Fetch a UniProt protein entry by accession (e.g. P04637 for p53, P38398 for BRCA1). Returns function, gene, organism, disease associations, cross-references.

Search UniProtKB. Examples: '(gene:TP53) AND (organism_id:9606)', 'kinase AND reviewed:true'. Set reviewed_only=true for Swiss-Prot only. Set organism to taxonomy ID or name.

Get protein sequence in FASTA format for a UniProt accession.

Get protein features: domains, binding sites, PTMs, signal peptides. Optional filter (comma-separated): 'Domain,Active site,Binding site,Modified residue'.

Get GO annotations grouped by aspect. Optional filter: 'F' (function), 'P' (process), 'C' (component).

Get cross-references to PDB, Pfam, ENSEMBL, Reactome, KEGG, STRING, etc. Optional database filter.

Get known natural variants and disease mutations for a protein.

Map between ID types. ids=comma-separated. Common db codes: UniProtKB_AC-ID, PDB, Ensembl, GeneID, Gene_Name.

Fetch multiple entries. accessions=comma-separated UniProt IDs (max 100).

Search UniProt taxonomy by organism name. Returns taxonomy IDs.

Fetch a UniProt keyword by ID (e.g. KW-0007 for Acetylation, KW-0539 for Nucleus). Returns name, definition, category, synonyms, GO cross-refs, and parent/child hierarchy.

Search UniProt's controlled keyword vocabulary by name or definition. Examples: 'acetylation', 'nucleus', 'kinase activity'.

Fetch a UniProt subcellular-location term by ID (e.g. SL-0039 Cell membrane, SL-0086 Cytoplasm, SL-0191 Nucleus). Returns name, definition, category, GO cross-refs, and the is-a / part-of hierarchy.

Search UniProt's controlled subcellular-location vocabulary. Examples: 'membrane', 'mitochondrion', 'cytoplasm'.

Fetch a UniRef cluster by ID. Examples: UniRef100_P04637 (100 % identity, only exact-match members), UniRef90_P04637 (90 % identity), UniRef50_P04637 (50 %, broadest grouping). Returns representative member, member list, common taxon, last-updated date.

Search UniRef clusters. identity_tier filters by % identity: "50" (loosest), "90", "100" (tightest), or empty for all tiers. Examples: query='kinase' identity_tier='90' returns the 90 % clusters.

Group every orthology cross-reference in a UniProt entry by source database (KEGG / OMA / OrthoDB / eggNOG / HOGENOM / PhylomeDB / InParanoid / TreeFam / GeneTree / PAN-GO / PANTHER / OrthoInspector). Different databases use different inference methods; surfacing them side-by-side lets the agent reason about consensus when comparing orthologs across species. Pure-Python — no extra HTTP call beyond the entry fetch.

One-call comprehensive characterisation of a UniProt entry, structured for drug-discovery / clinical workflows. Composes nine views over the same entry plus one FASTA fetch (so two upstream network calls, not nine):

Identity · Function · Sequence chemistry · Structural evidence (PDB count + best-resolution + AlphaFold model id + InterPro count) · Drug-target context (ChEMBL ids, DrugBank count) · Disease associations (with MIM IDs) · Variants count · Functional annotations (top GO MF, subcellular, ECO diversity) · Cross-references summary

For per-residue pLDDT confidence call uniprot_get_alphafold_confidence separately. For full disease detail call uniprot_get_disease_associations. The dossier is the entry- level summary that decides which deeper tools are worth calling.

Read a previously-cached UniProt response without hitting the upstream. The local provenance cache is opt-in via the UNIPROT_MCP_CACHE_DIR environment variable; when unset, this tool always reports cache-disabled.

Useful for: reproducing a year-old answer from a sealed cache snapshot; working offline / behind air-gaps; reducing UniProt's load when running benchmarks twice.

Returns the cached body text wrapped in the recorded Provenance. The annotation openWorldHint=False reflects that this tool consults the local file system only — no upstream call.

Look up ClinVar records for the gene encoded by a UniProt entry. First fetches the entry to extract the canonical gene symbol, then queries NCBI eutils ClinVar by gene (and optional protein-change filter, e.g. R175H). Returns clinical-significance classification, review status, condition list (trait_set), molecular consequence, and the protein-change list per record.

Critical for clinical workflows — UniProt's natural-variant annotations stop at literature-described variants. ClinVar carries every variant submitted by clinical labs, with curated significance classifications. Combine uniprot_lookup_variant (UniProt side) with uniprot_resolve_clinvar (population side) for a full variant-effect picture.

Calls https://eutils.ncbi.nlm.nih.gov — declared in PRIVACY.md.

Fetch AlphaFold-DB pLDDT confidence summary for a UniProt accession. Returns the global mean pLDDT score plus the four-band distribution (very high ≥ 90 / confident 70-90 / low 50-70 / very low < 50) so the agent can decide whether to trust the model. Critical for any structural-biology workflow that builds on a predicted model: a target with 95 % residues 'very high' is publication-grade; a target with 40 % 'very low' is largely disordered and structural inference is unsafe.

This tool calls https://alphafold.ebi.ac.uk — declared in PRIVACY.md as a third party. Provenance carries source = AlphaFoldDB.

