SMART (Simple Modular Architecture Research Tool) is a web-based tool designed to identify and annotate genetically mobile domains and analyze domain architectures. It covers over 400 domain families found in signaling, extracellular, and chromatin-associated proteins, with extensive annotations on phylogenetic distributions, functional classes, tertiary structures, and functionally important residues. The tool uses a relational database system to store information on domain hits, including boundaries, bit scores, E-values, protein accession codes, descriptions, sequence lengths, and taxonomic information. SMART employs hidden Markov models (HMMs) for improved domain detection and sensitivity. The tool offers various web interfaces for querying domain architectures, including specific taxonomic groups, and provides features like Architecture SMART and Alert SMART for advanced searches and notifications. SMART also integrates predictions of intrinsic features such as signal sequences, transmembrane helices, coiled-coil regions, and GPI anchors. Future work will focus on expanding the types of mobile domains detected and improving functional predictions within single families.SMART (Simple Modular Architecture Research Tool) is a web-based tool designed to identify and annotate genetically mobile domains and analyze domain architectures. It covers over 400 domain families found in signaling, extracellular, and chromatin-associated proteins, with extensive annotations on phylogenetic distributions, functional classes, tertiary structures, and functionally important residues. The tool uses a relational database system to store information on domain hits, including boundaries, bit scores, E-values, protein accession codes, descriptions, sequence lengths, and taxonomic information. SMART employs hidden Markov models (HMMs) for improved domain detection and sensitivity. The tool offers various web interfaces for querying domain architectures, including specific taxonomic groups, and provides features like Architecture SMART and Alert SMART for advanced searches and notifications. SMART also integrates predictions of intrinsic features such as signal sequences, transmembrane helices, coiled-coil regions, and GPI anchors. Future work will focus on expanding the types of mobile domains detected and improving functional predictions within single families.