claude-scientific-skills/scientific-skills/interpro-database/references/domain_analysis.md

InterPro Domain Analysis Reference

Entry Types

Type	Description	Example
family	Group of related proteins sharing common evolutionary origin	IPR013872: p53 family
domain	Distinct structural/functional unit that can exist independently	IPR011615: p53 tetramerisation domain
homologous_superfamily	Proteins related by structure but not necessarily sequence	IPR009003: Peptidase, aspartic
repeat	Short sequence unit that occurs in multiple copies	IPR000822: Ankyrin repeat
site	Residues important for function	IPR018060: Metalloprotease active site
conserved_site	Conserved sequence motif (functional)	IPR016152: PTB/PI domain binding site
active_site	Catalytic residues	IPR000743: RING domain
binding_site	Residues involved in binding	—
ptm	Post-translational modification site	—

Common Domain Accessions

Signaling Domains

Accession	Name	Function
IPR000719	Protein kinase domain	ATP-dependent phosphorylation
IPR001245	Serine-threonine/tyrosine-protein kinase	Kinase catalytic domain
IPR000980	SH2 domain	Phosphotyrosine binding
IPR001452	SH3 domain	Proline-rich sequence binding
IPR011993	PH domain	Phosphoinositide binding
IPR000048	IQ motif	Calmodulin binding
IPR000008	C2 domain	Ca2+/phospholipid binding
IPR001849	PH domain	Pleckstrin homology

DNA Binding Domains

Accession	Name	Function
IPR013087	Zinc finger, C2H2	DNA binding
IPR017456	CCCH zinc finger	RNA binding
IPR011991	Winged helix-turn-helix	Transcription factor DNA binding
IPR011607	MH1 domain	SMAD DNA binding
IPR003313	ARID domain	AT-rich DNA binding
IPR014756	E1-E2 ATPase, nucleotide-binding	—

Structural Domains

Accession	Name	Function
IPR001357	BRCT domain	DNA repair protein interaction
IPR000536	Nuclear hormone receptor, ligand-binding	Hormone binding
IPR001628	Zinc finger, nuclear hormone receptor	DNA binding (NHR)
IPR003961	Fibronectin type III	Cell adhesion
IPR000742	EGF-like domain	Receptor-ligand interaction

Domain Architecture Patterns

Common multi-domain architectures and their biological meanings:

Receptor Tyrosine Kinases

[EGF domain]... - [TM] - [Kinase domain]
e.g., EGFR: IPR000742 (EGF) + IPR000719 (kinase)

Adapter Proteins

[SH3] - [SH2] - [SH3]
e.g., Grb2, Crk — signaling adapters

Nuclear Receptors

[DBD/C2H2 zinc finger] - [Ligand binding domain]
e.g., ERα (ESR1)

Kinases

[N-lobe] - [Activation loop] - [C-lobe]
Standard protein kinase fold (IPR000719)

GO Term Categories

InterPro GO annotations use three ontologies:

Code	Ontology	Examples
P	Biological Process	GO:0006468 (protein phosphorylation)
F	Molecular Function	GO:0004672 (protein kinase activity)
C	Cellular Component	GO:0005886 (plasma membrane)

InterProScan for Novel Sequences

For protein sequences not in UniProt (novel/predicted sequences), run InterProScan:

# Command-line (install InterProScan locally)
./interproscan.sh -i my_proteins.fasta -f tsv,json -dp

# Options:
# -i: input FASTA
# -f: output formats (tsv, json, xml, gff3, html)
# -dp: disable precalculation lookup (use for non-UniProt sequences)
# --goterms: include GO term mappings
# --pathways: include pathway mappings

# Or use the web service:
# https://www.ebi.ac.uk/interpro/search/sequence/

Output fields (TSV):

1. Protein accession
2. Sequence MD5
3. Sequence length
4. Analysis (e.g., Pfam, SMART)
5. Signature accession (e.g., PF00397)
6. Signature description
7. Start
8. Stop
9. Score
10. Status (T = true)
11. Date
12. InterPro accession (if integrated)
13. InterPro description

Useful Entry ID Collections

Human Disease-Relevant Domains

DISEASE_DOMAINS = {
    # Cancer
    "IPR011615": "p53 tetramerization",
    "IPR012346": "p53/p63/p73, tetramerization domain",
    "IPR000719": "Protein kinase domain",
    "IPR004827": "Basic-leucine zipper (bZIP) TF",

    # Neurodegenerative
    "IPR003527": "MAP kinase, ERK1/2",
    "IPR016024": "ARM-type fold",

    # Metabolic
    "IPR001764": "Glycoside hydrolase, family 13 (amylase)",
    "IPR006047": "Glycoside hydrolase superfamily",
}

Commonly Referenced Pfam IDs

Pfam ID	Domain Name
PF00069	Pkinase (protein kinase)
PF00076	RRM_1 (RNA recognition motif)
PF00096	zf-C2H2 (zinc finger)
PF00397	WW domain
PF00400	WD40 repeat
PF00415	RasGEF domain
PF00018	SH3 domain
PF00017	SH2 domain
PF02196	zf-C3HC4 (RING finger)