protein-report

name	protein-report
description	Generate a protein-centric report combining UniProt, InterPro, AlphaFold, PDB, STRING, and post-translational modification data

Generate a comprehensive protein-centric report for: $ARGUMENTS

Use the MCP tools available to you to gather data from all relevant sources, then synthesize a single structured report. Follow the steps below in order. If a step fails or returns no data, note the gap and continue — do not stop the report.

Input Parsing

Determine the input type:

1. UniProt accession (e.g., P04637, Q9Y6K9) — use directly
2. Gene symbol (e.g., TP53, BRCA1) — resolve to UniProt accession in step 1
3. Protein name (e.g., tumor protein p53) — search UniProt in step 1

Data Gathering Steps

1. Protein Identity

• If the input is a gene symbol or protein name, call uniprot_search with the query and organism_id:9606 (reviewed: true) to find the canonical Swiss-Prot accession.
• Call uniprot_get_protein with the accession to get full protein details: function description, gene name, organism, sequence length, GO terms, subcellular localization.
• Note the UniProt accession, gene symbol, and protein name for subsequent queries.

2. Domain Architecture (InterPro)

• Call interpro_get_domains with the UniProt accession.
• Extract all domain entries: InterPro accession, name, type (domain/family/repeat), source database (Pfam, PROSITE, CDD, etc.), and amino acid positions.

3. Protein Features & Post-Translational Modifications

• Call uniprot_get_features with the UniProt accession and no type filter to get all features.
• Categorize features into:
  • Domains: Domain, Region
  • Active/binding sites: Active site, Binding site, Metal binding, Nucleotide binding
  • Secondary structure: Helix, Beta strand, Turn
  • PTMs: Modified residue, Cross-link, Lipidation, Glycosylation site, Disulfide bond
  • Processing: Signal peptide, Transit peptide, Chain, Propeptide
  • Variants: Natural variant, Mutagenesis
• Summarize each category — count entries and highlight the most important ones.

4. 3D Structures (PDB)

• Call pdb_search with the gene symbol (limit: 10) to find all available experimental structures.
• For the top 3 structures by resolution, call pdb_get_structure with the PDB ID to get detailed metadata (method, resolution, entity details).
• Note the best-resolution structure and any ligand-bound structures.

5. AlphaFold Predicted Structure

• Call alphafold_get_prediction with the UniProt accession.
• Extract: overall pLDDT confidence score, fraction of residues in each confidence bin (very high/confident/low/very low), model URLs.
• Note regions of high vs low confidence — low-confidence regions are often disordered or flexible.

6. Protein Interactions (STRING)

• Call string_get_interactions with the gene symbol (species: 9606, limit: 15, required_score: 700).
• Extract high-confidence interaction partners with scores and evidence types.

7. Tissue Expression (GTEx)

• Call gtex_get_expression with the gene symbol.
• Extract the top 10 tissues by expression level and the bottom 5 (tissues where the protein is minimally expressed).

8. Clinical Variants

• Call clinvar_search with the gene symbol to find pathogenic/likely pathogenic variants.
• Focus on variants that affect protein function (missense, nonsense, frameshift in the coding region).

9. Literature

• Call pubmed_search with the protein name or gene symbol + "protein structure function" (max_results: 5).
• Extract the most relevant recent publications.

Report Format

Present the gathered data as a structured report:

# Protein Report: [PROTEIN NAME] ([UNIPROT ACCESSION])

## Summary
One-paragraph overview: what this protein does, its key domains, clinical relevance, and structural knowledge.

## Protein Identity
- UniProt accession, entry name, gene symbol(s)
- Protein name (recommended name + alternative names)
- Organism, sequence length (amino acids)
- UniProt entry status (reviewed/unreviewed)

## Function
- Functional description (from UniProt)
- Catalytic activity (if enzyme)
- Subcellular localization(s)
- Key GO terms:
  - Biological Process (top 5)
  - Molecular Function (top 5)
  - Cellular Component (top 3)

## Domain Architecture
Visual-style representation of domains along the sequence:

[1]---[Signal peptide: 1-22]---[Domain A: 50-150]---[Domain B: 200-350]---[393]

Table of all InterPro domains with positions, source database, and description.

## Post-Translational Modifications
- Phosphorylation sites (count and key residues)
- Ubiquitination, acetylation, methylation sites
- Disulfide bonds
- Glycosylation sites
- Other modifications
- Signal/transit peptides and processing events

## Active Sites & Binding
- Active site residues with positions
- Metal binding sites
- Nucleotide/cofactor binding sites
- Key binding partners and interaction interfaces

## 3D Structures
### Experimental Structures (PDB)
| PDB ID | Title | Method | Resolution | Ligands |
|--------|-------|--------|------------|---------|
Best structure highlighted.

### AlphaFold Prediction
- Overall confidence (mean pLDDT)
- Confidence breakdown by region
- Disordered regions (pLDDT < 50)
- Model URLs (PDB, CIF)

## Protein Interactions
- Top interaction partners from STRING (sorted by confidence)
  | Partner | Score | Evidence Types |
  |---------|-------|---------------|
- Key functional interaction clusters

## Tissue Expression
- Top 10 tissues by expression level (median TPM from GTEx)
- Expression pattern interpretation (ubiquitous vs tissue-specific)

## Clinical Variants
- Pathogenic/likely pathogenic variants affecting this protein
- Variant hotspots (positions with multiple pathogenic variants)
- Domains most affected by pathogenic variation

## Key Publications
Top 3-5 recent papers on this protein's structure and function.

## Data Sources
List which databases were queried and whether each returned data successfully.

Keep the report factual — only include data returned by the tools. Do not hallucinate annotations, structures, or modifications. If a section has no data, write "No data available from [source]."