RNF125
Domain
The C2HC RNF-type zinc finger and the linker region stabilize the RING-type zinc finger, leading to promote binding of the RING-type zinc finger to the ubiquitin-conjugating enzyme E2 (donor ubiquitin) (PubMed:27411375).
Function
E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins, such as RIGI, MAVS/IPS1, IFIH1/MDA5, JAK1 and p53/TP53 (PubMed:15843525, PubMed:17460044, PubMed:17643463, PubMed:25591766, PubMed:26027934, PubMed:26471729, PubMed:27411375). Acts as a negative regulator of type I interferon production by mediating ubiquitination of RIGI at 'Lys-181', leading to RIGI degradation (PubMed:17460044, PubMed:26471729). Mediates ubiquitination and subsequent degradation of p53/TP53 (PubMed:25591766). Mediates ubiquitination and subsequent degradation of JAK1 (PubMed:26027934). Acts as a positive regulator of T-cell activation (PubMed:15843525).
Involvement in disease
Tenorio syndrome
TNORS
A disease characterized by overgrowth, macrocephaly, and intellectual disability. Some patients may have mild hydrocephaly, hypoglycemia, and inflammatory diseases resembling Sjogren syndrome.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Autoubiquitinated, leading to its subsequent proteasomal degradation.
Tissue Specificity
Predominantly expressed in lymphoid tissues, including bone marrow, spleen and thymus. Also weakly expressed in other tissues. Predominant in the CD4(+) and CD8(+) T-cells, suggesting that it is preferentially confined to T-cells.
Cellular localization
- Golgi apparatus membrane
- Lipid-anchor
- Shows a reticular staining pattern within the cell and is probably expressed at other intracellular membranes in addition to the Golgi membrane. Not detected at the plasma membrane.
Alternative names
E3 ubiquitin-protein ligase RNF125, RING finger protein 125, T-cell RING activation protein 1, TRAC-1, RNF125