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FUNCTION E3 ubiquitin-protein ligase component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:17006537, PubMed:19136968, PubMed:20005846, PubMed:21455173, PubMed:21455180, PubMed:21455181, PubMed:22863777, PubMed:28189684, PubMed:28481331). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:17006537, PubMed:19136968, PubMed:20005846, PubMed:21455173, PubMed:21455180, PubMed:21455181, PubMed:22863777, PubMed:28189684). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:21455173, PubMed:28189684). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex (PubMed:20005846, PubMed:27458237). The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria (PubMed:28481331, PubMed:34012115). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (PubMed:28481331). Recruited to the surface of bacteria by RNF213, which initiates the bacterial ubiquitin coat (PubMed:34012115). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:28481331, PubMed:34012115). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (PubMed:23708998). RNF31 is required for linear ubiquitination of BCL10, thereby promoting TCR-induced NF-kappa-B activation (PubMed:27777308). Binds polyubiquitin of different linkage types (PubMed:23708998).CATALYTIC ACTIVITY [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31 (PubMed:17006537, PubMed:21455173, PubMed:21455180, PubMed:21455181, PubMed:28481331). LUBAC has a MW of approximately 600 kDa suggesting a heteromultimeric assembly of its subunits (PubMed:17006537, PubMed:21455173, PubMed:21455180, PubMed:21455181). Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner (PubMed:20005846). Interacts (via the PUB domain) with OTULIN (via the PIM motif); the interaction is direct (PubMed:23708998, PubMed:24726323, PubMed:24726327). Interacts (via the PUB domain) with VCP (via the PIM motif) (PubMed:24726327). Interacts (via the PUB domain) with SPATA2 (via the PIM motif); interaction is direct and bridges RNF31 and CYLD (PubMed:27458237, PubMed:27545878, PubMed:27591049, PubMed:28189684). Interacts with CYLD; the interaction is indirect and is mediated via SPATA2 (PubMed:26997266, PubMed:27458237, PubMed:27545878). Interacts with MUSK (By similarity). Interacts with CARD11, promoting linear ubiquitination of BCL10 (PubMed:27777308).SUBUNIT (Microbial infection) Interacts with S.flexneri E3 ubiquitin-protein ligases IpaH1.4 and IpaH2.5, leading to its ubiquitination.INTERACTION Expressed in both normal and transformed breast epithelial cell lines.DOMAIN The PUB domain mediates interaction with the PIM motifs of VCP and RNF31, with a strong preference for RNF31.DOMAIN The RanBP2-type zinc fingers mediate the specific interaction with ubiquitin.DOMAIN The UBA domain mediates association with RBCK1/HOIL1 via interaction with its UBL domain.DOMAIN RING 1 and IBR zinc-fingers catalyze the first step transfer of ubiquitin from the E2 onto RING 2, to transiently form a HECT-like covalent thioester intermediate.DOMAIN The linear ubiquitin chain determining domain (LDD) mediates the final transfer of ubiquitin from RING 2 onto the N-terminus of a target ubiquitin.PTM Autoubiquitinated (PubMed:24726323). Interaction with OTULIN is required to suppress formation of 'Met-1'-linked polyubiquitin chains and prevent subsequent inactivation of the LUBAC complex (PubMed:24726323).PTM Cleaved by caspase during apoptosis.PTM (Microbial infection) Ubiquitinated by S.flexneri E3 ubiquitin-protein ligases IpaH1.4 and IpaH2.5, leading to its degradation by the proteasome, thereby preventing formation of the bacterial ubiquitin coat and activation of innate immunity.DISEASE The disease is caused by variants affecting the gene represented in this entry. The genetic variation producing the missense variant p.Q399H, associated with IMD115, has been shown to predominantly affect splicing, leading to in-frame skipping of exon 9 and lack of 84 amino acids from residue 496 to 579.SIMILARITY Belongs to the RBR family.SEQUENCE CAUTION Truncated C-terminus.SEQUENCE CAUTION Intron retention.
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