SMART
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"Accurate multiple alignments of 86 domains that occur in signalling proteins have been constructed and used to provide a WEB-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signalling domain sequences.
The majority of signalling proteins are multidomain with a considerable variety of domain combinations known.
Comparison with established collections of domain patterns and alignments showed that 25% of our domain set could not be deduced from sequence database entries and 41% could not be annotated by Pfam
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SMART can determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signalling domains, approximately 350 greater than previously annotated.
can determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signalling domains, approximately 350 greater than previously annotated.
The process of constructing the search tool predicted:
- additional homologues of previously-described domains in unexpected locations such as a band 4.1-homologous domain in focal adhesion kinase;
- previously-unknown domain families including a "CNH" or citron-homology domain and a domain preceding rasGEF-like guanine nucleotide exchange factor regions;
- candidate functions of domain families following identification of additional family members, for example, a ubiquitin-binding role for the UBA domain;
- cellular roles for proteins, such as the detection of a DEATH domain in netrin receptors further implicating these molecules in axonal guidance;
- signalling domains in known disease genes such as a SPRY domain in marenostrin/pyrin that is mutated in patients with Mediterranean fever;
- domains in unexpected phylogenetic contexts such as DAG kinase homologues in yeast and bacteria;
- likely misclassifications of proteins exemplified by the presence of a pleckstrin homology signalling domain in a C. albicans protein, previously described as an integrin."
References