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.
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.
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.
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.
Identity. P30291 is the reviewed canonical human WEE1 product (isoform 1, 646 aa; kinase domain 299-569, ACT_SITE 426, Mg2+ sites 342/431/463/465). It is not a fragment or alternative gene model. Isoform 2 (P30291-2, VSP_044959) lacks residues 1-214, i.e. the N-terminal regulatory region carrying the Ser53/Ser123 phosphodegrons, but keeps the kinase domain. No ProtNLM2 files were opened.
Evolutionary placement. PANTHER PTHR11042 (family label "EUKARYOTIC TRANSLATION INITIATION FACTOR 2-ALPHA KINASE ... RELATED"), subfamily SF72 "WEE1-LIKE PROTEIN KINASE", which holds vertebrate WEE1 (human, mouse P47810, rat Q63802, Xenopus wee1-a/b). WEE2 is SF75; Drosophila/plant/Dictyostelium Wee1 are SF185; yeast Wee1/Swe1 are SF196; worm wee-1.1/1.3 and PKMYT1-like are SF183. PAINT nodes: GO:0004713 at PTN008510964 (Eukaryota; seeds human WEE1, fly Wee1, Xenopus Wee2-A); GO:0010972 at PTN008510965 (Euteleostomi; seed human WEE1 only); GO:0004672, nucleus and cytoplasm at the family root PTN000113601. Human WEE1 seeds the root nucleus assertion but not the cytoplasm assertion. The PTHR11042 family review (interpro/panther/PTHR11042/) places human WEE1 in SF72, agreeing with UniProt; no subfamily disagreement.
Literature used. PMID:8428596 (exclusive CDK1 Tyr15 phosphorylation; Lys114 dead), PMID:7743995 (endogenous WEE1 phosphorylates several cyclin-CDKs on Tyr15; S/G2 rise, M-phase inactivation), PMID:7774574 (immunodepletion: WEE1 is the main CDK1-Tyr15 kinase in HeLa lysate), PMID:8348613 (nuclear; protects nucleus from cytoplasmically activated CDK1), PMID:15070733 (PLK1/CDK1 phosphodegrons, SCF-beta-TrCP), PMID:15837193 (kinase-domain structure, Ser/Thr-like fold), newly cached PMID:22907750 and PMID:20194642 (WEE1 restrains replication initiation; depletion causes S-phase DNA damage) and PMID:22885324 (H2B Tyr37 as a WEE1 substrate).
Changes versus the previous version.
- All 11 GO:0005515 rows -> REMOVE (repository protein-binding policy; WEE1 is the substrate/client of PLK1, beta-TrCP and 14-3-3; interactions not disputed).
- GO:0045740 positive regulation of DNA replication (Reactome TAS) -> MODIFY to GO:0032297 negative regulation of DNA-templated DNA replication initiation (sign correction; Reactome's own pathway summary describes WEE1 Tyr15 phosphorylation as inhibiting Cyclin A:CDK2; PMID:22907750).
- GO:0000086 and GO:0000278 -> MODIFY to GO:0010972 (WEE1 restrains rather than executes the transition; mitotic cell cycle is uninformative).
- GO:0005737 cytoplasm (IBA, IEA) -> MARK_AS_OVER_ANNOTATED (family-root inference whose seeds are other members; human WEE1 is experimentally nuclear). Propagation_review recorded.
- GO:0000287 and GO:0005524 -> KEEP_AS_NON_CORE (cofactor / ATP substrate of the core kinase).
- GO:0005730 nucleolus (HPA) kept UNDECIDED; the deep-research summary of McGowan & Russell 1995 full text says transfected WEE1 is excluded from nucleoli, which conflicts with the HPA call; full text not cached so not quoted.
- Tyrosine kinase rows (GO:0004713, GO:0004715), nucleus, nucleoplasm and GO:0010972 accepted; GO:2000134 kept as non-core.
- Core functions: (1) GO:0004715 in nucleus, negative regulation of G2/M; (2) GO:0004715, negative regulation of replication initiation via CDK2.
- H2B Tyr37 phosphorylation recorded in the description and as a suggested question, not as a NEW annotation.
Relative to review next. Mouse Wee1 (P47810, SF72, inside PAINT node PTN008510965 with human WEE1), the experimentally characterised SF72 ortholog in a model organism; no genes/mouse/Wee1 review exists. Note: a stray cache file publications/PMID_20679485.md (unrelated pombe Crb2 paper) was created by a mistaken lookup and is not cited.
Modules. modules/g2_m_transition.yaml and modules/cell_cycle_progression.yaml mention WEE1.