Ubiquitin-conjugating enzyme E2 H (UBE2H)

Ubiquitin-conjugating enzyme E2 H (UBE2H) is a member of the E2 ubiquitin-conjugating enzyme family responsible for transferring ubiquitin from E1 activating enzymes to substrate proteins, in processes mediated and regulated by E3 ubiquitin ligases such as the GID/CTLH complex[1][3][5][6]. This transfer is critical for tagging proteins for proteasomal degradation, thereby regulating protein turnover, signaling, and homeostasis in the cell[5]. UBE2H demonstrates specificity for certain polyubiquitin linkage types, such as Lys-11 and Lys-48 chains, and interacts with core components of the CTLH E3 ligase complex[1][3]. Recent structural studies show that multisite phosphorylation of UBE2H is crucial for selective pairing with the GID/CTLH complex, impacting catalytic efficiency and biological function[6]. The human UBE2H protein is highly conserved across vertebrates and exhibits distinct isoforms arising from alternative splicing[5]. Dysfunction of ubiquitin-conjugating enzymes is associated with various diseases, and UBE2H and its complexes have roles in cancer and metabolic regulation[6]. As of now, UBE2H itself is not a known direct drug target, but it is preparatory for therapeutic strategies aiming to modulate the ubiquitin-proteasome system.

Other names

UBCHUBC8GID3UBC8 homologUbiquitin-conjugating enzyme E2-20KUbiquitin carrier protein HUbiquitin-protein ligase HUbcH2(E3-independent) E2 ubiquitin-conjugating enzyme HGID complex subunit 3Ubiquitin-conjugating enzyme E2H (UBC8 homolog, yeast)Ubiquitin-conjugating enzyme E2H (homologous to yeast UBC8)

Catalytic transfer of ubiquitin from E1 enzyme to substrate proteins, generally in concert with E3 ligases such as GID/CTLH. Facilitates polyubiquitin chain formation (e.g., Lys-11 and Lys-48-linked chains). Requires phosphorylation-dependent multivalent interactions for selectivity in the GID/CTLH complex.