Dual Oxidase 1 (DUOX1) is a prominent immune system component primarily expressed in esophagus, lungs, skin, and urinary bladder including others. DUOX1 is involved in lactoperoxidase-mediated innate immunity at mucosal surfaces by generation of antimicrobial hypothiocyanite at the apical surface of epithelial lining. Upon detection of bacterial pathogens mainly Pseudomonas aeruginosa, DUOX1 is activated in bronchial epithelial cells. Both the host and pathogen enter a redox dual with DUOX1 and hypothiocyanite from host and Pyocyanin (PCN) as a redox active virulence factor from P. aeruginosa. The synergy of the both enzymes permanently oxidizes PCN and thus holds the potential to prevent PCN-induced virulence, which otherwise paves the way for establishment of persistent chronic infection. In this study, we structurally and functionally annotated the DUOX1, predicted its 3d structure, physio-chemical properties, post-translational modifications, and genetic polymorphism analysis with subsequent disease-associated single-nucleotide variations and their impact on DUOX1 functionality by employing in silico approaches. DUOX1 holds greater homology with gorilla and chimpanzee than other primates. The localization signal peptide was present at the beginning of the peptide with cleavage site at 22 aa position. Three distinct functional domains were observed based on homology: An_peroxidase, FRQ1, and oxido-reductase domains. Polymorphism analysis revealed > 60 SNPs associated with different cancers with probable damaging effects. No cancer-associated methylated island was observed for DUOX1. Three-dimensional structure was developed via homology modeling strategy. The proper annotation will help in characterization of DUOX1 and enhance our knowledge of its functionality and biological roles.

中文翻译：

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双氧化酶1（DUOX1）的功能注释和分析：潜在的抗花青素免疫成分。

双重氧化酶1（DUOX1）是主要在食道，肺，皮肤和膀胱等中表达的重要免疫系统成分。DUOX1通过在上皮衬里的根尖表面产生抗菌次硫氰酸盐而参与了在乳过氧化物酶介导的粘膜表面先天免疫中。在检测到主要为铜绿假单胞菌的细菌病原体后，DUOX1在支气管上皮细胞中被激活。宿主和病原体都与来自宿主的DUOX1和次硫氰酸盐以及绿脓杆菌的Pyocyanin（PCN）一起进入氧化还原对中，作为铜绿假单胞菌的氧化还原活性毒力因子。两种酶的协同作用会永久氧化PCN，因此具有预防PCN诱导的毒力的潜力，否则将为建立持久性慢性感染铺平道路。在这个研究中，我们在结构和功能上对DUOX1进行了注释，预测了其3d结构，理化性质，翻译后修饰以及遗传多态性分析，以及随后与疾病相关的单核苷酸变异及其通过计算机模拟方法对DUOX1功能的影响。与其他灵长类动物相比，DUOX1与大猩猩和黑猩猩的同源性更高。定位信号肽存在于该肽的开头，其切割位点在22个氨基酸位置。基于同源性观察到三个不同的功能域：An_peroxidase，FRQ1和氧化还原酶域。多态性分析显示> 60个与不同癌症相关的SNP，可能具有破坏作用。没有观察到与癌症相关的甲基化岛。通过同源建模策略开发了三维结构。正确的注释将有助于DUOX1的表征，并增强我们对其功能和生物学作用的了解。