List the publications UniProt cites on an entry, with PubMed IDs, DOIs, titles, authors, journal, year, and the 'reference position' annotation (the experimental work each citation supports — e.g. 'CRYSTALLIZATION', 'PHOSPHORYLATION AT SER-15', 'INVOLVEMENT IN LI-FRAUMENI SYNDROME'). Pure composition over the entry's references block — no extra HTTP call beyond the entry fetch.

Derived sequence chemistry for a UniProt entry: molecular weight, theoretical pI, GRAVY hydrophobicity, aromaticity, net charge at pH 7, extinction coefficient at 280 nm, amino-acid composition. Computed from the canonical FASTA via standard methods (Lehninger pK values, Kyte-Doolittle hydropathy, Pace 1995 ε₂₈₀ formula). Pure-Python — no additional external API call beyond the FASTA fetch.

List every UniProt feature that overlaps a residue position (1-indexed). Answers the question 'what's at residue 175 of TP53?' by intersecting the entry's features with the given position. Useful for variant-effect interpretation — surfaces every domain, binding site, modification, mutagenesis annotation, and natural variant at a single residue in one call.

Return the active sites, binding sites, metal-binding residues, and DNA-binding regions annotated on a UniProt entry. Filtered view over the entry's feature array — this is the residue-level chemistry of the protein, the input to enzyme drug-design and antibiotic target-validation workflows.

Return the maturation and processing features (signal peptide, propeptide, transit peptide, initiator methionine, chain, peptide). These describe how the translated polypeptide is cleaved and targeted into its mature form — essential for therapeutic-protein engineering and pathogen-secretion-system analysis.

Return the post-translational modification features (modified residues, glycosylation sites, lipidation sites, disulfide bonds, cross-links). PTMs are functionally critical: they switch enzymes on, target proteins for degradation, anchor them to membranes, and fold them via disulfides. The empty case carries an honest pointer to mass-spec databases (PhosphoSitePlus, GlyConnect) for additional evidence.

Look up an HGVS-shorthand amino-acid change (e.g. R175H, V600E, R248*) in the UniProt entry's natural-variant annotations. Returns the matching variant feature(s) including the UniProt-curated description (often a disease association). A null result here does NOT mean a variant is benign — UniProt only annotates literature-described variants; ClinVar / dbSNP carry population-level data.

Structured disease associations for a UniProt entry. Returns the diseases recorded in DISEASE-type comments with name, acronym, UniProt disease ID, OMIM cross-reference, description, and the annotation note. Critical for clinical interpretation — distinguishes a UniProt-curated disease association (literature-anchored) from a raw cross-reference. Empty result does not imply disease-irrelevant; see Open Targets / OMIM / DisGeNET for population-level evidence.

Fetch a UniParc sequence-archive record by UPI (e.g. UPI000002ED67). Returns sequence, MD5/CRC64 checksums, cross-reference counts, linked UniProtKB accessions, and the common-taxa list. UniParc is the non-redundant sequence archive — every protein sequence ever submitted to a major public database has exactly one UniParc record.

Search UniParc. Examples: 'taxonomy_id:9606' for human sequences, 'database:Ensembl' for Ensembl-derived entries.

Fetch a UniProt proteome by UP ID (e.g. UP000005640 = human reference). Returns organism, taxonomy lineage, protein count, gene count, BUSCO completeness score, annotation score, and component breakdown (chromosomes / contigs).

Search UniProt proteomes. Examples: 'organism_id:9606' for human, 'proteome_type:1' for reference proteomes only, 'taxonomy_name:bacteria' for all bacterial proteomes.

Fetch a UniProt citation record by ID (typically a PubMed ID, e.g. 9840937). Returns title, authors, journal, year, volume, pages, and cross-references.

Search the UniProt citations index. Examples: 'p53 AND author:Vogelstein', 'BRCA1 AND year:[2020 TO 2024]'.

List every PDB structure cross-referenced from a UniProt entry, with method, resolution, and chain coverage. Faster than parsing the raw cross-references blob — returns a structured list typed for downstream analysis.

Resolve the AlphaFoldDB cross-reference for a UniProt entry — typically one canonical model per accession. Includes a direct EBI viewer link.

List InterPro signatures (domain / family classifications) for a UniProt entry, with names extracted from the entry's cross-reference properties.

Resolve ChEMBL drug-target cross-references for a UniProt entry. Returns the ChEMBL target IDs with EBI viewer links — empty if the protein has no documented bioactivity data in ChEMBL.

Summarise the ECO (Evidence and Conclusion Ontology) codes attached to a UniProt entry's annotations. Counts how many features and comments cite each evidence code, distinguishing experimental from inferred annotations. Critical for distinguishing 'wet-lab confirmed' annotations from 'inferred by similarity' for any downstream agent that cares about evidence quality.

Re-fetch a previously recorded UniProt URL and verify it still returns the same release identifier and the same canonical response body (SHA-256). Pass the values from a prior response's provenance footer (url, release, response_sha256, accept_header); empty optional fields skip the corresponding check. Returns a verification report with explicit pass / drift / unreachable verdicts per check.

accept_header must match the Accept header used for the original request (default application/json; use text/plain;format=fasta for FASTA-originated provenance). Replaying the wrong header causes a guaranteed hash mismatch because the upstream serves different content depending on content negotiation.

This is the single tool that converts every prior uniprot-mcp response into an independently auditable artefact — a year from now, a third party can take the recorded provenance footer and confirm the upstream still serves the exact same bytes.