%0 Journal Article
%T Identification of Potential Drug Targets Implicated in Parkinson's Disease from Human Genome: Insights of Using Fused Domains in Hypothetical Proteins as Probes
%A N. Rathankar
%A K. A. Nirmala
%A Varun Khanduja
%A H. G. Nagendra
%J ISRN Neurology
%D 2011
%R 10.5402/2011/265253
%X High-throughput genome sequencing has led to data explosion in sequence databanks, with an imbalance of sequence-structure-function relationships, resulting in a substantial fraction of proteins known as hypothetical proteins. Functions of such proteins can be assigned based on the analysis and characterization of the domains that they are made up of. Domains are basic evolutionary units of proteins and most proteins contain multiple domains. A subset of multidomain proteins is fused domains (overlapping domains), wherein sequence overlaps between two or more domains occur. These fused domains are a result of gene fusion events and their implication in diseases is well established. Hence, an attempt has been made in this paper to identify the fused domain containing hypothetical proteins from human genome homologous to parkinsonian targets present in KEGG database. The results of this research identified 18 hypothetical proteins, with domains fused with ubiquitin domains and having homology with targets present in parkinsonian pathway. 1. Introduction Hypothetical proteins basically are defined as ¡°a protein coded by a gene with no known function based on its DNA sequence¡± [2]. Certain regions in hypothetical proteins are highly conserved between species in both composition and sequence. Proteins with such regions are annotated as conserved hypothetical proteins and range from 13% in E. coli and 14% in Rickettsia prowazekii to 40% in Pyrococcus abyssi and 47% in Plasmodium falciparum [3]. The human genome too has about 20% of them classified as hypothetical [4¨C6]. The function of such proteins can be predicted based on the arrangement of distinct domains [7] in them since this arrangement in proteomes reflects the fundamental evolutionary differences in their genomes [8]. But with proteins containing more than one domain, the general function can only be suggested. The difficulty one observes in predicting a protein¡¯s function based on domains alone would be when there are no clear cut boundaries between any two domains. Proteins with appreciable overlap in their domain boundaries are known as fused domain containing proteins or chimeric proteins. Such proteins are formed by the process of gene duplication and combination during evolution. Proteins containing such domains are created by joining two or more genes, which originally code for separate proteins [9]. Translation of this fusion gene results in a single polypeptide with functional properties derived from each of the original proteins [10]. Analysis of these fused domains in related genomes
%U http://www.hindawi.com/journals/isrn.neurology/2011/265253/