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Updated: Feb 26, 2026

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
Structural and functional diversity of EF-hand proteins: Evolutionary perspectives
Hiroshi Kawasaki1, Robert H Kretsinger2
1Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa, 230-0045, Japan.
We classified 865 EF-hand protein sequences into 156 subfamilies and six groups. Evolutionary analysis revealed EF-lobe positions formed early, with some subfamilies evolving via convergent evolution, not from a common precursor.
Area of Science:
- Biochemistry
- Evolutionary Biology
- Bioinformatics
Background:
- EF-hand proteins are crucial calcium-binding proteins.
- Understanding their evolutionary history is key to deciphering protein function.
- Previous classifications have not fully addressed evolutionary relationships.
Purpose of the Study:
- To classify EF-hand protein sequences and analyze their evolutionary relationships.
- To investigate the origin and evolution of EF-lobe arrangements.
- To identify instances of convergent evolution in EF-hand protein families.
Main Methods:
- Classification of 865 EF-hand protein sequences from five proteomes.
- Phylogenetic analysis using inferred ancestral sequences.
- Comparative analysis of EF-lobe structures and positions.
Main Results:
- 156 subfamilies and six major groups of EF-hand proteins were identified.
- The CTER, CPV, and PEF groups share a common EF-lobe precursor.
- EF-lobe relative positions were established early in evolution, prior to gene duplication/fusion.
- Convergent evolution was identified in some subfamilies with canonical EF-hand conformations but distinct origins.
Conclusions:
- The early establishment of EF-lobe positions shaped protein evolution.
- Convergent evolution plays a significant role in the diversity of EF-hand proteins.
- This study provides a comprehensive evolutionary framework for EF-hand proteins.
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