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Updated: Jun 24, 2025

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
C2H2 proteins: Evolutionary aspects of domain architecture and diversification
Artem N Bonchuk1,2, Pavel G Georgiev1
1Department of the Control of Genetic Processes, Institute of Gene Biology Russian Academy of Sciences, Moscow, Russia.
Abstract:
The largest group of transcription factors in higher eukaryotes are C2H2 proteins, which contain C2H2-type zinc finger domains that specifically bind to DNA. Few well-studied C2H2 proteins, however, demonstrate their key role in the control of gene expression and chromosome architecture. Here we review the features of the domain architecture of C2H2 proteins and the likely origin of C2H2 zinc fingers. A comprehensive investigation of proteomes for the presence of proteins with multiple clustered C2H2 domains has revealed a key difference between groups of organisms. Unlike plants, transcription factors in metazoans contain clusters of C2H2 domains typically separated by a linker with the TGEKP consensus sequence. The average size of C2H2 clusters varies substantially, even between genomes of higher metazoans, and with a tendency to increase in combination with SCAN, and especially KRAB domains, reflecting the increasing complexity of gene regulatory networks.
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