interpro-database

name	interpro-database
description	Query InterPro REST API for protein domain architecture, family classification, and member-DB integration. Search entries, retrieve a protein's domains, list family members, get taxonomic distribution, link to PDB. Unifies Pfam, PANTHER, PIRSF, PRINTS, PROSITE, SMART, CDD, NCBIfam. Use uniprot-protein-database for sequences; pdb-database for 3D structures.
license	CC-BY-4.0

InterPro Database

Overview

InterPro is the EBI's integrated protein family, domain, and functional site database. It consolidates signatures from 13 member databases (Pfam, PANTHER, PIRSF, PRINTS, PROSITE, SMART, CDD, NCBIfam, and others) into unified InterPro entries, each describing a homologous superfamily, domain, family, repeat, or conserved site. The REST API at https://www.ebi.ac.uk/interpro/api/ is free and requires no authentication.

When to Use

• Identifying all domains and families present in a protein by UniProt accession (domain architecture)
• Searching for proteins that contain a specific domain or belong to a specific family
• Finding the taxonomic distribution of organisms that encode a given domain or family
• Cross-linking a domain to experimental 3D structures in the PDB
• Checking which source databases (Pfam, PANTHER, SMART, etc.) cover an InterPro entry
• Discovering InterPro entries by keyword (e.g., "kinase domain") when you do not yet know the accession
• For protein sequence retrieval, functional annotations (GO, pathways, active sites), and ID mapping use uniprot-protein-database
• For downloading domain-aligned sequences or building HMM profiles use Pfam directly; InterPro is the meta-layer

Prerequisites

• Python packages: requests, pandas, matplotlib
• Data requirements: UniProt accessions (e.g., P04637) or InterPro accessions (e.g., IPR011009)
• Environment: internet connection; no API key required
• Rate limits: no published hard limit; use time.sleep(1.0) between requests for batch queries; paginate with ?cursor= or ?page_size=

pip install requests pandas matplotlib

Quick Start

import requests

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def interpro_get(path: str, params: dict = None) -> dict:
    """Send a GET request to the InterPro API and return parsed JSON."""
    r = requests.get(
        f"{INTERPRO_BASE}/{path}",
        params=params,
        headers={"Accept": "application/json"},
        timeout=30
    )
    r.raise_for_status()
    return r.json()

# Get domain architecture for TP53 (P04637)
# Note: `protein/uniprot/{acc}/` returns only {metadata}; the entries-per-protein
# data lives at `entry/interpro/protein/uniprot/{acc}/` and is keyed `results`.
data = interpro_get("entry/interpro/protein/uniprot/P04637/")
entries = data.get("results", [])
print(f"InterPro entries for TP53: {data.get('count')}  (this page: {len(entries)})")
for e in entries[:4]:
    m = e["metadata"]
    print(f"  {m['accession']}  {m['type']:<25}  {m['name']}")
# InterPro entries for TP53: 9
#   IPR002117  family                     p53 tumour suppressor family
#   IPR036674  homologous_superfamily     p53-like tetramerisation domain superfamily

Core API

Query 1: Entry Search

Search for InterPro entries by name keyword or fetch a specific entry by accession.

import requests

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def search_entries(query: str, entry_type: str = None,
                   page_size: int = 20) -> list:
    """Search InterPro entries by keyword; optionally filter by type."""
    params = {"search": query, "page_size": page_size}
    if entry_type:
        params["type"] = entry_type   # family, domain, homologous_superfamily, repeat, site
    r = requests.get(
        f"{INTERPRO_BASE}/entry/interpro/",
        params=params,
        headers={"Accept": "application/json"},
        timeout=30
    )
    r.raise_for_status()
    return r.json().get("results", [])

hits = search_entries("serine kinase", entry_type="domain")
print(f"InterPro domain entries matching 'serine kinase': {len(hits)}")
for h in hits[:5]:
    m = h["metadata"]
    print(f"  {m['accession']}  {m['type']:<10}  {m['name']}")
# InterPro domain entries matching 'serine kinase': 8
#   IPR000719  domain    Protein kinase domain
#   IPR008271  domain    Serine/threonine/tyrosine kinase, active site

