scholarly journals SwissPalm: Protein Palmitoylation database

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 261 ◽  
Author(s):  
Mathieu Blanc ◽  
Fabrice David ◽  
Laurence Abrami ◽  
Daniel Migliozzi ◽  
Florence Armand ◽  
...  
Keyword(s):  
Protein S ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Chemical Methods ◽  
Post Translational Modifications ◽  
P Protein ◽  
Multiple Alignments ◽  
Protein Palmitoylation ◽  
Recent Developments ◽  
Pathway Analyses

Protein S-palmitoylation is a reversible post-translational modification that regulates many key biological processes, although the full extent and functions of protein S-palmitoylation remain largely unexplored. Recent developments of new chemical methods have allowed the establishment of palmitoyl-proteomes of a variety of cell lines and tissues from different species.  As the amount of information generated by these high-throughput studies is increasing, the field requires centralization and comparison of this information. Here we present SwissPalm (http://swisspalm.epfl.ch), our open, comprehensive, manually curated resource to study protein S-palmitoylation. It currently encompasses more than 5000 S-palmitoylated protein hits from seven species, and contains more than 500 specific sites of S-palmitoylation. SwissPalm also provides curated information and filters that increase the confidence in true positive hits, and integrates predictions of S-palmitoylated cysteine scores, orthologs and isoform multiple alignments. Systems analysis of the palmitoyl-proteome screens indicate that 10% or more of the human proteome is susceptible to S-palmitoylation. Moreover, ontology and pathway analyses of the human palmitoyl-proteome reveal that key biological functions involve this reversible lipid modification. Comparative analysis finally shows a strong crosstalk between S-palmitoylation and other post-translational modifications. Through the compilation of data and continuous updates, SwissPalm will provide a powerful tool to unravel the global importance of protein S-palmitoylation.

scholarly journals PathwayMatcher: proteoform-centric network construction enables fine-granularity multi-omics pathway mapping

2018 ◽  
Author(s):  
Luis Francisco Hernández Sánchez ◽  
Bram Burger ◽  
Carlos Horro ◽  
Antonio Fabregat ◽  
Stefan Johansson ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Biomedical Data ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Network Construction ◽  
Gene Sets ◽  
Functional Knowledge ◽  
Pathway Analyses ◽  
Different Levels

AbstractBackgroundMapping biomedical data to functional knowledge is an essential task in bioinformatics and can be achieved by querying identifiers, e.g. gene sets, in pathway knowledgebases. However, the isoform and post-translational modification states of proteins are lost when converting input and pathways into gene-centric lists.FindingsBased on the Reactome knowledgebase, we built a network of protein-protein interactions accounting for the documented isoform and modification statuses of proteins. We then implemented a command line application called PathwayMatcher (github.com/PathwayAnalysisPlatform/PathwayMatcher) to query this network. PathwayMatcher supports multiple types of omics data as input, and outputs the possibly affected biochemical reactions, subnetworks, and pathways.ConclusionsPathwayMatcher enables refining the network-representation of pathways by including isoform and post-translational modifications. The specificity of pathway analyses is hence adapted to different levels of granularity and it becomes possible to distinguish interactions between different forms of the same protein.

scholarly journals eNOS-dependent S-nitrosylation of the NF-κB subunit p65 has neuroprotective effects

2020 ◽  
Author(s):  
Ariel Caviedes ◽  
Barbara Maturana ◽  
Katherina Corvalán ◽  
Alexander Engler ◽  
Felipe Gordillo ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Protein S ◽  
Subcellular Fractionation ◽  
Glutamate Excitotoxicity ◽  
Luciferase Reporter ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Neuroprotective Effects ◽  
Biotin Switch

