Functional Annotation and Analysis of Dual Oxidase 1 (DUOX1): a Potential Anti-pyocyanin Immune Component

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.