# Fetch a specific InterPro entry by accession
r = requests.get(
    f"{INTERPRO_BASE}/entry/interpro/IPR000719/",
    headers={"Accept": "application/json"},
    timeout=30
)
r.raise_for_status()
meta = r.json()["metadata"]
print(f"Accession    : {meta['accession']}")
print(f"Name         : {meta['name']}")
print(f"Type         : {meta['type']}")
print(f"Member DBs   : {list(meta.get('member_databases', {}).keys())}")
go_terms = meta.get("go_terms", [])
print(f"GO terms     : {[g['identifier'] for g in go_terms[:3]]}")
# Accession    : IPR000719
# Name         : Protein kinase domain
# Type         : domain
# Member DBs   : ['pfam', 'smart', 'cdd', 'ncbifam', 'panther']
# GO terms     : ['GO:0004672', 'GO:0005524', 'GO:0006468']

Query 2: Protein Domain Architecture

Retrieve all InterPro entries (domains, families, sites) matched in a protein by UniProt accession.

import requests

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def get_protein_domain_architecture(uniprot_acc: str) -> dict:
    """Return all InterPro entry matches for a protein. Uses the
    `entry/interpro/protein/uniprot/{acc}/` endpoint, which returns
    {count, next, previous, results}. Each result has metadata + a
    nested `proteins[0].entry_protein_locations` for the per-protein match."""
    r = requests.get(
        f"{INTERPRO_BASE}/entry/interpro/protein/uniprot/{uniprot_acc}/",
        headers={"Accept": "application/json"},
        timeout=60
    )
    r.raise_for_status()
    return r.json()

data = get_protein_domain_architecture("P04637")   # TP53
results = data.get("results", [])
# Pull length/source from the first match's nested protein record
prot0 = results[0]["proteins"][0] if results and results[0].get("proteins") else {}
print(f"Protein length : {prot0.get('protein_length')}")
print(f"Source DB      : {prot0.get('source_database')}")
print(f"InterPro entries: {data.get('count')}")
for entry in results[:6]:
    m = entry["metadata"]
    # Locations are nested under proteins[0].entry_protein_locations
    locs = entry["proteins"][0].get("entry_protein_locations", []) if entry.get("proteins") else []
    loc_str = ", ".join(
        f"{frag['start']}-{frag['end']}"
        for loc in locs for frag in loc.get("fragments", [])
    )
    print(f"  {m['accession']}  {m['type']:<25}  {m['name'][:35]:<35}  [{loc_str}]")

# Compare domain architectures of two proteins side-by-side
import pandas as pd

def domain_set(uniprot_acc: str) -> set:
    data = get_protein_domain_architecture(uniprot_acc)
    return {e["metadata"]["accession"] for e in data.get("results", [])}

brca1_domains = domain_set("P38398")   # BRCA1
tp53_domains   = domain_set("P04637")  # TP53

shared = brca1_domains & tp53_domains
unique_brca1 = brca1_domains - tp53_domains
unique_tp53  = tp53_domains - brca1_domains
print(f"Shared InterPro entries: {len(shared)}")
print(f"BRCA1-unique           : {len(unique_brca1)}")
print(f"TP53-unique            : {len(unique_tp53)}")

Query 3: Entry Proteins

List proteins that contain a specific InterPro entry (family or domain).

import requests, time

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def get_entry_proteins(interpro_acc: str, reviewed_only: bool = True,
                       page_size: int = 50) -> list:
    """Return proteins (UniProt) containing a given InterPro entry.
    Path order is `/protein/{db}/entry/interpro/{IPR}/` — the inverse
    `entry/interpro/{IPR}/protein/{db}/` times out (408) on large families."""
    db = "reviewed" if reviewed_only else "uniprot"
    r = requests.get(
        f"{INTERPRO_BASE}/protein/{db}/entry/interpro/{interpro_acc}/",
        params={"page_size": page_size},
        headers={"Accept": "application/json"},
        timeout=60
    )
    r.raise_for_status()
    return r.json().get("results", [])

proteins = get_entry_proteins("IPR011009")   # Protein kinase-like domain SF
print(f"Reviewed proteins with IPR011009 (page 1): {len(proteins)}")
for p in proteins[:4]:
    m = p["metadata"]
    # metadata fields: accession, gene, length, name, source_database, source_organism
    print(f"  {m['accession']}  {(m.get('gene') or ''):<8}  "
          f"len={m.get('length', '?')}  "
          f"org={(m.get('source_organism') or {}).get('scientificName', '')[:30]}")

