urPTMdb/TeaProt: Upstream and Downstream Proteomics Analysis

Molendijk, Jeffrey; Yip, Rui; Parker, Benjamin L.

doi:10.1021/acs.jproteome.2c00048

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…Pathway enrichment analysis was performed with Metascape 35 . GSEA against ChEA3 36 was performed in TeaProt 37 . Protein: protein interaction analysis was analysis was performed on STRING (v12.0).…”

Section: Methodsmentioning

confidence: 99%

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Characterization of the skeletal muscle arginine methylome in health and disease reveals remodeling in amyotrophic lateral sclerosis

Wong,

Blazev,

et al. 2024

The FASEB Journal

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Arginine methylation is a protein posttranslational modification important for the development of skeletal muscle mass and function. Despite this, our understanding of the regulation of arginine methylation under settings of health and disease remains largely undefined. Here, we investigated the regulation of arginine methylation in skeletal muscles in response to exercise and hypertrophic growth, and in diseases involving metabolic dysfunction and atrophy. We report a limited regulation of arginine methylation under physiological settings that promote muscle health, such as during growth and acute exercise, nor in disease models of insulin resistance. In contrast, we saw a significant remodeling of asymmetric dimethylation in models of atrophy characterized by the loss of innervation, including in muscle biopsies from patients with myotrophic lateral sclerosis (ALS). Mass spectrometry‐based quantification of the proteome and asymmetric arginine dimethylome of skeletal muscle from individuals with ALS revealed the largest compendium of protein changes with the identification of 793 regulated proteins, and novel site‐specific changes in asymmetric dimethyl arginine (aDMA) of key sarcomeric and cytoskeletal proteins. Finally, we show that in vivo overexpression of PRMT1 and aDMA resulted in increased fatigue resistance and functional recovery in mice. Our study provides evidence for asymmetric dimethylation as a regulator of muscle pathophysiology and presents a valuable proteomics resource and rationale for numerous methylated and nonmethylated proteins, including PRMT1, to be pursued for therapeutic development in ALS.

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Section: Methodsmentioning

confidence: 99%

“…35 GSEA against ChEA3 36 was performed in TeaProt. 37 Protein: protein interaction analysis was analysis was performed on STRING (v12.0). MCODE analysis was performed on Cytoscape (v3.10.0).…”

Section: Lc-ms/ms Data Processingmentioning

confidence: 99%

Characterization of the skeletal muscle arginine methylome in health and disease reveals remodeling in amyotrophic lateral sclerosis

Wong,

Blazev,

et al. 2024

The FASEB Journal

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“…CoffeeProt was used to assess protein-protein correlations and to produce network plots ( Molendijk et al, 2021b ). TeaProt was used to perform functional enrichment analyses ( Molendijk et al, 2022 ). The packages Gviz and TxDb.Mmusculus.UCSC.mm10.knownGene were used to produce genomic tracks ( Hahne and Ivanek, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function

Molendijk

Blazev

Mills

et al. 2022

eLife

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Improving muscle function has great potential to improve the quality of life. To identify novel regulators of skeletal muscle metabolism and function, we performed a proteomic analysis of gastrocnemius muscle from 73 genetically distinct inbred mouse strains, and integrated the data with previously acquired genomics and >300 molecular/phenotypic traits via quantitative trait loci mapping and correlation network analysis. These data identified thousands of associations between protein abundance and phenotypes and can be accessed online (https://muscle.coffeeprot.com/) to identify regulators of muscle function. We used this resource to prioritize targets for a functional genomic screen in human bioengineered skeletal muscle. This identified several negative regulators of muscle function including UFC1, an E2 ligase for protein UFMylation. We show UFMylation is up-regulated in a mouse model of amyotrophic lateral sclerosis, a disease that involves muscle atrophy. Furthermore, in vivo knockdown of UFMylation increased contraction force, implicating its role as a negative regulator of skeletal muscle function.

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“…CoffeeProtwas used to assess protein-protein correlations and to produce network plots ( Molendijk et al, 2021 ). TeaProt was used to perform functional enrichment analyses ( Molendijk et al, 2022 ). The packages Gviz and TxDb.Mmusculus.UCSC.mm1 were used to produce genomic tracks ( Hahne and Ivanek, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function

Molendijk

Blazev

Mills

et al. 2022

Preprint

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Improving muscle function has great potential to improve the quality of life. To identify novel regulators of skeletal muscle metabolism and function, we performed a proteomic analysis of gastrocnemius muscle from 73 genetically distinct inbred mouse strains, and integrated the data with genomics and >300 molecular/phenotypic traits via quantitative trait loci mapping and correlation network analysis. These data identified thousands of associations between protein abundance and phenotypes and can be accessed online (https://muscle.coffeeprot.com/) to identify regulators of muscle function. We used this resource to prioritize targets for a functional genomic screen in human bioengineered skeletal muscle. This identified several negative regulators of muscle function including UFC1, an E2 ligase for protein UFMylation. We show UFMylation is up-regulated in a mouse model of amyotrophic lateral sclerosis, a disease that involves of muscle atrophy. Furthermore, in vivo knockdown of UFMylation increased contraction force, implicating its role as a negative regulator of skeletal muscle function.

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urPTMdb/TeaProt: Upstream and Downstream Proteomics Analysis

Cited by 5 publications

References 27 publications

Characterization of the skeletal muscle arginine methylome in health and disease reveals remodeling in amyotrophic lateral sclerosis

Characterization of the skeletal muscle arginine methylome in health and disease reveals remodeling in amyotrophic lateral sclerosis

Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function

Proteome-wide systems genetics identifies UFMylation as a regulator of skeletal muscle function

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