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UBA domain found in probable E3 ubiquitin-protein ligase HERC1, HERC2 and similar proteins HERC1, also called HECT domain and RCC1-like domain-containing protein 1, p532, or p619, is an ubiquitously expressed giant protein involved in ubiquitin-dependent intracellular membrane trafficking through its interaction with vesicle coat proteins such as clathrin and ARF. Moreover, it has been identified as a tuberous sclerosis complex TSC2-interacting protein that may play a role in TSC-mTOR (mammalian target of rapamycin) pathway. HERC2, also called HECT domain and RCC1-like domain-containing protein 2, is a SUMO-regulated E3 ubiquitin ligase that plays an important role in the SUMO-dependent pathway which orchestrates the DNA double-strand break (DSB) response. Moreover, HERC2 functions as a RNF8 auxiliary factor that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. HERC1 and HERC2 are multi-domain proteins with different domain organizations. Both of them contain a ubiquitin-association (UBA) domain, more than one RCC1-like domains (RLDs) and a C-terminal HECT E3 ubiquitin ligase domain.
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