WEE1: paired human–horse review notes

Biological evidence

Human WEE1 is a nuclear CDK-inhibitory tyrosine kinase. Direct assays distinguish CDK1 Tyr15 phosphorylation from Thr14 phosphorylation. Mouse egg-activation experiments distinguish WEE2/Wee1B from WEE1/Wee1A: WEE2 depletion blocks pronuclear formation, whereas WEE1 depletion does not in that assay.

• PMID:8428596: Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15. — abstract cached; full-text availability must be checked separately.
• PMID:7743995: Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle. — abstract cached; full-text availability must be checked separately.
• PMID:8348613: Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase. — abstract cached; full-text availability must be checked separately.
• PMID:21454751: Protein tyrosine kinase Wee1B is essential for metaphase II exit in mouse oocytes. — full text cached.
• PMID:37527245: Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice. — full text cached.

Exact horse model

The full646-residue horse protein closely matches human WEE1 at95.4% identity. Nuclear phosphorylation is supported. The specific female-pronucleus prediction has a plausible paralog-transfer explanation, but remains UNC: differential necessity does not exclude redundant participation. Broad meiotic claims likewise remain unresolved. Electronic Ser/Thr assignments are refined to the demonstrated tyrosine activity.

The reproducible alignment, source paths and hashes are in the paired comparison. Current UniProt sequences have not been proven identical to the original ProtNLM input sequences. Sequence anomalies are therefore recorded as model/transfer limitations, not as proven wrong-input pipeline errors.

Evidence gaps

The2023Wee2 knockouts retain substantial fertility and support possible biological redundancy, so do not claim WEE2 is universally essential or WEE1 can never compensate. Check horse oocyte expression/perturbation before scoring broad meiosis. Separate kinase catalysis from regulation of a different phosphorylation reaction.

Review scope and checks

Every seeded annotation receives a current assessment. UNDECIDED marks unresolved source-specific or biological evidence; these are initial reviews rather than a claim that every original experimental assay has been independently reproduced or verified. The human Edison report is retained as a research synthesis and source-finding aid; decisive YAML excerpts cite primary publications, source records or reproducible analysis. The validator advisory to cite the deep-research file is deliberately not satisfied by citing AI prose as biological proof.

2026-10-20 — Full re-review, independent of the ProtNLM2 predictions

Identity of the benchmark accession

• F6TY09 (TrEMBL, Ensembl ENSECAP00000018436, VGNC:25026 WEE1, chr 7) is the canonical full-length horse WEE1: 646 aa, the same length as human WEE1 P30291, 95.4% identity over the whole length (file:HORSE/WEE1/WEE1-bioinformatics/RESULTS.md). Not a fragment, isoform or alternative gene model. Kinase domain 299-569, predicted proton acceptor D426, PIRSR ATP (305-313, K328) and Mg2+ (431, 463) positions all present.
• Phylogenetic placement: PANTHER PTHR11042:SF72 (WEE1-LIKE PROTEIN KINASE), the same subfamily as human P30291, mouse P47810 and rat Q63802 WEE1. WEE2 orthologs sit in SF75, PKMYT1/wee-1.1/wee-1.3 in SF183, S. pombe wee1 in SF196, Drosophila Wee1 in SF185 (interpro/panther/PTHR11042/PTHR11042-entries.csv). So human WEE1 is the experimentally characterised ortholog to transfer from; WEE2 oocyte/meiotic functions must not be transferred.
• PAINT: GO:0004713 IBD at PTN008510964 (seeds FB Wee1, human WEE1, Xenopus wee2-a); GO:0010972 IBD at PTN008510965 (seed human WEE1); nucleus/cytoplasm IBD at the deep node PTN000113601. GO:0004674 (Ser/Thr kinase) was placed by PAINT at PTN008683913, which does not reach the WEE1 clade (no IBA for it on F6TY09) — read as a deliberate decision.
• UniProt caveat: the F6TY09 FUNCTION comment is ARBA-derived (ARBA00059782) and describes the oocyte-specific WEE2 paralog (meiotic arrest, MII exit, pronuclear formation); the Meiosis keyword is likewise ARBA. These are mis-transfers from the paralog and are not used as evidence.

Deep research

• just deep-research HORSE WEE1 --provider falcon failed (Edison "Failed to authenticate"); no deep-research file was created for horse. Relied on the human WEE1 falcon report (genes/human/WEE1/WEE1-deep-research-falcon.md) as a source-finding aid and on cached primary abstracts PMID:8428596, PMID:7743995, PMID:8348613.

Changes vs previous review

• Description rewritten as a standalone biological summary (removed comparison prose about the horse model).
• GO:0000278 mitotic cell cycle: ACCEPT -> MODIFY to GO:0010972 (correct but general; gene already carries the specific term).
• Ser/Thr kinase rows (GO:0004674, GO:0106310): MODIFY -> GO:0004713 kept, reasoning now grounded in PAINT node placement and Tyr15-only specificity of human WEE1 ("purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected" PMID:8428596).
• Generic kinase/transferase rows: MODIFY -> GO:0004713 (unchanged action, new evolutionary reasoning).
• ATP/nucleotide/Mg binding: ACCEPT, now supported by PIRSR site features and SF72 membership rather than identity alone.
• Nucleolus (Compara copy of human HPA IDA): UNDECIDED, consistent with the human review.
• Cytoplasm: KEEP_AS_NON_CORE. Nucleus, PTK, non-membrane PTK, G2/M negative regulation: ACCEPT.
• No NEW terms: meiotic/oocyte processes belong to WEE2 (SF75); DNA-damage checkpoint roles are not separately annotated for this gene in GOA and were not added.