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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.

Publication

PubMed Id: 19268472

Journal: J. Mol. Biol. (0022-2836)

Year of Publication: 2009

Title: Novel insights into the mechanisms of CIN85 SH3 domains binding to Cbl proteins: solution-based investigations and in vivo implications.

Author List: Ababou A., Pfuhl M., Ladbury JE.

Cross References:

Experiment (6 interactions)

Accession: EBI-8584165

Name: ababou-2009-1

Host organism: In vitro

Organism: In vitro

Accession: EBI-1318

Name: in vitro

Description: In vitro

Cross References:

Database
Identifier
Secondary identifier
Qualifier
-

Annotations:

Topic
Text
�Host Organism' is in vitro on experiments when one of the interacting proteins is extracellular or has an extracellular domain that participates in the interaction and /or the interaction is shown to occur in a tube.
The term is also used to indicate in vitro produced protein e.g. by coupled in vitro transcription translation system.
1. Interaction between a cellsurface receptor and a labelled purified protein ligand; 2. Two cells each of which express cellsurface molecules and are demonstrated to interact; 3. One cell expressing two or more cellsurface molecules which are demonstrated to interact.

Interaction Detection Method: itc

Interaction detection method: itc
Accession: EBI-1159

Name: itc

Description: isothermal titration calorimetry

Cross References:
Database
Identifier
Secondary identifier
Qualifier
pubmed
11785756
-
primary-reference
psi-mi
MI:0065
-
identity


Annotations:
Topic
Text
definition
Isothermal titration calorimetry (ITC) measures directly the energy associated with a chemical reaction triggered by the mixing of two components. A typical ITC experiment is carried out by the stepwise addition of one of the reactants (~10-6 L per injection) into the reaction cell (~1mL) containing the second reactant. The chemical reaction occurring after each injection either releases or absorbs heat (qi) proportional to the amount of ligand that binds to the protein with a characteristic binding enthalpy (DH). As modern ITC instruments operate on the heat compensation principle, the instrumental response (measured signal) is the amount of power (microcalories per second) necessary to maintain constant the temperature difference between the reaction and the reference cells. Because the amount of uncomplexed protein available progressively decreases after each successive injection, the magnitude of the peaks becomes progressively smaller until complete saturation is achieved. The difference between the concentration of bound ligand in the ith and (i-1)th injections depends on the binding constant Ka and the total ligand injected. The calculations depend on the binding model (number of substrates). Analysis of the data yields DH and DG = -RTlnKa. The entropy change is obtained by using the standard thermodynamic expression DG = DH-TDS.


Participant Identification Method: predetermined

Participant identification method: predetermined
Accession: EBI-1465

Name: predetermined

Description: predetermined participant

Cross References:
Database
Identifier
Secondary identifier
Qualifier
psi-mi
MI:0396
-
identity
pubmed
14755292
-
primary-reference


Annotations:
Topic
Text
definition
Molecule whose sequence identity is not checked and has been assumed from external or previous experimental evidence(s).


Cross References:

Annotations:

Topic
Text
SH3
partial coverage
mimix curation
mimix curation

Interaction

Accession: EBI-8584235

Name: sh3kbp1-cbl-3

Description: -

Type: direct interaction

Interaction type: direct interaction
Accession: EBI-608833

Name: direct interaction

Description: direct interaction

Cross References:
Database
Identifier
Secondary identifier
Qualifier
psi-mi
MI:0407
-
identity
pubmed
14755292
-
primary-reference


Annotations:
Topic
Text
definition
Interaction between molecules that are in direct contact with each other.


Cross References:

Database
Identifier
Secondary identifier
Qualifier
-

Annotations:

Topic
Text
homomint
mint
f3a t1

Interaction Parameters:

Type
Value
Unit
Base
Exponent
Uncertainty
31.0
10
-6

Participants (2)

Legend:
A
Annotation and Cross Reference  
P
Experimental Parameter   
S
Stoichiometry   
F
Experimental Feature
C
Participant Confidence
#
Name
Links
Primary Identifier
Aliases
Description
Species
Expression system
Experimental role
Biological role
Interactor type
More...
1
EBI-346595
 logo
dastyLogo
SH3KBP1
CIN85
Cbl-interacting protein of 85 kDa

[+2]
SH3 domain-containing kinase-binding protein 1
Homo sapiens
Organism Details

Accession: EBI-874

Name: human

Description: Homo sapiens

Cross References:

Database
Identifier
Secondary identifier
Qualifier
human

Expressed In Details

Accession:

Name:

-
bait
Experimental role: bait
Accession: EBI-49

Name: bait

Description: bait

Cross References:
Database
Identifier
Secondary identifier
Qualifier
psi-mi
MI:0496
-
identity
pubmed
14755292
-
primary-reference


Annotations:
Topic
Text
definition
Molecule experimentally treated to capture its interacting partners.


unspecified role
Biological role: unspecified role
Accession: EBI-77781

Name: unspecified role

Description: unspecified role

Cross References:
Database
Identifier
Secondary identifier
Qualifier
psi-mi
MI:0499
-
identity
pubmed
14755292
-
primary-reference


Annotations:
Topic
Text
definition
Role not specified or not applicable to the data.


protein
Interactor type: protein
Accession: EBI-619654

Name: protein

Description: protein

Cross References:
Database
Identifier
Secondary identifier
Qualifier
psi-mi
MI:0326
-
identity
pubmed
14755292
-
primary-reference
so
SO:0000358
-
see-also


Annotations:
Topic
Text
definition
A linear polymer of amino acids joined by peptide bonds in a specific sequence.


