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Updated: Mar 6, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
Calcium dependent regulation of protein ubiquitination - Interplay between E3 ligases and calcium binding proteins
Rukmini Mukherjee1, Aneesha Das2, Saikat Chakrabarti2
1Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
Abstract:
The ubiquitination status of proteins and intracellular calcium levels are two factors which keep changing inside any living cell. These two events appear to be independent of each other but recent experimental evidences show that ubiquitination of cellular proteins are influenced by calcium, Calmodulin, Calmodulin-dependent kinase II and other proteins of calcium dependent pathways. E3 ligases like Nedd4, SCF complex, APC, GP78 and ITCH are important regulators of calcium mediated processes. A bioinformatics analysis to inspect sequences and interacting partners of 242 candidate E3 ligases show the presence of calcium and/or Calmodulin binding motifs/domains within their sequences. Building a protein-protein interaction (PPI) network of human E3 ligase proteins identifies Ca2+ related proteins as direct interacting partners of E3 ligases. Review of literature, analysis of E3 ligase sequences and their interactome suggests an interconnectivity between calcium signaling and the overall UPS system, especially emphasizing that a subset of E3 ligases have importance in physiological pathways modulated by calcium.
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