Vol. 95, pp. 5857–5864, May 1998 | JORG SCHULTZ*,†, FRANK MILPETZ*,†, PEER BORK**,†,‡, AND CHRIS P. PONTING§
The paper introduces SMART (Simple Modular Architecture Research Tool), a web-based tool designed for rapid identification and annotation of signaling domain sequences in proteins. SMART constructs multiple alignments of 86 signaling domains and uses these to predict the modular architectures of single sequences or genomes. The tool has been applied to the entire yeast genome, revealing that at least 6.7% of its genes contain one or more signaling domains, which is significantly higher than previously annotated. SMART has identified novel domain homologues, previously unknown domain families, and putative functions for domain families. It has also detected signaling domains in disease genes and in unexpected phylogenetic contexts. The tool's ability to facilitate predictions of protein structures and functions is demonstrated through several examples, including the identification of a phosphotyrosine binding domain in tensin and a DEP domain in ROM1 and ROM2. SMART's sensitivity and specificity are compared with those of other databases, showing its advantages in signaling domain detection. The paper discusses the importance of domain-level annotation for understanding multidomain proteins and the potential of SMART for large-scale genome analysis.The paper introduces SMART (Simple Modular Architecture Research Tool), a web-based tool designed for rapid identification and annotation of signaling domain sequences in proteins. SMART constructs multiple alignments of 86 signaling domains and uses these to predict the modular architectures of single sequences or genomes. The tool has been applied to the entire yeast genome, revealing that at least 6.7% of its genes contain one or more signaling domains, which is significantly higher than previously annotated. SMART has identified novel domain homologues, previously unknown domain families, and putative functions for domain families. It has also detected signaling domains in disease genes and in unexpected phylogenetic contexts. The tool's ability to facilitate predictions of protein structures and functions is demonstrated through several examples, including the identification of a phosphotyrosine binding domain in tensin and a DEP domain in ROM1 and ROM2. SMART's sensitivity and specificity are compared with those of other databases, showing its advantages in signaling domain detection. The paper discusses the importance of domain-level annotation for understanding multidomain proteins and the potential of SMART for large-scale genome analysis.