E3 ubiquitin-protein ligase HUWE1 (HUWE1)

E3 ubiquitin-protein ligase HUWE1 is a large, multi-domain enzyme encoded by the HUWE1 gene on the human X chromosome. HUWE1 belongs to the HECT (homologous to E6AP carboxy terminus) family of E3 ubiquitin ligases and is capable of mediating ubiquitination of a wide range of protein substrates, including both tumor suppressors (such as p53, ATM, CDKN2A) and oncoproteins (such as c-Myc, Mcl-1). It features a distinctive ring-shaped architecture with armadillo repeat domains that facilitate substrate recognition and a C-terminal HECT catalytic domain for ubiquitin transfer. HUWE1 is essential for neuronal development and has roles in cell proliferation, DNA repair, apoptosis, and maintenance of proteostasis. Its dysregulation is implicated in several malignancies and neurodevelopmental disorders, with context-dependent roles in either promoting or suppressing tumorigenesis. No small-molecule drug modulators are currently in routine clinical use, though genetic and proteasomal targeting strategies have been explored in cancer models.

Other names

ARF-BP1MuleHECTH9HSPC272Ib772LASU1URE-B1UREB1HECTUBA and WWE domain containing protein 1HECT, UBA and WWE domain containing E3 ubiquitin ligase 1MRXST

Modulation of HUWE1 expression (gene therapy/CRISPR-based modulation for tumor suppression) Proteasome-mediated degradation via ubiquitination of oncogenic and tumor suppressor proteins