AbstractCell death by glutamate excitotoxicity, mediated by N-methyl-D-aspartate (NMDA) receptors, negatively impacts brain function, including but not limited to hippocampal neurons. The NF-κB transcription factor (composed mainly of p65/p50 subunits) contributes to neuronal death in excitotoxicity, while its inhibition should improve cell survival. Using the biotin switch method, subcellular fractionation, immunofluorescence and luciferase reporter assays, we found that NMDA stimulated NF-κB activity selectively in hippocampal neurons, while endothelial nitric oxide synthase (eNOS), an enzyme expressed in neurons, is involved in the S-nitrosylation of p65 and consequent NF-κB inhibition in cerebrocortical, i.e., resistant neurons. The S-nitro proteomes of cortical and hippocampal neurons revealed that different biological processes are regulated by S-nitrosylation in susceptible and resistant neurons, bringing to light that protein S-nitrosylation is a ubiquitous post-translational modification, able to influence a variety of biological processes including the homeostatic inhibition of the NF-κB transcriptional activity in cortical neurons exposed to NMDA receptor overstimulation.

scholarly journals Profiling of lysine-acetylated proteins in human urine

2017 ◽  
Author(s):  
Weiwei Qin ◽  
Zhenhuan Du ◽  
He Huang ◽  
Youhe Gao
Keyword(s):  
Human Urine ◽  
High Resolution Mass Spectrometry ◽  
The Body ◽  
Lysine Acetylation ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Normal Human ◽  
Measurable Change

AbstractBiomarker is the measurable change associated with a physiological or pathophysiological process, its nature is change. Contrast to the blood which is under homeostatic controls, urine reflects changes in the body earlier and more sensitive therefore is a better biomarker source. Lysine acetylation is an abundant and highly regulated post-translational modification. It plays a pivotal role in modulating diverse biological processes and is associated with various important diseases. Enrichment or visualization of proteins with specific post-translational modifications provides a method for sampling the urinary proteome and reducing sample complexity. In this study, we used anti-acetyllysine antibody-based immunoaffinity enrichment combined with high-resolution mass spectrometry to profile lysine-acetylated proteins in normal human urine. A total of 629 acetylation sites on 315 proteins were identified, including some very low-abundance proteins. This is the first proteome-wide characterization of lysine acetylation proteins in normal human urine. Our dataset provides a useful resource for the further discovery of the lysine acetylated proteins as biomarker in urine.

scholarly journals In-Depth Mapping of the Urinary N-Glycoproteome: Distinct Signatures of ccRCC-related Progression

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 239 ◽  
Author(s):  
Lucia Santorelli ◽  
Giulia Capitoli ◽  
Clizia Chinello ◽  
Isabella Piga ◽  
Francesca Clerici ◽  
...  
Keyword(s):  
Clear Cell ◽  
Glycosylation Site ◽  
Biological Processes ◽  
Label Free ◽  
Post Translational Modification ◽  
Cell Renal Cell Carcinoma ◽  
Altered Expression ◽  
Post Translational Modifications ◽  
Novel Biomarkers

Protein N-glycosylation is one of the most important post-translational modifications and is involved in many biological processes, with aberrant changes in protein N-glycosylation patterns being closely associated with several diseases, including the progression and spreading of tumours. In light of this, identifying these aberrant protein glycoforms in tumours could be useful for understanding the molecular mechanism of this multifactorial disease, developing specific biomarkers and finding novel therapeutic targets. We investigated the urinary N-glycoproteome of clear cell renal cell carcinoma (ccRCC) patients at different stages (n = 15 at pT1 and n = 15 at pT3), and of non-ccRCC subjects (n = 15), using an N-glyco-FASP-based method. Using label-free nLC-ESI MS/MS, we identified and quantified several N-glycoproteins with altered expression and abnormal changes affecting the occupancy of the glycosylation site in the urine of RCC patients compared to control. In particular, nine of them had a specific trend that was directly related to the stage progression: CD97, COCH and P3IP1 were up-expressed whilst APOB, FINC, CERU, CFAH, HPT and PLTP were down-expressed in ccRCC patients. Overall, these results expand our knowledge related to the role of this post-translational modification in ccRCC and translation of this information into pre-clinical studies could have a significant impact on the discovery of novel biomarkers and therapeutic target in kidney cancer.

