STUB1 (CHIP) Recombinant Protein

Function: 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. Ref.2 Ref.10 Ref.11 Ref.12 Ref.22 Ref.23 Ref.25

Pathway: Protein modification; protein ubiquitination.

Subunit structure: Homodimer

By similarity. 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

By similarity. Interacts (via the U-box domain) with the UBE2V2-UBE2N heterodimer; the complex has a specific 'Lys-63'-linked polyubiquitination activity. Interacts with DNAJB6. Ref.2 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.18 Ref.23 Ref.24 Ref.31

Subcellular location: Cytoplasm Ref.2.

Tissue specificity: Highly expressed in skeletal muscle, heart, pancreas, brain and placenta. Detected in kidney, liver and lung. Ref.2

Domain: The TPR domain is essential for ubiquitination mediated by UBE2D1. Ref.17

Post-translational modification: Monoubiquitinated at Lys-2 following cell stress by UBE2W, promoting the interaction with ATXN3

By similarity. Auto-ubiquitinated; mediated by UBE2D1 and UBE2D2.

Miscellaneous: Antibodies against STUB1 are found in patients with chronic lymphocytic leukemia (CLL) and in colorectal cancer patients.

Sequence similarities: Contains 3 TPR repeats.Contains 1 U-box domain.