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What is this view?

Binary interactions

In this tab, we display the list of interactions that you have selected using one of our search features. Despite the fact that our data are annotated to accurately reflect the interactions reported in scientific literature, the data is shown in this view as binary interactions. Whenever the data was reported as a co-complex involving more than two molecules, we store it as such in the IntAct database and post-process it so the portal can show it as binary interaction. This post-processing is the Spoke Expansion model (connects bait to all preys):



sourceExp

At any moment you can choose to display the expansion column in this view in order to see which interaction are spoke expanded and which are not.

Description of what has changed

  • We have added more download options to allow users to retrieve their interaction set using more standard formats such as PSI-MI XML and PSIMITAB (version 2.5, 2.6 or 2.7) but also XGMML, RDF and Biopax (level 2 and 3).
  • We have now four different table views : minimal(molecule names and interaction AC), basic (minimal + molecule links, interaction detection method, negative), standard(minimal + molecule species, confidences, publication details, experiment details), expanded (standard + more experiment details) and complete (all mitab 2.7 columns).

Configuring the view to your need"

In the header of the interaction table you will find a button: ‘Change Column Display’ that will show you all the columns/Table views available and allow you to update the current selected set.

Downloading the data into Standard formats"

In the header of the interaction table you will find a drop down list that contains all the formats currently supported when downloading the interaction data. Select one of them and click the export button next to the list. Please note that PSI-MI XML is only available when the interaction set is no bigger than 1000 interactions.

Opening the interaction details"

Clicking on the magnifying glass in the first column of the interaction table will open the details of the corresponding interaction in the Interaction Details tab, giving you access to more details of the manually curated record.

What is this view?

Browsing (Browse Tab)

This tab is meant to give you access to more content based on the currently selected set of interactions. Please note that linking to third party resources will only include up to 200 molecules , if you exceed this number you will see the warning icon (This number has been reduced to 125 molecules for mRNA expression). Now let’s look at the features available to you:

Limiting the scope of the current dataset with the Uniprot Taxonomy ontology

Allows users to browse the Uniprot Taxonomy hierarchy as a tree and select terms in order to narrow down their dataset. Once a term is selected, you are taken back to the interaction tab to review your dataset.

Limiting the scope of the current dataset with the GO ontology

Allows users to browse the GO hierarchy as a tree and select terms in order to narrow down their dataset. Once a term is selected, you are taken back to the interaction tab to review your dataset.

Limiting the scope of the current dataset with the ChEBI ontology

Allows users to browse the ChEBI hierarchy as a tree and select terms in order to narrow down their dataset. Once a term is selected, you are taken back to the interaction tab to review your dataset.

Bulk linking to third party resources by using involved proteins

  • Proteins by Reactome pathway: Sends your proteins to the Reactome SkyPainter that will show you the pathways in which these molecules are know to play a role.
  • Proteins by Chromosomal location: Sends your list of proteins to Ensembl’s Karyotype viewer and overlays the proteins on the chromosomes.
  • Proteins by mRNA expression: Sends your set of proteins to the ArrayExpress Atlas that will show the known gene expression based on experimental studies.
What is this view?

Searching Interactions (Search Tab)

As you can see in this tab we are now trying to give you more targeted choice to do your queries, please note that the examples provided in this tab are live links so you can simply click them to see the resulting interactions sets.

Using the Quick Search

In this search panel you are free to type anything that might relate to interactions, whether it is properties of their interactor (gene name, identifiers, GO term…) or more specific to the interaction like publication, authors, experimental detection method, ...

Some examples:

  • Try the query: imatinib
    This is a drug for which we have curated a number of interactions.
    Once you press the search button you should be taken to the Interaction Tab that lists 130 binary interactions.
    If you want to construct more complex queries we recommend you take a look at the Molecular Interaction Query Language, accessible from the quick search panel.
  • Try the query: species:yeast AND type:"direct interaction"
    This query selects all interactions involving yeast interactors that have been shown to have direct interactions. If you customize the column display of the interaction tab, you will see that not only “direct interaction” have been selected but also children terms in the PSI-MI ontology.

Using the Ontology Search

Open the Rearch Tab. This panel is specialised to give you an easy access to ontology search. So far you can search on 4 ontologies:

  • Gene Ontology
  • InterPro
  • PSI-MI
  • ChEBI

Whenever you start typing a query in this search panel, the system will search as you type and propose a list of matching controlled vocabulary terms. You can then select one of them and select matching interactions.

For example, type: cancer
You will be presented with a few choices, please note that each term is followed by the count of matching interactions in the IntAct database.

Select a term with the mouse or using the keyboard cursor keys and you will be taken to the interaction tab.

Searching the Compound chemical structure

In this panel you will be able to draw all or part of a chemical structure and search for chemical compounds. If you get any matched, you can then see all interactions involving them.

