Ask about this productRelated genes to: FAM105A antibody
- Gene:
- OTULINL NIH gene
- Name:
- OTU deubiquitinase with linear linkage specificity like
- Previous symbol:
- FAM105A
- Synonyms:
- FLJ11127, NET20
- Chromosome:
- 5p15.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-12-22
- Date modifiied:
- 2018-03-15
Related products to: FAM105A antibody
Related articles to: FAM105A antibody
- Angioedema is a life-threatening adverse drug reaction associated with renin-angiotensin-aldosterone system (RAAS) inhibitors, characterized by localized swelling in the deep layers of the skin. Well-established evidence indicates an up to fivefold higher incidence of RAAS inhibitor-induced angioedema in self-identified Black patients compared to White patients. The mechanisms underlying this health disparity remain poorly understood and are often attributed to race, a poor proxy for interindividual genetic similarity and social stressors. Here, we investigate the genetic and social determinants of RAAS inhibitor-induced angioedema as well as the etiology of this racial difference. In particular, we (1) discovered and as novel loci for RAAS inhibitor-induced angioedema, (2) confirmed the importance of bradykinin for this adverse drug reaction, (3) reported the first significant genome-wide association in self-identified Black participants, (4) identified alcohol use as an important social determinant, (5) demonstrated the strong role of variants enriched in 1000 Genomes African superpopulation-like genomes as the driver of racially differential angioedema risk, and (6) demonstrated the combined role of polygenic effect size and allele frequency differences in explaining these racial differences. Our results suggest that a clinical precision medicine tool may more precisely predict for whom RAAS inhibitors should be avoided (to prevent angioedema) compared to using race. These findings ultimately underscore the value of an evidence-based approach to removing race from treatment guidelines, which carries less potential harm than other removal strategies. - Source: PubMed
Publication date: 2026/01/08
Toda NanaseHaldar TanushreeTeerlink Craig CHu DongleiDanilov PeterHuntsman ScottLu MengTsao Philip STcheandjieu CatherineIribarren CarlosBress AdamLynch Julie AZiv EladOni-Orisan Akinyemi - Ubiquitination, and its control by deubiquitinating enzymes (DUBs), mediates protein stability, function, signaling and cell fate. The ovarian tumor (OTU) family DUB OTULIN (FAM105B) exclusively cleaves linear (Met1-linked) poly-ubiquitin chains and plays important roles in auto-immunity, inflammation and infection. OTULIN regulates Met1-linked ubiquitination downstream of tumor necrosis factor receptor 1 (TNFR1), toll-like receptor (TLR) and nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) receptor activation and interacts with the Met1 ubiquitin-specific linear ubiquitin chain assembly complex (LUBAC) E3 ligase. However, despite extensive research efforts, the receptor and cytosolic roles of OTULIN and the distributions of multiple Met1 ubiquitin-associated E3-DUB complexes in the regulation of cell fate still remain controversial and unclear. Apart from that, novel ubiquitin-independent OTULIN functions have emerged highlighting an even more complex role of OTULIN in cellular homeostasis. For example, OTULIN interferes with endosome-to-plasma membrane trafficking and the OTULIN-related pseudo-DUB OTULINL (FAM105A) resides at the endoplasmic reticulum (ER). Here, we discuss how OTULIN contributes to cell fate control and highlight novel ubiquitin-dependent and -independent functions. - Source: PubMed
Publication date: 2020/12/07
Weinelt Nadinevan Wijk Sjoerd J L - Pseudoenzymes have been identified across a diverse range of enzyme classes and fulfill important cellular functions. Examples of pseudoenzymes exist within ubiquitin conjugating and deubiquitinase (DUB) protein families. Here we characterize FAM105A/OTULINL, the only putative pseudodeubiquitinase of the ovarian tumor protease (OTU domain) family in humans. The crystal structure of FAM105A revealed that the OTU domain possesses structural deficiencies in both active site and substrate-binding infrastructure predicted to impair normal DUB function. We confirmed the absence of catalytic function against all ubiquitin linkages and an inability of FAM105A to bind ubiquitin compared with catalytically active FAM105B/OTULIN. FAM105A co-localized with KDEL markers and Lamin B1 at the endoplasmic reticulum (ER) and nuclear envelope, respectively. Accordingly, the FAM105A interactome exhibited significant enrichment in proteins localized to the ER/outer nuclear, Golgi and vesicular membranes. In light of undetectable deubiquitinase activity, we posit that FAM105A/OTULINL functions through its ability to mediate protein-protein interactions. - Source: PubMed
Publication date: 2019/05/02
Ceccarelli Derek FIvantsiv SofiiaMullin Amber AnneCoyaud EtienneManczyk NoahMaisonneuve PierreKurinov IgorZhao LiangGo ChrisGingras Anne-ClaudeRaught BrianCordes SabineSicheri Frank