RNF144A
Domain
Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.
Function
E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:26216882). Mediates the ubiquitination and degradation of the DNA damage kinase PRKDC during DNA damage (PubMed:24979766). Positively regulates DNA virus or exogenous cytosolic DNA-triggered innate immune response by mediating STING1 ubiquitination and increasing its 'Lys-6'-linked ubiquitination and translocation from the endoplasmic reticulum to the Golgi leading to downstream signaling pathways (PubMed:37955227). Plays a positive role in EGF-dependent cell proliferation by prolonging EGF/EGFR signaling during EGF stimulation through EGFR ubiquitination (PubMed:30171075). Increases ERK activity independently of EGFR signaling by promoting polyubiquitination and subsequent degradation of VRK3 in the cytosol (PubMed:33067254).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Auto-ubiquitinated.
Sequence Similarities
Belongs to the RBR family. RNF144 subfamily.
Cellular localization
- Cell membrane
- Single-pass membrane protein
- Cytoplasmic vesicle membrane
- Endosome membrane
- Endoplasmic reticulum membrane
Alternative names
KIAA0161, RNF144, UBCE7IP4, RNF144A, E3 ubiquitin-protein ligase RNF144A, RING finger protein 144A, UbcM4-interacting protein 4, Ubiquitin-conjugating enzyme 7-interacting protein 4