HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1)

HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) is an enzyme that catalyzes the attachment of ubiquitin to specific substrate proteins, marking them for degradation or regulating their function. It belongs to the HECT (Homologous to the E6AP C-terminus) family of E3 ligases, characterized by having a catalytic cysteine that forms a thioester intermediate with ubiquitin. HACE1 contains multiple functional domains, including a HECT domain, ankyrin repeats for substrate recognition, and (as the historical name implies) regions homologous to C2 and WW domains, although the ankyrin repeat and HECT domain are functionally and structurally most characteristic[1][6]. HACE1 plays crucial roles in cellular homeostasis and tumor suppression, particularly by selective ubiquitination and degradation of active RAC1, a small GTPase involved in cell growth and migration. Mutations or loss of HACE1 function are implicated in several cancers. E3 ligases such as HACE1 are currently promising targets for drug development, especially in the context of novel strategies to degrade pathogenic proteins via the ubiquitin-proteasome system[5][6].

Other names

HACE1HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1Ankyrin repeat and HECT domain-containing E3 ubiquitin-protein ligase 1

Substrate-targeted ubiquitination leading to proteasomal degradation or altered cellular localization/function[5][6]. Selective modification of GTP-bound RAC1, controlling actin cytoskeletal dynamics and cell growth[1].