Ubiquitin-conjugating enzyme E2 G2 (UBE2G2)

Ubiquitin-conjugating enzyme E2 G2 (UBE2G2; also known as UBC7) is a class I E2 enzyme integral to the ubiquitination cascade, mainly functioning in the endoplasmic reticulum-associated degradation (ERAD) pathway[1][2][3]. UBE2G2 collaborates with specific E3 ligases—including gp78, HRD1, TEB4, and parkin—to assemble lysine-48 (K48)-linked polyubiquitin chains on substrate proteins, marking them for recognition and degradation by the proteasome[1][3][4]. UBE2G2 is widely expressed in human tissues and is essential for the identification and disposal of misfolded or excess proteins within the endoplasmic reticulum[1][2]. Its proper activity is critical for cellular homeostasis, affecting processes such as signal transduction, cell cycle regulation, proliferation, and apoptosis[1]. Dysfunction of UBE2G2 and disruption of the ERAD pathway have been implicated in neurodegenerative diseases (such as Parkinson’s disease) and disorders characterized by protein misfolding (such as cystic fibrosis)[1]. Structurally, UBE2G2 consists of a typical E2 core with an extended, highly dynamic loop region that is likely stabilized through binding interactions with E3 ligases or ubiquitin partners, which is crucial for its catalytic efficiency and substrate specificity[1][2]. No clinically approved drugs target UBE2G2 directly, but it remains of research interest as a component of the broader ubiquitin-proteasome system, which is a validated target in oncology and certain neurological disorders.

Other names

UBC7Ubiquitin-conjugating enzyme E2 G2E2 ubiquitin-conjugating enzyme G2Ubiquitin carrier protein G2Ubiquitin-protein ligase G2Ubiquitin conjugating enzyme 7Ubiquitin conjugating enzyme G2UBC7 homolog (yeast)Ubiquitin-conjugating enzyme E2G2

Inhibition or modulation of E2 enzymatic activity to alter ubiquitination and protein degradation; Targeting E2-E3 interactions to disrupt substrate ubiquitination