Analyze post-translational modifications (PTMs) of proteins — modification sites, types, proteoforms, functional effects at PTM sites, and PTM-dependent protein interactions. Integrates iPTMnet, ProtVar, UniProt, and STRING databases. Use when asked about protein phosphorylation, ubiquitination, acetylation, glycosylation, methylation, SUMOylation, or other PTMs; proteoform diversity; PTM-regulated interactions; or functional impact of PTM sites.
Comprehensive PTM analysis using iPTMnet (primary), ProtVar (functional context), UniProt (baseline), STRING (interactions), ELM (linear motifs), and MassIVE/ProteomeXchange (experimental data).
iPTMnet_get_ptm_sitesProtVar_get_function + iPTMnet_get_ptm_ppiiPTMnet_get_proteoformsELM_get_instancesWhen analysis requires computation (statistics, data processing, scoring, enrichment), write and run Python code via Bash. Don't describe what you would do — execute it and report actual results. Use ToolUniverse tools to retrieve data, then Python (pandas, scipy, statsmodels, matplotlib) to analyze it.
PTMs are context-dependent: same phosphorylation site can activate or inhibit depending on kinase and effectors. Always check: which enzyme, what functional consequence, in what cell context.
operation parameterPhase 0: Protein Disambiguation → UniProt accession
Phase 1: PTM Site Inventory → iPTMnet_get_ptm_sites
Phase 2: Proteoform Analysis → iPTMnet_get_proteoforms
Phase 3: PTM-Dependent Interactions → iPTMnet_get_ptm_ppi
Phase 4: Functional Context → ProtVar_get_function at key sites
Phase 4b: Linear Motif Context → ELM_get_instances for SLiM overlap
Phase 4c: Experimental Data → MassIVE/ProteomeXchange
Phase 5: Synthesis & Report
iPTMnet_search(operation="search", search_term="TP53", role="Substrate") -- find UniProt IDsiPTMnet_get_ptm_sites(operation="get_ptm_sites", uniprot_id="P04637") -- returns position, residue, modification type, enzyme, evidence. Group by modification type. Fallback: UniProt_get_entry_by_accession PTM annotations.
iPTMnet_get_proteoforms(operation="get_proteoforms", uniprot_id=...) -- distinct PTM combinations. Focus on those with functional/disease annotations if >20.
iPTMnet_get_ptm_ppi(operation="get_ptm_ppi", uniprot_id=...) -- interacting protein, PTM site, effect (enables/disrupts). Supplement with STRING_get_interaction_partners(identifiers=gene, species=9606, required_score=700).
ProtVar_get_function(accession=..., position=N, variant_aa=AA) -- domain, active site, binding site, conservation. Grade: active-site PTM > domain-core > disordered region.
ELM_get_instances(operation="get_instances", uniprot_id=..., motif_type="MOD") -- MOD = modification sites, DEG = degradation signals. Cross-reference with Phase 1 PTM positions. ELM_list_classes(operation="list_classes") for motif details.
MassIVE_search_datasets(species="9606"), MassIVE_get_dataset(accession="MSV...") for public MS datasets.
| Tier | Criteria |
|---|---|
| T1 | PTM at validated active/binding site with functional data |
| T2 | PTM in structured domain with ProtVar annotation |
| T3 | Correlation data only (mass spec detection) |
| T4 | Predicted, no experimental validation |
| Tool | Key Params |
|---|---|
iPTMnet_search | operation="search", search_term, role |
iPTMnet_get_ptm_sites | operation="get_ptm_sites", uniprot_id |
iPTMnet_get_proteoforms | operation="get_proteoforms", uniprot_id |
iPTMnet_get_ptm_ppi | operation="get_ptm_ppi", uniprot_id |
ELM_get_instances | operation="get_instances", uniprot_id, motif_type |
ELM_list_classes | operation="list_classes" |
MassIVE_search_datasets | page_size, species |
Critical: All iPTMnet and ELM tools require operation as first parameter (SOAP-style).
| Situation | Fallback |
|---|---|
| Not in iPTMnet | UniProt PTM/processing annotations |
| No PTM-PPI data | STRING general PPI |
| No ProtVar data | UniProt domain annotations |
| No ELM data | Proceed with iPTMnet/UniProt only |