Belotserkovskaya et al. 2003; Evans et al. 1998).
This is of particular relevance for astrogliogenesis as Stat3 has been shown to functionally interact with the BMP2-responsive transcription factor Smad1/5/8 at the p300 transcriptional coactivator and thereby synergistically promote astrogliogenesis [ 35].
The top two hub genes (FZD7 and CNIH2) are also enriched in human hippocampus (43) and CNIH2 has been shown to functionally interact with hippocampal AMPA receptor complexes, modulating receptor gating and trafficking (44, 45).
These observations suggested that these proteins are likely to functionally interact with three sub-networks of the SOS system that are dependent on different mutagenic polymerases and in some cases also with the end-joining repair system dependent on the Ku and the ATP-dependent ligase, along with additional partners such as the above Zn-chelating domains (Network in Figure 1).
The transcription factors Stat3 and FoxO1 (Figure S4A) are involved in the regulation of POMC gene expression, and both were shown to functionally interact with Sirt1 [29], [29].
