Proteome-wide analysis of single-nucleotide variations in the N-glycosylation sequon of human genes.
N-linked glycosylation is one of the most frequent post-translational modifications of proteins with a profound impact on their biological function. Besides other functions, N-linked glycosylation assists in protein folding, determines protein orientation at the cell surface, or protects proteins fr...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3346765?pdf=render |
| _version_ | 1818541335570808832 |
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| author | Raja Mazumder Krishna Sudeep Morampudi Mona Motwani Sona Vasudevan Radoslav Goldman |
| author_facet | Raja Mazumder Krishna Sudeep Morampudi Mona Motwani Sona Vasudevan Radoslav Goldman |
| author_sort | Raja Mazumder |
| collection | DOAJ |
| description | N-linked glycosylation is one of the most frequent post-translational modifications of proteins with a profound impact on their biological function. Besides other functions, N-linked glycosylation assists in protein folding, determines protein orientation at the cell surface, or protects proteins from proteases. The N-linked glycans attach to asparagines in the sequence context Asn-X-Ser/Thr, where X is any amino acid except proline. Any variation (e.g. non-synonymous single nucleotide polymorphism or mutation) that abolishes the N-glycosylation sequence motif will lead to the loss of a glycosylation site. On the other hand, variations causing a substitution that creates a new N-glycosylation sequence motif can result in the gain of glycosylation. Although the general importance of glycosylation is well known and acknowledged, the effect of variation on the actual glycoproteome of an organism is still mostly unknown. In this study, we focus on a comprehensive analysis of non-synonymous single nucleotide variations (nsSNV) that lead to either loss or gain of the N-glycosylation motif. We find that 1091 proteins have modified N-glycosylation sequons due to nsSNVs in the genome. Based on analysis of proteins that have a solved 3D structure at the site of variation, we find that 48% of the variations that lead to changes in glycosylation sites occur at the loop and bend regions of the proteins. Pathway and function enrichment analysis show that a significant number of proteins that gained or lost the glycosylation motif are involved in kinase activity, immune response, and blood coagulation. A structure-function analysis of a blood coagulation protein, antithrombin III and a protease, cathepsin D, showcases how a comprehensive study followed by structural analysis can help better understand the functional impact of the nsSNVs. |
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| format | Article |
| id | doaj.art-da40f953626d4ed899d175b99d09eb46 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T22:07:56Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-da40f953626d4ed899d175b99d09eb462022-12-22T00:48:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3621210.1371/journal.pone.0036212Proteome-wide analysis of single-nucleotide variations in the N-glycosylation sequon of human genes.Raja MazumderKrishna Sudeep MorampudiMona MotwaniSona VasudevanRadoslav GoldmanN-linked glycosylation is one of the most frequent post-translational modifications of proteins with a profound impact on their biological function. Besides other functions, N-linked glycosylation assists in protein folding, determines protein orientation at the cell surface, or protects proteins from proteases. The N-linked glycans attach to asparagines in the sequence context Asn-X-Ser/Thr, where X is any amino acid except proline. Any variation (e.g. non-synonymous single nucleotide polymorphism or mutation) that abolishes the N-glycosylation sequence motif will lead to the loss of a glycosylation site. On the other hand, variations causing a substitution that creates a new N-glycosylation sequence motif can result in the gain of glycosylation. Although the general importance of glycosylation is well known and acknowledged, the effect of variation on the actual glycoproteome of an organism is still mostly unknown. In this study, we focus on a comprehensive analysis of non-synonymous single nucleotide variations (nsSNV) that lead to either loss or gain of the N-glycosylation motif. We find that 1091 proteins have modified N-glycosylation sequons due to nsSNVs in the genome. Based on analysis of proteins that have a solved 3D structure at the site of variation, we find that 48% of the variations that lead to changes in glycosylation sites occur at the loop and bend regions of the proteins. Pathway and function enrichment analysis show that a significant number of proteins that gained or lost the glycosylation motif are involved in kinase activity, immune response, and blood coagulation. A structure-function analysis of a blood coagulation protein, antithrombin III and a protease, cathepsin D, showcases how a comprehensive study followed by structural analysis can help better understand the functional impact of the nsSNVs.http://europepmc.org/articles/PMC3346765?pdf=render |
| spellingShingle | Raja Mazumder Krishna Sudeep Morampudi Mona Motwani Sona Vasudevan Radoslav Goldman Proteome-wide analysis of single-nucleotide variations in the N-glycosylation sequon of human genes. PLoS ONE |
| title | Proteome-wide analysis of single-nucleotide variations in the N-glycosylation sequon of human genes. |
| title_full | Proteome-wide analysis of single-nucleotide variations in the N-glycosylation sequon of human genes. |
| title_fullStr | Proteome-wide analysis of single-nucleotide variations in the N-glycosylation sequon of human genes. |
| title_full_unstemmed | Proteome-wide analysis of single-nucleotide variations in the N-glycosylation sequon of human genes. |
| title_short | Proteome-wide analysis of single-nucleotide variations in the N-glycosylation sequon of human genes. |
| title_sort | proteome wide analysis of single nucleotide variations in the n glycosylation sequon of human genes |
| url | http://europepmc.org/articles/PMC3346765?pdf=render |
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