OTU deubiquitinase 7A (OTUD7A)

OTU deubiquitinase 7A (OTUD7A) is a cysteine protease and member of the OTU (ovarian tumor) family of deubiquitinases, characterized by a conserved catalytic triad comprising cysteine, histidine, and aspartate residues[4]. OTUD7A acts by cleaving Lys-11-linked polyubiquitin chains on target proteins[5], and has functional domains for ubiquitin association, OTU-type deubiquitinase activity, and an A20-like zinc finger[1]. Predominantly expressed in the brain, OTUD7A is enriched in excitatory neurons and plays a critical role in neuronal development, dendritic complexity, and synaptogenesis[1][2]. Loss-of-function mutations or deletions affecting OTUD7A are strongly linked to neurodevelopmental disorders such as intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder, largely due to impaired synaptic and network development[1][2][3]. OTUD7A may also act as a tumor suppressor and is involved in the regulation of the NF-κB signaling pathway via deubiquitination of TRAF6[3]. At present, there are no known drugs specifically targeting OTUD7A, and there are no established biomarkers or companion diagnostics; however, the enzyme's loss-of-function genetics confer significant neurodevelopmental risk[1][2][3].

Other names

OTU domain-containing protein 7AC15orf16CEZANNE2OTUD7Zinc finger protein Cezanne 2NEDHS

Cleavage of Lys-11-linked polyubiquitin chains on protein substrates, Regulation of inflammatory and synaptic pathways through deubiquitination