UniProt MCP Server

UniProt MCP server — a Model Context Protocol server for the UniProt protein knowledgebase with per-query provenance verification. 41 tools across 8 families. Apache-2.0. Every successful response carries a verifiable Provenance record — UniProt release, retrieval timestamp, resolved URL, and a SHA-256 of the canonical response body — that the agent (or a third party, a year later) can re-check with a single tool call: uniprot_provenance_verify.

The distinguishing capability: **per-response SHA-256 + verify primitive

• release pinning + offline replay** is, to the best of my survey of public MCPs as of 2026-04-26, absent from every other bio-MCP server I could find (BioMCP, Augmented-Nature/UniProt-MCP, biothings-mcp, gget-mcp, and others). If you are a regulated-bio-pharma user who needs to prove, years later, that a UniProt-derived claim still holds, this is the mechanism. Comparison and citations: docs/COMPETITIVE_LANDSCAPE.md.

Author: Santiago Maniches · ORCID 0009-0005-6480-1987 · TOPOLOGICA LLC

Run it in one line:

uvx uniprot-mcp-server

Verifiable provenance (the receipts)

Every answer this server returns is traceable to a primary-source URL and a content hash you can re-compute yourself. The walkthrough below is a real run against the live server (UniProt release 2026_01), independently confirmed against the UniProt REST API.

Question. What is the function of human p53 (UniProt P04637), what heritable cancer syndrome is it associated with, and is the R175H mutation a documented disease variant?

Answer, with its provenance footer (verbatim from the server):

• Function. Cellular tumor antigen p53 (gene TP53, Homo sapiens, 393 aa). "Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis... Acts as a tumor suppressor in many tumor types."

• Disease. Li-Fraumeni syndrome (acronym LFS, UniProt disease id DI-01904, OMIM 151623) — "an autosomal dominant familial cancer syndrome... Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers."

• Variant. R175H — "in LFS; germline mutation and in sporadic cancers; somatic mutation; does not induce SNAI1 degradation; reduces interaction with ZNF385A; dbSNP:rs28934578."

Source: UniProt release 2026_01 (28-January-2026) • Retrieved 2026-06-09T11:47:51Z
Query: https://rest.uniprot.org/uniprotkb/P04637
SHA-256: 0040d79bb39e2f7386d55f81071e87858ec2e5c2cd9552e93c3633897f78345e
Accept: application/json

Reproduce it

1. Run the server and ask the same question (any MCP client; tool calls shown):

uvx uniprot-mcp-server
# uniprot_get_entry(accession="P04637")               -> function + gene + diseases
# uniprot_get_disease_associations(accession="P04637") -> LFS, OMIM 151623
# uniprot_lookup_variant(accession="P04637", change="R175H") -> the LFS variant record

2. Confirm the hash re-verifies (re-fetches the URL and re-checks the release + canonical hash with the server's own code):

# uniprot_provenance_verify(
#   url="https://rest.uniprot.org/uniprotkb/P04637",
#   release="2026_01",
#   response_sha256="0040d79bb39e2f7386d55f81071e87858ec2e5c2cd9552e93c3633897f78345e")
# -> Status: verified  (release match + SHA-256 match)

3. Confirm the values against the primary source — no server in the loop:

curl -s -H "Accept: application/json" https://rest.uniprot.org/uniprotkb/P04637 -o p53.json

# UniProt release served (matches the footer):
curl -sI -H "Accept: application/json" https://rest.uniprot.org/uniprotkb/P04637 | grep -i x-uniprot-release
# -> X-UniProt-Release: 2026_01