A
Participant: SH3 domain-containing kinase-binding protein 1

Participant: SH3 domain-containing kinase-binding protein 1

Accession: EBI-8584245

Name: EBI-346595

Cross References:

Database
Identifier
Secondary identifier
Qualifier
-

P
Participant: SH3 domain-containing kinase-binding protein 1

Participant: SH3 domain-containing kinase-binding protein 1

Accession: EBI-8584245

Name: EBI-346595

Parameters:

Type
Value
Unit
Base
Exponent
Uncertainty
No records found.


S
Participant: SH3 domain-containing kinase-binding protein 1

Participant: SH3 domain-containing kinase-binding protein 1

Accession: EBI-8584245

Name: EBI-346595

Stoichiometry: 0.0

F
Participant: SH3 domain-containing kinase-binding protein 1

Participant: SH3 domain-containing kinase-binding protein 1

Accession: EBI-8584245

Name: EBI-346595

Features:

Legend:
A
Annotation and Cross Reference  
Feature Name
Feature Type
Detection Method
Range positions
More...
binding site
  • 2-58
  • A
    Feature: EBI-8584248

    Feature: binding site

    Accession: EBI-8584248

    Name: binding site

    Cross References:

    Database
    Identifier
    Secondary identifier
    Qualifier
    -
    -


    C
    Participant: SH3 domain-containing kinase-binding protein 1

    Participant: SH3 domain-containing kinase-binding protein 1

    Accession: EBI-8584245

    Name: EBI-346595

    Confidences:

    Type
    Value
    No records found.

    2
    EBI-518228
     logo
    dastyLogo
    Signal transduction protein CBL
    Proto-oncogene c-Cbl
    Casitas B-lineage lymphoma proto-oncogene

    [+4]
    E3 ubiquitin-protein ligase CBL
    Homo sapiens
    Organism Details

    Accession: EBI-874

    Name: human

    Description: Homo sapiens

    Cross References:

    Database
    Identifier
    Secondary identifier
    Qualifier
    human

    Expressed In Details

    Accession:

    Name:

    -
    prey
    Experimental role: prey
    Accession: EBI-58

    Name: prey

    Description: prey

    Cross References:
    Database
    Identifier
    Secondary identifier
    Qualifier
    psi-mi
    MI:0498
    -
    identity
    pubmed
    14755292
    -
    primary-reference


    Annotations:
    Topic
    Text
    definition
    Molecule experimentally identified as being captured by a given bait.


    unspecified role
    Biological role: unspecified role
    Accession: EBI-77781

    Name: unspecified role

    Description: unspecified role

    Cross References:
    Database
    Identifier
    Secondary identifier
    Qualifier
    psi-mi
    MI:0499
    -
    identity
    pubmed
    14755292
    -
    primary-reference


    Annotations:
    Topic
    Text
    definition
    Role not specified or not applicable to the data.


    protein
    Interactor type: protein
    Accession: EBI-619654

    Name: protein

    Description: protein

    Cross References:
    Database
    Identifier
    Secondary identifier
    Qualifier
    psi-mi
    MI:0326
    -
    identity
    pubmed
    14755292
    -
    primary-reference
    so
    SO:0000358
    -
    see-also


    Annotations:
    Topic
    Text
    definition
    A linear polymer of amino acids joined by peptide bonds in a specific sequence.


    A
    Participant: E3 ubiquitin-protein ligase CBL

    Participant: E3 ubiquitin-protein ligase CBL

    Accession: EBI-8584242

    Name: EBI-518228

    Cross References:

    Database
    Identifier
    Secondary identifier
    Qualifier
    -

    P
    Participant: E3 ubiquitin-protein ligase CBL

    Participant: E3 ubiquitin-protein ligase CBL

    Accession: EBI-8584242

    Name: EBI-518228

    Parameters:

    Type
    Value
    Unit
    Base
    Exponent
    Uncertainty
    No records found.


    S
    Participant: E3 ubiquitin-protein ligase CBL

    Participant: E3 ubiquitin-protein ligase CBL

    Accession: EBI-8584242

    Name: EBI-518228

    Stoichiometry: 0.0

    F
    Participant: E3 ubiquitin-protein ligase CBL

    Participant: E3 ubiquitin-protein ligase CBL

    Accession: EBI-8584242

    Name: EBI-518228

    Features:

    Legend:
    A
    Annotation and Cross Reference  
    Feature Name
    Feature Type
    Detection Method
    Range positions
    More...
    binding site
  • 817-833
  • A
    Feature: EBI-8584252

    Feature: binding site

    Accession: EBI-8584252

    Name: binding site

    Cross References:

    Database
    Identifier
    Secondary identifier
    Qualifier
    -
    -


    C
    Participant: E3 ubiquitin-protein ligase CBL

    Participant: E3 ubiquitin-protein ligase CBL

    Accession: EBI-8584242

    Name: EBI-518228

    Confidences:

    Type
    Value
    No records found.


    Graphical Representation of Experimental Features