Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The human phosphatase interactome: An intricate family portrait.

ABSTRACT: The concerted activities of kinases and phosphatases modulate the phosphorylation levels of proteins, lipids and carbohydrates in eukaryotic cells. Despite considerable effort, we are still missing a holistic picture representing, at a proteome level, the functional relationships between kinases, phosphatases and their substrates. Here we focus on phosphatases and we review and integrate the available information that helps to place the members of the protein phosphatase superfamilies into the human protein interaction network. In addition we show how protein interaction domains and motifs, either covalently linked to the phosphatase domain or in regulatory/adaptor subunits, play a prominent role in substrate selection.

SUBMITTER: Sacco F

PROVIDER: S-EPMC3437441 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The human phosphatase interactome: An intricate family portrait.

Sacco Francesca F Perfetto Livia L Castagnoli Luisa L Cesareni Gianni G

FEBS letters 20120521 17

The concerted activities of kinases and phosphatases modulate the phosphorylation levels of proteins, lipids and carbohydrates in eukaryotic cells. Despite considerable effort, we are still missing a holistic picture representing, at a proteome level, the functional relationships between kinases, phosphatases and their substrates. Here we focus on phosphatases and we review and integrate the available information that helps to place the members of the protein phosphatase superfamilies into the h ...[more]

PMID: 22626554

Similar Datasets

A Human Tyrosine Phosphatase Interactome Mapped by Proteomic Profiling.

Project description:Tyrosine phosphatases play a critical role in many cellular processes and pathogenesis, yet comprehensive analysis of their functional interacting proteins in the cell is limited. By utilizing a proteomic approach, here we present an interaction network of 81 human tyrosine phosphatases built on 1884 high-confidence interactions of which 85% are unreported. Our analysis has linked several phosphatases with new cellular processes and unveiled protein interactions genetically linked to various human diseases including cancer. We validated the functional importance of an identified interaction network by characterizing a distinct novel interaction between PTPN5 and Mob1a. PTPN5 dephosphorylates Mob1a at Y26 residue. Further, we identify that PTPN5 is required for proper midbody abscission during cytokinesis through regulation of Mob1a dephosphorylation. In conclusion, our study provides a valuable resource of tyrosine phosphatase interactions, which can be further utilized to dissect novel cellular functions of these enzymes.

| S-EPMC5548413 | biostudies-literature

Completing the structural family portrait of the human EphB tyrosine kinase domains.

Project description:The EphB receptors have key roles in cell morphology, adhesion, migration and invasion, and their aberrant action has been linked with the development and progression of many different tumor types. Their conflicting expression patterns in cancer tissues, combined with their high sequence and structural identity, present interesting challenges to those seeking to develop selective therapeutic molecules targeting this large receptor family. Here, we present the first structure of the EphB1 tyrosine kinase domain determined by X-ray crystallography to 2.5Å. Our comparative crystalisation analysis of the human EphB family kinases has also yielded new crystal forms of the human EphB2 and EphB4 catalytic domains. Unable to crystallize the wild-type EphB3 kinase domain, we used rational engineering (based on our new structures of EphB1, EphB2, and EphB4) to identify a single point mutation which facilitated its crystallization and structure determination to 2.2 Å. This mutation also improved the soluble recombinant yield of this kinase within Escherichia coli, and increased both its intrinsic stability and catalytic turnover, without affecting its ligand-binding profile. The partial ordering of the activation loop in the EphB3 structure alludes to a potential cis-phosphorylation mechanism for the EphB kinases. With the kinase domain structures of all four catalytically competent human EphB receptors now determined, a picture begins to emerge of possible opportunities to produce EphB isozyme-selective kinase inhibitors for mechanistic studies and therapeutic applications.

| S-EPMC4005714 | biostudies-literature

Atypical cyclins: the extended family portrait.

Project description:Regulation of cell division is orchestrated by cyclins, which bind and activate their catalytic workmates, the cyclin-dependent kinases (CDKs). Cyclins have been traditionally defined by an oscillating (cyclic) pattern of expression and by the presence of a characteristic "cyclin box" that determines binding to the CDKs. Noteworthy, the Human Genome Sequence Project unveiled the existence of several other proteins containing the "cyclin box" domain. These potential "cyclins" have been named new, orphan or atypical, creating a conundrum in cyclins nomenclature. Moreover, although many years have passed after their discovery, the scarcity of information regarding these possible members of the family has hampered the establishment of criteria for systematization. Here, we discuss the criteria that define cyclins and we propose a classification and nomenclature update based on structural features, interactors, and phylogenetic information. The application of these criteria allows to systematically define, for the first time, the subfamily of atypical cyclins and enables the use of a common nomenclature for this extended family.

| S-EPMC6971155 | biostudies-literature

The functional interactome landscape of the human histone deacetylase family.

Project description:Histone deacetylases (HDACs) are a diverse family of essential transcriptional regulatory enzymes, that function through the spatial and temporal recruitment of protein complexes. As the composition and regulation of HDAC complexes are only partially characterized, we built the first global protein interaction network for all 11 human HDACs in T cells. Integrating fluorescence microscopy, immunoaffinity purifications, quantitative mass spectrometry, and bioinformatics, we identified over 200 unreported interactions for both well-characterized and lesser-studied HDACs, a subset of which were validated by orthogonal approaches. We establish HDAC11 as a member of the survival of motor neuron complex and pinpoint a functional role in mRNA splicing. We designed a complementary label-free and metabolic-labeling mass spectrometry-based proteomics strategy for profiling interaction stability among different HDAC classes, revealing that HDAC1 interactions within chromatin-remodeling complexes are largely stable, while transcription factors preferentially exist in rapid equilibrium. Overall, this study represents a valuable resource for investigating HDAC functions in health and disease, encompassing emerging themes of HDAC regulation in cell cycle and RNA processing and a deeper functional understanding of HDAC complex stability.

| S-EPMC3964310 | biostudies-literature

Towards the construction of an interactome for Human WD40 protein family.

