STIP1 homology and U-box containing protein 1 (STUB1)

STIP1 homology and U-box containing protein 1 (abbreviated as STUB1, commonly known as CHIP) is an E3 ubiquitin-protein ligase involved in the cellular protein quality control system. CHIP functions as a co-chaperone by binding to heat shock proteins (HSP70/HSC70/HSP90), inhibiting their ATPase activity, and channeling damaged, misfolded, or surplus proteins toward ubiquitin-mediated proteasomal degradation. Structurally, CHIP contains an N-terminal TPR (tetratricopeptide repeat) domain for chaperone interaction, a central coiled-coil domain, and a C-terminal U-box domain conferring E3 ligase enzymatic activity. STUB1/CHIP plays central roles in maintaining proteostasis, especially under stress, and regulates key processes such as autophagy, apoptosis, cell proliferation, and signal transduction by controlling the turnover of receptors and transcription factors. Mutations in STUB1 cause autosomal dominant spinocerebellar ataxia type 48 (SCA48) and recessive ataxia SCAR16 due to loss of CHIP function and impaired neuronal protein homeostasis. CHIP is linked to multiple neurodegenerative and neoplastic conditions and is of emerging interest as a therapeutic target and biomarker for diseases involving protein aggregation and dysregulated degradation.

Other names

E3 ubiquitin-protein ligase CHIPCHIP (C-terminus of HSC70-interacting protein)Carboxy-terminus of Hsp70-interacting proteinUBOX1HSPABP2NY-CO-7PP1131SDCCAG7Antigen NY-CO-7CLL-associated antigen KW-8Serologically defined colon cancer antigen 7

Promotes ubiquitination and proteasomal degradation of misfolded, damaged, or excess client proteins (including tau, α-synuclein, p53, ErbB2, androgen receptor). E3 ligase activity depends on its U-box domain and interaction with E2 ubiquitin-conjugating enzymes.