Origin of MultifacetedProtDB.


Databases such as UniProt, NCBI protein, and PDB lack explicit labelling of multifunctional proteins. Recent progresses in research highlight how the number of multifunctional proteins is increasing as well as their involvement in human diseases. To date, three resources collecting data with experimental evidence are available: Moon DB, MoonProt, and MultitaskProtDB II. When restricted to humans, these databases collect 47, 103, and 184 proteins, respectively. Noticeably, the overlap among the three databases is limited (only 15 human proteins) and, when merged, they provide information on 241 human proteins. We generate a new collection, MultifacetedProtDB, deriving from the previous existing databases, from a careful bibliographic search of the last years and from UniProt/SwissProt (Release 2023_03). We focused also on enzymes with multiple EC numbers (SwissProt) and the association of multifunctional proteins to human disease. Our collection is addressed as multifaceted, including moonlight, promiscuous and multifunctional proteins. The number of proteins in MultifacetedProtein DB is 1103, of which 812 are enzymes.

What MultifacetedProtDB offers.


MultifacetedProtDB links directly to GeneCard and to UniProt/Swissprot for functional and structural features, providing access to protein structures from PDB, and AlphaFold models, when available. Furthermore, evidence of protein family classification is provided by InterPro and Pfam. Catalytic reactions and EC numbers, when it is the case, GO terms including biological pathways, molecular functions, and cellular components, and subcellular location are derived from Uniprot. Biological pathways link directly to Reactome. The database enables easy access to protein variants (Uniprot variant viewer) and protein interactions with other partners from Uniprot. Entries in MultifacetedProtDB are associated to diseases, deriving from UniProt, Humsavar, Monarch, and Clinvar. Diseases are categorized according to MONDO, ICD10, Orphanet, and OMIM. Links are provided to HPO phenotypes along with valuable insights into tissue and cell type expression patterns, sourced from the Human Protein Atlas. We also include information, when available, on specific drugs, by linking to GeneCard. Links to quoted literature is preserved and/or included (Publications). We offer an advanced search option with which the user can browse the dataset including up to four conditions, which can be selected from a drop-down menu, and are connected by logical operators (AND, OR, NOT).