Protein families

Where family-level annotation holds, and where it does not

AI Gene Review · projects/FAMILIES · 2026

Bottom line

  • GO annotations propagate from reusable sources: PAINT/IBA descends from PANTHER tree nodes; InterPro2GO fires on InterPro/Pfam signature matches.
  • We review PANTHER family scope and Pfam mapping viability: family-wide, subfamily-only, residue-determined or not at all?
  • 353 entries catalogued (218 complete). 151 families are heterogeneous; only 98 of 391 term calls are safe family-wide.

Why review families

  • Per-gene reviews kept tracing over-propagated rows back to the same heterogeneous families.
  • An IBA reflects a PAINT curator's node placement; the question is whether the target sits inside the clade that inherited the function, and whether it kept the residues.
  • Fixing one gene at a time leaves the source in place. A family review records the boundary once, with evidence, for every member.

The question a family review answers

What one entry looks like

interpro/panther/PTHR10102/PTHR10102-review.yaml, phage-type RNA polymerase

  • functional_coherence: MOSTLY_COHERENT: DNA-directed RNA synthesis is conserved; mitochondrial targeting and the Mtf1 partner are lineage-specific.
  • GO:0003899 DNA-directed RNA polymerase activity → FAMILY_WIDE, supported by PMID:21357609 (purified S. pombe Rpo41 + Mtf1 transcribe in vitro).
  • Representative member linked to its gene review: genes/SCHPO/rpo41/.

What the catalog holds

The catalog page

pages/projects/FAMILIES.html: searchable and filterable by database, review status, coherence and Pfam mapping viability.

Findings so far

  1. Heterogeneity is the norm: 151 heterogeneous vs 33 coherent families.
  2. Most term calls are still open: 211 of 391 unresolved; 98 family-wide, 61 subfamily-only.
  3. Residue-determined scope (7 calls) handles mixed subfamilies: PTHR10256:SF0 holds both active E. coli SelD and the Arg-substituted Drosophila Sps1.
  4. Pfam mappings: all 9 Pfam domains reviewed were judged not viable for a domain-level GO mapping.

Status and next steps

  • PANTHER status: 218 complete; 85 draft, 8 in progress, 28 need review, 5 not recorded.
  • Open work: 211 unresolved term scopes; 89 entries with no coherence call yet.
  • Related: projects/IBA_REVIEW.md, projects/PANTHER_IBA_REVIEW/, projects/CASPL_FAMILY.md, projects/INTERPRO.md.

Read more: projects/FAMILIES.md · interpro/panther/<PTHR>/ · just validate-families