Protein Domain Characterization: Conflicting results from Interpro
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11 months ago
venura ▴ 70

Hi,

When I was trying to characterize a set of proteins using Interpro, I came across the following scenario. One of the proteins there is a Leucine zipper domain (SSF57959 : Superfamily database). However, it was not recognized by PFAM or other databases. Also, bZIP related IPR004827 (interpro ID) was also not recognized there. I was using the presence of IPR004827 as a filtering step for bZIPs. My question is, can I identify this specific gene as a bZIP transcription factor, or do I need to exclude it? Thanks in advance!

interpro PFAM • 280 views
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11 months ago
Mensur Dlakic ★ 13k

Various databases of protein families are redundant to a good degree, but not completely. Otherwise, what would be the point of having so many databases if all of them were reporting identical results? This is to say that it is normal here and there to have a domain identified using models from one of the databases but not the others. Without knowing the details of your study or your goals, I would not exclude this protein jusb because it is not identified by IPR004827.

It is for practical purposes impossible to have a single model (in your case IPR004827) that will identify all proteins belonging to a diverse protein (super)family such as bZIP proteins. They are not easy to identify because the zipper part has a strong signal only once in 7 residues, and the rest of it is fairly degenerate. Add a basic DNA-binding region that can also be different (e.g., between AP-1 and Maf proteins), and that makes it very difficult to identify with a single model.

My advice to you is to use multiple bZIP models from different databases, as each of them will be better at identifying a subset of bZIP proteins. As a separate check, you can validate the presence of coiled coils in these proteins using a variety of resources, some of which I list below.

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Thank you Dr. Dlakic. I will use the approach you suggested.

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