DDX58

Disease related genes, Enzymes, Human disease related genes, Potential drug targets

Intracellular

Cell type enhanced (Adipocytes)

Immune cell enhanced (neutrophil)

Group enriched (BJ hTERT+ SV40 Large T+, BJ hTERT+ SV40 Large T+ RasG12V, GAMG)

Monomer; maintained as a monomer in an autoinhibited state. Upon binding of viral RNAs and conformational shift, homooligomerizes and forms filaments on these molecules (PubMed:26471729). Interacts (via tandem CARD domain) with MAVS/IPS1 promoting its filamentation. Interacts with DHX58/LGP2, IKBKE, TBK1 and STING1. Interacts (via CARD domain) with TRIM25 (via SPRY domain). Interacts (double-stranded RNA-bound oligomeric form) with RNF135 (homodimer); involved in RNA length-dependent activation of the RIG-I signaling pathway (PubMed:19017631, PubMed:19484123, PubMed:23950712, PubMed:28469175, PubMed:31006531). Interacts with CYLD. Interacts with NLRC5; blocks the interaction of MAVS/IPS1 to DDX58. Interacts with SRC. Interacts with DDX60. Interacts with isoform 2 of ZC3HAV1 (via zinc-fingers) in an RNA-dependent manner. Interacts (via tandem CARD domain) with SEC14L1; the interaction is direct and impairs the interaction of DDX58 with MAVS/IPS1. Interacts with VCP/p97; interaction is direct and allows the recruitment of RNF125 and subsequent ubiquitination and degradation (PubMed:26471729). Interacts with NOP53; may regulate DDX58 through USP15-mediated 'Lys-63'-linked deubiquitination (PubMed:27824081). Interacts with SIGLEC10, CBL and PTPN11; within a negative feedback loop leading to DDX58 degradation (By similarity). Interacts with LRRC25 (PubMed:29288164). Interacts with ZCCHC3; leading to activation of DDX58/RIG-I (PubMed:30193849). Interacts with RNF123 (PubMed:27312109). Interacts with UBE2D3 and UBE2N; E2 ubiquitin ligases involved in RNF135-mediated ubiquitination of DDX58 and activation of the RIG-I signaling pathway (PubMed:28469175). Interacts with IFIT3 (PubMed:21813773). Interacts with DDX3X (PubMed:20127681). Interacts with RTN3 (PubMed:34313226). Interacts with ARL16; this interaction is GTP-dependent and induced upon viral infection; this interaction suppresses the RNA sensing activity of DDX58 (PubMed:21233210). (Microbial infection) Interacts with protein Z of Guanarito virus, Machupo virus, Junin arenavirus and Sabia virus. This interaction disrupts its interaction with MAVS/IPS1, impeding downstream IRF3 and NF-kappa-B activation and resulting in decreased IFN-beta induction (PubMed:20007272). (Microbial infection) Interacts (via CARD domain) with Human respiratory syncytial virus A non-structural protein 2 (NS2) and this interaction disrupts its interaction with MAVS/IPS1, impeding downstream IRF3 activation (PubMed:19193793). (Microbial infection) Interacts with Rotavirus A non-structural protein 1 (NSP1) and this interaction induces down-regulation of DDX58/RIG-I (PubMed:22152002). (Microbial infection) Interacts with herpes simplex virus 1 protein US11; this interaction prevents the interaction of MAVS/IPS1 to DDX58 (PubMed:22301138). (Microbial infection) Interacts with herpes simplex virus 1 protein UL37; this interaction deaminates DDX58 and inhibits its activation.

Helicase, Hydrolase, RNA-binding