HuPho: the human phosphatase portal

Liberti, Susanna; Sacco, Francesca; Calderone, Alberto; Perfetto, Livia; Iannuccelli, Marta; Panni, Simona; Santonico, Elena; Palma, Anita; Nardozza, Aurelio Pio; Castagnoli, Luisa

doi:10.1111/j.1742-4658.2012.08712.x

Cited by 57 publications

(51 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Phosphatase-substrate interaction is weak and transient, thus it is unlikely that substrates can be identified by co-immunoprecipitation. In fact none of the interactors identified in the affinity purification experiments are among the validated substrates annotated in the HUPHO and DEPOD databases (Li et al, 2013; Liberti et al, 2013). It has been reported that much of phosphatase substrate specificity, localization and activity is modulated by the interaction with scaffold/regulatory proteins that target them to specific locations (Roy and Cyert, 2009; Sacco et al, 2012b).…”

Section: Resultsmentioning

confidence: 99%

“…However, evidence accumulated over the past decades have indicated that this enzyme class plays an important regulatory role and that the deregulation of the concentration or activity of specific phosphatases correlate with a variety of human disorders (Wera and Hemmings, 1995; Tonks, 2006). Notably, approximately 40% of protein phosphatases are implicated in tumor development, highlighting the central role of this enzyme group in growth regulation and identifying some members of this enzyme class as promising therapeutic targets (Julien et al, 2011; Liberti et al, 2013). One of the problems in the characterization, on a large scale, of the functional role of members of the phosphatase family is the lack of a simple, robust, method to identify physiologically relevant substrates.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Combining affinity proteomics and network context to identify new phosphatase substrates and adapters in growth pathways

et al. 2014

Self Cite

View full text Add to dashboard Cite

Edited by:Protein phosphorylation homoeostasis is tightly controlled and pathological conditions are caused by subtle alterations of the cell phosphorylation profile. Altered levels of kinase activities have already been associated to specific diseases. Less is known about the impact of phosphatases, the enzymes that down-regulate phosphorylation by removing the phosphate groups. This is partly due to our poor understanding of the phosphatase-substrate network. Much of phosphatase substrate specificity is not based on intrinsic enzyme specificity with the catalytic pocket recognizing the sequence/structure context of the phosphorylated residue. In addition many phosphatase catalytic subunits do not form a stable complex with their substrates. This makes the inference and validation of phosphatase substrates a non-trivial task. Here, we present a novel approach that builds on the observation that much of phosphatase substrate selection is based on the network of physical interactions linking the phosphatase to the substrate. We first used affinity proteomics coupled to quantitative mass spectrometry to saturate the interactome of eight phosphatases whose down regulations was shown to affect the activation of the RAS-PI3K pathway. By integrating information from functional siRNA with protein interaction information, we develop a strategy that aims at inferring phosphatase physiological substrates. Graph analysis is used to identify protein scaffolds that may link the catalytic subunits to their substrates. By this approach we rediscover several previously described phosphatase substrate interactions and characterize two new protein scaffolds that promote the dephosphorylation of PTPN11 and ERK by DUSP18 and DUSP26, respectively.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combining affinity proteomics and network context to identify new phosphatase substrates and adapters in growth pathways

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…The Human Phosphatase Portal (HuPho) [38] reports 135 protein phosphatases of which 107 are Protein Tyrosine Phosphatases (PTPs). The remaining 28 S/T phosphatases consist of two families, Metal Dependent Protein Phosphatases (PPMs or PP2Cs) and Phosphoserine Protein Phosphatases (PPPs).…”

