scholarly journals Nonsynonymous Single-Nucleotide Variations on Some Posttranslational Modifications of Human Proteins and the Association with Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Bo Sun ◽  
Menghuan Zhang ◽  
Peng Cui ◽  
Hong Li ◽  
Jia Jia ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Single Nucleotide ◽  
Inherited Diseases ◽  
Cellular Processes ◽  
Protein Functions ◽  
Human Proteins ◽  
Working Together ◽  
Single Nucleotide Variations ◽  
Protein Posttranslational Modifications ◽  
Relationship Of

Protein posttranslational modifications (PTMs) play key roles in a variety of protein activities and cellular processes. Different PTMs show distinct impacts on protein functions, and normal protein activities are consequences of all kinds of PTMs working together. With the development of high throughput technologies such as tandem mass spectrometry (MS/MS) and next generation sequencing, more and more nonsynonymous single-nucleotide variations (nsSNVs) that cause variation of amino acids have been identified, some of which result in the damage of PTMs. The damaged PTMs could be the reason of the development of some human diseases. In this study, we elucidated the proteome wide relationship of eight damaged PTMs to human inherited diseases and cancers. Some human inherited diseases or cancers may be the consequences of the interactions of damaged PTMs, rather than the result of single damaged PTM site.

scholarly journals Proteome-wide analysis of nonsynonymous single-nucleotide variations in active sites of human proteins

FEBS Journal ◽  
2013 ◽  
Vol 280 (6) ◽  
pp. 1542-1562 ◽  
Author(s):  
Hayley Dingerdissen ◽  
Mona Motwani ◽  
Konstantinos Karagiannis ◽  
Vahan Simonyan ◽  
Raja Mazumder
Keyword(s):  
Active Sites ◽  
Single Nucleotide ◽  
Human Proteins ◽  
Single Nucleotide Variations

scholarly journals Posttranslational modifications in proteins: resources, tools and prediction methods

Database ◽  
2021 ◽  
Author(s):  
Shahin Ramazi ◽  
Javad Zahiri
Keyword(s):  
Computational Methods ◽  
Posttranslational Modifications ◽  
Side Chain ◽  
Amino Acid Side Chain ◽  
Cellular Processes ◽  
Online Databases ◽  
Different Types ◽  
Protein Functions ◽  
And Function ◽  
Molecular Regulatory Mechanisms

Abstract Posttranslational modifications (PTMs) refer to amino acid side chain modification in some proteins after their biosynthesis. There are more than 400 different types of PTMs affecting many aspects of protein functions. Such modifications happen as crucial molecular regulatory mechanisms to regulate diverse cellular processes. These processes have a significant impact on the structure and function of proteins. Disruption in PTMs can lead to the dysfunction of vital biological processes and hence to various diseases. High-throughput experimental methods for discovery of PTMs are very laborious and time-consuming. Therefore, there is an urgent need for computational methods and powerful tools to predict PTMs. There are vast amounts of PTMs data, which are publicly accessible through many online databases. In this survey, we comprehensively reviewed the major online databases and related tools. The current challenges of computational methods were reviewed in detail as well.

scholarly journals E3 ligase Nedd4l promotes antiviral innate immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Peng Gao ◽  
Xianwei Ma ◽  
Ming Yuan ◽  
Yulan Yi ◽  
Guoke Liu ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Type I Interferon ◽  
Zinc Fingers ◽  
E3 Ligase ◽  
Type I ◽  
E3 Ligases ◽  
Protein Posttranslational Modifications ◽  
Antiviral Innate Immunity

AbstractUbiquitination is one of the most prevalent protein posttranslational modifications. Here, we show that E3 ligase Nedd4l positively regulates antiviral immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3. Deficiency of Nedd4l significantly impairs type I interferon and proinflammatory cytokine production induced by virus infection both in vitro and in vivo. Nedd4l deficiency inhibits virus-induced ubiquitination of TRAF3, the binding between TRAF3 and TBK1, and subsequent phosphorylation of TBK1 and IRF3. Nedd4l directly interacts with TRAF3 and catalyzes K29-linked ubiquitination of Cys56 and Cys124, two cysteines that constitute zinc fingers, resulting in enhanced association between TRAF3 and E3 ligases, cIAP1/2 and HECTD3, and also increased K48/K63-linked ubiquitination of TRAF3. Mutation of Cys56 and Cys124 diminishes Nedd4l-catalyzed K29-linked ubiquitination, but enhances association between TRAF3 and the E3 ligases, supporting Nedd4l promotes type I interferon production in response to virus by catalyzing ubiquitination of the cysteines in TRAF3.