# Paginate all proteins for a family using cursor
def get_all_entry_proteins(interpro_acc: str,
                            reviewed_only: bool = True) -> list:
    INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"
    db = "reviewed" if reviewed_only else "uniprot"
    # Path-inverted: /protein/{db}/entry/interpro/{IPR}/ is the working order
    url = f"{INTERPRO_BASE}/protein/{db}/entry/interpro/{interpro_acc}/"
    all_proteins = []
    params = {"page_size": 200}
    while url:
        r = requests.get(url, params=params,
                         headers={"Accept": "application/json"}, timeout=60)
        r.raise_for_status()
        data = r.json()
        all_proteins.extend(data.get("results", []))
        url = data.get("next")
        params = None   # next URL already has params encoded
        if url:
            time.sleep(1.0)
    return all_proteins

proteins = get_all_entry_proteins("IPR000719")   # Protein kinase domain
print(f"Total reviewed proteins with protein kinase domain: {len(proteins)}")

Query 4: Entry Taxonomy

Get the taxonomic distribution of proteins annotated with a given InterPro entry.

import requests

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def get_entry_taxonomy(interpro_acc: str,
                        page_size: int = 50) -> list:
    """Return taxonomic summary for proteins in a given InterPro entry.
    Path-inverted: `/taxonomy/uniprot/entry/interpro/{IPR}/`. Each result
    has `metadata` (taxon: accession=taxId, name, parent, children, rank)
    and `entries[]` (representative protein-match locations for that taxon)."""
    r = requests.get(
        f"{INTERPRO_BASE}/taxonomy/uniprot/entry/interpro/{interpro_acc}/",
        params={"page_size": page_size},
        headers={"Accept": "application/json"},
        timeout=90
    )
    r.raise_for_status()
    return r.json().get("results", [])

# Use a smaller entry (p53 DBD); IPR000719 (kinase) has ~270k taxa and times out.
taxa = get_entry_taxonomy("IPR011615")
print(f"Top taxa for IPR011615 (p53 DNA-binding domain):")
for t in taxa[:8]:
    m = t["metadata"]
    print(f"  taxId={m['accession']:>10}  {m.get('name', ''):<30}  "
          f"rank={m.get('rank') or 'n/a'}")

Query 5: Structure Integration

Retrieve PDB structures associated with an InterPro entry.

import requests

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def get_entry_structures(interpro_acc: str, page_size: int = 25) -> list:
    """Return PDB structures that include a match to a given InterPro entry.
    Path-inverted: `/structure/pdb/entry/interpro/{IPR}/`. The flat form with
    `?entry_interpro=...` is silently slow / 408s on this resource."""
    r = requests.get(
        f"{INTERPRO_BASE}/structure/pdb/entry/interpro/{interpro_acc}/",
        params={"page_size": page_size},
        headers={"Accept": "application/json"},
        timeout=60
    )
    r.raise_for_status()
    return r.json().get("results", [])

structures = get_entry_structures("IPR011009")   # Protein kinase-like SF
print(f"PDB structures linked to IPR011009 (page 1): {len(structures)}")
for s in structures[:5]:
    m = s["metadata"]
    print(f"  {m['accession'].upper()}  resolution={m.get('resolution', 'N/A')} Å  "
          f"experiment={m.get('experiment_type', 'N/A')}")
# PDB structures linked to IPR011009: ~8,000+
#   1A06  resolution=2.5 Å  experiment=x-ray
#   ...

