Zinc finger CCHC domain-containing protein 3

Definition:

Nucleic acid-binding protein involved in innate immune response to DNA and RNA viruses. Binds DNA and RNA in the cytoplasm and acts by promoting recognition of viral nucleic acids by virus sensors, such as RIGI, IFIH1/MDA5 and CGAS. Acts as a co-sensor for recognition of double-stranded DNA (dsDNA) by cGAS in the cytoplasm, thereby playing a role in innate immune response to cytosolic dsDNA and DNA virus. Binds dsDNA and probably acts by promoting sensing of dsDNA by CGAS, leading to enhance CGAS oligomerization and activation. Promotes sensing of viral RNA by RIGI-like receptors proteins RIGI and IFIH1/MDA5 via two mechanisms: binds double-stranded RNA (dsRNA), enhancing the binding of RIGI and IFIH1/MDA5 to dsRNA and promotes 'Lys-63'-linked ubiquitination and subsequent activation of RIGI and IFIH1/MDA5.

References:

[1]. Huan Lian, et al. ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response. Nat Commun. 2018 Aug 22;9(1):3349. [Content Brief]

[2]. Huan Lian, et al. The Zinc-Finger Protein ZCCHC3 Binds RNA and Facilitates Viral RNA Sensing and Activation of the RIG-I-like Receptors. Immunity. 2018 Sep 18;49(3):438-448.e5. [Content Brief]

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