In-silico Functional and Structural Annotation of Rheumatoid arthritis linked Gene and Protein

Abstract

Background: Rheumatoid arthritis (RA) is an autoimmune disease marked by chronic inflammation and immune system dysregulation. The Ankyrin repeat domain 55 (ANKRD55) gene, located on chromosome 5q11.2, has been associated with RA susceptibility. Understanding the gene and protein characteristics could illuminate pathways involved in RA and aid in the development of targeted therapies. Objective: To conduct a detailed analysis of the ANKRD55 gene and protein, focusing on its structure, expression profile, functional domains, and polymorphisms, thereby establishing its role in RA and potential as a therapeutic target. Methods: Using bioinformatics tools, we analyzed ANKRD55's genomic localization (NCBI), peptide sequences (Uniprot), physicochemical properties (Protparam Server), signal peptides (SignalP v4.1), transmembrane helices (TMHMM), and glycosylation sites (NetNGlyc 1.0). Polymorphism and methylation patterns were examined using PolyPhen and MethyCancer, respectively. Splice variants were identified, and protein-protein interaction networks were assessed (STRING database). Protein domains were characterized, including the prediction of RhoGAP domains. Structural modeling was conducted to identify potential drug-binding pockets with the DoGSite Scorer server. Results: ANKRD55's expression was predominantly observed in the testis (RPKM 1.8) and to a lesser extent in lymph nodes (0.8), appendix (0.6), and brain (0.2). It encodes a 614-amino-acid protein with a molecular weight of approximately 68.4 kDa and a pI of 6.72. Six splice variants were identified, enriching the understanding of its potential isoform diversity. No significant N-glycosylation sites were predicted, and methylation analysis suggested a nuclear localization without DNA methylation sites. Structural analysis revealed drug-binding pockets with volumes ranging from 233.35 to 5389.58 A^3, with drug scores between 0.78 and 0.82. Conclusion: The study concludes that while several factors contribute to student satisfaction in public sector medical colleges, infrastructure and facilities, along with quality instructional materials and clinical exposure, are key drivers. Enhancing these areas could lead to a more positive educational experience for students.