STUB1 Gene - STIP1 Homology and U-Box Containing Protein 1
E3 ubiquitin-protein ligase STUB1: roles in protein quality control, neurodegeneration, and cancer
Gene Information Card
| Symbol | STUB1 |
|---|---|
| Full Name | STIP1 homology and U-box containing protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 10273 ncbi.nlm.nih.gov/gene/10273 |
| Ensembl ID | ENSG00000103266 |
| UniProt ID | |
| OMIM ID | 607207 |
| HGNC ID | 11427 |
| Aliases | CHIP, HSPABP2, NY-CO-7, SDCCAG7, UBOX1 |
Description
The STUB1 gene encodes the E3 ubiquitin-protein ligase CHIP (C-terminus of Hsc70-interacting protein). CHIP mediates ubiquitination and proteasomal degradation of misfolded proteins, interacting with molecular chaperones HSP70 and HSP90. It is critical for protein quality control, cellular stress responses, and regulation of signaling pathways. Loss-of-function mutations cause spinocerebellar ataxia autosomal recessive 16 (SCAR16) and are implicated in cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia autosomal recessive 16 (SCAR16) | Loss-of-function mutations impair ubiquitination of misfolded proteins, leading to Purkinje cell degeneration and ataxia. | ClinVar, OMIM #607207 |
| Autosomal dominant cerebellar ataxia (ADCA) | Dominant-negative or gain-of-function mutations disrupt chaperone binding and ubiquitin ligase activity. | ClinVar, OMIM #607207 |
| Breast cancer | STUB1 downregulation or mutation reduces degradation of oncogenic proteins (e.g., HER2, ERα), promoting tumorigenesis. | COSMIC, NCBI PubMed |
| Colorectal cancer | Altered STUB1 expression affects β-catenin and p53 turnover, influencing cell proliferation. | COSMIC, NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 15.2 | Medium |
| Kidney | 10.1 | Medium |
| Testis | 18.7 | High |
| Skeletal muscle | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.5 | Embryonic kidney; high STUB1 expression |
| HeLa | 11.2 | Cervical carcinoma; moderate expression |
| SH-SY5Y | 9.8 | Neuroblastoma; relevant for neurodegeneration studies |
| MCF7 | 7.3 | Breast cancer; reduced expression linked to poor prognosis |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.823C>T (p.Arg275*) | Nonsense | Rare | Loss of function; truncation of U-box domain; associated with SCAR16 |
| c.472G>A (p.Gly158Arg) | Missense | Rare | Impaired HSP70 binding; dominant-negative effect in ADCA |
| c.589C>T (p.Arg197Trp) | Missense | Rare | Reduced E3 ligase activity; linked to early-onset ataxia |
| c.1003G>A (p.Glu335Lys) | Missense | Rare | Altered substrate recognition; reported in cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg275*, p.Arg197Trp) that abolish or severely reduce ubiquitin ligase activity, leading to accumulation of misfolded proteins and neurodegeneration (SCAR16).
Gain of Function (GOF)
Rare missense variants (e.g., p.Glu335Lys) may enhance ubiquitination of specific substrates, potentially contributing to oncogenic signaling in cancer.
Dominant Negative (DN)
Mutations such as p.Gly158Arg disrupt chaperone binding, interfering with wild-type STUB1 function and causing autosomal dominant ataxia.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin protein ligase activity | • protein ubiquitination |
| • chaperone binding | • protein folding |
| • cellular response to heat | • proteasome-mediated ubiquitin-dependent protein catabolic process |
| • negative regulation of apoptotic process | • regulation of protein stability |
Pathways
• Ubiquitin mediated proteolysis (KEGG hsa04120)
• Protein processing in endoplasmic reticulum (KEGG hsa04141)
• Chaperone-mediated protein folding (Reactome R-HSA-390466)
• p53-independent DNA damage response (Reactome R-HSA-6798695)
Protein Summary
The STUB1 protein (CHIP) is a 303-amino-acid E3 ubiquitin ligase containing an N-terminal tetratricopeptide repeat (TPR) domain for chaperone binding and a C-terminal U-box domain for ubiquitin conjugation. It targets misfolded proteins for proteasomal degradation, maintains proteostasis, and modulates signaling pathways (e.g., p53, NF-κB). Mutations cause spinocerebellar ataxia and are linked to cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STUB1 Knockout MB49 Cell Line | EDJ-KQ53 | Mouse | 56424 | Details Get a Quote |
| STUB1 Knockout HEK293 Cell Line | EDJ-KQ50950 | Human | 10273 | Details Get a Quote |
| STUB1 Knockout HeLa Cell Line | EDC90406 | Human | 10273 | Details Get a Quote |
| STUB1 Knockout A-549 Cell Line | EDJ-KQ63846 | Human | 10273 | Details Get a Quote |
| STUB1 Knockout HCT 116 Cell Line | EDJ-KQ72305 | Human | 10273 | Details Get a Quote |
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