STUB1
STUB1 (STIP1 homology and U-box containing protein 1), also known as CHIP, UBOX1, SDCCAG7, HSPABP2 and NY-CO-7, is a U-box E3 ubiquitin ligase and chaperone co-factor. It directs misfolded chaperone substrates and many regulatory proteins to proteasomal degradation. Browse Assay Genie's current range of STUB1 research reagents below, or read on for the biology behind the target.
STUB1 is an E3 ubiquitin-protein ligase that targets misfolded chaperone substrates towards proteasomal degradation. It also acts as a co-chaperone for HSPA1A and HSPA1B, and modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90. It collaborates with ATXN3, which restricts the length of the ubiquitin chain attached to STUB1 substrates and prevents further chain extension. STUB1 can also transfer non-canonical short ubiquitin chains to HSPA8 without affecting HSPA8 degradation.
The ligase has a broad set of substrates. It ubiquitinates MYOCD, FOXO1, NFATC3, the ICER-type isoforms of CREM, SMAD3, TP53, RIPK3, FOXP3, ESR1, CHRNA3, EPHA2, CYP3A4 and PPARG, and likely PD-L1/CD274, with effects on smooth muscle contraction, cardiomyocyte survival, TGF-beta signalling, regulatory T-cell function and macrophage polarisation. It mediates polyubiquitination of DNA polymerase beta (POLB) in base-excision repair, amplifying HUWE1-dependent monoubiquitination. In contrast, it monoubiquitinates SIRT6 and so prevents its proteasomal degradation. In mitochondria, STUB1 helps maintain morphology and promotes mitophagic removal of dysfunctional organelles, protecting against stress-induced apoptosis.
The STUB1 gene encodes a protein with tetratricopeptide repeat and U-box domains, and belongs to the HGNC U-box domain containing and tetratricopeptide repeat domain containing groups. The protein binds and ubiquitinates Hspa8 and Polb, among other targets. Mutations in the gene cause autosomal recessive spinocerebellar ataxia 16. Alternative splicing gives multiple transcript variants, and a pseudogene lies on chromosome 2. Mouse and rat orthologs are both named Stub1.
STUB1 links chaperones such as Hsp70, Hsc70 and Hsp90 to the ubiquitin-proteasome system, targeting misfolded substrates for degradation.
STUB1 helps maintain mitochondrial morphology and promotes mitophagic removal of dysfunctional mitochondria, protecting cells from stress-induced apoptosis.
STUB1 degrades MYOCD, FOXO1, CREM ICER isoforms and NFATC3, shaping smooth muscle contraction and cardiomyocyte survival.
STUB1 regulates FOXP3 in regulatory T-cells, likely PD-L1/CD274 expression, and TP53, RIPK3 and PPARG, linking it to immune and tumour signalling.
STUB1 is a U-box E3 ubiquitin ligase and co-chaperone. Working with Hsp70, Hsc70 and Hsp90, it ubiquitinates misfolded chaperone substrates and many regulatory proteins, such as TP53, SMAD3 and FOXO1, and directs them to proteasomal degradation.
Yes. CHIP is the name used in the UniProt entry, E3 ubiquitin-protein ligase CHIP. Other aliases are UBOX1, SDCCAG7, HSPABP2 and NY-CO-7. The HGNC name is STIP1 homology and U-box containing protein 1, and the enzyme carries EC number 2.3.2.27.
Mutations in the STUB1 gene cause autosomal recessive spinocerebellar ataxia 16. The gene has mouse and rat orthologs, both called Stub1. Check the datasheet of any product for its validated reactivity.
Chaperones, ubiquitin-pathway partners and substrates of STUB1 with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9UNE7; product specifications from Assay Genie datasheets.