FOXJ3 (donkey, A0A9L0JKH1) notes

2026-10-14 DONKEY40 review

• Record: TrEMBL, 580 aa, "Forkhead box J3", Ensembl gene model from the donkey genome project (PMID:33293529; genome sequencing, no FOXJ3 experiment). 8 GOA rows, all IEA: TreeGrafter (GO_REF:0000118, PTN000215310) x3, InterPro2GO x3, UniRule x1, combined x1.
• Sequence: [file:EQUAS/FOXJ3/FOXJ3-bioinformatics/RESULTS.md "The donkey sequence A0A9L0JKH1 (580 residues) aligns to human Q9UPW0 (622 residues) with 98.1% identity among 579 paired residues."]; lacks human 211-253 (disordered region); fork-head domain intact.
• Human FOXJ3 function is by similarity to mouse Foxj3: [file:EQUAS/FOXJ3/FOXJ3-bioinformatics/human-Q9UPW0-uniprot.txt "Transcriptional activator of MEF2C involved in the regulation"]; spermatogenesis role [same file, "Plays an important role in spermatogenesis (By"]. Human GO (from the UniProt DR lines) includes IDA sequence-specific DNA binding and IDA DNA-binding transcription activator activity, RNA polymerase II-specific (NTNU_SB), IBA nucleus and RNA polymerase II cis-regulatory region sequence-specific DNA binding.
• Forkhead (FOX) domain proteins are sequence-specific RNA polymerase II transcription factors; the TreeGrafter MF/BP terms are at the right level. The generic InterPro2GO/UniRule terms (DNA binding, sequence-specific DNA binding, DNA-binding TF activity, regulation of DNA-templated transcription) are ancestors of accepted terms -> TOO_GENERAL.
• Not added: positive regulation of transcription by RNA pol II / activator activity (supported in human by IDA) and spermatogenesis/muscle fiber type (mouse). Left as suggested questions rather than NEW, because the donkey record carries no tissue or target-gene information and the specific developmental roles are inferred from mouse knockouts.
• ProtNLM2 GO: sequence-specific DNA binding and DNA-binding transcription factor activity; both exact terms are in GOA (InterPro2GO), and both are less specific than the TreeGrafter RNA pol II-specific terms -> LSP. No ProtNLM2 function or location text for this accession.

2026-10-21 — Full re-review, independent of the ProtNLM2 predictions

• Deep research: just deep-research EQUAS FOXJ3 --provider falcon failed twice (Edison API "Failed to authenticate", HTTP 403; the perplexity-lite fallback reported an exhausted quota). No deep-research file was written. Literature was gathered from Europe PMC title search for FOXJ3 and the key papers cached with just fetch-pmid.
• Identity: UniProt has five unreviewed donkey FOXJ3 entries; A0A8C4PFN5 (623 aa), A0A9L0JPR6 (614 aa) and the benchmark A0A9L0JKH1 (580 aa) are all transcripts of Ensembl gene ENSEASG00005001210 and all in PTHR46078:SF3. [file:EQUAS/FOXJ3/FOXJ3-bioinformatics/RESULTS-rereview.md "This is an alternative transcript of the same gene (an internal exon-skipping isoform), not a fragment and not a different gene."] The benchmark is 100% identical to A0A8C4PFN5 over its 580 residues and lacks A0A8C4PFN5 211-253; the fork-head domain is intact. The missing segment is not the one removed in human isoform 2 (human 177-210). No reviewed donkey FOXJ3 entry exists; A0A8C4PFN5 is the full-length (canonical-length) product, matching human Q9UPW0 (622 aa, 98.23% identity) and mouse (623 aa) PMID:15366017.
• Evolutionary grounding: human Q9UPW0 and mouse Q8BUR3 are both in PTHR46078:SF3 (FORKHEAD BOX PROTEIN J3) per interpro/panther/PTHR46078/PTHR46078-entries.csv, the same subfamily as the donkey models. No PANTHER FamilyReview exists for PTHR46078 (only entries/metadata files), so no subfamily disagreement to report. Transfers below are within SF3 only.
• Molecular evidence (mouse): PMID:19914232; the activation domain lies C-terminal to residue 176 PMID:19914232. The donkey isoform's 43-residue deletion falls in this C-terminal region, so activator capacity of this isoform is untested.
• Sign of regulation varies: Xenopus Foxj3 represses Nodal/BMP-responsive genes PMID:40522413; mouse targets (Mef2c, Pgc1a/Ucp1 PMID:37939221, Pten PMID:41803108) are activated. Hence the sign-neutral GO:0000981 / GO:0006357 are kept rather than refined to activator/positive regulation.
• Organismal roles (muscle fiber type, spermatogenesis PMID:27739607, brown fat thermogenesis, cortical lamination) come from mouse knockouts/knockdowns: necessity data, used in the description only, not added as NEW process annotations.
• Actions unchanged from the 2026-10-14 review (ACCEPT 4: GO:0000978, GO:0000981, GO:0005634, GO:0006357; TOO_GENERAL 4: GO:0003677, GO:0003700, GO:0006355, GO:0043565), but support now cites the primary mouse experiment rather than only the human UniProt by-similarity text, and the description records isoform identity.
• Relative: because the benchmark is an alternative transcript, the relative to review next is the full-length product of the same donkey gene, A0A8C4PFN5 (623 aa, same Ensembl gene, PTHR46078:SF3), which has no review (folder would be genes/EQUAS/FOXJ3__A0A8C4PFN5, since genes/EQUAS/FOXJ3 is keyed to A0A9L0JKH1). No reviewed donkey entry exists. Beyond that, the experimentally characterised SF3 member is mouse Foxj3 (Q8BUR3; human Q9UPW0 function text is by similarity to mouse); neither Q8BUR3 nor Q9UPW0 has a review in genes/.
• Modules: no module in modules/ mentions FOXJ3 or PTHR46078.