python - <<'PY'
import json, hashlib
d = json.load(open("p53.json", encoding="utf-8"))
print("gene        :", d["genes"][0]["geneName"]["value"])                       # TP53
print("protein     :", d["proteinDescription"]["recommendedName"]["fullName"]["value"])  # Cellular tumor antigen p53
print("organism    :", d["organism"]["scientificName"], "| length", d["sequence"]["length"])  # Homo sapiens | 393
for c in d["comments"]:
    if c.get("commentType") == "DISEASE" and c["disease"].get("acronym") == "LFS":
        x = c["disease"]
        print("disease     :", x["diseaseId"], "| OMIM", x["diseaseCrossReference"]["id"])  # Li-Fraumeni syndrome | 151623
for f in d["features"]:
    if f.get("type") == "Natural variant" and f["location"]["start"]["value"] == 175:
        a = f.get("alternativeSequence", {})
        if a.get("originalSequence") == "R" and a.get("alternativeSequences") == ["H"]:
            print("variant     : R175H |", f["description"])  # in LFS; germline mutation ...

# The footer SHA-256 is reproducible from these exact bytes (no server):
# the server hashes the JSON re-serialized with sorted keys + compact separators.
canonical = json.dumps(d, sort_keys=True, separators=(",", ":"), ensure_ascii=False).encode("utf-8")
print("sha-256     :", hashlib.sha256(canonical).hexdigest())
# -> 0040d79bb39e2f7386d55f81071e87858ec2e5c2cd9552e93c3633897f78345e
PY

What this proves: every returned claim is traceable to a primary-source URL and a content hash. The gene, protein name, disease (with OMIM id), and variant the server reports all match the live UniProt entry; the footer SHA-256 is reproducible byte-for-byte from the primary source using a documented, server-independent recipe. A third party can re-run all three checks today, or a year from now, without trusting this server.

Note on the hash: the footer SHA-256 is of the canonical UniProt response body — the JSON re-serialized with sorted keys and compact separators (json.dumps(obj, sort_keys=True, separators=(",", ":"), ensure_ascii=False)), so harmless key-order changes within a release do not break verification. A raw curl | sha256sum of the bytes will therefore differ; apply the same canonicalization (step 3 above) or use uniprot_provenance_verify.

Related MCP server: SureChEMBL MCP Server

Installation

Run without installing (recommended):

uvx uniprot-mcp-server

Or install into an environment:

pip install uniprot-mcp-server

Note: There is an unrelated package named uniprot-mcp on PyPI (different author, 5 tools, MIT). This package is uniprot-mcp-server. Running pip install uniprot-mcp will install the wrong package silently.

For researchers — where to start

If you are a biomedical researcher visiting this repo, the highest-signal places to look are:

Issues / corrections welcome at https://github.com/smaniches/uniprot-mcp/issues. The atlas in particular is community-reviewable — see METHODOLOGY.md for what is machine-verified vs what needs human review.

What makes this different

The provenance + verify chain is, in my 2026-04-26 survey, absent from every other bio-MCP I could find. A regulated user can take any prior uniprot-mcp answer and prove — without contacting the author — that UniProt still returns the same bytes, or detect exactly how the upstream has drifted. If you find a counter-example I missed, please file an issue and I will update the comparison.

Tools (41)

Eight endpoint families. All read-only (readOnlyHint: true). All but uniprot_replay_from_cache interact with at least one upstream service (openWorldHint: true). No UniProt API key required.

Core UniProtKB (10)

Controlled vocabularies (4)

Sequence archives & clusters (4)

Proteomes & literature (4)

Structured cross-DB resolvers (4)

Gateway-only — no calls leave the UniProt origin. These extract the relevant cross-references from a UniProt entry and return structured records (typed lists / objects, not passthrough strings).

Biomedical features (7)

Pure-Python compositions over the entry — no extra origin. The first four answer per-residue and per-variant questions; the last three are the v1.1.0 expansion targeting drug discovery, therapeutic-protein engineering, and pathogen-secretion analysis: each is a filter over the entry's features array, with a structured grouping by feature type and an honest empty-set advisory.

Cross-origin enrichment (3)

The only tools that consult origins outside rest.uniprot.org. Each is documented in PRIVACY.md and in the threat model.

