tooluniverse-protein-modification-analysis

Original：🇺🇸 English

Translated

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.

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Sourcemims-harvard/tooluniverse

Added on2026-05-09

NPX Install

npx skill4agent add mims-harvard/tooluniverse tooluniverse-protein-modification-analysis

SKILL.md Content

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Protein Post-Translational Modification Analysis

Comprehensive PTM analysis using iPTMnet (primary), ProtVar (functional context), UniProt (baseline), STRING (interactions), ELM (linear motifs), and MassIVE/ProteomeXchange (experimental data).

LOOK UP DON'T GUESS

PTM sites/enzymes:
```
iPTMnet_get_ptm_sites
```
Functional consequence:
```
ProtVar_get_function
```
+
```
iPTMnet_get_ptm_ppi
```
Proteoforms:
```
iPTMnet_get_proteoforms
```
Linear motifs:
```
ELM_get_instances
```

COMPUTE, DON'T DESCRIBE

When 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.

Domain Reasoning

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.

KEY PRINCIPLES

Disambiguation first -- resolve to UniProt accession before iPTMnet calls
iPTMnet is SOAP-style -- every call requires
```
operation
```
parameter
Evidence-graded -- distinguish experimental (T1) from predicted (T4)
English-first queries

Workflow

Phase 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

Phase 0: Disambiguation

iPTMnet_search(operation="search", search_term="TP53", role="Substrate")

-- find UniProt IDs

If user provides UniProt accession directly, use it
Select human entry if multiple hits

Phase 1: PTM Sites

iPTMnet_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.

Phase 2: Proteoforms

iPTMnet_get_proteoforms(operation="get_proteoforms", uniprot_id=...)

-- distinct PTM combinations. Focus on those with functional/disease annotations if >20.

Phase 3: PTM-Dependent Interactions

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)

.

Phase 4: Functional Context

ProtVar_get_function(accession=..., position=N, variant_aa=AA)

-- domain, active site, binding site, conservation. Grade: active-site PTM > domain-core > disordered region.

Phase 4b: Linear Motifs (ELM)

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.

Phase 4c: Experimental Data

MassIVE_search_datasets(species="9606")

,

MassIVE_get_dataset(accession="MSV...")

for public MS datasets.

Evidence Grading

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 Parameter Reference

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).

Fallbacks

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

Limitations

iPTMnet biased toward well-studied proteins
Proteoform data covers observed combinations only
PTM-PPI: only PTM-specific evidence; more PPIs exist in STRING