Query 6: Domain Sequence Retrieval

Download the FASTA sequences of proteins in an InterPro family for alignment or phylogenetics.

import requests, time

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def get_family_fasta(interpro_acc: str,
                      reviewed_only: bool = True,
                      max_sequences: int = 100) -> str:
    """Retrieve FASTA sequences for proteins in an InterPro entry."""
    db = "reviewed" if reviewed_only else "uniprot"
    proteins = []
    # Path-inverted: protein-list-for-entry is /protein/{db}/entry/interpro/{IPR}/
    url = f"{INTERPRO_BASE}/protein/{db}/entry/interpro/{interpro_acc}/"
    params = {"page_size": min(max_sequences, 200)}
    while url and len(proteins) < max_sequences:
        r = requests.get(url, params=params,
                         headers={"Accept": "application/json"}, timeout=60)
        r.raise_for_status()
        data = r.json()
        proteins.extend(data.get("results", []))
        url = data.get("next") if len(proteins) < max_sequences else None
        params = None
        if url:
            time.sleep(1.0)

    # Fetch FASTA from UniProt for each accession
    accessions = [p["metadata"]["accession"] for p in proteins[:max_sequences]]
    fasta_url = "https://rest.uniprot.org/uniprotkb/stream"
    query = " OR ".join(f"accession:{acc}" for acc in accessions)
    r = requests.get(fasta_url,
                     params={"query": query, "format": "fasta"},
                     timeout=120)
    r.raise_for_status()
    return r.text

fasta = get_family_fasta("IPR000719", reviewed_only=True, max_sequences=20)
seq_count = fasta.count(">")
print(f"FASTA sequences retrieved: {seq_count}")
print(fasta[:300])   # preview first sequence header + start

Key Concepts

InterPro Entry Types

InterPro classifies entries into five types. The type determines what biological relationship the match implies:

Type	Description	Example
family	Homologous group of proteins sharing common ancestry and function	IPR000719 (Protein kinase)
domain	Discrete structural and functional unit that can occur in multiple protein contexts	IPR011009 (Protein kinase-like SF)
homologous_superfamily	Structurally similar domains that may have diverged in sequence	IPR011993 (Pleckstrin-like)
repeat	Short, repeated sequence unit that occurs multiple times within a protein	IPR001440 (TPR repeat)
site	Short conserved motif: active site, binding site, or post-translational modification site	IPR008271 (Ser/Thr kinase active site)

Member Database Hierarchy

Each InterPro entry integrates signatures from one or more member databases. The InterPro accession (IPR...) is the unified meta-entry; member database accessions point to the underlying models:

Member DB	Accession prefix	Modeling approach
Pfam	PF	Hidden Markov Models (profile HMMs)
PANTHER	PTHR	Phylogenetic trees + HMMs
PIRSF	PIRSF	Full-length HMMs
PRINTS	PR	Fingerprint motif groups
PROSITE	PS	Patterns and profiles
SMART	SM	HMMs with database integration
CDD	cd	Position-specific scoring matrices (PSSMs)
NCBIfam	NF	NCBI-curated HMMs

Pagination

The InterPro API paginates results at the collection level. Each response includes a next URL (or null when exhausted) and a count field. For large families (e.g., kinases: 10,000+ proteins) always iterate using the next cursor.

import requests, time

def iterate_interpro(url: str, page_size: int = 200) -> list:
    """Generic paginator for any InterPro list endpoint."""
    results = []
    params = {"page_size": page_size}
    while url:
        r = requests.get(url, params=params,
                         headers={"Accept": "application/json"}, timeout=60)
        r.raise_for_status()
        data = r.json()
        results.extend(data.get("results", []))
        url = data.get("next")
        params = None
        if url:
            time.sleep(1.0)
    return results

Common Workflows

Workflow 1: Domain Architecture Report for a Protein Set

Goal: Retrieve all InterPro domains for a list of proteins and produce a summary table showing which domains each protein carries.

import requests, time, pandas as pd

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def get_domains(uniprot_acc: str) -> list:
    """List InterPro entries for a protein. Uses the
    `entry/interpro/protein/uniprot/{acc}/` endpoint (keyed `results`)."""
    r = requests.get(
        f"{INTERPRO_BASE}/entry/interpro/protein/uniprot/{uniprot_acc}/",
        headers={"Accept": "application/json"}, timeout=60
    )
    if r.status_code == 404:
        return []
    r.raise_for_status()
    data = r.json()
    return [
        {
            "protein": uniprot_acc,
            "accession": e["metadata"]["accession"],
            "name": e["metadata"]["name"],
            "type": e["metadata"]["type"],
            "source_db": list(e["metadata"].get("member_databases", {}).keys()),
        }
        for e in data.get("results", [])
    ]

proteins = ["P04637", "P38398", "Q00987", "P10415"]  # TP53, BRCA1, MDM2, BCL2
rows = []
for acc in proteins:
    rows.extend(get_domains(acc))
    time.sleep(1.0)

df = pd.DataFrame(rows)
print(f"Total domain matches: {len(df)}")
print(df.groupby(["protein", "type"])["accession"].count().unstack(fill_value=0))

