Since 2002 a merger and collaboration of three databases:

Swiss-Prot & TrEMBL PIR-PSD

Funded mainly by NIH (US) to be the highest quality, most thoroughly annotated protein sequence database o A high quality protein sequence database A non redundant protein database, with maximal coverage including splice isoforms, disease variant and PTMs. Sequence archiving essential. o Easy protein identification Stable identifiers and consistent nomenclature/controlled vocabularies o Thorough protein annotation Detailed information on protein function, biological processes, molecular interactions and pathways cross-referenced to external source

UniProtKB/TrEMBL UniProtKB/Swiss-Prot 1 entry per nucleotide submission 1 entry per protein

Redundant, automatically Non-redundant, high-quality manual annotated - unreviewed annotation - reviewed UniProt/TrEMBL

Sub/ ENA (EMBL) DNA database PDB Peptide Ensembl Data

VEGA mRNA Patent FlyBase WormBase (Sanger) Data Data

6 02.06.2014 Manual annotation of UniProtKB/Swiss-Prot

Splice variants

Sequence Sequence features

UniProtKB Ontologies Annotations

Nomenclature References www.uniprot.org Beta.uniprot.org Sequence curation, stable identifiers, versioning and archiving

For example – erroneous gene model predictions, frameshifts….

..premature stop codons, read-throughs, erroneous initiator methionines…..

Master headline Splice isoforms Identification of amino acid variants

..and of PTMs

… and also

Master headline Sequence annotation

Master headline Protein nomenclature

Master headline Master headline Controlled vocabularies used whenever possible…

Master headline Annotation comments

FUNCTION PTM SUBCELLULAR LOCATION RNA EDITING ALTERNATIVE PRODUCTS MASS SPECTROMETRY TISSUE SPECIFICITY DOMAIN DEVELOPMENTAL STAGE POLYMORPHISM INDUCTION DISRUPTION PHENOTYPE SIMILARITY ALLERGEN CATALYTIC ACTIVITY DISEASE COFACTOR TOXIC DOSE ENZYME REGULATION BIOTECHNOLOGY BIOPHYSICOCHEMICAL- PHARMACEUTICAL PROPERTIES MISCELLANEOUS PATHWAY CAUTION SUBUNIT SEQUENCE CAUTION INTERACTION WEB RESOURCE Automatic Annotation for UniProtKB/TrEMBL • UniProtKB/Swiss-Prot – manually curated proteins, capturing information available in the literature (~545,000 entries) • UniProtKB/Trembl – automated annotation only (~56,000,000 entries)

Most proteins we now know the sequence of have not been biochemically profiled in any laboratory – and probably never will • InterPro - a database which integrates predictive information about proteins' function from partner resources, giving an overview of the families that a protein belongs to and the domains and sites it contains. • Users who have novel nucleotide or protein sequences to functionally characterise can use the software package InterProScan to run the scanning algorithms from the InterPro database Master headline

Automatic Annotation o UniProtKB employs two prediction programs which are referred to as UniRule and SAAS.

SAAS, Statistical UniRule maintains a Automatic Annotation set of manually System, generates a established and new set of decision-trees maintained annotation with every UniProtKB rules. release using data- mining.

Swiss-Prot InterPro Master headline Proteomes

Definition: The complete proteome of an organism is all the proteins expressed by that organism Two types of Proteomes

Complete proteomes Complete sets of proteins thought to be expressed by organisms whose genomes have been completely sequenced.

Reference proteomes Some complete proteomes have been selected as reference proteome sets. These cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical research. Requirements for Complete Proteomes

• Completely sequenced genome

• Good gene prediction models

• Proteins are mapped to genome

• Good quality transcriptome/proteome data

Obtaining Proteomes

• Stuck? Just ask – active help and support team

• Feedback – if you find something incorrect, outdated, missing etc please tell us.

[email protected] Thanks for your attention