MoonProt 4.0: 2026 Update of the Moonlighting Proteins Database

Area of Science:

• Biochemistry
• Molecular Biology
• Bioinformatics

Background:

• Moonlighting proteins possess multiple distinct physiological functions within a single polypeptide chain.
• The MoonProt database provides manually-curated annotations for these multifunctional proteins.
• Previous versions of the database have been reported, with the last update in 2021.

Purpose of the Study:

• To report the expansion and update of the MoonProt database, version 4.0.
• To document the addition of approximately 200 new protein entries, bringing the total to over 700.
• To highlight new categories of proteins included, such as plant proteins and transmembrane proteins.

Main Methods:

• Manual curation of protein annotations by trained undergraduate annotators.
• Expansion of the existing MoonProt database infrastructure.
• Inclusion of diverse protein types and functional combinations.

Main Results:

• The MoonProt database (version 4.0) now contains over 700 manually-curated moonlighting proteins.
• Approximately 200 new entries have been added since the 2021 update.
• The updated database features increased representation of plant proteins, transmembrane proteins, and novel functional combinations.

Conclusions:

• The expanded MoonProt database is a valuable resource for studying proteins with multiple functions.
• It facilitates the development of algorithms for predicting protein functions.
• The database provides insights into protein evolution and aids in the design of novel proteins with engineered functions.