ID:WEE1_HUMAN DESCRIPTION: RecName: Full=Wee1-like protein kinase; Short=WEE1hu; EC=2.7.10.2; AltName: Full=Wee1A kinase; FUNCTION: Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15'. Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase. Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur. Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated. A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. COFACTOR: Binds 2 magnesium ions per subunit. ENZYME REGULATION: Synthesis is increased during S and G2 phases, presumably by an increase in transcription; activity is decreased by phosphorylation during m phase. Protein levels fall in M phase as a result of decreased synthesis combined with degradation. Activity seems to be negatively regulated by phosphorylation upon entry into mitosis, although N-terminal phosphorylation might also regulate the protein stability via protection from proteolysis or might regulate the subcellular location. INTERACTION: Q9Y297:BTRC; NbExp=2; IntAct=EBI-914695, EBI-307461; Q9UKB1:FBXW11; NbExp=2; IntAct=EBI-914695, EBI-355189; SUBCELLULAR LOCATION: Nucleus. PTM: Phosphorylated during M and G1 phases. Also autophosphorylated. Phosphorylation at Ser-642 by BRSK1 and BRSK2 in post-mitotic neurons, leads to down-regulate WEE1 activity in polarized neurons. Phosphorylated at Ser-53 and Ser-123 by PLK1 and CDK1, respectively, generating an signal for degradation that can be recognized by the SCF(BTRC) complex, leading to its ubiquitination and degradation at the onset of G2/M phase. PTM: Dephosphorylated at Thr-239 by CTDP1. PTM: Ubiquitinated and degraded at the onset of G2/M phase. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily. SIMILARITY: Contains 1 protein kinase domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P30291
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
U10564 - Human CDK tyrosine 15-kinase WEE1Hu (Wee1Hu) mRNA, complete cds. JD060364 - Sequence 41388 from Patent EP1572962. BC070052 - Homo sapiens WEE1 homolog (S. pombe), mRNA (cDNA clone MGC:87158 IMAGE:30336707), complete cds. JD419395 - Sequence 400419 from Patent EP1572962. X62048 - H.sapiens Wee1 hu gene. JD127821 - Sequence 108845 from Patent EP1572962. JD128745 - Sequence 109769 from Patent EP1572962. JD109289 - Sequence 90313 from Patent EP1572962. BC051831 - Homo sapiens WEE1 homolog (S. pombe), mRNA (cDNA clone MGC:60116 IMAGE:6147695), complete cds. JD128494 - Sequence 109518 from Patent EP1572962. AB384747 - Synthetic construct DNA, clone: pF1KB3098, Homo sapiens WEE1 gene for WEE1-like protein kinase, complete cds, without stop codon, in Flexi system. EU832410 - Synthetic construct Homo sapiens clone HAIB:100067439; DKFZo004E1028 WEE1 homolog (S. pombe) protein (WEE1) gene, encodes complete protein. EU832325 - Synthetic construct Homo sapiens clone HAIB:100067354; DKFZo008E1027 WEE1 homolog (S. pombe) protein (WEE1) gene, encodes complete protein. LF369450 - JP 2014500723-A/176953: Polycomb-Associated Non-Coding RNAs. AK122837 - Homo sapiens cDNA FLJ16446 fis, clone BRAMY3010008, highly similar to Wee1-like protein kinase (EC 2.7.10.2). LF384292 - JP 2014500723-A/191795: Polycomb-Associated Non-Coding RNAs. BX641032 - Homo sapiens mRNA; cDNA DKFZp686I18166 (from clone DKFZp686I18166). LF369451 - JP 2014500723-A/176954: Polycomb-Associated Non-Coding RNAs. LF369452 - JP 2014500723-A/176955: Polycomb-Associated Non-Coding RNAs. LF369453 - JP 2014500723-A/176956: Polycomb-Associated Non-Coding RNAs. LF369454 - JP 2014500723-A/176957: Polycomb-Associated Non-Coding RNAs. LF369455 - JP 2014500723-A/176958: Polycomb-Associated Non-Coding RNAs. JD025466 - Sequence 6490 from Patent EP1572962. JD035861 - Sequence 16885 from Patent EP1572962. JD022876 - Sequence 3900 from Patent EP1572962. JD509018 - Sequence 490042 from Patent EP1572962. JD033864 - Sequence 14888 from Patent EP1572962. JD232355 - Sequence 213379 from Patent EP1572962. JD106262 - Sequence 87286 from Patent EP1572962. LF369456 - JP 2014500723-A/176959: Polycomb-Associated Non-Coding RNAs. JD412118 - Sequence 393142 from Patent EP1572962. JD327337 - Sequence 308361 from Patent EP1572962. JD454874 - Sequence 435898 from Patent EP1572962. JD300150 - Sequence 281174 from Patent EP1572962. JD279859 - Sequence 260883 from Patent EP1572962. JD295259 - Sequence 276283 from Patent EP1572962. JD125164 - Sequence 106188 from Patent EP1572962. JD143848 - Sequence 124872 from Patent EP1572962. MA605027 - JP 2018138019-A/176953: Polycomb-Associated Non-Coding RNAs. MA619869 - JP 2018138019-A/191795: Polycomb-Associated Non-Coding RNAs. MA605028 - JP 2018138019-A/176954: Polycomb-Associated Non-Coding RNAs. MA605029 - JP 2018138019-A/176955: Polycomb-Associated Non-Coding RNAs. MA605030 - JP 2018138019-A/176956: Polycomb-Associated Non-Coding RNAs. MA605031 - JP 2018138019-A/176957: Polycomb-Associated Non-Coding RNAs. MA605032 - JP 2018138019-A/176958: Polycomb-Associated Non-Coding RNAs. MA605033 - JP 2018138019-A/176959: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_rbPathway - RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage h_g2Pathway - Cell Cycle: G2/M Checkpoint h_cdc25Pathway - cdc25 and chk1 Regulatory Pathway in response to DNA damage
Reactome (by CSHL, EBI, and GO)
Protein P30291 (Reactome details) participates in the following event(s):
R-HSA-75028 Phosphorylation of Wee1 kinase by Chk1 R-HSA-156699 Inactivation of Wee1 kinase R-HSA-1013881 Cables1 links CDK2 and WEE1 R-HSA-69195 Phosphorylation of Cyclin E:Cdk2 complexes by Wee-1 R-HSA-170070 Wee1-mediated phosphorylation of Cyclin B1:phospho-Cdc2 complexes R-HSA-170156 Wee1-mediated phosphorylation of Cyclin A:phospho-Cdc2 complexes R-HSA-174164 Phosphorylation of Cyclin A:Cdk2 at Tyr 15 R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex R-HSA-156711 Polo-like kinase mediated events R-HSA-983231 Factors involved in megakaryocyte development and platelet production R-HSA-69473 G2/M DNA damage checkpoint R-HSA-69275 G2/M Transition R-HSA-109582 Hemostasis R-HSA-69202 Cyclin E associated events during G1/S transition R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition R-HSA-69478 G2/M DNA replication checkpoint R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry R-HSA-69481 G2/M Checkpoints R-HSA-453274 Mitotic G2-G2/M phases R-HSA-69206 G1/S Transition R-HSA-69242 S Phase R-HSA-69620 Cell Cycle Checkpoints R-HSA-69278 Cell Cycle (Mitotic) R-HSA-453279 Mitotic G1-G1/S phases R-HSA-1640170 Cell Cycle
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
