SEA-PHAGES | justbecause 252 @ 149782 "ADP-ribosyltransferase"

Link to this post \| posted 03 Jul, 2018 19:54
cdshaffer	Phage Justbecuase (cluster BM, available on pecaan) gene 252 starting at 149782 has a more than 50 HHPRED hits all with >99% probability and 85%-95% coverage with a variety of descriptions. Examples include "RNase III inhibitor", "Appr-1-p processing domain", "O-acetyl-ADP-ribose deacetylase", and most commonly something about "Macrodomain protein". It turns out there is a large body of literature on "macrodomain" proteins which have been shown to be involved in a wide variety of biological functions across all kingdoms (this wikipedia article is pretty good at summarizing). Interestingly, one of the well characterized prokaryotic uses of this domain has been shown to be involved a toxin/antitoxin system that use UDP-riboylation of DNA. This domain was found and annotated previously in phage Trina gene 253. Here full annotation in the genbank file is "ADP ribose-1-P processing protein, antitoxin" while phagesdb appears to drop the last part and just has "ADP ribose-1-P processing protein". Looking over quite a few of the published structures and enzymatic functions of many of the HHPREd hits, the common thread appears to be enzymes that break/create bonds between an ADP-ribose moiety and something else, be that a protein (see the PARPS), a nucleic acid (as in the DART/G toxin anti-toxin), a phosphate group (in the APPR1-p processing proteins), nicotinamide (see the NAD(+) ADP-ribosyltransferases) , or an acetyl group (see the O-acetyl-ADP-ribose deacetylases). I really don't like the generic term "macro domain" even though most of the literature uses that term. Instead I would propose the term "ADP-ribosyltransferase" which I think does a good job of summarizing all the different activities that have been associated with various macrodomain proteins. While the toxin/antitoxin angle is intriguing I am not sure there is sufficient evidence to support including this biological role as part of the annotation without supporting evidence from something other than HHPRED or BLAST alignments.

Link to this post | posted 03 Jul, 2018 19:54

Phage Justbecuase (cluster BM, available on pecaan) gene 252 starting at 149782 has a more than 50 HHPRED hits all with >99% probability and 85%-95% coverage with a variety of descriptions. Examples include "RNase III inhibitor", "Appr-1-p processing domain", "O-acetyl-ADP-ribose deacetylase", and most commonly something about "Macrodomain protein".

It turns out there is a large body of literature on "macrodomain" proteins which have been shown to be involved in a wide variety of biological functions across all kingdoms (this wikipedia article is pretty good at summarizing).

Interestingly, one of the well characterized prokaryotic uses of this domain has been shown to be involved a toxin/antitoxin system that use UDP-riboylation of DNA.

This domain was found and annotated previously in phage Trina gene 253. Here full annotation in the genbank file is "ADP ribose-1-P processing protein, antitoxin" while phagesdb appears to drop the last part and just has "ADP ribose-1-P processing protein".

Looking over quite a few of the published structures and enzymatic functions of many of the HHPREd hits, the common thread appears to be enzymes that break/create bonds between an ADP-ribose moiety and something else, be that a protein (see the PARPS), a nucleic acid (as in the DART/G toxin anti-toxin), a phosphate group (in the APPR1-p processing proteins), nicotinamide (see the NAD(+) ADP-ribosyltransferases) , or an acetyl group (see the O-acetyl-ADP-ribose deacetylases).

I really don't like the generic term "macro domain" even though most of the literature uses that term. Instead I would propose the term "ADP-ribosyltransferase" which I think does a good job of summarizing all the different activities that have been associated with various macrodomain proteins. While the toxin/antitoxin angle is intriguing I am not sure there is sufficient evidence to support including this biological role as part of the annotation without supporting evidence from something other than HHPRED or BLAST alignments.

Link to this post \| posted 05 Jul, 2018 20:13
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justbecause 252 @ 149782 "ADP-ribosyltransferase"