E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (    ). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 . Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair . Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 ( ). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC . Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination . Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN . May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation . Mediates polyubiquitination of isoform 2 of PA2G4 . Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 . Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling .
Subcellular locations: Cytoplasm, Nucleus, Mitochondrion
Mainly expressed in the cytoplasm of most tissues, except in the nucleus of spermatogonia, primary spermatocytes and neuronal cells (By similarity). Recruited to mitochondria following interaction with AMBRA1 .
Weakly expressed in heart, brain and placenta but not in other tissues. Expressed in a number of cell lines, predominantly in those from colorectal carcinomas.