Section: Resultsmentioning

confidence: 99%

The reduced kinome of Ostreococcus tauri: core eukaryotic signalling components in a tractable model species

et al. 2014

View full text Add to dashboard Cite

BackgroundThe current knowledge of eukaryote signalling originates from phenotypically diverse organisms. There is a pressing need to identify conserved signalling components among eukaryotes, which will lead to the transfer of knowledge across kingdoms. Two useful properties of a eukaryote model for signalling are (1) reduced signalling complexity, and (2) conservation of signalling components. The alga Ostreococcus tauri is described as the smallest free-living eukaryote. With less than 8,000 genes, it represents a highly constrained genomic palette.ResultsOur survey revealed 133 protein kinases and 34 protein phosphatases (1.7% and 0.4% of the proteome). We conducted phosphoproteomic experiments and constructed domain structures and phylogenies for the catalytic protein-kinases. For each of the major kinases families we review the completeness and divergence of O. tauri representatives in comparison to the well-studied kinomes of the laboratory models Arabidopsis thaliana and Saccharomyces cerevisiae, and of Homo sapiens. Many kinase clades in O. tauri were reduced to a single member, in preference to the loss of family diversity, whereas TKL and ABC1 clades were expanded. We also identified kinases that have been lost in A. thaliana but retained in O. tauri. For three, contrasting eukaryotic pathways – TOR, MAPK, and the circadian clock – we established the subset of conserved components and demonstrate conserved sites of substrate phosphorylation and kinase motifs.ConclusionsWe conclude that O. tauri satisfies our two central requirements. Several of its kinases are more closely related to H. sapiens orthologs than S. cerevisiae is to H. sapiens. The greatly reduced kinome of O. tauri is therefore a suitable model for signalling in free-living eukaryotes.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-640) contains supplementary material, which is available to authorized users.

show abstract

“…Phosphatome of Lm has 172 phosphatases, while its kinome has 199 kinases [15], Gl has a phosphatome size of 151 phosphatases and its kinome consists of 278 kinases (Table 1). Human phosphatome has 199 proteins consisting of phosphatase domain [28]. There was a variation in apicomplexan phosphatomes size between different genera.…”

Section: Resultsmentioning

confidence: 99%

“…Eh has the highest percentage of phosphatases followed by Lm and Cp . The percentage of phosphatome in Hs is 0.6% of its proteome (Fig 1) [5, 28], which is much less than the selected parasites phosphatomes, indicating that vertebrates have various other mechanisms for the regulation of proteins but in protozoan parasites phosphorylation is an integral mechanism for protein regulation.…”

Section: Resultsmentioning

confidence: 99%

Deep Insight into the Phosphatomes of Parasitic Protozoa and a Web Resource ProtozPhosDB

Anwar¹,

Gourinath²

2016

PLoS ONE

View full text Add to dashboard Cite

Phosphorylation dynamically regulates the function of proteins by maintaining a balance between protein kinase and phosphatase activity. A comprehensive understanding of the role phosphatases in cellular signaling is lacking in case of protozoans of medical and veterinary importance worldwide. The drugs used to treat protozoal diseases have many undesired effects and the development of resistance, highlights the need for new effective and safer antiprotozoal agents. In the present study we have analyzed phosphatomes of 15 protozoans of medical significance. We identified ~2000 phosphatases, out of which 21% are uncharacterized proteins. A significant positive correlation between phosphatome and proteome size was observed except for E. histolytica, having highest density of phosphatases irrespective of its proteome size. A difference in the number of phosphatases among different genera shows the variation in the signaling pathways they are involved in. The phosphatome of parasites is dominated by ser/thr phosphatases contrary to the vertebrate host dominated by tyrosine phosphatases. Phosphatases were widely distributed throughout the cell suggesting physiological adaptation of the parasite to regulate its host. 20% to 45% phosphatome of different protozoa consists of ectophosphatases, i.e. crucial for the survival of parasites. A database and a webserver “ProtozPhosDB” can be used to explore the phosphatomes of protozoans of medical significance.

show abstract

HuPho: the human phosphatase portal

Cited by 57 publications

References 47 publications

Combining affinity proteomics and network context to identify new phosphatase substrates and adapters in growth pathways

Combining affinity proteomics and network context to identify new phosphatase substrates and adapters in growth pathways

The reduced kinome of Ostreococcus tauri: core eukaryotic signalling components in a tractable model species

Deep Insight into the Phosphatomes of Parasitic Protozoa and a Web Resource ProtozPhosDB

Contact Info

Product

Resources

About