Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Apr 23;3(3):228-237.
doi: 10.1016/j.gendis.2016.04.004. eCollection 2016 Sep.

Computational identification and analysis of neurodegenerative disease associated protein kinases in hominid genomes

Saranya Jayapalan  1 , Devika Subramanian  1 , Jeyakumar Natarajan  1
Affiliations

Computational identification and analysis of neurodegenerative disease associated protein kinases in hominid genomes

Saranya Jayapalan et al. Genes Dis. .

Abstract

Protein kinases play an important role in the incidence of neurodegenerative diseases. However their incidence in non-human primates is found to be very low. Small differences among the genomes might influence the disease susceptibilities. The present study deals with finding the genetic differences of protein kinases in humans and their three closest evolutionary partners chimpanzee, gorilla and orangutan for three neurodegenerative diseases namely, Alzheimer's, Parkinson's and Huntington's diseases. In total 47 human protein kinases associated with three neurodegenerative diseases and their orthologs from other three non-human primates were identified and analyzed for any possible susceptibility factors in humans. Multiple sequence alignment and pairwise sequence alignment revealed that, 18 human protein kinases including DYRK1A, RPS6KB1, and GRK6 contained significant indels and substitutions. Further phosphorylation site analysis revealed that eight kinases including MARK2 and LTK contained sites of phosphorylation exclusive to human genomes which could be particular candidates in determining disease susceptibility between human and non-human primates. Final pathway analysis of these eight kinases and their targets revealed that these kinases could have long range consequences in important signaling pathways which are associated with neurodegenerative diseases.

Keywords: Hominids; Interaction analysis; Neurodegenerative diseases; Phosphorylation sites; Protein kinases.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Gene-disease network for Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD).
Fig. 2
Fig. 2
a) Deletion of 22 amino acid residues in human RPS6KB1 sequence associated with Alzheimer's disease. b) Sequence variation in Huntington's disease associated GRK6 sequence.
Fig. 3
Fig. 3
The network of selected protein kinases and their targets. Red nodes: Protein kinases. Blue nodes: First neighbor interactors; Nodes that interact with more than one protein kinases are denoted with a corresponding increase in size. Links: Interactions.
Fig. 4
Fig. 4
a) Phosphorylation site inserted in human MARK2. b) Phosphorylation site variation and missed glycine repeats in human LTK.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Bertram L., Tanzi R.E. The genetic epidemiology of neurodegenerative disease. J Clin Invest. 2005;115:1449–1457. - PMC - PubMed
    1. Wetzel E.B., Schwarzenbacher R., Lipton S.A. Molecular pathways to neurodegeneration. Nat Med. 2004;10:S2–S9. - PubMed
    1. Delacourte A., Buee L. Tau pathology: a marker of neurodegenerative disorders. Curr Opin Neurol. 2000;13:371–376. - PubMed
    1. Perl D.P. Neuropathology of Alzheimer's disease. Mt Sinai J Med. 2010;77:32–42. - PMC - PubMed
    1. Maslow K. Alzheimer's disease facts and figures. Alzheimer's Dement. 2008;4:110–133. - PubMed