Composition + provenance (5)

Provenance & verification

Every successful tool response includes a footer like:

---
_Source: UniProt release 2026_01 (28-January-2026) • Retrieved 2026-04-25T17:09:00Z_
_Query: https://rest.uniprot.org/uniprotkb/P04637_
_SHA-256: 0040d79bb39e2f7386d55f81071e87858ec2e5c2cd9552e93c3633897f78345e_

A year later, an auditor can call uniprot_provenance_verify with those exact fields:

> uniprot_provenance_verify(
    url="https://rest.uniprot.org/uniprotkb/P04637",
    release="2026_01",
    response_sha256="0040d79bb39e2f7386d55f81071e87858ec2e5c2cd9552e93c3633897f78345e"
  )

## Provenance Verification

**Status:** verified

**URL:** https://rest.uniprot.org/uniprotkb/P04637
- ✓ URL resolves (HTTP 200)
- ✓ Release: recorded '2026_01', current '2026_01'
- ✓ Response SHA-256: recorded 0040d79bb39e2f73…, current 0040d79bb39e2f73…

**Advice:** Both checks passed. The recorded provenance is reproducible against the live UniProt API.

If UniProt has moved on, the tool tells you exactly how:

For strict reproducibility, opt into release pinning:

export UNIPROT_PIN_RELEASE=2026_01
uniprot-mcp
# every response is checked against the pinned release;
# any drift raises `ReleaseMismatchError`, which the server surfaces
# as an agent-actionable error envelope.

For offline replay, uniprot_replay_from_cache(url) reads a previously-recorded response from a directory pointed at by UNIPROT_MCP_CACHE_DIR:

export UNIPROT_MCP_CACHE_DIR=~/.uniprot-mcp-cache
uniprot-mcp
# uniprot_replay_from_cache(url) returns the entry at
# $UNIPROT_MCP_CACHE_DIR/<sha256(url)>.json if present.

Status note (v1.1.3). uniprot_replay_from_cache is a read primitive. The cache must currently be populated by an external process — for example, by the maintainer-provided benchmark capture script, or by you wrapping httpx calls and writing to the directory yourself in the documented JSON shape (see src/uniprot_mcp/cache.py). Automatic write-through on every successful tool call is a tracked v1.2.0 roadmap item; the production code in v1.1.x does not mirror responses to disk by default.

A live end-to-end demonstration is committed at tests/benchmark/run-2026-04-25-roundtrip/transcript.md — real values, real verdicts, no mocks.

Pre-registered benchmark

tests/benchmark/ ships a 30-prompt evaluation (Tier A / B / C × 10) with SHA-256-committed expected answers on main. The plaintext expected.jsonl is held local-only until a benchmark run is published; the cryptographic commitments mean the author cannot rewrite "correct" answers post-hoc.

Third-party reproducibility path (no seal file required). Re-derive every Tier A / B answer live from UniProt and print it — no expected.jsonl required. This confirms the answers are independently reproducible from the primary source today; it does not recompute the seal (the committed SHA-256 binds a withheld rationale — see below):

python tests/benchmark/verify_against_hashes.py tests/benchmark/expected.hashes.jsonl
# Re-derives all 30 answers live and prints them (informational; exit 0).

Maintainer cryptographic verification path (with the local plaintext seal). The committed digests in expected.hashes.jsonl are sealed over {prompt_id, answer, rationale}; the rationale is deliberately withheld as part of the sealed pre-registration, so the full cryptographic check requires the local expected.jsonl:

python tests/benchmark/verify_answers.py tests/benchmark/expected.jsonl
# OK: all 30 prompts verified against https://rest.uniprot.org

python tests/benchmark/verify.py tests/benchmark/expected.jsonl tests/benchmark/expected.hashes.jsonl
# OK: 30 commitments verified

See tests/benchmark/AUDIT.md for the per-prompt source attribution and the formal independence statement (uniprot-mcp was not used during answer authoring).