Project description:WD40 proteins are involved in a variety of protein-protein interactions as part of a multi-protein assembly modulating diverse and critical cellular process. It is known that several proteins of this family have been implicated in different disorders such as developmental abnormalities and cancer. However, molecular functions of many proteins in this family are yet unknown and it is of clinical interest. Therefore, it is of interest to define, construct, understand, analyze, evaluate, redefine and refine an interactome for WD40 protein family. We used data from literature mining using Cytoscape followed by linear regression analysis between Betweenness centrality and stress scores to define a model to filter the nodes in a representative WD40 interactome construction. We identified 10 ranked nodes in this analysis and subsequent microarray data selected three of them in insulin resistance that is further demonstrated in HepG2 cell culture models. We also observed the expression of GRWD1, RBBP5 and WDR5 genes during perturbation. Thus, we report hub nodes of WD40 interactome in insulin resistance. It should be noted that the pipeline using protein interaction network help find new proteins of clinical importance.

| S-EPMC5237648 | biostudies-literature

Using PrISMa to reveal the interactome of the human claudins family.

Project description:Here, we provide a protocol for the systematic screening of protein-protein interactions mediated by short linear motifs using the Protein Interaction Screen on a peptide Matrix (PrISMa) technique. We describe how to pull down interacting proteins in a parallelized manner and identify them by mass spectrometry. Finally, we describe a bioinformatic workflow necessary to identify highly probable interaction partners in the large-scale dataset. We describe the application of this method for the transient interactome of the claudin protein family. For complete details on the use and execution of this protocol, please refer to Suarez-Artiles et al.1.

| S-EPMC10542633 | biostudies-literature

The X family portrait: structural insights into biological functions of X family polymerases.

Project description:The mammalian family X DNA polymerases (DNA polymerases beta, lambda, mu, and TdT) contribute to base excision repair and double-strand break repair by virtue of their ability to fill short gaps in DNA. Structural information now exists for all four of these enzymes, making this the first mammalian polymerase family whose structural portrait is complete. Here we consider how distinctive structural features of these enzymes contribute to their biological functions in vivo.

| S-EPMC2128704 | biostudies-literature

The extracellular interactome of the human adenovirus family reveals diverse strategies for immunomodulation.

Project description:Viruses encode secreted and cell-surface expressed proteins essential to modulate host immune defenses and establish productive infections. However, to date there has been no systematic study of the extracellular interactome of any human virus. Here we utilize the E3 proteins, diverse and rapidly evolving transmembrane-containing proteins encoded by human adenoviruses, as a model system to survey the extracellular immunomodulatory landscape. From a large-scale protein interaction screen against a microarray of more than 1,500 human proteins, we find and validate 51 previously unidentified virus-host interactions. Our results uncover conserved strategies as well as substantial diversity and multifunctionality in host targeting within and between viral species. Prominent modulation of the leukocyte immunoglobulin-like and signalling lymphocyte activation molecule families and a number of inhibitory receptors were identified as hubs for viral perturbation, suggesting unrecognized immunoregulatory strategies. We describe a virus-host extracellular interaction map of unprecedented scale that provides new insights into viral immunomodulation.

| S-EPMC4858740 | biostudies-literature

The human brain somatostatin interactome: SST binds selectively to P-type family ATPases.

Project description:Somatostatin (SST) is a cyclic peptide that is understood to inhibit the release of hormones and neurotransmitters from a variety of cells by binding to one of five canonical G protein-coupled SST receptors (SSTR1 to SSTR5). Recently, SST was also observed to interact with the amyloid beta (Aβ) peptide and affect its aggregation kinetics, raising the possibility that it may bind other brain proteins. Here we report on an SST interactome analysis that made use of human brain extracts as biological source material and incorporated advanced mass spectrometry workflows for the relative quantitation of SST binding proteins. The analysis revealed SST to predominantly bind several members of the P-type family of ATPases. Subsequent validation experiments confirmed an interaction between SST and the sodium-potassium pump (Na+/K+-ATPase) and identified a tryptophan residue within SST as critical for binding. Functional analyses in three different cell lines indicated that SST might negatively modulate the K+ uptake rate of the Na+/K+-ATPase.

| S-EPMC6538167 | biostudies-literature

The interactome of the atypical phosphatase Rtr1 in Saccharomyces cerevisiae.

Project description:The phosphatase Rtr1 has been implicated in dephosphorylation of the RNA Polymerase II (RNAPII) C-terminal domain (CTD) during transcription elongation and in regulation of nuclear import of RNAPII. Although it has been shown that Rtr1 interacts with RNAPII in yeast and humans, the specific mechanisms that underlie Rtr1 recruitment to RNAPII have not been elucidated. To address this, we have performed an in-depth proteomic analysis of Rtr1 interacting proteins in yeast. Our studies revealed that hyperphosphorylated RNAPII is the primary interacting partner for Rtr1. To extend these findings, we performed quantitative proteomic analyses of Rtr1 interactions in yeast strains deleted for CTK1, the gene encoding the catalytic subunit of the CTD kinase I (CTDK-I) complex. Interestingly, we found that the interaction between Rtr1 and RNAPII is decreased in ctk1? strains. We hypothesize that serine-2 CTD phosphorylation is required for Rtr1 recruitment to RNAPII during transcription elongation.

| S-EPMC4074173 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data