First you have to open up the chemical search panel so that the applet can load, it might take a few seconds. Then you can start drawing your structure, for instance:

Once you have drawn your structure, select Similarity and press Search. You should be presented with a list of matching compound. Now choose one molecule and click the link: IntAct interactions. You will be taken to the interaction tab to review the data.

Complex Expansion

Binary interactions generated by co-complex expansion

Why should you care about complex expansion ?

Some experimental methods such as Tandem Affinity Purification do generate molecular interactions that can involve more than 2 molecules. Despite the fact that IntAct curation team do capture the molecular interaction as they were reported in the corresponding experiment, when you search using the intact web site, the results of your query is always shown as set of binary interactions (i.e. 2 molecules). We would like to draw your attention on the fact that whenever the reported interaction was a co-complex we do apply an expansion algorithm that transform this n-ary interaction into a set of binary interactions. While none of these agorithms is perfect and will very likely generate some false positive interactions, it is useful to present the data in a consistent manner. Bear in mind that we will strive to differentiate in the search results which interactions are a real experimental binary from expanded ones.

Existing expansion algorithm

There are several known algorithm allowing to transform an n-ary interaction into a set of binaries. The illustration below present the two well known expansion model and illustrates why they can be incorrect.



sourceExp

  • Spoke expansion: Links the bait molecule to all prey molecules. If N is the count of molecule in the complex, it generated N-1 binary interactions.
  • Matrix expansion: Links all molecule to all other molecule present in the complex. If N is the count of molecule in the complex, it generated (N*(N-1))/2 binary interactions.

Now the issue (as illustrated at the bottom right of the diagram above) with these two models lies in the fact that the real complex might not be articulated around the experimental bait but instead, this bait might be linked to a smaller complex, hence most binary interaction generated by spoke and matrix expansion result in false positive.



PSICQUIC

How is the number of interactions in other databases obtained?

PSICQUIC is a standard way to access molecular interaction databases across which it repeats the same query. The number of databases providing data may vary, depending on the status of their services and only those that are active are used in this query. By clicking on the number of interactions you will be redirected to the PSICQUIC View, where you can browse the results in those other resources.

The services currently active are:

Check the PSICQUIC site for more information.

IMEx

What is the significance of the IMEx dataset?"

IMEx is a network of databases which have agreed to supply a non-redundant set of data expertly manually annotated to the same consistent detailed standard which, as such, represents a high-quality subset of the data each individually provides. The number of databases providing data may vary, depending on the status of their services and only those that are active are used in this query. By clicking on the number of interactions you will be redirected to the IMEx View, where you can browse the results in those other resources.

The services currently active are:

Check the IMEx site for more information.

What is this view?

Representation of Experimental Features

This section shows the graphical representation of experimental features, where each participant is represented as a white rectangle with a black border and a line for each hundredth amino acid. All available features are attached to their associated participant and their categories are represented in the right side of the legend. The left side of the legend dynamically shows the range statuses occuring in the shown interaction. These are the possible range statuses:

sourceExp

Interacting with the widget

Hover over a feature to see more information in a tooltip.
sourceExp

To display a single interacting region click on it and click again to display all interacting regions.
Displaying all interacting regionsDisplaying one interacting region
sourceExpsourceExp
What is this view?

Dynamic molecular interaction data

This section shows the graphical representation of dynamic molecular interactions. By default it displays all the interactions from one experiment using radio buttons to allow users to highlight interactions in different variable conditions.

