UbE3-APA

UbE3-APA profiles ubiquitin E3 ligase activities from quantitative ubiquitylome proteomics data to infer ligase activation or suppression and facilitate functional analysis of ubiquitination-mediated protein regulation.

Key Features:

• Integrated Annotation Database: Incorporates an extensive annotation database for identification and mapping of ubiquitin E3 ligases and their substrates.
• Statistical Analysis: Employs statistical methods to identify significantly activated or suppressed E3 ligases from quantitative ubiquitylome datasets.
• Benchmarking Capability: Validated against published quantitative ubiquitylome analyses, including detection of SPOP overexpression and mutation effects.
• Mass Spectrometry Compatibility: Leverages mass spectrometry-based quantitative proteomics workflows, including targeted and data-independent acquisition (DIA) approaches.
• Implementation: Implemented as a computational algorithm with a stand-alone Python-based software implementation.

Scientific Applications:

• Ubiquitylome Dynamics: Enables functional analysis of ubiquitylome dynamics and pathway-level changes in E3 ligase activity.
• Mitophagy Analysis: Detects activation of PARKIN and co-activation of other E3 ligases during mitochondria depolarization-induced mitophagy.
• Genetic Perturbation Profiling: Detects effects of genetic manipulations such as SPOP overexpression and mutation on E3 ligase activity profiles.
• Disease Mechanism Investigation: Supports investigation of ubiquitination dysregulation in disease-relevant pathways.

Methodology:

Operates on mass spectrometry-based quantitative ubiquitylome data, supports targeted and data-independent acquisition (DIA) workflows, is implemented as a computational algorithm with a Python-based software implementation, and applies statistical analyses to identify significantly activated or suppressed E3 ligases.