ZCCHC3
Description
The ZCCHC3 (zinc finger CCHC-type containing 3) is a protein-coding gene located on chromosome 20.
ZCCHC3 is a nucleic acid-binding protein that plays a crucial role in the innate immune response against DNA and RNA viruses. It operates in the cytoplasm, where it binds to both DNA and RNA, facilitating the recognition of viral nucleic acids by key immune sensors. These sensors include RIGI, IFIH1/MDA5, and CGAS, which are responsible for detecting and responding to viral threats. ZCCHC3 acts as a co-sensor for dsDNA recognition by cGAS, enhancing the innate immune response against cytosolic dsDNA and DNA viruses. It achieves this by promoting the sensing of dsDNA by CGAS, leading to increased CGAS oligomerization and activation. ZCCHC3 also promotes the recognition of viral RNA by RIGI-like receptors (RLRs), specifically RIGI and IFIH1/MDA5, through two primary mechanisms. Firstly, it binds to dsRNA, enhancing the binding affinity of RIGI and IFIH1/MDA5 to dsRNA. Secondly, ZCCHC3 promotes the 'Lys-63'-linked ubiquitination of RIGI and IFIH1/MDA5, further activating these immune receptors.
ZCCHC3 is also known as C20orf99.
Associated Diseases
- plasma fibronectin deficiency
- Crigler-Najjar syndrome type 2
- transient familial neonatal hyperbilirubinemia
- gluthathione peroxidase deficiency
- Rotor syndrome
- Dubin-Johnson syndrome
- hypercholanemia, familial, 2
- hemolytic anemia due to glutathione reductase deficiency
- congenital lethal erythroderma
- Crigler-Najjar syndrome type 1
- neonatal intrahepatic cholestasis due to citrin deficiency