Install

pip install uniprot-mcp-server   # PyPI distribution
# or, for a pinned, isolated install:
uvx --from uniprot-mcp-server uniprot-mcp

Why three different names? This is the standard Python packaging pattern, exactly because PyPI's namespace is global and collisions force disambiguation:

Concept	Value	What it is
GitHub repository	smaniches/uniprot-mcp	source code + issue tracker
PyPI distribution	uniprot-mcp-server	what you pip install (the bare uniprot-mcp name was already claimed on PyPI when this project published)
Python module	uniprot_mcp	what you import (PEP-8 underscore form)
Console script + MCP server identity	uniprot-mcp	what you run from the shell and what Claude Desktop sees

Cross-checks that prove the wheel you installed was built from this repo: each release ships a Sigstore signature, SLSA build provenance, and a CycloneDX SBOM, all attached to the v1.1.0 GitHub Release. Run bash scripts/replicate.sh (POSIX) or pwsh scripts/replicate.ps1 (Windows) to verify the full chain end-to-end. Common precedents for the same one-thing-three-names pattern: pillow/PIL, python-dateutil/dateutil, beautifulsoup4/bs4, python-Levenshtein/Levenshtein.

From source:

git clone https://github.com/smaniches/uniprot-mcp.git
cd uniprot-mcp
pip install -e .

Claude Desktop

claude_desktop_config.json:

{
  "mcpServers": {
    "uniprot": {
      "command": "uvx",
      "args": ["uniprot-mcp-server"]
    }
  }
}

For pinned, reproducibility-grade access:

{
  "mcpServers": {
    "uniprot": {
      "command": "uniprot-mcp",
      "args": ["--pin-release=2026_01"]
    }
  }
}

To enable uniprot_replay_from_cache reads against a cache directory you have populated yourself (write-through is a v1.2.0 roadmap item — see §Provenance & verification):

{
  "mcpServers": {
    "uniprot": {
      "command": "uniprot-mcp",
      "env": {
        "UNIPROT_MCP_CACHE_DIR": "/absolute/path/to/cache"
      }
    }
  }
}

Claude Code (CLI)

claude mcp add uniprot -- uniprot-mcp

Self-test (live UniProt smoke check)

uniprot-mcp --self-test
# [tools] registered: 41/41
# [live] P04637 -> TP53 OK
# [PASS]

Example workflows

1. Clinical-variant interpretation packet for TP53 R175H.

> What's at residue 175 of P04637? Is R175H a known variant? Pull
> the UniProt and ClinVar evidence and tell me how confident the
> AlphaFold model is at that residue.
→ uniprot_features_at_position("P04637", 175)
→ uniprot_lookup_variant("P04637", "R175H")
→ uniprot_resolve_clinvar("P04637", change="R175H")
→ uniprot_get_alphafold_confidence("P04637")

2. Drug-target dossier in one call.

> Give me a complete drug-target characterisation of human BRCA1.
→ uniprot_target_dossier("P38398")
   # nine sections, two upstream calls (entry + FASTA), one tool call.

3. Sequence chemistry for buffer choice / expression-system selection.

> What's the molecular weight, pI, and hydrophobicity of human insulin?
→ uniprot_compute_properties("P01308")
   # MW 11,981 Da, pI 4.93, ε₂₈₀ 24,980 M⁻¹·cm⁻¹ — pure Python on the FASTA.

4. Provenance round-trip — proving an answer is reproducible.

> [later, with the provenance footer from a prior session in hand]
> Verify the recorded provenance for P04637.
→ uniprot_provenance_verify(
    url="https://rest.uniprot.org/uniprotkb/P04637",
    release="2026_01",
    response_sha256="0040d79bb39e2f7386d55f81071e87858ec2e5c2cd9552e93c3633897f78345e"
  )

5. Replay a previously-cached answer offline (read primitive — see status note below).

# Pre-condition: $UNIPROT_MCP_CACHE_DIR/<sha256(url)>.json already exists,
# populated by the maintainer benchmark capture script or an external
# wrapper. Automatic write-through on every successful tool call is a
# tracked v1.2.0 roadmap item — uniprot-mcp 1.1.x does NOT mirror
# responses to disk by default.
export UNIPROT_MCP_CACHE_DIR=~/sealed-cache
> uniprot_replay_from_cache("https://rest.uniprot.org/uniprotkb/P04637")

