Author:
Graef Isabella A.,Gastier Julie M.,Francke Uta,Crabtree Gerald R.
Abstract
The recent sequencing of several complete genomes has made it
possible to track the evolution of large gene families by their genomic
structure. Following the large-scale association of exons encoding
domains with well defined functions in invertebrates could be useful in
predicting the function of complex multidomain proteins in mammals
produced by accretion of domains. With this objective, we have
determined the genomic structure of the 14 genes in invertebrates and
vertebrates that contain rel domains. The sequence encoding the rel
domain is defined by intronic boundaries and has been recombined with
at least three structurally and functionally distinct genomic sequences
to generate coding sequences for: (i) the
rel/Dorsal/NFκB proteins that are retained in the cytoplasm by
IkB-like proteins; (ii) the NFATc proteins that sense
calcium signals and undergo cytoplasmic-to-nuclear translocation in
response to dephosphorylation by calcineurin; and (iii)
the TonEBP tonicity-responsive proteins. Remarkably, a single exon in
each NFATc family member encodes the entire
Ca2+/calcineurin sensing region, including nuclear
import/export, calcineurin-binding, and substrate regions. The
Rel/Dorsal proteins and the TonEBP proteins are present in
Drosophila but not Caenorhabditis
elegans. On the other hand, the calcium-responsive NFATc
proteins are present only in vertebrates, suggesting that the NFATc
family is dedicated to functions specific to vertebrates such as a
recombinational immune response, cardiovascular development, and
vertebrate-specific aspects of the development and function of the
nervous system.
Publisher
Proceedings of the National Academy of Sciences
Cited by
85 articles.
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