Identification and Analysis of Long Repeats of Proteins at the Domain Level

Abstract

Amino acid repeats play an important role in the structure and function of proteins. Analysis of long repeats in protein sequences enables one to understand their abundance, structure and function in the protein universe. In the present study, amino acid repeats of length >50 (long repeats) were identified in a non-redundant set of UniProt sequences using the RADAR program. The underlying structures and functions of these long repeats were carried out using the Gene3D for structural domains, Pfam for functional domains and enzyme and non-enzyme functional classification for catalytic and binding of the proteins. From a structural perspective, these long repeats seem to predominantly occur in certain architectures such as sandwich, bundle, barrel, and roll and within these architectures abundant in the superfolds. The lengths of the repeats within each fold are not uniform exhibiting different structures for different functions. We also observed that long repeats are in the domain regions of the family and are involved in the function of the proteins. After grouping based on enzyme and non-enzyme classes, we observed the abundant occurrence of long repeats in specific catalytic and binding of the proteins. In this study, we have analyzed the occurrence of long repeats in the protein sequence universe apart from well-characterized short tandem repeats in sequences and their structures and functions of the proteins at the domain level. The present study suggests that long repeats may play an important role in the structure and function of domains of the proteins.

Characterization of two bacterial multi-flavinylated proteins harboring multiple covalent flavin cofactors

“…Protein sequence analysis by using the RADAR (Rapid Automatic Detection and Alignment of Repeats in protein sequences tool, https://www.ebi.ac.uk/Tools/pfa/radar/ ) showed that both proteins harbor several highly homologous domains [21] . A previous study suggests that such organization of three/four long repeat sequences may hint to an important role in the structure and function of the protein [22] . TMHMM (TransMembrane prediction using Hidden Markov Models, https://dtu.biolib.com/DeepTMHMM ) [23] analysis predicted that both proteins have a secretion signal and a transmembrane sequence at their N-terminus [24] .…”

Search for Highly Divergent Tandem Repeats in Amino Acid Sequences

“…Thus, proteins with repeats represent structural elements of cells and tissues (e.g., collagen and keratin) and provide a framework for protein-protein interactions [8] or, conversely, prevent cross-domain aggregation [9]. They may have catalytic [10] or inhibitory activity [11]. Furthermore, changes in the number of repetitive motifs and their consensuses can lead to genetic diseases [12][13][14].…”

HPREP: a comprehensive database for human proteome repeats

“…Several web servers and tools such as RADAR, TRUST, XSTREAM, T-REKS, and PTRStalker etc., that use different methods of sub-optimal alignment, short seed expansion, K-means clustering and normalized BLOSUM-weighted edit distance [9][10][11][12][13] for repeats detection have been developed. Further, the repeats in the sequences of Protein Data Bank (PDB) [14] and UniProtKB/Swiss-Prot [15] identified by using RADAR have been analyzed at the structural and functional level. Several databases for amino acid repeats from different set of protein sequences were constructed for large scale analysis.…”