Editing Proteasome (section)

=== Proteasomal Ligases ===
While Ubp6 and UCH37 can remodel the ubiquitin code on a substrate by removing Ubiquitins, [[Ubiquitin ligase]]s can also associate with the proteasome and attach ubiquitins.  For the 26S, this includes Hul5 in yeast (or [[UBE3C]] in humans) and [[UBE3A]]/E6AP in humans.

Hul5 was first identified in yeast as a 26S associated ligase along with Ubp6 and they were proposed to remodel ubiquitin chains at the proteasome. Biochemical studies show that Hul5 can attach additional ubiquitins onto a ubiquitinated substrate effectively acting as an [[Ubiquitin ligase]].  Hul5 has been proposed to bind Rpn2 in yeast, however this interaction has not been shown structurally.  Further work needs to be done to understand how Hul5 works and what substrates are processed by Hul5.

UBE3A/E6AP binds the C-terminus of Rpn10 in mammals.  NMR has shown that a previously described disordered region of Rpn10 becomes order upon binding E6AP forming a tight interaction in the low nanomolar range.<ref>{{cite journal |last1=Buel |first1=Gwen R. |last2=Chen |first2=Xiang |last3=Chari |first3=Raj |last4=O'Neill |first4=Maura J. |last5=Ebelle |first5=Danielle L. |last6=Jenkins |first6=Conor |last7=Sridharan |first7=Vinidhra |last8=Tarasov |first8=Sergey G. |last9=Tarasova |first9=Nadya I. |last10=Andresson |first10=Thorkell |last11=Walters |first11=Kylie J. |title=Structure of E3 ligase E6AP with a proteasome-binding site provided by substrate receptor hRpn10 |journal=Nature Communications |date=10 March 2020 |volume=11 |issue=1 |page=1291 |doi=10.1038/s41467-020-15073-7|pmid=32157086 |pmc=7064531 |bibcode=2020NatCo..11.1291B }}</ref>