this study by Maji et al. is of great interest and will be very useful for the scientific committee working on transcription. So many functions of the Mediator complex are still awaiting discovery and this webtool to search for protein-protein interaction (PPI) with focus on the Mediator complex will be very valuable. In general, despite the interest, I found the manuscript not easy to read, mainly because the authors do not separate the results from the discussion. Major comments/questions are detailed below.
1- The overall clarity of this manuscript can be improved by rewriting and re-organizing the manuscript to split the results from the discussion part. The manuscript is sometimes unnecessarily lengthy and some information are repeated here and there.
2- The weight of the 2 case studies, in my opinion, is disproportionate. The authors might need to relook at this part of the manuscript and include more data for the role of Mediator complex in either functions. As it is now, the conclusions and the significance are debatable.
3- The survey and compilation of the protein-protein interaction can be still improved before the publication of this database. I was surprised that recent datasets from plants are not included. A very few examples below
-For example the paper of He et al published in ‘The Plant Cell’ about MED8 contains a nice dataset obtained using pull down of MED8, belonging to the head module. https://pubmed.ncbi.nlm.nih.gov/33713138/. This dataset can be very useful for the discussion of different observations raised by the authors for example new function of the Mediator complex, interaction of the head module with transcription factors and interaction with other RNA dependent pathways etc etc.
-another example of more direct interactions within plants is the interaction of MED25 and MED8 (again) with FAMA transcription factors in the context of immunity (Plos One paper from 2018 https://pubmed.ncbi.nlm.nih.gov/29513733/)

4- It was not clear for me if analysis of the Mediator orthologs is feasible with this web tool. It will be really valuable if this information is added and if this webtool will also integrate expression data to allow to generate data as in Figure 6B. I know that this is a huge amount of work but I believe it will greatly increase the impact (and the citations) of this manuscript.

The revised work by Maji et al has improved to some extent. However, I believe that the user experience with the interface could be more enjoyable.
1-How can users download the network for a given search and the tables for further use (publication)? Although Mediatorweb is designed to visualize interaction, I was unable to download any of the networks at first glance. It will be also very useful to be able to download an input fil to cytoscape.
2-The dataset published in He et al Plant Cell 2021 contains a useful list of interactions that can be used as 'indirect' interactions according to the criteria set by the authors here. The authors have only added NOT2a because it was validated by CoIP and not all the proteins detected by pull down. I think this dataset should be added as it is relevant and the manuscript should be cited and used for the discussion.
3-Additionally, what is the authors' opinion on the interaction with 'Unknown Mediators' (MED34, MED35, MED36 and MED37)? My search did not yield any results for these.
4-Similarly, what is the author's opinion on interactions with the Mediator complex that occur outside the nucleus in plants, can the authors speculate on pathways that might involve Mediator as a complex or as a subunit?
5-Some part of the discussion are confusing, it seems that the authors draw general conclusions without much data to support these and that the organism is sometimes not mentioned (for example interaction of the Head module with TFs)