Hierarchical structure of the ubiquitin system.

The enzyme classes involved in ubiquitin tagging of proteins that have to be degraded are organized in an hierachical order.

A small number of E1(ubiquitin activating) and E2 (ubiquitin conjugating) enzymes face towards a huge and as yet unknown number of E3 enzymes (ligases).

Single E2 enzymes can cooperate with different E3 ligases.

Single E3 ligases target different protein substrates.
i.e. mdm2 targets HIF-1alpha and p53.

Single protein substrates are targets of different E3-ligases.
i.e. HIF-1alpha is a substrate of the von Hippel Lindau E3 complex (= pVHL complex) as well as of mdm2, and p53 is a substrate of E6-AP as well as of mdm2.

References

Degradation of proteins by the ubiquitin-proteasome-system

Substrate specificity of the ubiquitination