# Pivot: proteins × domain accessions
pivot = df[df["type"] == "domain"].pivot_table(
    index="protein", columns="accession", aggfunc="size", fill_value=0
)
pivot.to_csv("domain_architecture_matrix.csv")
print(f"\nDomain × protein matrix: {pivot.shape}")

Workflow 2: Find Kinase Family Members with PDB Structures

Goal: Retrieve proteins in a kinase domain family that have experimental structures in the PDB, ranked by resolution.

import requests, time, pandas as pd

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

# Step 1: Get PDB structures linked to the protein kinase-like SF entry.
# Use the path-inverted form; the flat `?entry_interpro=` filter 408s.
r = requests.get(
    f"{INTERPRO_BASE}/structure/pdb/entry/interpro/IPR011009/",
    params={"page_size": 200},
    headers={"Accept": "application/json"}, timeout=60
)
r.raise_for_status()
structures = r.json().get("results", [])
print(f"PDB structures with IPR011009 (kinase-like SF, page 1): {len(structures)}")

rows = []
for s in structures:
    m = s["metadata"]
    rows.append({
        "pdb_id": m["accession"],
        "resolution": m.get("resolution"),
        "experiment": m.get("experiment_type", ""),
        "name": m.get("name", ""),
    })

df = pd.DataFrame(rows)
df = df.dropna(subset=["resolution"]).sort_values("resolution")
print(f"\nTop 10 highest-resolution kinase structures:")
print(df[["pdb_id", "resolution", "experiment", "name"]].head(10).to_string(index=False))
df.to_csv("kinase_structures.csv", index=False)
print(f"\nSaved kinase_structures.csv ({len(df)} X-ray / cryo-EM structures)")

Workflow 3: Taxonomic Coverage Bar Chart for a Domain

Goal: Visualize how many reviewed proteins in each major kingdom carry a given InterPro domain.

import requests, time
import pandas as pd
import matplotlib.pyplot as plt

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def get_taxonomy_counts(interpro_acc: str, page_size: int = 100,
                        max_pages: int = 5) -> pd.DataFrame:
    """Walk the taxonomy results for an InterPro entry. The API does not
    expose a per-taxon protein count at this endpoint — instead each
    paged record is one (taxon × representative protein-match) row.
    Aggregate client-side by taxon name to approximate frequency."""
    rows, url = [], f"{INTERPRO_BASE}/taxonomy/uniprot/entry/interpro/{interpro_acc}/"
    params = {"page_size": page_size}
    for _ in range(max_pages):
        if not url:
            break
        r = requests.get(url, params=params,
                         headers={"Accept": "application/json"}, timeout=90)
        r.raise_for_status()
        data = r.json()
        for t in data.get("results", []):
            m = t["metadata"]
            rows.append({
                "taxon_id": m["accession"],
                "name": m.get("name", ""),
                "rank": m.get("rank") or "",
            })
        url = data.get("next")
        params = None
        if url:
            time.sleep(1.0)
    return pd.DataFrame(rows)

IPR_ACC = "IPR011615"   # p53 DNA-binding domain (smaller; kinase 408s)
df = get_taxonomy_counts(IPR_ACC, max_pages=3)
print(f"Tax entries pulled for {IPR_ACC}: {len(df)}")

