The E3 ligases are responsible for substrate specificity of the ubiquitin proteasome system.
E3 ligases consist of a single protein (= HECT-domain E3-ligases) or a protein complex (i.e. RING finger containing E3s) able to bind to the substrate and to interact with the E2 conjugating enzyme.
The interaction between E3-ligase and substrate is either direct or via an ancillary protein.
The protein substrates are specified for ubiquitination by special recognition signals.