OTUD5 is a member of the OTU (ovarian tumor) domain-containing cysteine protease superfamily. The OTU domain confers deubiquitinase activity and OTUD5 has been shown to suppress the type I interferon (IFN-I)-dependent innate immune response by cleaving the polyubiquitin chain from TRAF3, an essential type I interferon adaptor protein. Cleavage results in disassociation of TRAF3 from a downstream signaling complex containing TBK1 and the disruption of the IFN-I signaling cascade, indicating that OTUD5 acts as a negative regulator of innate immune responses. It has been suggested that by suppressing IFN-I production, OTUD5 may function to inhibit the emergence of certain autoimmune disorders such as systemic lupus erythematosus. Multiple isoforms of OTUD5 are known to exist.
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