SUMO: getting it on

2007 ◽  
Vol 35 (6) ◽  
pp. 1409-1413 ◽  
Author(s):  
J. Anckar ◽  
L. Sistonen
Keyword(s):  
Biological Processes ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Sumo Conjugation ◽  
Lysine Residues ◽  
Ubiquitin Conjugating Enzyme ◽  
Specificity Determinants ◽  
Conjugating Enzyme

Post-translational modification of cellular proteins by the SUMO (small ubiquitin-related modifier) is involved in numerous modes of regulation in widely different biological processes. In contrast with ubiquitination, SUMO conjugation is highly specific in terms of target lysine residues, but many aspects of substrate and lysine selection by the SUMO conjugating machinery are still poorly understood. SUMOylation events usually occur on the ΨKXE SUMO consensus motifs, which mediate binding to Ubc9 (ubiquitin-conjugating enzyme 9), the SUMO E2 conjugating enzyme. Although most, if not all, SUMO conjugations are catalysed by Ubc9, far from all ΨKXE tetrapeptides are modified, demonstrating a need for additional specificity determinants in SUMOylation. Recent results intimately link regulation of SUMOylation to other post-translational modifications, including phosphorylation and acetylation and reveal that certain lysine residues are marked for SUMOylation by negatively charged amino acid residues or phosphorylation events immediately downstream of the consensus site. In the present review, we explore the intriguing role of extended motifs in the regulation of SUMO conjugation.

scholarly journals Protein S-palmitoylation in cellular differentiation

2017 ◽  
Vol 45 (1) ◽  
pp. 275-285 ◽  
Author(s):  
Mingzi M. Zhang ◽  
Howard C. Hang
Keyword(s):  
Posttranslational Modification ◽  
Protein Function ◽  
Cellular Differentiation ◽  
Protein S ◽  
Biological Processes ◽  
Global Studies ◽  
Technological Advances ◽  
Protein Palmitoylation ◽  
Spatiotemporal Control

Reversible protein S-palmitoylation confers spatiotemporal control of protein function by modulating protein stability, trafficking and activity, as well as protein–protein and membrane–protein associations. Enabled by technological advances, global studies revealed S-palmitoylation to be an important and pervasive posttranslational modification in eukaryotes with the potential to coordinate diverse biological processes as cells transition from one state to another. Here, we review the strategies and tools to analyze in vivo protein palmitoylation and interrogate the functions of the enzymes that put on and take off palmitate from proteins. We also highlight palmitoyl proteins and palmitoylation-related enzymes that are associated with cellular differentiation and/or tissue development in yeasts, protozoa, mammals, plants and other model eukaryotes.

scholarly journals Therapeutic targeting of protein S-acylation for the treatment of disease

2019 ◽  
Vol 48 (1) ◽  
pp. 281-290 ◽  
Author(s):  
Niall J. Fraser ◽  
Jacqueline Howie ◽  
Krzysztof J. Wypijewski ◽  
William Fuller
Keyword(s):  
Critical Role ◽  
Cardiac Contractility ◽  
Protein S ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Target Proteins ◽  
Specific Target ◽  
Receptor Signalling ◽  
Therapeutic Drugs ◽  
Wide Range

The post-translational modification protein S-acylation (commonly known as palmitoylation) plays a critical role in regulating a wide range of biological processes including cell growth, cardiac contractility, synaptic plasticity, endocytosis, vesicle trafficking, membrane transport and biased-receptor signalling. As a consequence, zDHHC-protein acyl transferases (zDHHC-PATs), enzymes that catalyse the addition of fatty acid groups to specific cysteine residues on target proteins, and acyl proteins thioesterases, proteins that hydrolyse thioester linkages, are important pharmaceutical targets. At present, no therapeutic drugs have been developed that act by changing the palmitoylation status of specific target proteins. Here, we consider the role that palmitoylation plays in the development of diseases such as cancer and detail possible strategies for selectively manipulating the palmitoylation status of specific target proteins, a necessary first step towards developing clinically useful molecules for the treatment of disease.

scholarly journals Structural Diversity of Ubiquitin E3 Ligase

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6682
Author(s):  
Sachiko Toma-Fukai ◽  
Toshiyuki Shimizu
Keyword(s):  
E3 Ligase ◽  
Structural Diversity ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin E3 Ligase ◽  
Ubiquitin Ligase E3 ◽  
Ubiquitin Conjugating Enzyme

