This SPRY domain is found in the HERC1, a large protein related to chromosome condensation regulator RCC1. It is widely expressed in many tissues, playing an important role in intracellular membrane trafficking in the cytoplasm as well as Golgi apparatus [, ]. It is both a ubiquitin-protein ligase and a guanine nucleotide exchange factor for ARF and Rab family GTPases. Like other HERC proteins, HERC1 also interacts with tuberous sclerosis 2 (TSC2, tuberin), which suppresses cell growth, and results in the destabilization of TSC2 []. HERC1 is essential for neurotransmitter release and neuronal activity [, ]. Mutations in HERC1 lead to syndromic intellectual disability [, ].