Targeted proteomics of myofilament phosphorylation and other protein posttranslational modifications

2014 ◽  
Vol 8 (7-8) ◽  
pp. 543-553 ◽  
Author(s):  
Genaro A. Ramirez-Correa ◽  
Maria Isabel Martinez-Ferrando ◽  
Pingbo Zhang ◽  
Anne M. Murphy
Keyword(s):  
Posttranslational Modifications ◽  
Targeted Proteomics ◽  
Protein Posttranslational Modifications

scholarly journals Cytosine and adenine deaminase base-editors induce broad and nonspecific changes in gene expression and splicing

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jiao Fan ◽  
Yige Ding ◽  
Chao Ren ◽  
Ziguo Song ◽  
Jie Yuan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Double Strand Breaks ◽  
Great Promise ◽  
Single Nucleotide ◽  
Strand Breaks ◽  
Dna Base ◽  
Target Dna ◽  
Single Nucleotide Variations ◽  
Adenine Deaminase ◽  
Target Rna

AbstractCytosine or adenine base editors (CBEs or ABEs) hold great promise in therapeutic applications because they enable the precise conversion of targeted base changes without generating of double-strand breaks. However, both CBEs and ABEs induce substantial off-target DNA editing, and extensive off-target RNA single nucleotide variations in transfected cells. Therefore, the potential effects of deaminases induced by DNA base editors are of great importance for their clinical applicability. Here, the transcriptome-wide deaminase effects on gene expression and splicing is examined. Differentially expressed genes (DEGs) and differential alternative splicing (DAS) events, induced by base editors, are identified. Both CBEs and ABEs generated thousands of DEGs and hundreds of DAS events. For engineered CBEs or ABEs, base editor-induced variants had little effect on the elimination of DEGs and DAS events. Interestingly, more DEGs and DAS events are observed as a result of over expressions of cytosine and adenine deaminases. This study reveals a previously overlooked aspect of deaminase effects in transcriptome-wide gene expression and splicing, and underscores the need to fully characterize such effects of deaminase enzymes in base editor platforms.

scholarly journals Deciphering and engineering chromodomain-methyllysine peptide recognition

2018 ◽  
Vol 4 (11) ◽  
pp. eaau1447 ◽  
Author(s):  
Ryan Hard ◽  
Nan Li ◽  
Wei He ◽  
Brian Ross ◽  
Gary C. H. Mo ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Large Scale ◽  
Regulation Of Gene Expression ◽  
Live Cells ◽  
Lysine Methylation ◽  
Dynamic Regulation ◽  
Peptide Recognition ◽  
Protein Functions ◽  
Domain Peptide

Posttranslational modifications (PTMs) play critical roles in regulating protein functions and mediating protein-protein interactions. An important PTM is lysine methylation that orchestrates chromatin modifications and regulates functions of non-histone proteins. Methyllysine peptides are bound by modular domains, of which chromodomains are representative. Here, we conducted the first large-scale study of chromodomains in the human proteome interacting with both histone and non-histone methyllysine peptides. We observed significant degenerate binding between chromodomains and histone peptides, i.e., different histone sites can be recognized by the same set of chromodomains, and different chromodomains can share similar binding profiles to individual histone sites. Such degenerate binding is not dictated by amino acid sequence or PTM motif but rather rooted in the physiochemical properties defined by the PTMs on the histone peptides. This molecular mechanism is confirmed by the accurate prediction of the binding specificity using a computational model that captures the structural and energetic patterns of the domain-peptide interaction. To further illustrate the power and accuracy of our model, we used it to effectively engineer an exceptionally strong H3K9me3-binding chromodomain and to label H3K9me3 in live cells. This study presents a systematic approach to deciphering domain-peptide recognition and reveals a general principle by which histone modifications are interpreted by reader proteins, leading to dynamic regulation of gene expression and other biological processes.

