RNF31
The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. The encoded protein is the E3 ubiquitin-protein ligase component of the linear ubiquitin chain assembly complex. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]
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:28481331, PubMed:28189684).
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).
Biological Process
Biological Process CD40 signaling pathwayISS:BHF-UCL
Biological Process defense response to bacteriumManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of necroptotic processIEA:Ensembl
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of protein targeting to mitochondrionManual Assertion Based On ExperimentHMP:ParkinsonsUK-UCL
Biological Process positive regulation of xenophagyManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein linear polyubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein polyubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process T cell receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
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).
Cleaved by caspase during apoptosis.
(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.