Domain of unknown function (DUFs) form a substantial part of protein domain databases like pfam (about 3,500 DUF families). Many of the DUFs are shared across bacteria, archaea and eukaryota kingdom. Yet, they have not been characterized. What could be the reason? Any insights on them will be helpful.
Because it is very difficult to figure out the function of something if you have no hint where to start looking. If the knockout of the corresponding gene does not result in an easily detectable phenotype, the possibility space is usually just to big to explore. Even if you know that the DUF is, for example, somehow involved in the utilization of a carbon-containing compound, there are simply too many to test them all.
Thought experiment: How would someone who has never seen snow and ski before figure out the function of a pair of skis, especially if they come without the shoes to fit in the binding (the co-factor in this scenario)? He might conclude that they are meant for some kind of movement, but that is likely the end of it.
Because very often the proteins containing a DUF are not essential and become important only under specific conditions, which makes the screening for a phenotype even more fun.
Not essential or we don't know their precise function, so decide to ignore them, as we do with the hypothetical proteins.
We certainly do not now their precise function (yet) and some of them are not essential, too. I do not see a conflict here.
And I think people are realizing the potential of novel structure + function hidden in DUFs, but is a bit harder to start with these proteins.
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