DDX58 is K63 polyubiquitinated

Stable Identifier
R-HSA-918224
Type
Reaction
Species
Homo sapiens
Related Species
Rotavirus, Influenza A virus, Hepatitis C Virus
Compartment
Synonyms
K-63-linked polyubiquitination of RIG-I
Locations in the PathwayBrowser
Summation

On viral infection Probable ATP-dependent RNA helicase DDX58 (DDX58, RIG-I, RIG-1) undergoes robust ubiquitination at its N-terminal Caspase activation and recruitment domain (CARD) region. E3 ubiquitin/ISG15 ligase TRIM25 (TRIM25), a member of the tripartite motif (TRIM) protein family and E3 ubiquitin-protein ligase RNF135 (RNF135, REUL) are the E3 ligases involved in K63-linked polyubiquitination (K63polyUb) of DDX58. TRIM25 contains a cluster of domains including a RING-finger domain, a B box/coiled-coil domain and a SPRY domain. The interaction is mediated by the SPRY domain of TRIM25 and the N-terminal CARDs of DDX58. The polyubiquitin chains added by TRIM25 are unanchored. The lysine-172 (K172) residue of DDX58 is critical for efficient TRIM25-mediated ubiquitination and for binding of Mitochondrial antiviral-signaling protein (MAVS, IPS-1), as well as the ability of DDX58 to induce antiviral signal transduction. RNF135 associates with DDX58 through its PRY and SPRY domains. The K154, K164, and K172 residues of the DDX58 CARD domain were determined to be critical for efficient RNF135-mediated ubiquitination and for the ability of DDX58 to induce antiviral signal transduction. (Michaela et al. Goa et al. 2009).

Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ubiquitin-protein transferase activity of RNF135,TRIM25 [cytosol]
Physical Entity
Activity
Authored
Reviewed