DisProt 7.0: a major update of the database of disordered proteins

Piovesan, Damiano; Tabaro, Francesco; Mičetić, Ivan; Necci, Marco; Quaglia, Federica; Oldfield, Christopher C.J.; Aspromonte, Maria Cristina; Davey, Norman E.; Davidović, Radoslav; Dosztányi, Zsuzsanna; Elofsson, Arne; Gasparini, Alessandra; Hatos, András; Kajava, Andrey V.; Kalmár, Lajos; Leonardi, Emanuela; Lázár, Tamás; Macedo-Ribeiro, Sandra; Macossay-Castillo, Mauricio; Mészáros, Attila; Minervini, Giovanni; Murvai, Nikoletta; Pujols, Jordi; Roche, Daniel B.; Salladini, Edoardo; Schád, Éva; Schramm, Antoine; Szabó, Beáta; Tantos, Ágnes; Tonello, Fiorella; Tsirigos, Konstantinos; Veljković, Nevena; Ventura, Salvador; Vranken, Wim; Warholm, Per; Uversky, Vladimir V.N.; Dunker, A. Keith; Longhi, Sonia; Tompa, Péter; Tosatto, Silvio C. E.

doi:10.1093/nar/gkw1279

Cited by 45 publications

(43 citation statements)

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“…3), a functional region responsible for the interaction with pVHL7. Data in the literature394041 as well as secondary structure prediction of CDI performed with FELLS42 suggested this short segment to adopt random coil structure when not in complex to cyclin A. Combining these findings, we asked whether CDI may sustain the interaction with pVHL in a HIF-1α like fashion.…”

Section: Resultsmentioning

confidence: 97%

Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors

Minervini

Lopreiato

Bortolotto

et al. 2017

Sci Rep

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Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor predisposes patients to develop different highly vascularized cancers. pVHL targets the hypoxia-inducible transcription factor (HIF-1α) for degradation, modulating the activation of various genes involved in hypoxia response. Hypoxia plays a relevant role in regulating cell cycle progression, inducing growth arrest in cells exposed to prolonged oxygen deprivation. However, the exact molecular details driving this transition are far from understood. Here, we present novel interactions between pVHL and the cyclin-dependent kinase inhibitor family CDKN1 (p21, p27 and p57). Bioinformatics analysis, yeast two-hybrid screening and co-immunoprecipitation assays were used to predict, dissect and validate the interactions. We found that the CDKN1 proteins share a conserved region mimicking the HIF-1α motif responsible for pVHL binding. Intriguingly, a p27 site-specific mutation associated to cancer is shown to modulate this novel interaction. Our findings suggest a new connection between the pathways regulating hypoxia and cell cycle progression.

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Section: Resultsmentioning

confidence: 97%

Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors

Minervini

Lopreiato

Bortolotto

et al. 2017

Sci Rep

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“…It has been recently upgraded and updated. 11 The current release contains information on more than 800 entries and has been curated to remove conflicting cases. As such, the information stored therein is highly valuable since it is experimentally assessed.…”

Section: Searching Databases Dedicated To Idpsmentioning

confidence: 99%

“…While previous reports set the limit to 20 residues, 1 the minimal length of an IDPR in DisProt 7.0 (i.e. the database of experimentally validated IDPs/IDPRs, see below), 11 is 5 residues, and the minimal length of 4 residues was used to annotate disordered regions used in the CASP experiments. 12,13 In protein science, the existence of intrinsic disorder in proteins has been known for a long time.…”

Section: Introductionmentioning

confidence: 99%

How disordered is my protein and what is its disorder for? A guide through the “dark side” of the protein universe

Lieutaud

Ferrón

Uversky

et al. 2016

Intrinsically Disordered Proteins

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In the last 2 decades it has become increasingly evident that a large number of proteins are either fully or partially disordered. Intrinsically disordered proteins lack a stable 3D structure, are ubiquitous and fulfill essential biological functions. Their conformational heterogeneity is encoded in their amino acid sequences, thereby allowing intrinsically disordered proteins or regions to be recognized based on properties of these sequences. The identification of disordered regions facilitates the functional annotation of proteins and is instrumental for delineating boundaries of protein domains amenable to structural determination with X-ray crystallization. This article discusses a comprehensive selection of databases and methods currently employed to disseminate experimental and putative annotations of disorder, predict disorder and identify regions involved in induced folding. It also provides a set of detailed instructions that should be followed to perform computational analysis of disorder.KEYWORDS disorder databases and metaservers; induced folding; intrinsic disorder; intrinsically disordered proteins; intrinsically disordered regions; prediction methods

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“…These features make tracking IDPs over evolutionary time scales immensely challenging. Although a number of databases with either experimental data or predictive methods of protein disorder are available (for review, see Piovesan et al, 2017), the tools available to assess large-scale proteomics data for IDP evolution are lacking (Varadi et al, 2015). The methods available still rely on significant conservation of sequence order, as they utilize (PSI)-BLAST to retrieve sequences, a user-generated multiple sequence alignment, or knowledge of function (Varadi et al, 2015;Khan and Kihara, 2016).…”

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confidence: 99%

Pipeline to Identify Hydroxyproline-Rich Glycoproteins

et al. 2017

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Intrinsically disordered proteins (IDPs) are functional proteins that lack a well-defined three-dimensional structure. The study of IDPs is a rapidly growing area as the crucial biological functions of more of these proteins are uncovered. In plants, IDPs are implicated in plant stress responses, signaling, and regulatory processes. A superfamily of cell wall proteins, the hydroxyprolinerich glycoproteins (HRGPs), have characteristic features of IDPs. Their protein backbones are rich in the disordering amino acid proline, they contain repeated sequence motifs and extensive posttranslational modifications (glycosylation), and they have been implicated in many biological functions. HRGPs are evolutionarily ancient, having been isolated from the protein-rich walls of chlorophyte algae to the cellulose-rich walls of embryophytes. Examination of HRGPs in a range of plant species should provide valuable insights into how they have evolved. Commonly divided into the arabinogalactan proteins, extensins, and proline-rich proteins, in reality, a continuum of structures exists within this diverse and heterogenous superfamily. An inability to accurately classify HRGPs leads to inconsistent gene ontologies limiting the identification of HRGP classes in existing and emerging omics data sets. We present a novel and robust motif and amino acid bias (MAAB) bioinformatics pipeline to classify HRGPs into 23 descriptive subclasses. Validation of MAAB was achieved using available genomic resources and then applied to the 1000 Plants transcriptome project (www.onekp.com) data set. Significant improvement in the detection of HRGPs using multiple-kmer transcriptome assembly methodology was observed. The MAAB pipeline is readily adaptable and can be modified to optimize the recovery of IDPs from other organisms.

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DisProt 7.0: a major update of the database of disordered proteins

Cited by 45 publications

References 0 publications

Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors

Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors

How disordered is my protein and what is its disorder for? A guide through the “dark side” of the protein universe

Pipeline to Identify Hydroxyproline-Rich Glycoproteins

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