Testing

956 offline + 44 live integration tests, all green on main (real counts via pytest --collect-only --ignore=tests/integration and pytest --collect-only tests/integration; the offline count includes the v1.1.x mutation-killer files for cache, proteinchem, client, the contract tests for atlas-manifest / version-consistency / changelog-presence, and the coverage-gap test files that restored full coverage). Line + branch coverage is 100.00 % across all seven source files, with the [tool.coverage.report] gate set to fail_under = 100 so CI enforces it. Three branches carry a justified # pragma: no cover for genuinely-unreachable import-time / defensive fallbacks (documented inline and in pyproject.toml). Reproduce locally with pytest tests/unit tests/property tests/client tests/contract --cov=uniprot_mcp --cov-branch --cov-report=term-missing. Mypy (strict), ruff (check + format), bandit (0 issues at any severity), pip-audit (--strict, no known vulnerabilities) all clean. Mutation testing infrastructure ships and is measurement-first: see the per-module table at docs/MUTATION_SCORES.md for the latest matrix-workflow results; the ≥ 95 % gate is the v1.2.0 target, not the current state.

# Fast, offline (CI on every push):
pytest tests/unit tests/property tests/client tests/contract -v

# Live UniProt (opt-in, nightly in CI):
pytest --integration tests/integration -v

# Lint / type-check / security / SCA:
ruff check . && ruff format --check . && mypy src/uniprot_mcp
bandit -r src/uniprot_mcp && pip-audit --strict

Architecture & threat model

• docs/THREAT_MODEL.md — twelve STRIDE-shaped threats, each receipt-anchored to a code path or commit SHA, plus the cross-origin allowlist policy (§T3b).

• docs/INCIDENT_POLICY.md + docs/POSTMORTEM_TEMPLATE.md + docs/INCIDENT_LOG.md — every nightly integration breakage triggers a postmortem entry.

• AUDIT.md — pre-1.0.1 professional audit, P0/P1 remediations recorded.

• docs/RELEASE.md — release runbook covering the tag → PyPI → MCP Registry → Sigstore → GitHub Release → Zenodo chain, including the release-verify.yml post-tag verification job and the one-time setup for the Zenodo + PyPI webhooks.

• docs/archive/ — pre-flip planning docs retained for audit trail (PENDING_V1.md, MERGE_PLAN.md, RELEASE_AUDIT_v1.1.3.md). Not part of the published docs site; current operational status lives in README.md, CHANGELOG.md, and docs/MUTATION_SCORES.md.

• mkdocs.yml — Material-themed docs site, deployable to gh-pages via .github/workflows/docs.yml. Build locally with pip install -e ".[docs]" && mkdocs serve.

Related MCP servers by the same author

• alphafold-sovereign-mcp — Model Context Protocol server for AlphaFold DB and 13 other biomedical data sources, with a local SQLite knowledge graph (pip install --pre alphafold-sovereign-mcp).

• semantic-scholar-mcp — Model Context Protocol server for Semantic Scholar (200M+ academic papers), providing 14 tools for paper search, citation graph traversal, author profiles, and recommendations (pip install s2-mcp-server).

Citation

Cite via CITATION.cff (GitHub renders a "Cite this repository" button). Always also cite the UniProt Consortium:

The UniProt Consortium. UniProt: the Universal Protein Knowledgebase in 2025. Nucleic Acids Research (2025). doi:10.1093/nar/gkae1010

License

Apache-2.0 — see LICENSE and NOTICE.

This project is the gateway layer of the planned Topologica Bio MCP suite. Multi-source orchestration and tamper-evident provenance ledgers will live in a companion topologica-bio repository under BUSL-1.1 (Change Date 2030-04-19, auto-reverts to Apache-2.0). That companion repository is currently private; this README will be updated with a public link when it ships. uniprot-mcp itself is and will remain permissively Apache-2.0 regardless of the Topologica Bio side.

Copyright © 2026 Santiago Maniches. TOPOLOGICA LLC.