Browse All / Genes / STUB1

STUB1

STIP1 homology and U-box containing protein 1
3 disorders 3 causative 16p13.3 gene with protein product
HGNC:11427MonarchNCBI Gene 10273ENSG00000103266UniProt Q9UNE7OMIM 607207

Aliases: UBOX1, CHIP, SDCCAG7, HSPABP2, NY-CO-7.

Normal function · from ai-gene-review (Q9UNE7, commit 79fe13b38970) · AI-generated, not KB evidence

STUB1 (E3 ubiquitin-protein ligase CHIP, C-terminus of HSC70-interacting protein) is a cytoplasmic protein that couples the molecular-chaperone and ubiquitin-proteasome systems. It has a bipartite architecture: an N-terminal tetratricopeptide repeat (TPR) domain that binds the C-terminal EEVD/MEEVD motifs of HSP70/HSC70 and HSP90, and a C-terminal U-box domain that confers RING-type E3 ubiquitin-ligase activity. Acting as a chaperone-associated 'triage' factor, CHIP ubiquitinates chaperone-bound misfolded or damaged client proteins (in cooperation with E2 enzymes such as UBE2D and UBE2N/UBE2V1) and targets them for proteasomal degradation, while also modulating the activity of the HSP70/HSC70/HSP90 chaperone cycle as a co-chaperone. CHIP functions as a homodimer and additionally participates in protein quality control, ERAD, chaperone-mediated autophagy and mitophagy, and the regulated turnover of numerous specific substrates (e.g. tau, FOXO1, NOS1, POLB, ESR1). Loss of CHIP ubiquitin-ligase activity causes autosomal-recessive (SCAR16) and autosomal-dominant (SCA48) spinocerebellar ataxia.

U-box-type E3 ubiquitin-protein ligase that, in cooperation with E2 enzymes, ubiquitinates chaperone-bound misfolded/damaged client proteins and targets them for proteasomal degradation.
molecular function: ubiquitin protein ligase activity · locations: cytosol
HSP70/HSC70/HSP90 co-chaperone: via its TPR domain CHIP binds these chaperones and modulates their activity, coupling client triage to the chaperone cycle.
molecular function: Hsp70 protein binding · locations: cytosol
Protein quality control: CHIP recognizes misfolded chaperone substrates and routes them to ubiquitin-dependent proteasomal degradation, integrating folding and degradation decisions.
molecular function: ubiquitin-protein transferase activity · locations: cytosol
In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

DisorderRelationshipWhere the gene appears
Autosomal Recessive Spinocerebellar Ataxia 16 causative
mechanism: Biallelic STUB1 Loss-of-Function Variants
Cerebellar Ataxia-Hypogonadism Syndrome causative germline
mechanism: STUB1 CHIP ubiquitin ligase deficiency
subtype: STUB1-related Gordon Holmes syndrome
Spinocerebellar Ataxia 48 causative germline
mechanism: CHIP Loss of Function from Heterozygous STUB1 Variants

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.