The Simple Modular Architecture Research Tool (SMART) is an online resource for protein domain identification and analysis. It has been updated with new features to improve accessibility for scientists across various fields. A new 'Genomic' mode allows easy analysis of domain architectures in completely sequenced genomes. Domain annotation now includes detailed taxonomic breakdowns and predictions of catalytic activity for 50 SMART domains based on essential amino acids. Intrinsically disordered protein regions can also be identified and displayed. The network context is now displayed for over 350,000 proteins, enabling analysis of domain interactions. SMART's database contains high-quality manually derived alignments of protein domain families. These allow identification of protein domains in sequence databases. The database provides a framework for understanding the evolution and function of genes and proteins. New genome views have been developed to better integrate with genome data, allowing cross-referencing with protein-protein interaction maps. To reduce redundancy, SMART now includes only proteins from 170 completely sequenced genomes. This database has minimal redundancy and is particularly useful for whole genome studies of domain architectures. Catalytic activity prediction has been improved by annotating essential catalytic sites for all enzymatic domains. This allows for the identification of inactive enzyme homologs. SMART now predicts the taxonomic class where a protein's domain architecture was invented. This helps infer the distribution and presence of these architectures in not yet or incompletely sequenced genomes. The latest version of SMART provides information about putative interaction partners for over 350,000 proteins, integrated from the STRING database. This information includes physical binding interactions and functional associations. New database features include a relational database management system that stores information on SMART domains. The database now includes information on domain presence in all proteins, with added data on catalytic activity for 50 domains. Domain architecture analysis results include this information, with domains missing essential amino acids marked as 'inactive'. New analysis methods include predictions of intrinsic protein disorder from DisEMBL. The user interface has been completely rewritten to comply with web standards, improving speed and features. Taxonomic trees have been introduced to group domain architecture query results and show detailed taxonomic distribution of domains. These improvements make SMART an invaluable tool for systems biologists to interpret pathways and networks.The Simple Modular Architecture Research Tool (SMART) is an online resource for protein domain identification and analysis. It has been updated with new features to improve accessibility for scientists across various fields. A new 'Genomic' mode allows easy analysis of domain architectures in completely sequenced genomes. Domain annotation now includes detailed taxonomic breakdowns and predictions of catalytic activity for 50 SMART domains based on essential amino acids. Intrinsically disordered protein regions can also be identified and displayed. The network context is now displayed for over 350,000 proteins, enabling analysis of domain interactions. SMART's database contains high-quality manually derived alignments of protein domain families. These allow identification of protein domains in sequence databases. The database provides a framework for understanding the evolution and function of genes and proteins. New genome views have been developed to better integrate with genome data, allowing cross-referencing with protein-protein interaction maps. To reduce redundancy, SMART now includes only proteins from 170 completely sequenced genomes. This database has minimal redundancy and is particularly useful for whole genome studies of domain architectures. Catalytic activity prediction has been improved by annotating essential catalytic sites for all enzymatic domains. This allows for the identification of inactive enzyme homologs. SMART now predicts the taxonomic class where a protein's domain architecture was invented. This helps infer the distribution and presence of these architectures in not yet or incompletely sequenced genomes. The latest version of SMART provides information about putative interaction partners for over 350,000 proteins, integrated from the STRING database. This information includes physical binding interactions and functional associations. New database features include a relational database management system that stores information on SMART domains. The database now includes information on domain presence in all proteins, with added data on catalytic activity for 50 domains. Domain architecture analysis results include this information, with domains missing essential amino acids marked as 'inactive'. New analysis methods include predictions of intrinsic protein disorder from DisEMBL. The user interface has been completely rewritten to comply with web standards, improving speed and features. Taxonomic trees have been introduced to group domain architecture query results and show detailed taxonomic distribution of domains. These improvements make SMART an invaluable tool for systems biologists to interpret pathways and networks.