Alternative titles; symbols
HGNC Approved Gene Symbol: YOD1
Cytogenetic location: 1q32.1 Genomic coordinates (GRCh38): 1:207,043,849-207,053,116 (from NCBI)
Deubiquitinating enzymes (DUBs; see 603478) are proteases that specifically cleave ubiquitin (191339) linkages, negating the action of ubiquitin ligases. DUBA8 belongs to a DUB subfamily characterized by an ovarian tumor (OTU) domain.
Kayagaki et al. (2007) identified ovarian tumor domain (OTU)-containing protein-2 (OTUD2) in a small interfering RNA (siRNA)-based screen for OTU deubiquitinating enzyme (DUB) family members. The 6,265-basepair mRNA contains an open reading frame (ORF) predicting a 348-amino acid protein. In addition to an OTU domain, the protein contains a zinc finger (ZNF) C2H2 domain.
Liu et al. (2019) found that Sendai virus infection induced YOD1 expression to promote virus amplification through the deubiquitinase activity of YOD1. YOD1 expression negatively regulated activation of IFN-beta (IFNB1; 147640) signaling to promote virus replication, as overexpression of YOD1 in HEK293T cells inhibited poly(I:C)- and Sendai virus-induced IFN-beta signaling, whereas knockdown enhanced it. Further analyses demonstrated that YOD1 negatively regulated MAVS (609676)-mediated IFN-beta signaling in a deubiquitinase activity-dependent manner. Immunoprecipitation analysis revealed that YOD1 and MAVS interacted to form a complex after Sendai virus infection through the UBX and zinc finger domains of YOD1 and the proline-rich domain of MAVS. After Sendai virus infection, cytoplasmic YOD1 was recruited to mitochondria, where it interacted and colocalized with MAVS and cleaved lys63 (K63)-linked ubiquitination chains from MAVS to suppress aggregation of MAVS.
The YOD1 gene maps to chromosome 1q32.1 (Kayagaki et al., 2007).
Kayagaki, N., Phung, Q., Chan, S., Chaudhari, R., Quan, C., O'Rourke, K. M., Eby, M., Pietras, E., Cheng, G., Bazan, J. F., Zhang, Z., Arnott, D., Dixit, V. M. DUBA: a deubiquitinase that regulates type I interferon production. Science 318: 1628-1632, 2007. [PubMed: 17991829] [Full Text: https://doi.org/10.1126/science.1145918]
Liu, C., Huang, S., Wang, X., Wen, M., Zheng, J., Wang, W., Fu, Y., Tian, S., Li, L., Li, Z., Wang, X. The otubain YOD1 suppresses aggregation and activation of the signaling adaptor MAVS through Lys63-linked deubiquitination. J. Immun. 202: 2957-2970, 2019. [PubMed: 30952814] [Full Text: https://doi.org/10.4049/jimmunol.1800656]