The eukaryotic linear motif resource – 2018 update

Gouw, Marc; Michael, Sushama; Sámano-Sánchez, Hugo; Kumar, Manjeet; Zeke, András; Lang, Benjamin; Bely, Benoît; Chemes, Lucía B.; Davey, Norman E.; Deng, Ziqi; Diella, Francesca; Gürth, Clara-Marie; Huber, Ann-Kathrin; Kleinsorg, Stefan; Schlegel, Lara S.; Palopoli, Nicolás; Roey, Kim Van; Altenberg, Brigitte; Reményi, Attila; Dinkel, Holger; Gibson, Toby J.

doi:10.1093/nar/gkx1077

Cited by 191 publications

(202 citation statements)

References 51 publications

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“…Phylogenetically, their catalytic domains are part of the ADP-ribosyl superfamily (Pfam clan CL0084) (Amé et al 2004) and three main clades are generally distinguished based on their characteristic catalytic motif: (1) the H-H-Φ clade, containing TRPT1/KtpA (also termed Tpt1); (2) the R-S-E clade, containing the cholera toxin-like ARTs (ARTCs); and (3) the H-Y- [EDQ] clade, including the diphtheria toxin-like ARTs (ARTDs) (Aravind et al 2015). [Sequence motifs are given following the regular expression syntax of the ELM resource (http://www.elm.eu.org; Aasland et al 2002;Gouw et al 2018). ] Functionally, the majority of ARTs catalyze the transfer of a single ADPr moiety onto an acceptor site, termed mono(ADP-ribosyl)ation (MARylation).…”

Section: Adp-ribosylation-intricate and Versatilementioning

confidence: 99%

(ADP-ribosyl)hydrolases: structure, function, and biology

2020

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ADP-ribosylation is an intricate and versatile posttranslational modification involved in the regulation of a vast variety of cellular processes in all kingdoms of life. Its complexity derives from the varied range of different chemical linkages, including to several amino acid side chains as well as nucleic acids termini and bases, it can adopt. In this review, we provide an overview of the different families of (ADP-ribosyl)hydrolases. We discuss their molecular functions, physiological roles, and influence on human health and disease. Together, the accumulated data support the increasingly compelling view that (ADP-ribosyl)hydrolases are a vital element within ADP-ribosyl signaling pathways and they hold the potential for novel therapeutic approaches as well as a deeper understanding of ADP-ribosylation as a whole.

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Section: Adp-ribosylation-intricate and Versatilementioning

confidence: 99%

(ADP-ribosyl)hydrolases: structure, function, and biology

2020

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“…Such regions can tolerate mutations; hence, they evolve rapidly and acquire functionality through both convergent evolution and divergent evolution (van der Lee et al , ; Tompa et al , ; Davey et al , ). Although computational approaches have estimated that there could be up to a million functional IDRs in the human proteome (Tompa et al , ), only a small fraction of them have been characterized so far (Gouw et al , ), limiting our understanding of the disordered proteome.…”

Section: Introductionmentioning

confidence: 99%

High‐throughput discovery of functional disordered regions: investigation of transactivation domains

Ravarani

Erkina

Baets

et al. 2018

Molecular Systems Biology

159

155

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Over 40% of proteins in any eukaryotic genome encode intrinsically disordered regions (IDRs) that do not adopt defined tertiary structures. Certain IDRs perform critical functions, but discovering them is non‐trivial as the biological context determines their function. We present IDR‐Screen, a framework to discover functional IDRs in a high‐throughput manner by simultaneously assaying large numbers of DNA sequences that code for short disordered sequences. Functionality‐conferring patterns in their protein sequence are inferred through statistical learning. Using yeast HSF1 transcription factor‐based assay, we discovered IDRs that function as transactivation domains (TADs) by screening a random sequence library and a designed library consisting of variants of 13 diverse TADs. Using machine learning, we find that segments devoid of positively charged residues but with redundant short sequence patterns of negatively charged and aromatic residues are a generic feature for TAD functionality. We anticipate that investigating defined sequence libraries using IDR‐Screen for specific functions can facilitate discovering novel and functional regions of the disordered proteome as well as understand the impact of natural and disease variants in disordered segments.

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“…Nonetheless, even if we cannot be conclusive as to whether Nup188 biochemically interacts with Sas6, we favor models in which it acts through a mechanism analogous to Cep192, which provides a platform for Plk4 responsible for Sas6 recruitment (Arquint and Nigg, 2016;Kim et al, 2013;Sonnen et al, 2013). Certainly, as with many nups, Nup188 is a target of kinases with several predicted potential polo kinase sites (Gouw et al, 2018), suggesting this as a likely possibility for future investigation.…”

Section: Discussionmentioning

confidence: 94%

Differential turnover of Nup188 controls its levels at centrosomes and role in centriole duplication

Vishnoi

Dhanasekeran

Chalfant

et al. 2019

Preprint

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NUP188 encodes a scaffold component of the nuclear pore complex (NPC) and has been implicated as a congenital heart disease gene through an ill-defined function at centrioles. Here, we explore the mechanisms that physically and functionally segregate Nup188 between the pericentriolar material (PCM) and NPCs throughout the cell cycle. Pulse-chase fluorescent labeling approaches indicate that Nup188 populates centrosomes with newly synthesized protein that does not exchange with NPCs even after mitotic NPC breakdown. In addition, the steady-state level of Nup188 at centrosomes is controlled by the sensitivity of the PCM pool, but not the NPC pool, to proteasomal degradation. Proximity-labeling and super-resolution microscopy supports that Nup188 interacts with components of PCM including Cep192 and the centriolar satellite component, PCM1. Consistent with this, Nup188 plays a role in centriole duplication at or upstream of Sas6 loading. Together, our data establish Nup188 as a functional component of PCM and potentially provides insight into the pathogenesis of congenital heart disease.

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The eukaryotic linear motif resource – 2018 update

Cited by 191 publications

References 51 publications

(ADP-ribosyl)hydrolases: structure, function, and biology

(ADP-ribosyl)hydrolases: structure, function, and biology

High‐throughput discovery of functional disordered regions: investigation of transactivation domains

Differential turnover of Nup188 controls its levels at centrosomes and role in centriole duplication

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