E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation. Ubiquitinates NOS1 in concert with Hsp70 and Hsp40. Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90. Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation. Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome. Mediates polyubiquitination of CYP3A4.
Highly expressed in skeletal muscle, heart, pancreas, brain and placenta. Detected in kidney, liver and lung.
Protein modification; protein ubiquitination.
Contains 3 TPR repeats. Contains 1 U-box domain.
The TPR domain is essential for ubiquitination mediated by UBE2D1.
Phosphorylated upon DNA damage, probably by ATM or ATR. Auto-ubiquitinated; mediated by UBE2D1 and UBE2D2.
El-Kasaby A et al. A cytosolic relay of heat shock proteins HSP70-1A and HSP90ß monitors the folding trajectory of the serotonin transporter. J Biol Chem289:28987-9000 (2014).
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