The post-translational modification of proteins regulates many biological processes. Their dysfunction relates to diseases. Ubiquitination is one of the post-translational modifications that target lysine residue and regulate many cellular processes. Three enzymes are required for achieving the ubiquitination reaction: ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3). E3s play a pivotal role in selecting substrates. Many structural studies have been conducted to reveal the molecular mechanism of the ubiquitination reaction. Recently, the structure of PCAF_N, a newly categorized E3 ligase, was reported. We present a review of the recent progress toward the structural understanding of E3 ligases.

scholarly journals Metal–organic framework incorporated monolithic capillary for selective enrichment of phosphopeptides

RSC Advances ◽  
2017 ◽  
Vol 7 (26) ◽  
pp. 15894-15902 ◽  
Author(s):  
Daojin Li ◽  
Zijun Bie
Keyword(s):  
Protein Phosphorylation ◽  
Cellular Signaling ◽  
Metal Organic Framework ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Selective Enrichment ◽  
P Protein ◽  
Metal Organic ◽  
Organic Framework

Protein phosphorylation is a major post-translational modification, which plays a central role in the cellular signaling of numerous biological processes.

APT1-Mediated Cross-Talk Between Palmitoylation and Phosphorylation Events of the BCR Pathway Sensitizes CLL Cells Towards BCR-Associated Kinase Inhibitors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4361-4361
Author(s):  
Valeska Berg ◽  
Dunja Baatout ◽  
Clemens Wendtner ◽  
Michael Hallek ◽  
Lukas P. Frenzel
Keyword(s):  
Research Funding ◽  
Kinase Inhibitors ◽  
Cell Receptor ◽  
Fine Tuning ◽  
Post Translational Modification ◽  
Protein Activity ◽  
Post Translational Modifications ◽  
Protein Palmitoylation ◽  
Bcr Signaling ◽  
Support Research

Abstract Post-translational modifications are important fine-tuning elements for controlling protein activity and signaling. Regulation of phosphorylation events of the BCR is critical for survival and proliferation of CLL cells. Palmitoylation, a common post-translational modification defined as the addition of palmitic acid to internal cysteins, was shown recently to regulate phosphorylation of proteins by controlling their localization and activity. Many proteins in the B cell receptor (BCR) signaling pathway in CLL cells are primarily cytosolic, but upon activation transiently located to the plasma membrane to fulfill their functions. Some of these proteins, like Src kinase family members Lyn, Yes and Fyn, are already reported to be palmitoylated. Previous studies by our group showed that global protein palmitoylation is deregulated in CLL cells and primarily caused by overexpression of the depalmitoylating enzyme APT1. To investigate, if overexpressed APT1 directly targets BCR signaling, we inhibited (genetically and pharmacologically) APT1 in CLL cells and analyzed occurring changes in 45 different phosphorylation-sites of major signaling pathways. Interestingly, we found that APT1 controls the central phosphorylation events within Akt/mTOR/p70S6 signaling. For example, phosphorylation of Akt (T308, S473) and p70S6 (T389, T421, S424) was significantly decreased after interference with protein depalmitoylation. By biochemical dissection of these pathways with acyl-biotin exchange (ABE) assays we identified novel palmitoylation candidates particularly within the PI3K/Akt axis, which are indispensable for phosphorylation of kinases of the Akt/mTOR/p70S6 axis. Functionally, pharmacological inhibition of APTs and genetic knockdown of APT1 sensitizes CLL cells towards BCR-associated KIs like Ibrutinib and Idelalisib. Our data uncovers that central phosphorylation events within the BCR pathway are dependent on palmitoylation controlled by APT1. Future studies should therefore investigate more in detail how addition of APT1 inhibitors can improve clinical outcome of patients treated with Idelalisib or Ibrutinib-based regimens. Disclosures Wendtner: Hoffmann-La Roche, Mundipharma, Janssen, Gilead, Abbvie, Servier, Morphosys: Consultancy, Other: Travle grants, Research Funding. Hallek:Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau.

Sign in / Sign up

Export Citation Format

Share Document