scholarly journals Proteome-Wide Analysis of Single-Nucleotide Variations in the N-Glycosylation Sequon of Human Genes

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e36212 ◽  
Author(s):  
Raja Mazumder ◽  
Krishna Sudeep Morampudi ◽  
Mona Motwani ◽  
Sona Vasudevan ◽  
Radoslav Goldman
Keyword(s):  
Single Nucleotide ◽  
Human Genes ◽  
Single Nucleotide Variations

scholarly journals Sequence variability ofChrysanthemum stunt viroidin different chrysanthemum cultivars

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2933 ◽  
Author(s):  
Hoseong Choi ◽  
Yeonhwa Jo ◽  
Ju-Yeon Yoon ◽  
Seung-Kook Choi ◽  
Won Kyong Cho
Keyword(s):  
Infectious Agents ◽  
Sequence Variability ◽  
Rt Pcr ◽  
Genome Sequences ◽  
Single Nucleotide ◽  
Genomic Variations ◽  
The Family ◽  
Chrysanthemum Plant ◽  
Single Nucleotide Variations ◽  
Polymerase Chain

Viroids are the smallest infectious agents, and their genomes consist of a short single strand of RNA that does not encode any protein.Chrysanthemum stunt viroid(CSVd), a member of the familyPospiviroidae, causes chrysanthemum stunt disease. Here, we report the genomic variations of CSVd to understand the sequence variability of CSVd in different chrysanthemum cultivars. We randomly sampled 36 different chrysanthemum cultivars and examined the infection of CSVd in each cultivar by reverse transcription polymerase chain reaction (RT-PCR). Eleven cultivars were infected by CSVd. Cloning followed by Sanger sequencing successfully identified a total of 271 CSVd genomes derived from 12 plants from 11 cultivars. They were further classified into 105 CSVd variants. Each single chrysanthemum plant had a different set of CSVd variants. Moreover, different single plants from the same cultivar had different sets of CSVd variants but identical consensus genome sequences. A phylogenetic tree using 12 consensus genome sequences revealed three groups of CSVd genomes, while six different groups were defined by the phylogenetic analysis using 105 variants. Based on the consensus CSVd genome, by combining all variant sequences, we identified 99 single-nucleotide variations (SNVs) as well as three nucleotide positions showing high mutation rates. Although 99 SNVs were identified, most CSVd genomes in this study were derived from variant 1, which is identical to known CSVd SK1 showing pathogenicity.

scholarly journals Sensitive detection of tumor mutations from blood and its application to immunotherapy prognosis

2020 ◽  
Author(s):  
Shuo Li ◽  
Zorawar Noor ◽  
Weihua Zeng ◽  
Xiaohui Ni ◽  
Zuyang Yuan ◽  
...  
Keyword(s):  
Low Frequency ◽  
Sequencing Data ◽  
Real Patient ◽  
Single Nucleotide ◽  
Lung Cancer Patients ◽  
Wide Range ◽  
Single Nucleotide Variations ◽  
Innovative Techniques ◽  
Error Suppression ◽  
Mutation Profiling

AbstractLiquid biopsy using cell-free DNA (cfDNA) is attractive for a wide range of clinical applications, including cancer detection, locating, and monitoring. However, developing these applications requires precise and sensitive calling of somatic single nucleotide variations (SNVs) from cfDNA sequencing data. To date, no SNV caller addresses all the special challenges of cfDNA to provide reliable results. Here we present cfSNV, a revolutionary somatic SNV caller with five innovative techniques to overcome and exploit the unique properties of cfDNA. cfSNV provides hierarchical mutation profiling, thanks to cfDNA’s complete coverage of the clonal landscape, and multi-layer error suppression. In both simulated datasets and real patient data, we demonstrate that cfSNV is superior to existing tools, especially for low-frequency somatic SNVs. We also show how the five novel techniques contribute to its performance. Further, we demonstrate a clinical application using cfSNV to select non-small-cell lung cancer patients for immunotherapy treatment.

Sign in / Sign up

Export Citation Format

Share Document