Phosphorylation refactor

Finding genes annotated to "protein phosphorylation" that are not kinases

AI Gene Review · projects/PHOSPHORYLATION_REFACTOR · 2026

Bottom line

  • Query: genes with a phosphorylation process term (GO:0016310 branch) but no protein kinase activity (GO:0004672), across 9 MODs.
  • 60 mouse and human genes reviewed; of 68 flagged rows, 34 REMOVE and 26 MODIFY (mostly to GO:0045859 regulation of protein kinase activity).
  • Errors cluster: substrates called enzymes, regulators called catalysts, phosphatases on the opposite reaction. SGD, PomBase and WormBase had none.

Why this filter works

  • A kinase activity MF annotation is a direct claim with strong evidence; it is rarely over-annotated.
  • A phosphorylation BP annotation is heterogeneous: the gene may catalyse, regulate, scaffold, or be the substrate.
  • So the set difference BP phosphorylation minus MF kinase is a priori suspect: cheap to compute in the GO DuckDB files, precise to review.
  • Lipid and sugar kinases fall out of the same query as a separate class.

Who performs the step?

Error taxonomy

Code Error Examples Usual action
S substrate annotated as enzyme CREB1, ATF2, RUNX3, Bcl2, LIMD1 REMOVE
R regulator (cyclin, ligand, adapter) CCNE1, GAS6, IL15, YWHAZ MODIFY → GO:0045859
W lipid/sugar kinase on protein term PIK3CD, IP6K3, GLYCTK MODIFY or REMOVE
O phosphatase, opposite reaction CDC25B, PPP3CB, PTPN6 REMOVE
C scaffold of a kinase-bearing complex COPS2, COPS8 MODIFY
U / A / X E3 ligase, ATPase, wrong PMID MEX3B, MORC3, TOLLIP REMOVE

Results

Worked examples

  • CDC25B (IDA, PMID:17332740): the paper calls it "the phosphatase required for activation of mitotic cyclin/Cdk1 complexes". A phosphatase on protein phosphorylation → REMOVE.
  • TOLLIP: the cited PMID:1085432 is a 1976 lymphoma paper → REMOVE (wrong reference).
  • COPS2 / COPS8: the COP9 signalosome co-purifies with CK2 and PKD; the PCI scaffold subunits do not phosphorylate → MODIFY.
  • ABI3: the only ACCEPT is a NOT row: the paper found Abi-3 "had no such effect" on c-Abl phosphorylation.

Status and next steps

  • ✅ Mouse (15 genes) and human (45 genes) reviews in genes/mouse/, genes/human/.
  • ⚠️ The page's per-gene lists predate later edits: Ang2, BIRC6 now UNDECIDED; ADM2 REMOVE; Egf, Ednra over-annotated; Drd1 non-core.
  • ⬜ Fly, zebrafish, Arabidopsis, rat findings are query-level only; no reviews yet (e.g. TAIR TOPP4, RGD Ppp3cb, 29 TAIR IEA rows).
  • ⬜ Feed the taxonomy back to GO as ISS-transfer and training guidance.

Read more: projects/PHOSPHORYLATION_REFACTOR.md