Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants

This data respository contains data associated with a study to characterize how missense mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP2, alter the protein-protein interactions and localization. SHP2 has a catalytic domain that dephosphorylates proteins and two phosphotyrosine-binding SH2 domains. One part of this respository contains data that were used to map the sequence recognition profiles of the two wild-type SH2 domains of SHP2. These sequence recognition profiles were used to predict binding sites for each SH2 domain across the human proteome, and they are juxtaposed with the proteomics data presented in the parent study. Another part of the repository contains microscopy data examining the mitochondrial localization of wild-type SHP2. A third part includes a structural model of SHP2 bound to an interactor, PPIF, identified from proximity-labeling proteomics experiments.
, The deep sequencing data were generated using a high-throughput method for profiling the sequence specificities of SH2 domains. This method has been documented extensively in two published manuscripts:
https://doi.org/10.7554/elife.82345
https://doi.org/10.1073/pnas.2407159121
The overall approach entails the use of degenerate, genetically-encoded peptide libraries, with a structure X5-Y-X5, where X is any of the 20 canonical amino acids and Y is tyrosine. The libraries (approximately 1 million random sequences) are displayed on the surface of E. coli cells, then enzymatically phosphorylated using a mixture of tyrosine kinases. Then, SH2 domains immobilized on magnetic beads are used to enriched those phosphorylated cells with optimal peptide sequences for the particular SH2 domain. These cells are isolated, and DNA encoding the peptides is amplified by PCR and subject to deep sequencing. An input library that has not been selected by any SH2 domain is also sequenced.
Next, the sequence..., , # Data from: Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants

[https://doi.org/10.5061/dryad.wstqjq2xv](https://doi.org/10.5061/dryad.wstqjq2xv)

## Description of the data and file structure

There are two data types in this repository: deep sequencing data and associated analysis files, and microscopy data.

The deep sequencing data were generated using a high-throughput method for profiling the sequence specificities of SH2 domains. This method has been documented extensively in two published manuscripts:

[https://doi.org/10.7554/elife.82345](https://doi.org/10.7554/elife.82345)\
[https://doi.org/10.1073/pnas.2407159121](https://doi.org/10.1073/pnas.2407159121)

The overall approach entails the use of degenerate, genetically-encoded peptide libraries, with a structure X5-Y-X5, where X is any of the 20 canonical amino acids and Y is tyrosine. The libraries (approximately 1 million random sequences) are displayed on the...,