# Aggregate by name and take top 15 (each row = one rep. protein-match)
top = (df.groupby("name").size().sort_values(ascending=False).head(15)
       .reset_index(name="rep_matches"))
fig, ax = plt.subplots(figsize=(10, 5))
bars = ax.barh(top["name"], top["rep_matches"], color="#2171B5")
ax.bar_label(bars, fmt="%d", padding=3, fontsize=8)
ax.set_xlabel("Representative protein-matches")
ax.set_title(f"Taxonomic distribution of {IPR_ACC} (p53 DNA-binding domain)")
ax.invert_yaxis()
plt.tight_layout()
plt.savefig(f"{IPR_ACC}_taxonomy.png", dpi=150, bbox_inches="tight")
print(f"Saved {IPR_ACC}_taxonomy.png")

Key Parameters

Parameter	Endpoint	Default	Range / Options	Effect
search	entry/interpro/	—	free-text string	Keyword filter on entry name and short name
type	entry/interpro/	all types	family, domain, homologous_superfamily, repeat, site	Filter entries by InterPro type
page_size	all list endpoints	20	1–200	Results returned per page
entry_interpro	structure/pdb/	—	IPR######	Filter structures by linked InterPro entry
source_database	protein/	—	reviewed, uniprot, trembl	Filter proteins by UniProt curation level
reviewed (URL path)	entry/{ipr}/{acc}/protein/	uniprot	reviewed, uniprot	Swiss-Prot reviewed only vs all UniProtKB
relations	entry/interpro/{acc}/	—	contains, contained_by, child_of, parent_of	Navigate the InterPro hierarchy
next	all list endpoints	—	URL from response	Cursor-based pagination; use the full URL from the next field

Best Practices

1. Use reviewed proteins for curated domain lists: The unreviewed TrEMBL set is 5–10× larger and contains automated predictions. For benchmarking, family analysis, or training sets, restrict to reviewed (Swiss-Prot) entries to avoid noise from unreviewed predictions.

2. Chunk large taxonomy or protein lists: Retrieving all 10,000+ proteins for a broad family like the protein kinase superfamily can take minutes and produce large payloads. Limit queries with page_size=200 and the next cursor; store intermediate results to disk.

3. Add time.sleep(1.0) between paginated calls: The InterPro API is shared EBI infrastructure with no published rate limit. A 1-second pause per page is a safe minimum for batch scripts.

4. Prefer InterPro accessions over member DB accessions for cross-database queries: A Pfam PF00069 and PANTHER PTHR24340 both model kinase domains but with different protein coverage. Using the parent InterPro IPR000719 gives the union of all member DB matches in one query.

5. Check type before interpreting entry_protein_locations: Only domain, repeat, and site entries carry meaningful position information. family and homologous_superfamily entries typically span the full protein and their coordinates are less informative.

Common Recipes

Recipe: Quick Domain Check for a Protein

When to use: Given a UniProt accession, rapidly list which InterPro domains it contains.

import requests

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def list_protein_domains(uniprot_acc: str) -> list:
    """Return list of (accession, type, name) tuples for a protein."""
    r = requests.get(
        f"{INTERPRO_BASE}/entry/interpro/protein/uniprot/{uniprot_acc}/",
        headers={"Accept": "application/json"}, timeout=60
    )
    r.raise_for_status()
    return [
        (e["metadata"]["accession"], e["metadata"]["type"], e["metadata"]["name"])
        for e in r.json().get("results", [])
    ]

domains = list_protein_domains("P00533")   # EGFR
print(f"InterPro entries in EGFR (P00533): {len(domains)}")
for acc, etype, name in domains:
    print(f"  {acc}  {etype:<25}  {name}")
# InterPro entries in EGFR (P00533): 10
#   IPR009030  homologous_superfamily   Growth factor receptor, cysteine-rich
#   IPR000719  domain                   Protein kinase domain

Recipe: Find All Proteins in a Family with Source DB Coverage

When to use: Map how many proteins in a domain family are covered by each member database (Pfam vs PANTHER vs SMART, etc.).

import requests, time
import pandas as pd

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

interpro_acc = "IPR000719"   # Protein kinase domain
r = requests.get(
    f"{INTERPRO_BASE}/entry/interpro/{interpro_acc}/",
    headers={"Accept": "application/json"}, timeout=30
)
r.raise_for_status()
member_dbs = r.json()["metadata"].get("member_databases", {})
print(f"Member databases for {interpro_acc}:")
for db, details in member_dbs.items():
    print(f"  {db}: {details}")

