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). {ECO:0000250, ECO:0000269|PubMed:24979766, ECO:0000269|PubMed:26216882, ECO:0000269|PubMed:30171075, ECO:0000269|PubMed:33067254, ECO:0000269|PubMed:37955227}. This is the function of ENSG00000151692 (RNF144A, ring finger protein 144A).