Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity (PubMed:21799892, PubMed:26126547, PubMed:26278786, PubMed:26766444, PubMed:30705059, PubMed:32139119, PubMed:34012115). Acts as a key immune sensor by catalyzing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS (PubMed:34012115). Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains (PubMed:34012115). Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader (PubMed:34012115). Involved in lipid metabolism by regulating fat storage and lipid droplet formation; act by inhibiting the lipolytic process (PubMed:30705059). Also regulates lipotoxicity by inhibiting desaturation of fatty acids (PubMed:30846318). Also acts as an E3 ubiquitin-protein ligase via its RING-type zinc finger: mediates 'Lys-63'-linked ubiquitination of target proteins (PubMed:32139119, PubMed:33842849). Involved in the non-canonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway and promoting vessel regression (PubMed:26766444). Also has ATPase activity; ATPase activity is required for ubiquitination of LPS (PubMed:34012115). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. ATP + H2O = ADP + H(+) + phosphate Protein modification; protein ubiquitination. Monomer (By similarity). Interacts with UBE2L3/UBCH7; UBE2L3/UBCH7 is the most efficient ubiquitin-conjugating enzyme E2 for the ubiquitin ligase activity (By similarity). Interacts with UBE2N/UBC13; promoting 'Lys-63'-linked ubiquitination of target proteins (PubMed:32139119, PubMed:33842849). (Microbial infection) Interacts with M.tuberculosis protein Rv3655c, which impairs caspase-8 activation and suppresses macrophage apoptosis by blocking the extrinsic pathway. Widely expressed (at protein level). Major isoform detected in all tissues examined. Minor isoform with restricted expression. Down-regulated by let-7c miRNA, which binds to the 3'-UTR transcript of RNF213 (PubMed:26070522). Induced by pro-inflammatory cytokines (PubMed:26278786). (Microbial infection) Up-regulated in macrophages infected by M.tuberculosis. Composed of an N-terminal stalk, a dynein-like core comprised of two catalytically active and four inactive ATPase domains, and a C-terminal E3 module. The ATPase regions do not generate movement but rather act like an intricate molecular 'switch'. The RING-type zinc finger domain is required for the ubiquitin-protein ligase activity. The RZ-type (RNF213-ZNFX1) zinc-finger is required for the ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS). Autoubiquitinated. Disease susceptibility is associated with variants affecting the gene represented in this entry. A chromosomal aberration involving RNF213 is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALK. Belongs to the AAA ATPase family. The stoichiometry is unclear: was initially thought to form homohexamers (PubMed:24658080, PubMed:26126547). However, the electron microscopy structure showed that it is monomeric and is composed of six ATPase modules within a single polypeptide chain (By similarity). Truncated N-terminus. Probable cloning artifact. Truncated N-terminus. Truncated N-terminus. Truncated C-terminus. Truncated N-terminus. Truncated N-terminus.