SEA-PHAGES | Pham 37120

Link to this post \| posted 25 Apr, 2018 18:07
balish	There are some genes/proteins out there that have two or more completely different annotations depending on which phage you’re in, undoubtedly resulting from propagation of errors. I don’t want to continue to propagate those errors. Pham 37120 proteins (from M. smeg phages) are sometimes annotated as "tail protein" and sometimes as "terminase, small subunit." Interestingly, they have very significant BLAST hits to genes in the chromosomes of many Actinobacteria, and they don’t match any gene annotated as either a terminase or a tail protein from any phages other than the ones from within the SEA-PHAGES program. Taken together, the features of this gene don’t strike me as being consistent with either ascribed function, although anything is possible. It seems to me that it’s a gene that was picked up from a host a long time ago and has been carried around ever since. It's also closely related to genes in other Phams, like 37118, so it's even more widespread than it appears simply based on the number of genes in the Pham. So what is the function of this protein? What's the correct annotation? I’m copying the amino acid sequence from Magnar’s Pham 37120 protein. MGTRGPIPNRSDERVRRNKEEYGEVTTLPVSGPVKSPPLGLTDPHPIVRDLYNSLAESAQAALYQPSDWSYAKFTLHFADQLLKKSDPSAMMLATVNQMLSSLLVSEGDRRRVRIEVERTKSDGPDASVTTMGELFERALRKPKSS Best, Mitch Edited 25 Apr, 2018 18:08

Link to this post | posted 25 Apr, 2018 18:07

There are some genes/proteins out there that have two or more completely different annotations depending on which phage you’re in, undoubtedly resulting from propagation of errors. I don’t want to continue to propagate those errors.

Pham 37120 proteins (from M. smeg phages) are sometimes annotated as "tail protein" and sometimes as "terminase, small subunit." Interestingly, they have very significant BLAST hits to genes in the chromosomes of many Actinobacteria, and they don’t match any gene annotated as either a terminase or a tail protein from any phages other than the ones from within the SEA-PHAGES program. Taken together, the features of this gene don’t strike me as being consistent with either ascribed function, although anything is possible. It seems to me that it’s a gene that was picked up from a host a long time ago and has been carried around ever since. It's also closely related to genes in other Phams, like 37118, so it's even more widespread than it appears simply based on the number of genes in the Pham.

So what is the function of this protein? What's the correct annotation? I’m copying the amino acid sequence from Magnar’s Pham 37120 protein.

MGTRGPIPNRSDERVRRNKEEYGEVTTLPVSGPVKSPPLGLTDPHPIVRDLYNSLAESAQAALYQPSDWSYAKFTLHFADQLLKKSDPSAMMLATVNQMLSSLLVSEGDRRRVRIEVERTKSDGPDASVTTMGELFERALRKPKSS

Best,
Mitch

Edited 25 Apr, 2018 18:08

Link to this post \| posted 26 Apr, 2018 16:00
cdshaffer	An HHpred search shows weak evidence for a terminase with matches of 95% (e .11) to COG3747; Phage terminase, small subunit, and to PF05119 Terminase_4 Phage terminase, small subunit 94% (e .24). The issue here is you won't find those if you use the default PDB database, you have to add the other databases before you do the search. See this page for the list of databases: https://seaphagesbioinformatics.helpdocsonline.com/article-19 I would say the evidence is pretty weak on its own but if you look at this page: https://seaphagesbioinformatics.helpdocsonline.com/article-91 you will see that at least one but no more than two terminase proteins must be present somewhere in your phage's genome. So annotation of this gene probably depends on if you have better evidence that some other gene or genes have stronger support for being a terminase, in which case one would probably argue that this protein is, as you suggest, a distant relative of a terminase but is not THE terminase. On the other hand if no other protein in the genome has even a hint of being a terminase then I think that combining the expectation that there must be a terminase somewhere with the hhpred hits is strong enough to justify the terminase annotation.

Link to this post | posted 26 Apr, 2018 16:00

cdshaffer

An HHpred search shows weak evidence for a terminase with matches of 95% (e .11) to COG3747; Phage terminase, small subunit, and to PF05119 Terminase_4 Phage terminase, small subunit 94% (e .24). The issue here is you won't find those if you use the default PDB database, you have to add the other databases before you do the search. See this page for the list of databases:

https://seaphagesbioinformatics.helpdocsonline.com/article-19

I would say the evidence is pretty weak on its own but if you look at this page:

https://seaphagesbioinformatics.helpdocsonline.com/article-91

you will see that at least one but no more than two terminase proteins must be present somewhere in your phage's genome. So annotation of this gene probably depends on if you have better evidence that some other gene or genes have stronger support for being a terminase, in which case one would probably argue that this protein is, as you suggest, a distant relative of a terminase but is not THE terminase. On the other hand if no other protein in the genome has even a hint of being a terminase then I think that combining the expectation that there must be a terminase somewhere with the hhpred hits is strong enough to justify the terminase annotation.

Link to this post \| posted 26 Apr, 2018 16:04
balish	Thanks, that's very helpful!

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Pham 37120