Check Conservation of a Given Protein Domain

Question

[DVA]

Hello,

I am interested in a small domain of a well studied and well defined protein (Huntingtin), and would like to see how conserved this domain is across species. In particular, I would like to address two questions in a scientific (publishable) way:

How well conserved across species is this domain relative to the rest of the protein and relative to other proteins in general?

How far can I go from humans (evolutionary speaking) and find that this domain is still very similar (say >90% sequence identity) to what is found in humans?

Sorry if this is unclear, or has already been addressed. I tried to search for questions that addressed these issues but could not find anything. I have tried BLASTing the protein sequence, but that just gets me close relatives (e.g. chimps) that are almost identical. I am actually more interested in distant relatives. Any helpful program(s) or methods would be greatly appreciated.

Thanks a lot in advance for your help.

[GenoMax]

Have you looked at this page at NCBI: https://www.ncbi.nlm.nih.gov/cdd/?term=Huntingtin

Answer 1

[Bill Pearson]

If the region you are interested in is the 40 amino-acid huntington domain linked above, then you can answer your question by going to Pfam pfam.xfam.org) and looking up DUF3652 (or PF12372). That page has a link to the evolutionary tree for the domain [1]. If you are looking for a different region of the protein, then you might try using PSI-BLAST or JACKHMMER with the specific domain that you are interested in, to build a more sensitive model. The huntington domain is very short (40 aa), so it will be difficult to find very distant relatives, because there relatively little signal (because of the length). The Pfam domain set is probably the best you can do.