DDX58 is K63 polyubiquitinated

Stable Identifier
Reaction [transition]
Homo sapiens
Related Species
Rotavirus, Influenza A virus, Hepatitis C Virus
K-63-linked polyubiquitination of RIG-I
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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).

Literature References
PubMed ID Title Journal Year
19017631 Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection

Oshiumi, H, Matsumoto, M, Hatakeyama, S, Seya, T

J Biol Chem 2009
17392790 TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity

Gack, MU, Shin, YC, Joo, CH, Urano, T, Liang, C, Sun, L, Takeuchi, O, Akira, S, Chen, Z, Inoue, S, Jung, JU

Nature 2007
20403326 Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity

Zeng, W, Sun, L, Jiang, X, Chen, X, Hou, F, Adhikari, A, Xu, M, Chen, ZJ

Cell 2010
19484123 REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I

Gao, D, Yang, YK, Wang, RP, Zhou, X, Diao, FC, Li, MD, Zhai, ZH, Jiang, ZF, Chen, DY

PLoS One 2009
Participant Of
Catalyst Activity
Catalyst Activity
ubiquitin-protein transferase activity of RNF135,TRIM25 [cytosol]
Physical Entity
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