STUB1

STUB1 (STIP1 homology and U-Box containing protein 1) is a human gene that codes for the protein CHIP (C terminus of HSC70-Interacting Protein).

Function The CHIP protein encoded by this gene binds to and inhibits the ATPase activity of the chaperone proteins HSC70 and HSP70 and blocks the forward reaction of the HSC70-HSP70 substrate-binding cycle. In addition, CHIP possesses E3 ubiquitin ligase activity and promotes ubiquitylation, mainly of chaperone-bound misfolded proteins.

CHIP enhances HSP70 induction during acute stress and also mediates its turnover during the stress recovery process. Hence CHIP appears to maintain protein homeostasis by controlling chaperone levels during stress and recovery.

Mutations in STUB1 cause spinocerebellar ataxia type 16.

STUB1 regulates cytokine receptors in T cells and myeloid cells.LaFleur, M.W., Milling, L.E., Prathima, P. et al. A STUB1–CHIC2 complex inhibits CD8+ T cells to restrain tumor immunity. Nat Immunol (2025). https://doi.org/10.1038/s41590-025-02231-6A STUB1 ubiquitin ligase/CHIC2 protein complex negatively regulates the IL-3, IL-5, and GM-CSF cytokine receptor common β chain (CSF2RB) protein stability. Koochaki, Sebastian H.J. et al. Journal of Biological Chemistry, Volume 298, Issue 10, 102484https://www.jbc.org/article/S0021-9258(22)00927-9/fulltext

Interactions

STUB1 has been shown to interact with:

C-Raf, DNAJB1, HSPA1A, HSPA4, HSPA8, Parkin (ligase), and RUNX2.

References

Further reading

External links