PhosphoSIGNOR Website Tutorial

Overview

PhosphoSIGNOR is a specialized resource within the SIGNOR platform, focusing on phosphorylation-mediated signaling events. It provides curated information on phosphorylation sites, including kinases, phosphatases, substrates, and their functional consequences.

Navigating the Homepage

• Search by Protein – Look up curated data for kinases, phosphatases, or substrates.
  Search Example: PKA

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• Search by Modified Residue – Search based on specific phosphorylated amino acid residues or sequences.
  Search Example: CREB1_Ser119

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• Advanced Search(beta) – Search paths that link phenotypes to specific phosphorylation/dephosphorylation sites.
  Search Example: CREB1_Ser119

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• Multi-protein Search – Search a list of proteins to generate their phospho-interaction networks.
  Search Example: VCP, RERBB2, PTPRO

How to Use PhosphoSIGNOR

1. Search by Protein

1. Select the protein type: Kinase, Phosphatase, or Substrate.
2. Enter the protein gene name (autocomplete function can assist with the selection within curated biological entities) or UniProt identifier.
3. Click Submit to view associated phosphorylation/dephosphorylation data.

2. Search by Modified Residue

• Residue Search: type protein ID or gene name, select specific curated residue from the dropdown menu.
• Sequence Search:
• Search by alignment: type protein sequence and search within curated data by alignment with sequences annotated in the SIGNOR dataset.
  
• Quick search: type protein ID or gene name, select specific sequence from the dropdown menu.
• Advanced Search: type protein gene name or UniProt ID, select specific curated residue. Click on Find Path to Phenotype to access results.
  

3. Multi-protein Search

Type a list of proteins to generate a network among them.

• select Connect to view a network of only interactions the searched proteins have with each other.
• select All to view a network of all the interactions the searched proteins are in.
• select Include Bridge Proteins to view a network of interactions the searched proteins have with each other, including bridge proteins (first neighbors).

Results

The results page provides three complementary data formats (Data Summary, PTM Format, SIGNOR Summary) that highlight distinct features of the annotated PTM interactions.

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The PTM format allows you to view the interaction as two separate events that together define the modification process. This is also reflected within the interactive viewer.

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To explore how PTMs are dynamically regulated across cancer progression, we linked phosphosites — wherever possible — to phosphoproteomic data from 10 tumor types and 1,680 patients available through the CPTAC portal, and displayed the results as boxplots.

Tips for Effective Use

• Use precise protein identifiers (e.g., UniProt IDs) for better results.
• Explore the API and Download section for large-scale or automated analysis.