SEA-PHAGES | FIC family protein

Link to this post \| posted 12 Nov, 2017 15:56
beckiebortz	Kiko_draft_36 BLAST data (attached) shows strong hits to FIC family protein in many bacteria. HHpred also hits FIC protein/domain as well as many other things (attached). What do you think is the appropriate functional call? I have also attached the product sequence if you want to take it to HHpred yourself to see the full data. Edited 12 Nov, 2017 15:57 480Kb 240Kb 11Kb

Link to this post \| posted 15 Jan, 2018 04:20
dbolliva	Beckie, I think the big question to ask is what does it mean to be an FIC protein. When I did a quick search I found that these proteins contain a domain that is HPFXXGNG and indeed your protein has this conserved domain. What I also found was that this family of proteins has a member called DOC that stands for death on curing and somehow leads to cell death if the P1 prophage is lost. In this case the lysogen is carried as a plasmid and can be lost during cell division but if cells lose the plasmid lysogen they die. This seems like a really cool and possible function for your protein. Hopefully Welkin will look at this and make a decision. Best, Dave

Link to this post | posted 15 Jan, 2018 04:20

dbolliva

Beckie,

I think the big question to ask is what does it mean to be an FIC protein. When I did a quick search I found that these proteins contain a domain that is HPFXXGNG and indeed your protein has this conserved domain. What I also found was that this family of proteins has a member called DOC that stands for death on curing and somehow leads to cell death if the P1 prophage is lost. In this case the lysogen is carried as a plasmid and can be lost during cell division but if cells lose the plasmid lysogen they die. This seems like a really cool and possible function for your protein.

Hopefully Welkin will look at this and make a decision.

Best,

Dave

Link to this post \| posted 08 Jan, 2019 19:23
welkin	Hi All, BAsed on this paper, https://onlinelibrary.wiley.com/doi/full/10.1002/prot.22338 I think we are not going to add "FIC" to the list. As Dave said, FIC proteins are now identified just by a single short sequence, and can do all sorts of things. This means that we will not be adding this as a function at this time.

Link to this post \| posted 21 Mar, 2019 15:13
cdherren	We also have a Fic/DOC family hit in EnalisNailo_33. It's being annotated by others as NKF, helix turn helix DNA binding domain, DNA binding protein, DNA primase/helicase, and capsid maturation protease. The only non-phage hits are Fic/DOC in HHPred and a really low hit in CDD. Our's is 100% prob., 85.5% coverage, e-36 in HHPred. Kiko_36 ultimately went with NKF, but pollux submitted to NCBI as helix-turn-helix DNA binding domain protein. Is there a consensus on the function? I'm leaning towards NKF right now. 26Kb

Link to this post | posted 21 Mar, 2019 15:13

cdherren

We also have a Fic/DOC family hit in EnalisNailo_33.

It's being annotated by others as NKF, helix turn helix DNA binding domain, DNA binding protein, DNA primase/helicase, and capsid maturation protease.

The only non-phage hits are Fic/DOC in HHPred and a really low hit in CDD. Our's is 100% prob., 85.5% coverage, e-36 in HHPred.

Kiko_36 ultimately went with NKF, but pollux submitted to NCBI as helix-turn-helix DNA binding domain protein. Is there a consensus on the function? I'm leaning towards NKF right now.

Link to this post \| posted 21 Mar, 2019 15:47
cdshaffer	To me annotations like helix-turn-helix DNA binding domain should be added only if there is sufficient evidence that the protein really does have a domain of that type AND, more importantly, there is not a more specific approved term that is also supported by the evidence. For example many (if not all??) sigma factors contain HTH domains but "sigma factor" so either term would apply. However sigma factor is a much better annotation than HTH binding domain protein since it is a more specific term. So you have to look at the evidence with an eye toward the validity of "sigma factor" vs "HTH domain", this is why each match should be evaluated with respect to the size and location of the exact match with respect to the whole proteins. Full length alignments are much better than short little domain matches, but if all you have is a short high quality match to an HTH domain then I would add it. I think for short domain matches I would also focus on the HHPRED results. A "helix-turn-helix domain" is really annotating the presence of a structural domain so I would want to focus on the programs that are trying to find similarity at the structural level (HHPRED, Phyre2 etc), not the primary amino acid level (i.e. BLASTP) In this particular case since FIC has been rejected as a term, there is no better approved term that HTH domain. Thus, I would just evaluate the evidence from hhpred as to the question do I really have a HTH domain and add it if I felt the evidence justified it.

Link to this post | posted 21 Mar, 2019 15:47

cdshaffer

To me annotations like helix-turn-helix DNA binding domain should be added only if there is sufficient evidence that the protein really does have a domain of that type AND, more importantly, there is not a more specific approved term that is also supported by the evidence. For example many (if not all??) sigma factors contain HTH domains but "sigma factor" so either term would apply. However sigma factor is a much better annotation than HTH binding domain protein since it is a more specific term. So you have to look at the evidence with an eye toward the validity of "sigma factor" vs "HTH domain", this is why each match should be evaluated with respect to the size and location of the exact match with respect to the whole proteins. Full length alignments are much better than short little domain matches, but if all you have is a short high quality match to an HTH domain then I would add it. I think for short domain matches I would also focus on the HHPRED results. A "helix-turn-helix domain" is really annotating the presence of a structural domain so I would want to focus on the programs that are trying to find similarity at the structural level (HHPRED, Phyre2 etc), not the primary amino acid level (i.e. BLASTP)

In this particular case since FIC has been rejected as a term, there is no better approved term that HTH domain. Thus, I would just evaluate the evidence from hhpred as to the question do I really have a HTH domain and add it if I felt the evidence justified it.

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FIC family protein