# Visualize member database source breakdown
labels = list(member_dbs.keys())
import matplotlib.pyplot as plt
fig, ax = plt.subplots(figsize=(7, 4))
ax.bar(labels, [1] * len(labels), color="#4472C4")   # presence/absence per DB
ax.set_ylabel("Integrated (1=yes)")
ax.set_title(f"Member databases in {interpro_acc}")
plt.tight_layout()
plt.savefig(f"{interpro_acc}_member_dbs.png", dpi=150, bbox_inches="tight")

Recipe: Get GO Terms for an InterPro Entry

When to use: Bridge from structural domain to functional GO annotation.

import requests

INTERPRO_BASE = "https://www.ebi.ac.uk/interpro/api"

def get_go_terms_for_entry(interpro_acc: str) -> list:
    """Return GO terms associated with an InterPro entry."""
    r = requests.get(
        f"{INTERPRO_BASE}/entry/interpro/{interpro_acc}/",
        headers={"Accept": "application/json"}, timeout=30
    )
    r.raise_for_status()
    go_terms = r.json()["metadata"].get("go_terms", [])
    return [
        {"id": g["identifier"], "name": g["name"],
         "category": g.get("category", {}).get("name", "")}
        for g in go_terms
    ]

go_terms = get_go_terms_for_entry("IPR000719")
print(f"GO terms for IPR000719 (protein kinase domain): {len(go_terms)}")
for g in go_terms:
    print(f"  {g['id']}  [{g['category'][:2].upper()}]  {g['name']}")
# GO terms for IPR000719 (protein kinase domain): 3
#   GO:0004672  [MO]  protein kinase activity
#   GO:0005524  [MO]  ATP binding
#   GO:0006468  [BI]  protein phosphorylation

Troubleshooting

Problem	Cause	Solution
HTTP 404 on protein lookup	Accession not found in InterPro	Verify the UniProt accession exists; isoform accessions (P12345-2) may not be indexed separately
Empty entries list for a protein	Protein has no InterPro matches (e.g., intrinsically disordered)	Check UniProt directly; not all proteins have classified domains
protein/uniprot/{acc}/ returns only metadata (no entries)	That endpoint is protein-only; entry matches live elsewhere	Use entry/interpro/protein/uniprot/{acc}/ and read the results[] key
entry/interpro/{IPR}/protein/{db}/ returns 408 / hangs	The path with entry/... first does a slow join	Invert the path: protein/{db}/entry/interpro/{IPR}/
structure/pdb/?entry_interpro={IPR} times out (408)	Same join order issue	Use structure/pdb/entry/interpro/{IPR}/
entry/interpro/{IPR}/taxonomy/uniprot/ 408s for large families	Same	Use taxonomy/uniprot/entry/interpro/{IPR}/; for very large entries (e.g. IPR000719 kinase) the inverted form may still 408 — fall back to a more specific sub-family entry
HTTP 400 on entry search	Invalid query parameters or unsupported type value	Use one of: family, domain, homologous_superfamily, repeat, site
Pagination stops early	next is null before expected count	This is correct; all results have been returned
Very slow response for large families	Protein set has thousands of members	Increase page_size to 200; persist results after each page
ConnectionError or Timeout	Transient network or server issue	Retry with exponential backoff; EBI services occasionally have brief downtimes
Member DB accessions missing	Entry is new and member DB integration is pending	Use the InterPro accession for queries; member DB-level details update with each release

Related Skills

• uniprot-protein-database — UniProt REST API for protein sequences, Swiss-Prot functional annotations (active sites, PTMs, disease associations), and ID mapping
• esm-protein-language-model — Generate protein language model embeddings for sequences; useful after identifying a protein family with InterPro
• pdb-database — Retrieve and download experimental 3D structures by PDB ID; cross-reference structure IDs discovered via InterPro structure queries

References

• InterPro REST API documentation — Endpoint reference, filters, and example queries
• Blum et al., Nucleic Acids Research 2021 — InterPro flagship paper describing member database integration
• InterPro web portal — Interactive protein domain browser
• Paysan-Lafosse et al., Nucleic Acids Research 2023 — InterPro 2023 update describing new entry types and member databases