TRIM22
Domain
The C-terminal SPRY domain is required for the transcriptional suppressor activity, probably by mediating correct nuclear localization. Residues 491-494 are essential for nuclear localization and nuclear bodies formation.
The RING domain is essential for antiviral activity and for TRIM22 nuclear bodies (NB) formation but is not necessary for nuclear localization.
Function
Interferon-induced E3 ubiquitin ligase that plays important roles in innate and adaptive immunity (PubMed:25683609, PubMed:35777501). Restricts the replication of many viruses including HIV-1, encephalomyocarditis virus (EMCV), hepatitis B virus (HBV), hepatitis C virus (HCV) or Zika virus (ZIKV) (PubMed:25683609, PubMed:35777501, PubMed:36042495). Mechanistically, negatively regulates HCV replication by promoting ubiquitination and subsequent degradation of viral NS5A (PubMed:25683609). Acts also by promoting the degradation of Zika virus NS1 and NS3 proteins through proteasomal degradation (PubMed:36042495). Acts as a suppressor of basal HIV-1 LTR-driven transcription by preventing Sp1 binding to the HIV-1 promoter (PubMed:26683615). Plays also a role in antiviral immunity by co-regulating together with NT5C2 the RIGI/NF-kappa-B pathway by promoting 'Lys-63'-linked ubiquitination of RIGI, while NT5C2 is responsible for 'Lys-48'-linked ubiquitination of RIGI (PubMed:36159777). Participates in adaptive immunity by suppressing the amount of MHC class II protein in a negative feedback manner in order to limit the extent of MHC class II induction (PubMed:35777501).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Auto-ubiquitinated.
Sequence Similarities
Belongs to the TRIM/RBCC family.
Tissue Specificity
Strongly expressed in peripheral blood leukocytes, spleen, thymus, and ovary. Expressed at basal levels in other tissues.
Cellular localization
- Cytoplasm
- Nucleus
- Nucleus speckle
- Nucleus
- Cajal body
- Localizes predominantly to the nucleus, found in cytoplasm to some extent. Forms distinct nuclear bodies that undergo dynamic changes during cell cycle progression. Nuclear bodies start to form in the early G0/G1 phase but become speckle-like in the S-phase and completely dispersed in mitosis. 35% of TRIM22 nuclear bodies overlap or are found adjacent to Cajal bodies.
Alternative names
RNF94, STAF50, TRIM22, E3 ubiquitin-protein ligase TRIM22, 50 kDa-stimulated trans-acting factor, RING finger protein 94, RING-type E3 ubiquitin transferase TRIM22, Staf-50, Tripartite motif-containing protein 22