Interaction methods

Protein interactions

Protein-protein interactions are essential for many processes in cellular life, such as cell signaling, gene expression and control and antibody–antigen binding, and they are often blocked or altered in disease. Knowledge about interaction networks can therefore help in understanding disease mechanisms and in developing diagnostic and therapeutic strategies.

The Interaction resource presents interaction networks for 15216 genes based on protein-protein interaction data from IntAct, BioGRID, BioPlex and OpenCell that has been integrated with data related to protein expression, location and classification.

For 7855 genes and the 22979 of their interactions present in more than one dataset, so called consensus interactions, interactive 3D protein structures based on predictions generated using the AlphaFold 3 source code are also displayed. More information about the specific content and the generation of the data in this section can be found in the Methods summary.

Learn about:

• the interaction partners of proteins
• the predicted 3D structure of all consensus interactions
• the predicted and subcellular location of the proteins in the network
• the expression specificity of the proteins in the network
• the interaction partners expressed in the same cell type for genes with specific expression

The protein-protein interaction network plots for each gene is based on data from IntAct, BioPlex, OpenCell and BioGRID and enables exploration of the interaction partners in each dataset separately and, if applicable, in a consensus network showing only interactions present in more than one of the datasets. More information about the genes in the network is displayed by mouse-over and the network can be extended by clicking on a gene of interest.

Figure 1. First-level consensus interactions for the nuclear protein AURKB colored according to subcellular location (left) and cell type specificity (right). The edge colors represent the number of datasets for the interacting pair and datasets involved are shown by mouse-over. By clicking on the blue points on the edges the corresponding 3D structure for the interaction together with scores and and a PAE plot is displayed as shown in Figure 2.

To allow for deeper understanding of the interaction partners and their context the genes in a network can be colored according to experimental subcellular location based on data in the Subcellular resource, predicted location based on signal peptide and transmembrane region predictors, tissue specificity based on RNA tissue expression profiles or protein class. This is exemplified by the first-level consensus network for the AURKB gene colored according to subcellular location and cell type specificity, respectively, in Figure 1. There is also a highlight option for genes categorised as cell type enriched that will show interaction partners expressed in the same cell type(s) and thus indicate the most probable interactors in the particular cell type(s). Custom highlighting of genes is possible using the query builder in the Filter option.

For consensus interactor pairs the 3D structure of the interaction predicted by AlphaFold 3 including predicted template modelling scores and the corresponding predicted aligned error (PAE) plot are also displayed as shown in Figure 2.

Figure 2. The AlphaFold 3 predicted structures of the interactions between CCNE1 (blue) and CDK2 (red),as well as between TNF (blue) and TNFRSF1B (red) are shown together with the corresponding predicted template modelling scores and PAE plots. Structures are for non-commercial use only, subject to AlphaFold3 Output Terms of Use

In the current data 15216 genes have documented interactions and of these 7855 have at least one consensus interaction, an interaction present in at least two of the datasets. The bar plot in Figure 3 shows the distribution of the number of consensus interactions for these genes.

Among the 2430 genes with a single consensus interaction 369 are tissue or group enriched, while corresponding number for genes having more than five consensus interactions is 133 out of 2267. The bar plot in Figure 4 shows the fraction of the single cell type specificity categories in all different groups.