Datasets of the month - Archive

  • An inter-species protein-protein interaction network across vast evolutionary distance.
  • A combined binary interaction and phenotypic map of C. elegans cell polarity proteins.
  • Analysis of the Rab GTPase Interactome in Dendritic Cells Reveals Anti-microbial Functions of the Rab32 Complex in Bacterial Containment (PMID:26885862).
  • Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins.
  • Systematic profiling of the human centrosome-cilium proximity interaction landscape.
  • A human protein interactome in three quantitative dimensions.
  • TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial complex I assembly factor through association with the MCIA complex.
  • Identification of the Mitochondrial Heme Biosynthesis Metabolon.
  • A Floor-Plate Extracellular Protein-Protein Interaction Screen Identifies Draxin as a Secreted Netrin-1 Antagonist..
  • A protein interaction map of the LSU processome.
  • A protein interaction map of the LSU processome.
  • Phospho-tyrosine dependent protein-protein interaction network..
  • Phospho-tyrosine dependent protein-protein interaction network..
  • A proteome-scale map of the human interactome network..
  • The EHEC-host interactome reveals novel targets for the translocated intimin receptor.
  • A DEK Domain-Containing Protein Modulates Chromatin.
  • The protein-tyrosine kinases and phosphatases of Bacillus subtilis from the groups of Marie-Francoise Noirot-Gros and Ivan Mijakovic.
  • Analysis of the expression patterns, subcellular localisations and interaction partners of Drosophila proteins using a pigP protein trap library..
  • Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
  • A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways.
  • Ribosomal Protein s15 Phosphorylation Mediates LRRK2 Neurodegeneration in Parkinson's Disease.
  • Enhanced prediction of SH2 domain binding potentials using a fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen receptor interactome.
  • Butland et al. The Palmitoyl acyltransferase HIP14 Shares a High Proportion of Interactors with Huntingtin: Implications for a Role in the Pathogenesis of Huntington Disease.
  • Interactomics of Qa-SNARE in Arabidopsis thaliana.
  • The binary protein-protein interaction landscape of Escherichia coli.
  • Protein interaction network of the Mammalian hippo pathway reveals mechanisms of kinase-phosphatase interactions..
  • Protein interaction network of the Mammalian hippo pathway reveals mechanisms of kinase-phosphatase interactions..
  • Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.
  • Identification and Comparative Analysis of Hepatitis C Virus-Host Cell Protein Interactions.
  • The protein interaction network of bacteriophage lambda with its host, Escherichia coli..
  • A conserved N-terminal motif is required for complex formation between FUS, EWSR1, TAF15 and their oncogenic fusion proteins..
  • Extensive Rewiring and Complex Evolutionary Dynamics in a C. elegans Multiparameter Transcription Factor Network.
  • Global T cell protein interaction network for human HDACs.
  • SH3 interactome conserves general function over specific form.
  • Protein Complexes Are under Evolutionary Selection to Assemble via Ordered Pathways. Data submitted directly to IntAct.
  • Dynamic Circadian PPI Networks Reveal Temporal Organization of Cellular Functions. Data submitted directly to IntAct.
  • Interlaboratory reproducibility of large-scale human protein-complex analysis by AP-MS. Data directly submitted to IntAct.
  • Development of a DNA microarray-based yeast two-hybrid system. Data directly submitted to IntAct.
  • Silencing of MYC-mediated miR-29 by HDAC3 and EZH2 as a target of histone modification in aggressive B-Cell lymphomas..
  • Human VRK2 (Vaccinia-related Kinase 2) modulates tumor cell invasion - data submitted directly to IntAct..
  • A Human Skeletal Muscle Interactome Centered on Proteins involved in Muscular Dystrophies - data submitted directly to IntAct.
  • VEGF Inhibits Tumor Cell Invasion and Mesenchymal Transition through a MET/VEGFR2 Complex.
  • Viral immune modulators perturbing the human molecular network - data directly submitted to IntAct.
  • VRK2 anchors KSR1-MEK1 to endoplasmic reticulum forming a macromolecular complex that compartmentalizes MAPK signaling - data submitted directly to IntAct.
  • Exploring respiratory virus interactions - data directly submitted to IntAct.
  • CRFs form protein-protein interactions with each other and with members of the cytokinin signalling pathway in Arabidopsis via the CRF domain..
  • Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks.
  • Conserved BK channel-protein interactions reveal signals relevant to cell death and survival.
  • A Systematic Screen for CDK4/6 Substrates Links FOXM1 Phosphorylation to Senescence Suppression in Cancer Cells.
  • A Systematic Screen for CDK4/6 Substrates Links FOXM1 Phosphorylation to Senescence Suppression in Cancer Cells.
  • Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome.
  • Evidence for network evolution in an Arabidopsis interactome map.
  • Toward an understanding of the protein interaction network of human liver.
  • Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA chromatin remodeling complexes.
  • Selected reaction monitoring mass spectrometry reveals the dynamics of signaling through the GRB2 adaptor.
  • Linking Chromatin remodelling, DNA repair and genomic stability through INO80 network.
  • Mpk1 MAPK Association with the Paf1 Complex Blocks Sen1-Mediated Premature Transcription Termination.
  • The Impact of a Novel Apolipoprotein E and Amyloid-β Protein Precursor-Interacting Protein on the Production of Amyloid-β.
  • In vivo analysis of proteomes and interactomes using parallel affinity capture (iPAC) coupled to mass spectrometry..
