Compendium of protein lysine acetylation (CPLA)

Compendium of protein lysine acetylation (CPLA) catalogs experimentally validated lysine acetylation sites and substrates to support analysis of protein lysine acetylation's regulatory roles in cellular processes.

Key Features:

• Curated dataset: 7,151 experimentally validated acetylation sites across 3,311 protein targets extracted from scientific literature through manual curation.
• Annotations: Substrates are annotated with Gene Ontology (GO) and InterPro classifications.
• Protein–protein interaction integration: Protein–protein interaction data are integrated to construct a human lysine acetylation network (HLAN) linking histone acetyltransferases (HATs), substrates, and histone deacetylases (HDACs).
• Triplet relationships: Identification of 1,862 triplet relationships within HLAN, including at least 13 experimentally verified interactions.
• CPLM 4.0 expansion: An expanded resource aggregates over 450,378 protein lysine modification events and, integrated with PLMD 3.0, provides 592,606 experimentally identified modification events across 29 PTM types in proteins from 219 species.
• Cross-resource annotations: CPLM 4.0 incorporates annotations from 102 additional resources covering genetic variation, disease associations, protein interactions, functional annotations, and structural data.

Scientific Applications:

• Functional analysis: Investigating lysine acetylation's roles in metabolic regulation and other biological processes using site- and protein-level data.
• Network analysis: Elucidating interaction relationships among HATs, substrates, and HDACs via the HLAN and identified triplets.
• Cross-PTM comparative studies: Leveraging CPLM 4.0 to compare multiple lysine-centered PTM types across species.
• Disease and variation studies: Integrating genetic variation and disease-association annotations from CPLM 4.0 for studies of modification-disease links.
• Annotation-driven enrichment: Performing GO- and InterPro-based functional enrichment analyses on acetylated proteins.

Methodology:

Manually curate experimentally validated acetylation sites from literature; integrate protein–protein interaction data to construct HLAN and identify triplet relationships; aggregate literature and public database entries and integrate with PLMD 3.0; incorporate annotations from 102 external resources.