<p>The post-translational attachment of ubiquitin (<db_xref db="INTERPRO" dbkey="IPR000626"/>) to proteins (ubiquitinylation) alters the function, location or trafficking of a protein, or targets it to the 26S proteasome for degradation [<cite idref="PUB00015621"/>, <cite idref="PUB00015619"/>, <cite idref="PUB00015625"/>]. Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2, <db_xref db="INTERPRO" dbkey="IPR000608"/>), and a ubiquitin ligase (E3, <db_xref db="INTERPRO" dbkey="IPR000569"/>, <db_xref db="INTERPRO" dbkey="IPR003613"/>), which work sequentially in a cascade [<cite idref="PUB00015620"/>]. The E1 enzyme is responsible for activating ubiquitin, the first step in ubiquitinylation. The E1 enzyme hydrolyses ATP and adenylates the C-terminal glycine residue of ubiquitin, and then links this residue to the active site cysteine of E1, yielding a ubiquitin-thioester and free AMP. To be fully active, E1 must non-covalently bind to and adenylate a second ubiquitin molecule. The E1 enzyme can then transfer the thioester-linked ubiquitin molecule to a cysteine residue on the ubiquitin-conjugating enzyme, E2, in an ATP-dependent reaction.</p><p>This entry represents conserved sequence regions found in these enzymes. Oneof these patterns (UBIQUITIN_ACTIVAT_2) contains the active site cysteine [<cite idref="PUB00002725"/>]. </p>