  • Two datasets from the Weisz group (Proteomics, January 2011) describe the estrogen interactome involved in breast cancer.
  • Interactions of the regulator of actin filament dynamics, LIM domain kinase 1 .
  • A stele-enriched gene regulatory network in the Arabidopsis root.
  • Network organization of the human autophagy system.
  • Defining the Budding Yeast Chromatin Associated Interactome.
  • The involvement of leucine-rich repeat kinase 2 in actin cytoskeleton dynamics.
  • Allostery and intrinsic disorder mediate transcription regulation by conditional cooperativity.
  • Experimentally identified RNA-binding proteins in Oryza sativa L.
  • The Human-Bacterial Pathogen Protein Interaction Networks of Bacillus anthracis, Francisella tularensis and Yersinia pestis.
  • The mapping of interacting regions of transcription factor-related protein complexes using a high-throughput mRNA display screen.
  • Interactome mapping of the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway.
  • Interactions of p63, a key player in multiple facets of epithelial cell biology.
  • Characterisation of human protein complexes with a role in chromosome segregation and cell division.
  • The Varicella Zoster Virus interactome.
  • Proteome Organization in a Genome-Reduced Bacterium - the interactome of Mycoplasma pneumoniae provides a blueprint of the minimal cellular machinery required for life.
  • A PP2A phosphatase interaction network involves the cerebral cavernous malformation 3 (CCM3) protein.
  • Analysis of interaction partners of H4 histone by a new proteomics approach.
  • Addition of novel interactions to IntAct's Alzheimer's network.
  • A zebrafish cell surface interaction network of neural leucine-rich repeat receptors.
  • A protein interaction network for the large conductance Ca(2+)-activated K(+) channel in the mouse cochlea.
  • Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins.
  • The Human E2 Ubiquitin Conjugating Enzyme Protein Interaction Network.
  • A Smart Pooling approach where reagents are multiplexed in a highly redundant manner provides a strategy for achieving high efficiency, sensitivity, and specificity in yeast two hybrid screens.
  • Exploring the human phosphatome.
  • Two novel GPCR-type G proteins are abscisic acid receptors in Arabidopsis.
  • An in vitro microfluidic approach to generating protein-interaction networks.
  • Submitted datasets - Improved approaches to largescale interactome mapping.
  • In vivo interactome of yeast.
  • Controlling the cell cycle - interactions of VRK1.
  • Investigating HIF1alpha turnover - regulating the adaptive response to hypoxia.
  • Interactome network for C. elegans early embryogenesis.
  • The identification of nuclear Ran GTPase as a regulator of the Vaccinia-Related Kinases.
  • Focus on Apoptosis.
  • Resolving and Identifying Protein Components of Plant Mitochondrial Respiratory Complexes Using Three Dimensions of Gel Electrophoresis.
  • Protein interactions in the Syphilis Spirochete.
  • Protein-protein interactions between two-component system transmitter and receiver domains of Myxococcus xanthus.
  • A medium-scale proteomics study of interactions between transcription factors with roles in liver cell proliferation.
  • Avexis - A novel method to screen low-affinity extracellular interactions.
  • the systematic identification of protein interactions for the unicellular cyanobacterium Synechocystis sp. strain PCC6803. Using a modified high-throughput yeast two-hybrid assay a total of 3236 independent two-hybrid interactions involving 1920 proteins were detected.
  • A protein-interaction network formed by the ARP2-ARP3 complex which is known to controls cell shape in Arabidopsis.
  • Focus on interactions of PI3-kinase subunits.
  • A selection of papers from 2007 describing protein-protein interactions involving p53.
  • A quantitative chemical proteomics approach reveals novel modes of action of clinical ABL kinase inhibitors. Bantscheff et al report a large-scale approach to profile the interaction of protein kinases with small inhibitory molecules. This study advances the understanding of the modes of action of clinical ABL kinase inhibitors and also identifies novel drug targets.
  • With more than 12,000 interactions, Parrish et al. provide a major bacterial interactome.
  • High throughput proteomic analysis of Ring1B/Rnf2 interactors identifies a novel complex with the Fbxl10/Jmjd1B histone demethylase and the BcoR corepressor.
  • Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach.
  • Two cancer-related medium-scale proteomics papers.
  • Large-scale mapping of human protein-protein interactions by mass spectrometry.
  • Exploring the mammalian NF-kappaB pathway.
  • The Conserved KNL-1/Mis12complex/Ndc80 Network.
  • Role of SMC proteins in chromatin modulation.
  • Large-scale identification of protein-protein interaction of Escherichia coli K-12.
  • Chl12 (Ctf18) forms a novel replication factor C-related complex and functions redundantly with Rad24 in the DNA replication checkpoint pathway.
  • More than 750 interactions of human proteins with a potential role in ataxia, the neurodegenerative condition caused by cerebellar Purkinje cell degeneration.
  • Landscape of the hnRNP K protein-protein interactome.
  • Stable isotope labeling by amino acids in cell culture (SILAC) to identify proteins that interact with GLUT4 in an insulin-regulated manner.
  • Biochemical niche of C. elegans DCR-1 in small-RNA-mediated pathways.
  • A protein interaction network of the malaria parasite Plasmodium falciparum.
  • Genome-wide screen for complexes in yeast: purifications and computed complexes.
  • Proteomic characterization of the components and multiprotein complexes of the mouse brain PSD.
  • Extending the human and yeast protein interaction network: more than 6200 new interactions in IntAct!.