ELiAH2: update of the atlas of E3 ligases in human tissues by integrating tissue-specificity and docking properties of ligands for targeted protein degradation
Year: 2026
Type: preprint
Abstract: ABSTRACT Targeted protein degradation (TPD), including proteolysis-targeting chimeras (PROTACs), requires coordinated selection of E3 ligases, target proteins, and ligands to achieve efficient and tissue-selective degradation. However, current TPD resources provide limited support for integrating tissue-specific transcriptomic evidence with structural compatibility during early candidate prioritization. Here, we present ELiAH2, an expanded database for transcriptome- and structure-guided prioritization of TPD candidates. ELiAH2 integrates GTEx RNA-seq profiles across 24 human tissues to characterize tissue-specific expression patterns of E3 ligases and target genes. Compared with the previous version, ELiAH, current update presented over 200% of expansion for the number of covered tissues and samples. Previously, E3 ligase– target gene associations were inferred using mutual information-based network analysis, enabling users to explore transcriptomic relationships. To further support structural evaluation, ELiAH2 provides large-scale docking datasets comprising 827,385 E3 ligase–target protein pairs and 7,800,521 protein–ligand docking models, including E3 ligase–ligand and target protein–ligand interactions. Docking scores, ranked interaction tables, gene and ligand identifiers, and downloadable PDB structures are incorporated into the web interface. By combining tissue specificity, E3–target association, protein–protein docking, and protein– ligand docking, ELiAH2 provides a comprehensive resource for narrowing the TPD search space and supporting rational degrader design. ELiAH2 is freely available at https://eliahdb.org .
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7222847639