[1] Proteins containing this domain at the C terminus include ubiquitin-protein ligase, which regulates ubiquitination of CDC25.

Ubiquitin-protein ligase accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester, and then directly transfers the ubiquitin to targeted substrates.

A cysteine residue is required for ubiquitin-thioester formation.

Human thyroid receptor interacting protein 12 (TRIP12), which also contains this domain, is a component of an ATP-dependent multisubunit protein that interacts with the ligand binding domain of the thyroid hormone receptor.

The E6/E6-AP complex binds to and targets the p53 tumour-suppressor protein for ubiquitin-mediated proteolysis.