Ask about this productRelated genes to: KIAA1618 antibody
- Gene:
- RNF213 NIH gene
- Name:
- ring finger protein 213
- Previous symbol:
- C17orf27, KIAA1618, MYMY2
- Synonyms:
- KIAA1554, NET57, ALO17
- Chromosome:
- 17q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-03-05
- Date modifiied:
- 2019-04-16
Related products to: KIAA1618 antibody
Related articles to: KIAA1618 antibody
- Listeria monocytogenes (Lm) is an intracellular pathogen that can cause life-threatening systemic infections. Internalin C (InlC) is a secreted factor required for full Lm virulence in systemic models of infection by mechanisms that remain unclear. Here, we show that InlC binds to CYLD, a host deubiquitinase and regulator of innate immunity. Structurally, we reveal the LRR domain of InlC binds the CAP-Gly2 domain of CYLD, independently of InlC's binding site for other host target proteins. Lm strains harboring amino acid substitutions in InlC that selectively disrupt binding to CYLD were examined. We demonstrate that after Lm accesses the host cytosol, InlC recruits CYLD to ubiquitin-positive bacteria. Recruitment of CYLD was dependent on the host E3 ligase RNF213, a major initiator of ubiquitin-mediated defenses. Furthermore, InlC-CYLD binding contributed to Lm virulence in mice. Together, these findings reveal how a secreted bacterial factor promotes the recruitment of a host deubiquitinase to cytosolic bacteria in response to ubiquitin-mediated defenses. - Source: PubMed
Publication date: 2026/08/31
Ammendolia Dustin AEllison Cara JZheng YuelinCoyaud EtienneLaurent Estelle M NYan Bing-RuManning BriWaldmann Anna KTan Joel M JFrendo-Cumbo ScottLyons CarinaYoun Ji-YoungRaught BrianIreton KeithHiggins Darren EElliott Paul RBrumell John H - Quality control of biomolecules is vital for organismal health. While DNA repair and protein quality control are well understood, how cells monitor other important biomolecules such as glycogen remains ill-defined. The accumulation of aberrant, poorly branched glycogen into insoluble polyglucosan bodies causes severe disease. Here, we discover autophagy of ubiquitylated aberrant glycogen as a previously unrecognized quality control mechanism safeguarding the brain from polyglucosan buildup. This mechanism depends on the E3 ubiquitin ligase RNF213. Mice lacking ligase activity in RNF213 accumulate polyglucosan in cerebellum, pons, and hippocampus. Using cells engineered to produce polyglucosan, we show that RNF213 selectively ubiquitylates abnormal glycogen. Cryo-EM analysis of RNF213 bound to glycogen-derived maltoheptaose revealed its CBM20 domain binds linear oligosaccharides. Disrupting carbohydrate binding results in gain of E3 ligase activity towards physiological glycogen, indicating the CBM20 domain limits RNF213 activity towards physiological glycogen. Epistasis analysis places RNF213 upstream of LUBAC, suggesting a hierarchical network of multiple E3 ligases surveying glycogen quality. Ubiquitylated polyglucosan recruits the autophagy receptors SQSTM1, TAX1BP1, and optineurin, thereby triggering uptake into autophagosomes. These findings identify RNF213 as a quality control factor preventing polyglucosan accumulation in astrocytes through direct ubiquitylation of polyglucosan, revealing an essential role for non-protein ubiquitylation in glycogen quality control. - Source: PubMed
Publication date: 2026/09/15
Yip Matthew C JNaydenova KaterinaOtten Elsje GHeatley AlexanderMoe AgnesAnton Leoniede Los Reyes-Ramírez LucíaJolin Helen ELangevin FredericWiacek MichalFranco CatarinaBertolotti AnneKukulski WandaMcKenzie Andrew N JRandow Felix - RNF213 was originally identified as a susceptibility gene for Moyamoya disease (MMD), and its variants are also associated with other vascular occlusive disorders, including pulmonary arterial hypertension and large-artery atherosclerosis. RNF213 encodes a large protein with AAA+ ATPase and E3 ubiquitin ligase activities and has been implicated in vasculopathy as well as cellular responses to microbial infection and lipid stress. However, the precise biological functions of RNF213 and the pathogenic mechanisms underlying disease-associated mutations remain poorly understood. Recent studies have suggested lipid-induced stress may play a key role in MMD pathogenesis. Therefore, we performed temporal transcriptomic analyses to identify RNF213-regulated signaling pathways in response to palmitate, the most common saturated fatty acid. Our results demonstrate that RNF213 is required for activation of apoptosis, the unfolded protein response, and NFκB signaling, as well as for the regulation of autophagy and oxidative stress responses following palmitate exposure. These functions were dependent on both the AAA+ ATPase and RZ-finger domains of RNF213 while MMD-associated RNF213 mutations enhanced palmitate-induced signaling responses. Together, these findings suggest that gain-of-function RNF213 mutations, combined with dysregulated lipid metabolism, contribute to the pathogenesis of RNF213-associated vasculopathies. - Source: PubMed
Publication date: 2026/09/01
Huang QianyingTezuka TohruIida KeiYang LirongKoizumi AkioMineharu YoheiMizushima TsunehiroKim MinsooYoussefian Shohab - Moyamoya disease (MMD) is an idiopathic cerebrovascular disorder in which chronic inflammation has been implicated, along with genetic susceptibility, including the RNF213 variants. In this study, we examined the relationship between type 2 inflammation and MMD. - Source: PubMed
Publication date: 2026/08/25
Park SilsuMineharu YoheiFunaki TakeshiChihara HideoSasagasako TomokiKamata TakahikoNakajima KotaMiyamoto SusumuArakawa Yoshiki - The cytokine gamma-interferon promotes antimicrobial cell-autonomous immunity by inducing hundreds of interferon-stimulated genes (ISGs). Among these ISGs is the ubiquitin E3 ligase RNF213 which protects host cells from a wide range of intracellular pathogens including the obligate intracellular bacterium The human pathogen normally employs its secreted virulence effector GarD to evade RNF213-mediated killing. However, in the absence of GarD, RNF213 is recruited to the vacuolar compartment in which replicates, called the inclusion. Once localized to inclusions, RNF213 ubiquitylates unknown substrates associated with the inclusion membrane and eliminates through mechanisms that are not yet defined. Ubiquitylation of pathogen-containing vacuoles often results in xenophagy, an autophagy-related defense program. Here, we show that although inclusions can be degraded via xenophagy, this pathway is dispensable for RNF213-dependent inhibition of replication. In addition to xenophagy, we find that RNF213 targeting can lead to antimicrobial inclusion lysis, thereby releasing bacteria into the host cell cytosol and triggering host cell death. Two cell death pathways occur downstream from RNF213-dependent inclusion rupture: a rapid cell death that despite its apoptosis-like morphology occurs independent of the apoptosis effectors caspase-3 and caspase-7 and instead requires the secreted protease CPAF, and a slow cell death that is independent of CPAF and instead requires the cytosolic proinflammatory pattern-recognition receptors RIG-I or STING. Thus, RNF213-driven lysis of pathogen-containing vacuoles represents a previously unrecognized mechanism by which RNF213 mediates host defense and triggers a host-pathogen battle over cytosolic immune activation. - Source: PubMed
Publication date: 2026/08/27
Dickinson Mary SWalsh Stephen CBastidas Robert JValdivia Raphael HCoers Jörn