E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation. Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. 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. Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation. Homodimer. Interacts with BAG2, and with the E2 ubiquitin conjugating enzymes UBE2D1, UBE2D2 and UBE2D3. Interacts with the C-terminal domains of HSPA8 and HSPA1A. Detected in a ternary complex containing STUB1, HSPA1A and HSPBP1. Interacts with MKKS. Interacts with DYX1C1 and POLB. Interacts (via TPR repeats) with HSP90AA1. Interacts (when monoubiquitinated) with ATXN3. Interacts with UBE2W. Interacts (via the U-box domain) with the UBE2V2- UBE2N heterodimer; the complex has a specific 'Lys-63'-linked polyubiquitination activity. Interacts with DNAJB6. Highly expressed in skeletal muscle, heart, pancreas, brain and placenta. Detected in kidney, liver and lung. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Molecular Function: enzyme binding; G-protein-coupled receptor binding; Hsp70 protein binding; Hsp90 protein binding; kinase binding; ligase activity; misfolded protein binding; protein binding; protein binding, bridging; protein homodimerization activity; SMAD binding; TPR domain binding; ubiquitin protein ligase binding; ubiquitin-protein ligase activity
Biological Process: DNA repair; misfolded or incompletely synthesized protein catabolic process; negative regulation of protein binding; negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of protein ubiquitination; positive regulation of ubiquitin-protein ligase activity; proteasomal ubiquitin-dependent protein catabolic process; protein autoubiquitination; protein maturation; protein polyubiquitination; protein ubiquitination; protein ubiquitination during ubiquitin-dependent protein catabolic process; regulation of glucocorticoid metabolic process; regulation of protein stability; ubiquitin-dependent protein catabolic process; ubiquitin-dependent SMAD protein catabolic process; unfolded protein response
LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.