uniprot

name	uniprot
description	Protein sequence, function, and annotation lookup. Query MUST be a bare gene symbol or protein name — 1 to 3 words maximum. Valid examples: 'KRAS', 'EGFR', 'BTK', 'TP53', 'Bruton tyrosine kinase', 'P01116'. If the topic is 'sotorasib KRAS G12C', the correct query is 'KRAS'. If the topic is 'imatinib BCR-ABL resistance', the correct query is 'BCR-ABL'. Strip the drug name, mutation label, and all mechanism words — pass only the protein or gene name.
metadata	null

UniProt Protein Lookup

Query the UniProt protein database to retrieve protein sequences, annotations, functional information, and cross-references.

Overview

UniProt is the world's most comprehensive protein sequence and functional annotation database. This skill provides access to:

• Protein sequences (FASTA format)
• Functional annotations
• Gene ontology (GO) terms
• Protein domains and families
• Cross-references to PDB, Pfam, InterPro, etc.

Usage

Fetch protein by accession:

python3 {baseDir}/scripts/uniprot_fetch.py --accession P53_HUMAN

Fetch by UniProt ID:

python3 {baseDir}/scripts/uniprot_fetch.py --accession P04637

Search for proteins:

python3 {baseDir}/scripts/uniprot_fetch.py --search "insulin human"

Get sequence only:

python3 {baseDir}/scripts/uniprot_fetch.py --accession P53_HUMAN --format fasta

Get full entry with all annotations:

python3 {baseDir}/scripts/uniprot_fetch.py --accession P53_HUMAN --format detailed

Parameters

Parameter	Description	Default
--accession	UniProt accession or entry name	-
--search	Search query	-
--organism	Filter by organism (e.g., "human", "9606")	-
--reviewed	Only Swiss-Prot (reviewed) entries	False
--max-results	Maximum results for search	10
--format	Output format: summary, detailed, fasta, json	summary
--include-features	Include sequence features	False
--include-xrefs	Include cross-references	False

Examples

Look up human p53 tumor suppressor:

python3 {baseDir}/scripts/uniprot_fetch.py --accession P53_HUMAN --format detailed

Search for kinases in human:

python3 {baseDir}/scripts/uniprot_fetch.py --search "kinase" --organism human --reviewed --max-results 20

Get FASTA sequence for multiple proteins:

python3 {baseDir}/scripts/uniprot_fetch.py --accession "P53_HUMAN,BRCA1_HUMAN,EGFR_HUMAN" --format fasta

Search with advanced query:

python3 {baseDir}/scripts/uniprot_fetch.py --search "gene:TP53 AND organism_id:9606"

Get protein with PDB cross-references:

python3 {baseDir}/scripts/uniprot_fetch.py --accession P53_HUMAN --include-xrefs

Output Fields

Summary

• Accession, entry name, protein name
• Gene name, organism
• Sequence length
• Reviewed status

Detailed

• Full protein name and alternative names
• Function description
• Subcellular location
• Gene ontology terms
• Protein domains
• Post-translational modifications
• Disease associations
• Literature references

FASTA

Standard FASTA format sequence output.

JSON

Full UniProt entry in JSON format.

Cross-References

UniProt entries contain cross-references to:

• PDB: 3D protein structures
• Pfam: Protein families
• InterPro: Protein signatures
• GO: Gene Ontology terms
• KEGG: Pathway information
• Reactome: Reaction pathways
• DrugBank: Drug interactions
• OMIM: Disease associations

Query Limitations — Read Before Using

UniProt is a protein database, not a drug/chemistry database. Queries must target proteins by name, gene, or accession. Drug or chemistry concepts will return zero results.

❌ Fails (not a protein query)	✅ Works
"KRAS covalent inhibitors"	"KRAS_HUMAN" or "P01116"
"BTK warhead optimization"	"BTK" or "BTK_HUMAN" or "Q06187"
"covalent inhibitor design"	"Bruton tyrosine kinase"
"BBB penetration ADMET"	"ABCB1 human" or "MDR1"
"kinase inhibitor selectivity"	"EGFR kinase" or "EGFR_HUMAN"

Rule: If your query describes a drug, chemical process, mechanism, or assay — use PubChem or TDC instead. UniProt answers: "What is this protein and what does it do?"

For KRAS covalent inhibitor research, the correct two-step workflow is:

1. UniProt: --search "KRAS_HUMAN" or --accession P01116 → get KRAS protein structure, active site residues (Cys12, Gly12), domains
2. PubChem/ChEMBL: search "KRAS G12C inhibitor" or "sotorasib" → get inhibitor SMILES, IC50, selectivity data

Notes

• UniProt accession numbers (e.g., P04637) are stable identifiers
• Entry names (e.g., P53_HUMAN) may change
• Reviewed (Swiss-Prot) entries are manually curated
• Unreviewed (TrEMBL) entries are computationally annotated
• API has no authentication requirement