Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1
Roquin-1, also known as RING finger and C3H zinc finger protein 1 (RC3H1), or RING finger protein 198 (RNF198), is a ubiquitously expressed RNA-binding protein essential for degradation of inflammation-related mRNAs and maintenance of immune homeostasis. It is localized in cytoplasmic granules and binds to the 3' untranslated region (3'UTR) of inducible costimulator (ICOS) mRNA to post-transcriptionally repress its expression. Roquin-1 interacts with 3'UTR of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and tumor-necrosis factor-alpha (TNFalpha), and post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kappaB pathway. Moreover, Roquin-1 shares functions with its paralog Roquin-2 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Roquin-1 contains an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 ubiquitin-ligase function, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger that is involved in RNA recognition, typically contacting AU-rich elements. In addition, both N- and C-terminal to the ROQ domain are combined to form a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain that is highly likely to function as a RNA-binding domain.