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Comprehensive in-silico prediction of damage associated SNPs in Human Prolidase gene

Prolidase is cytosolic manganese dependent exopeptidase responsible for the catabolism of imido di and tripeptides. Prolidase levels have been associated with a number of diseases such as bipolar disorder, erectile dysfunction and varied cancers. Single nucleotide polymorphism present in coding regi...

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Autores principales: Bhatnager, Richa, Dang, Amita S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013436/
https://www.ncbi.nlm.nih.gov/pubmed/29930383
http://dx.doi.org/10.1038/s41598-018-27789-0
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author Bhatnager, Richa
Dang, Amita S.
author_facet Bhatnager, Richa
Dang, Amita S.
author_sort Bhatnager, Richa
collection PubMed
description Prolidase is cytosolic manganese dependent exopeptidase responsible for the catabolism of imido di and tripeptides. Prolidase levels have been associated with a number of diseases such as bipolar disorder, erectile dysfunction and varied cancers. Single nucleotide polymorphism present in coding region of proteins (nsSNPs) has the potential to alter the primary structure as well as function of the protein. Hence, it becomes necessary to differentiate the potential harmful nsSNPs from the neutral ones. 19 nsSNPs were predicted as damaging by in-silico analysis of 298 nsSNPs retrieved from dbSNP database. Consurf analysis showed 18 out of 19 substitutions were present in the conserved regions. 4 substitutions (D276N, D287N, E412K, and G448R) that observed to have damaging effect are present in catalytic pocket. Four SNPs listed in splice site region were found to affect splicing of mRNA by altering acceptor site. On 3′UTR scan of 77 SNPs listed in SNP database, 9 SNPs were lead to alter miRNA target sites. These results provide a filtered data to explore the effect of uncharacterized nsSNP and SNP related to UTRs and splice site of prolidase to find their association with the disease susceptibility and to design the target dependent drugs for therapeutics.
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spelling pubmed-60134362018-06-27 Comprehensive in-silico prediction of damage associated SNPs in Human Prolidase gene Bhatnager, Richa Dang, Amita S. Sci Rep Article Prolidase is cytosolic manganese dependent exopeptidase responsible for the catabolism of imido di and tripeptides. Prolidase levels have been associated with a number of diseases such as bipolar disorder, erectile dysfunction and varied cancers. Single nucleotide polymorphism present in coding region of proteins (nsSNPs) has the potential to alter the primary structure as well as function of the protein. Hence, it becomes necessary to differentiate the potential harmful nsSNPs from the neutral ones. 19 nsSNPs were predicted as damaging by in-silico analysis of 298 nsSNPs retrieved from dbSNP database. Consurf analysis showed 18 out of 19 substitutions were present in the conserved regions. 4 substitutions (D276N, D287N, E412K, and G448R) that observed to have damaging effect are present in catalytic pocket. Four SNPs listed in splice site region were found to affect splicing of mRNA by altering acceptor site. On 3′UTR scan of 77 SNPs listed in SNP database, 9 SNPs were lead to alter miRNA target sites. These results provide a filtered data to explore the effect of uncharacterized nsSNP and SNP related to UTRs and splice site of prolidase to find their association with the disease susceptibility and to design the target dependent drugs for therapeutics. Nature Publishing Group UK 2018-06-21 /pmc/articles/PMC6013436/ /pubmed/29930383 http://dx.doi.org/10.1038/s41598-018-27789-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Bhatnager, Richa
Dang, Amita S.
Comprehensive in-silico prediction of damage associated SNPs in Human Prolidase gene
title Comprehensive in-silico prediction of damage associated SNPs in Human Prolidase gene
title_full Comprehensive in-silico prediction of damage associated SNPs in Human Prolidase gene
title_fullStr Comprehensive in-silico prediction of damage associated SNPs in Human Prolidase gene
title_full_unstemmed Comprehensive in-silico prediction of damage associated SNPs in Human Prolidase gene
title_short Comprehensive in-silico prediction of damage associated SNPs in Human Prolidase gene
title_sort comprehensive in-silico prediction of damage associated snps in human prolidase gene
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013436/
https://www.ncbi.nlm.nih.gov/pubmed/29930383
http://dx.doi.org/10.1038/s41598-018-27789-0
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