The His-Me finger endonucleases, also known as
HNH or -metal endonucleases, form a large and
diverse protein superfamily. The His-Me finger domain
can be found in proteins that play an essential
role in cells, including genome maintenance, intron
homing, host defense and target offense. Its overall
structural compactness and non-specificity make
it a perfectly-tailored pathogenic module that participates
on both sides of inter- and intra-organismal
competition. An extremely low sequence similarity
across the superfamily makes it difficult to identify
and classify new His-Me fingers. Using state-of-theart
distant homology detection methods, we provide
an updated and systematic classification of His-Me
finger proteins. In this work, we identified over 100
000 proteins and clustered them into 38 groups, of
which three groups are new and cannot be found in
any existing public domain database of protein families.
Based on an analysis of sequences, structures,
domain architectures, and genomic contexts, we provide
a careful functional annotation of the poorly
characterized members of this superfamily. Our results
may inspire further experimental investigations
that should address the predicted activity and clarify
the potential substrates, to provide more detailed insights
into the fundamental biological roles of these
proteins
