Ubiquitin-conjugating enzyme E2 K (UBE2K) (UBE2K)

Ubiquitin-conjugating enzyme E2 K (UBE2K), also known as Huntingtin-interacting protein 2 (HIP2), is a specialized E2 enzyme within the ubiquitin-proteasome system (UPS) that facilitates the synthesis of Lys-48-linked polyubiquitin chains [1, 2]. These chains are the primary signal for targeting proteins for degradation by the 26S proteasome. UBE2K is unique due to its C-terminal ubiquitin-associated (UBA) domain, which allows it to bind ubiquitin and promote the elongation of ubiquitin chains, often independently of an E3 ligase [1, 3]. The enzyme is significantly involved in neurodegenerative pathologies; it has been shown to mediate the neurotoxicity of amyloid-beta in Alzheimer's disease and to interact with mutant huntingtin protein in Huntington's disease [4, 5]. Targeting UBE2K mRNA via RNA interference (RNAi) or antisense oligonucleotides (ASOs) represents a therapeutic approach to downregulate the protein's expression, thereby potentially reducing the accumulation of toxic protein aggregates and mitigating disease progression [6]. While no UBE2K-targeted therapies are currently in clinical trials, it remains a key target for research into neurodegeneration and protein homeostasis [2, 7].

Other names

HIP2E2-25KHuntingtin-interacting protein 2LIGUbiquitin-protein ligase KHYPGUbiquitin-conjugating enzyme E2-25KUBE2K mRNA

Antisense-mediated mRNA degradation or RNA interference (RNAi) leading to reduced expression of the UBE2K protein and subsequent inhibition of Lys-48-linked polyubiquitination.