What will neXtProt help us achieve in 2020 and beyond?

Zahn-Zabal, Monique; Lane, Lydie

doi:10.1080/14789450.2020.1733418

Cited by 5 publications

(7 citation statements)

References 16 publications

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“…A fraction of this dataset is expected to be updated into fully characterized LINC-encoded microproteins [ 44 ]. In the most recent protein evidence update of NeXtProt [ 20 ], 1, 12 and 8 of the 83 uncertain protein products of LINC genes were, respectively, upgraded to PE1, PE2 and PE4 levels. Overall, these results imply that the present reconstruction of the human protein interactome may indeed be covering a higher than 90% part of RHCP than the current annotation is showing.…”

Section: Discussionmentioning

confidence: 99%

“…More specifically, the PICKLE meta-database integrates the primary PPI datasets over the genetic information ontological network of the manually curatedUniProt/SwissProt reviewed human complete proteome (RHCP), which is used as the reference protein set. RHCP is supported by the proteomics data of NeXtProt, the reference knowledge base for the Human Protein Organization (HUPO) human proteome project (HPP) [ 19 , 20 ]. In this way, a comparison between different PICKLE releases can provide information about the global (over the entire proteome) and the local (around specific nodes) expansion of the human protein interactome at any level of genetic information (gene, RNA or protein), also providing information about the part of the proteome that remains without known PPIs [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

2022

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After more than fifteen years from the first high-throughput experiments for human protein–protein interaction (PPI) detection, we are still wondering how close the completion of the genome-scale human PPI network reconstruction is, what needs to be further explored and whether the biological insights gained from the holistic investigation of the current network are valid and useful. The unique structure of PICKLE, a meta-database of the human experimentally determined direct PPI network developed by our group, presently covering ~80% of the UniProtKB/Swiss-Prot reviewed human complete proteome, enables the evaluation of the interactome expansion by comparing the successive PICKLE releases since 2013. We observe a gradual overall increase of 39%, 182%, and 67% in protein nodes, PPIs, and supporting references, respectively. Our results indicate that, in recent years, (a) the PPI addition rate has decreased, (b) the new PPIs are largely determined by high-throughput experiments and mainly concern existing protein nodes and (c), as we had predicted earlier, most of the newly added protein nodes have a low degree. These observations, combined with a largely overlapping k-core between PICKLE releases and a network density increase, imply that an almost complete picture of a structurally defined network has been reached. The comparative unsupervised application of two clustering algorithms indicated that exploring the full interactome topology can reveal the protein neighborhoods involved in closely related biological processes as transcriptional regulation, cell signaling and multiprotein complexes such as the connexon complex associated with cancers. A well-reconstructed human protein interactome is a powerful tool in network biology and medicine research forming the basis for multi-omic and dynamic analyses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

2022

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“…Engineered mouse models deficient in KAT2A, -3A, -3B, -5, -6A, -6B, or -8 exhibit a lethal phenotype that demonstrates a vital role for the KATs during embryonic development [129,130]. To understand the tissue-wide expression of KATs, websites including human protein atlas [62], uniport [131], antibodypedia [132], metabolic atlas [133] and nextprot [134,135] were reviewed. These websites showcased expression levels for RNA and protein for each KAT.…”

Section: Genome-wide Expression Of Katsmentioning

confidence: 99%

The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics

et al. 2021

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The molecular interplay between nucleosomal packaging and the chromatin landscape regulates the transcriptional programming and biological outcomes of downstream genes. An array of epigenetic modifications plays a pivotal role in shaping the chromatin architecture, which controls DNA access to the transcriptional machinery. Acetylation of the amino acid lysine is a widespread epigenetic modification that serves as a marker for gene activation, which intertwines the maintenance of cellular homeostasis and the regulation of signaling during stress. The biochemical horizon of acetylation ranges from orchestrating the stability and cellular localization of proteins that engage in the cell cycle to DNA repair and metabolism. Furthermore, lysine acetyltransferases (KATs) modulate the functions of transcription factors that govern cellular response to microbial infections, genotoxic stress, and inflammation. Due to their central role in many biological processes, mutations in KATs cause developmental and intellectual challenges and metabolic disorders. Despite the availability of tools for detecting acetylation, the mechanistic knowledge of acetylation-mediated cellular processes remains limited. This review aims to integrate molecular and structural bases of KAT functions, which would help design highly selective tools for understanding the biology of KATs toward developing new disease treatments.

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“…In neXtProt 2020-01-17, there are 1,813 PE1-4 proteins with no function annotated. Among them, 559 have not been confidently detected at protein level in a human sample and are considered as "missing" (PE2-4), whereas 1254 have been experimentally verified (PE1) and are called "uPE1" 3 . The present study focuses on the uPE1 proteins whose expression is elevated in the male reproductive system.…”

Section: Introductionmentioning

confidence: 99%

The Functionally Unannotated Proteome of Human Male Tissues: A Shared Resource to Uncover New Protein Functions Associated with Reproductive Biology

2020

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What will neXtProt help us achieve in 2020 and beyond?

Cited by 5 publications

References 16 publications

How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics

The Functionally Unannotated Proteome of Human Male Tissues: A Shared Resource to Uncover New Protein Functions Associated with Reproductive Biology

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