HECT

HECT stands for Homologous to E6-AP C-Terminus and designates a family of E3 ubiquitin ligases characterized by a catalytic cysteine-containing HECT domain at their C-terminus. HECT E3 ligases facilitate the transfer of ubiquitin from an E2 enzyme to substrate proteins, thereby regulating protein degradation, localization, and activity. The family participates in a wide range of cellular processes, including protein turnover, receptor trafficking, and signal transduction.

The HECT domain forms a thioester intermediate with ubiquitin before transferring it to substrates. This provides a distinct mechanism from RING-type E3 ligases, which recruit ubiquitin directly to substrates. Most HECT ligases are multi-domain proteins, often containing regulatory motifs such as C2 domains or WW domains that influence localization, substrate recognition, and interactions with other proteins. The best-known member is E6AP, also called UBE3A, which is linked to Angelman syndrome when disrupted. Other notable HECT E3 ligases include the NEDD4 family (NEDD4, NEDD4L, ITCH, WWP1-2, SMURF1-2) and the HERC family (HERC1, HERC2), each with distinct domain architectures and cellular roles.

Roles in health and disease: HECT E3 ligases regulate processes such as endocytosis and receptor downregulation, as well as broader signaling pathways. Mutations or dysregulation of HECT family members have been associated with neurodevelopmental disorders, cancer, and immune system functions. UBE3A/Angelman syndrome is a prominent example where maternal gene loss leads to disease.

In other contexts, HECT also refers to the SI prefix hecto-, meaning a factor of 100, with the symbol h. This usage is unrelated to the ubiquitin ligase family but shares the same acronym.