Abstract : Domains are the functional units of protein that folds and functions independently from the rest of the protein. Ubiquitin associated domains (UBA) are approximately 45 amino acid residues that help in cellular processes like nucleotide excision repair, spindle pole body duplication and cell growth. In order to see the extent of sequential and functional diversity in this domain 13 different protein-containing UBA domains in humans were randomly selected and their respective domain was retrieved through the SMART database. Multiple Sequence Alignment shows except for two amino acid positions the rest of the positions were not conserved. Phylogenetic tree showed an evolutionary relationship between these domains and showed the SQSTM1 domain as an outlier. GO molecular functions analysis from UNIPROT, showed that though there were common functions shared by some of the domains they had unique functions associated with each of them. The same methods were applied for UBA domains in different organisms. The RAD23 protein domain was taken for further analysis through Jackhammer. 2 isoforms UBA1 and UBA2 were identified in RAD23. UBA2 was more conserved among reptiles, aves, mammalians, fishes and amphibians. Though functions are spread across the different organisms they seem to be not completely unrelated. Mutational analysis on mutations in the SQSTM1 gene domain, causing Paget disease of bone (PDB), was done in model organisms. MSA and CONSURF analysis showed that I424S (UK), G425R, and A427D associated with PDB were found to be highly conserved.

Keywords: UBA domain , Multiple sequence alignment, Conserved position, Sequestasome, functional diversity, Rad23, TNRC6C, UBE2K, UBAC1, UBL7, USP5, UBXN1, UBQLN3, MARK1, CBLB, and SQSTM1, Phylogenetic tree

| DOI: 10.17148/IARJSET.2022.9277