MultifacetedProtDB

MultifacetedProtDB provides an integrated, manually curated database of multifunctional human proteins aggregating annotations, structural data, expression profiles, and disease associations to support analysis of pleiotropy, multidomain architecture, enzymatic promiscuity, and moonlighting activities.

Key Features:

• Manual curation: Entries are manually curated and integrated from primary sources.
• Data sources: Integrates records from UniProt, GeneCards, Human Protein Atlas (HPA), Human Phenotype Ontology (HPO), MONDO, Protein Data Bank (PDB), Reactome, Orphanet, and OMIM.
• Multifunctionality annotation: Identifies and annotates proteins exhibiting pleiotropy, multidomain structures, enzymatic promiscuity, and moonlighting activities that perform two or more molecular functions.
• Functional annotations: Provides Enzyme Commission (EC) numbers and Gene Ontology (GO) terms covering biological processes, molecular functions, and cellular components.
• Pathway mapping: Maps proteins to Reactome pathways.
• Localization and expression: Includes subcellular localization from UniProt and tissue and cell type expression data from HPA.
• Disease associations: Links proteins to disease classifications in MONDO, Orphanet, and OMIM.
• Structural data and interactors: Includes available Protein Data Bank (PDB) structures, structural models, and molecular interactors.
• Retrieval of challenging proteins: Facilitates identification of multifunctional proteins that are difficult to retrieve via non-specific databases.

Scientific Applications:

• Signal transduction and metabolism analysis: Enables analysis of multifunctional proteins involved in signal transduction and metabolic processes.
• Gene regulation and cellular communication studies: Supports investigation of multifunctional roles in gene regulation and cellular communication.
• Disease mechanism and progression research: Facilitates study of protein contributions to disease progression and associations using MONDO, Orphanet, and OMIM links.
• Functional and structural interpretation: Aids interpretation of enzymatic promiscuity and moonlighting functions using EC, GO, and structural evidence from PDB and models.

Methodology:

Manual curation and integration of data from UniProt, GeneCards, HPA, HPO, MONDO, PDB, Reactome, Orphanet, and OMIM with annotations including EC numbers, GO terms, Reactome pathways, UniProt subcellular localization, HPA tissue/cell expression, PDB structures, structural models, and interactors.