We developed two CNNs for predicting ubiquitination sites in Arabidopsis thaliana, demonstrated their competitive performance, analyzed amino acid physicochemical properties and the CNN structures, and predicted ubiquitination sites in Arabidopsis. As an important posttranslational protein modification, ubiquitination plays critical roles in plant physiology, including plant growth and development, biotic and abiotic stress, metabolism, and so on. A lot of ubiquitination site prediction models have been developed for human, mouse and yeast. However, there are few models to predict ubiquitination sites for the plant Arabidopsis thaliana. Based on this context, we proposed two convolutional neural network (CNN) based models for predicting ubiquitination sites in A. thaliana. The two models reach AUC (area under the ROC curve) values of 0.924 and 0.913 respectively in five-fold cross-validation, and 0.921 and 0.914 respectively in independent test, which outperform other models and demonstrate the competitive edge of them. We in-depth analyze the amino acid physicochemical properties in the neighboring sequence regions of the ubiquitination sites, and study the influence of the CNN structure to the prediction performance. Potential ubiquitination sites in the global Arbidopsis proteome are predicted using the two CNN models. To facilitate the community, the source code, training and test dataset, predicted ubiquitination sites in the Arbidopsis proteome are available at GitHub ( http://github.com/nongdaxiaofeng/CNNAthUbi ) for interest users.
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Nat Commun
December 2024
Laboratory of Retrovirology, The Rockefeller University, New York, NY, 10065, USA.
ZAP is an antiviral protein that binds to and depletes viral RNA, which is often distinguished from vertebrate host RNA by its elevated CpG content. Two ZAP cofactors, TRIM25 and KHNYN, have activities that are poorly understood. Here, we show that functional interactions between ZAP, TRIM25 and KHNYN involve multiple domains of each protein, and that the ability of TRIM25 to multimerize via its RING domain augments ZAP activity and specificity.
View Article and Find Full Text PDFMol Cancer
December 2024
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Background: Posttranslational modifications (PTMs) play critical roles in hepatocellular carcinoma (HCC). However, the locations of PTM-modified sites across protein secondary structures and regulatory patterns in HCC remain largely uncharacterized.
Methods: Total proteome and nine PTMs (phosphorylation, acetylation, crotonylation, ubiquitination, lactylation, N-glycosylation, succinylation, malonylation, and β-hydroxybutyrylation) in tumor sections and paired normal adjacent tissues derived from 18 HCC patients were systematically profiled by 4D-Label free proteomics analysis combined with PTM-based peptide enrichment.
Protein Sci
January 2025
Department of Physical Chemistry, Institute of Biotechnology, and Unit of Excellence in Chemistry Applied to Biomedicine and Environment, School of Sciences, University of Granada, Granada, Spain.
The ubiquitin E2 variant domain of TSG101 (TSG101-UEV) plays a pivotal role in protein sorting and virus budding by recognizing PTAP motifs within ubiquitinated proteins. Disruption of TSG101-UEV/PTAP interactions has emerged as a promising strategy for the development of host-oriented broad-spectrum antivirals with low susceptibility to resistance. TSG101 is a challenging target characterized by an extended and flat binding interface, low affinity for PTAP ligands, and complex binding energetics.
View Article and Find Full Text PDFFront Immunol
December 2024
School of Marine Sciences, State Key Laboratory for Biocontrol/Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering & Guangdong Provincial Observation and Research Station for Marine Ranching of the Lingdingyang Bay, Sun Yat-sen University, Guangzhou, China.
Stimulator of interferon genes (STING) is a key connector protein in interferon (IFN) signaling, crucial for IFN induction during the activation of antiviral innate immunity. In mammals, ring finger protein 5 (RNF5) functions as an E3 ubiquitin ligase, mediating STING regulation through K150 ubiquitylation to prevent excessive IFN production. However, the mechanisms underlying RNF5's regulation of STING in teleost fish remain unknown.
View Article and Find Full Text PDFAm J Hum Genet
December 2024
Department of Genetics, CHU Sainte-Justine, Montréal, QC, Canada. Electronic address:
E3 ubiquitin ligases have been linked to developmental diseases including autism, Angelman syndrome (UBE3A), and Johanson-Blizzard syndrome (JBS) (UBR1). Here, we report variants in the E3 ligase UBR5 in 29 individuals presenting with a neurodevelopmental syndrome that includes developmental delay, autism, intellectual disability, epilepsy, movement disorders, and/or genital anomalies. Their phenotype is distinct from JBS due to the absence of exocrine pancreatic insufficiency and the presence of autism, epilepsy, and, in some probands, a movement disorder.
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