SWISS-PROT and TrEMBL are protein knowledgebases that provide high-quality annotations of protein sequences. SWISS-PROT contains manually annotated entries for all species, with a focus on human and model organisms. TrEMBL complements SWISS-PROT by including sequences not yet in SWISS-PROT, with mostly automated annotations. Both databases are integrated with other specialized databases, allowing users to access detailed information on protein functions, structures, and modifications. SWISS-PROT uses standardized nomenclature and controlled vocabularies to ensure consistency and facilitate searches. It minimizes redundancy by merging data from different sources and includes detailed annotations on protein features such as function, domain, post-translational modifications, and subcellular localization. TrEMBL provides a computer-annotated supplement to SWISS-PROT, including sequences from literature and user submissions. The Human Proteomics Initiative (HPI) focuses on annotating all known human protein sequences and their orthologs, emphasizing proteins involved in generating protein diversity. HPI includes annotations for post-translational modifications (PTMs), splice variants, and single nucleotide polymorphisms (SNPs). The International Protein Index (IPI) serves as a guide to major human proteome databases, providing cross-references to ensure minimal redundancy. The HAMAP project automatically annotates microbial proteins, maintaining high-quality standards. It includes rules for protein families and subfamilies, and has annotated over 36,000 proteins. Model organisms such as Arabidopsis thaliana, Caenorhabditis elegans, and Saccharomyces cerevisiae are prioritized for annotation. The Plant Proteome Annotation Project (PPAP) focuses on plant-specific protein families. The New Taxonomy database (NEWT) provides taxonomic information for species in SWISS-PROT and TrEMBL. Cross-references and unique feature identifiers (FTIds) allow precise linking to specific annotations. SWISS-PROT and TrEMBL are available via FTP and web servers, with documentation and tools for sequence retrieval and analysis. They are maintained as flat files but are being transitioned to a relational database system with XML-based formats. Submission of new data is possible via email or web forms. Academic users have free access, while commercial users are charged annual subscription fees. The databases are continuously updated to reflect new findings and improve annotation quality.SWISS-PROT and TrEMBL are protein knowledgebases that provide high-quality annotations of protein sequences. SWISS-PROT contains manually annotated entries for all species, with a focus on human and model organisms. TrEMBL complements SWISS-PROT by including sequences not yet in SWISS-PROT, with mostly automated annotations. Both databases are integrated with other specialized databases, allowing users to access detailed information on protein functions, structures, and modifications. SWISS-PROT uses standardized nomenclature and controlled vocabularies to ensure consistency and facilitate searches. It minimizes redundancy by merging data from different sources and includes detailed annotations on protein features such as function, domain, post-translational modifications, and subcellular localization. TrEMBL provides a computer-annotated supplement to SWISS-PROT, including sequences from literature and user submissions. The Human Proteomics Initiative (HPI) focuses on annotating all known human protein sequences and their orthologs, emphasizing proteins involved in generating protein diversity. HPI includes annotations for post-translational modifications (PTMs), splice variants, and single nucleotide polymorphisms (SNPs). The International Protein Index (IPI) serves as a guide to major human proteome databases, providing cross-references to ensure minimal redundancy. The HAMAP project automatically annotates microbial proteins, maintaining high-quality standards. It includes rules for protein families and subfamilies, and has annotated over 36,000 proteins. Model organisms such as Arabidopsis thaliana, Caenorhabditis elegans, and Saccharomyces cerevisiae are prioritized for annotation. The Plant Proteome Annotation Project (PPAP) focuses on plant-specific protein families. The New Taxonomy database (NEWT) provides taxonomic information for species in SWISS-PROT and TrEMBL. Cross-references and unique feature identifiers (FTIds) allow precise linking to specific annotations. SWISS-PROT and TrEMBL are available via FTP and web servers, with documentation and tools for sequence retrieval and analysis. They are maintained as flat files but are being transitioned to a relational database system with XML-based formats. Submission of new data is possible via email or web forms. Academic users have free access, while commercial users are charged annual subscription fees. The databases are continuously updated to reflect new findings and improve annotation quality.