Wee1-like protein 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.

Classification

Family (Pfam)

PF00069 Pkinase

InterPro

CC_SR_Kinase, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS, Wee1-like_protein_kinase

Functional cluster

RNA Polymerase II Transcription Factors

Experimental structures · PDB · 26

• 1X8B X-ray 1.81A
• 2IN6 X-ray 1.90A
• 2IO6 X-ray 2.20A
• 2Z2W X-ray 2.22A
• 3BI6 X-ray 2.20A
• 3BIZ X-ray 2.20A
• 3CQE X-ray 2.50A
• 3CR0 X-ray 2.30A
• 5V5Y X-ray 1.90A
• 5VC3 X-ray 1.97A
• 5VC4 X-ray 2.10A
• 5VC5 X-ray 1.93A
• … and 14 more

A predicted model is available from AlphaFold.

Gene Ontology · 13

• GO:0005737 cytoplasm
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005524 ATP binding
• GO:0000287 magnesium ion binding
• GO:0004715 non-membrane spanning protein tyrosine kinase activity
• GO:0004713 protein tyrosine kinase activity
• GO:0051301 cell division
• GO:0000086 G2/M transition of mitotic cell cycle
• GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
• GO:0010972 negative regulation of G2/M transition of mitotic cell cycle
• GO:0045740 positive regulation of DNA replication

Drugs targeting this protein · 2

• ADAVOSERTIB inhibitor
• AZENOSERTIB inhibitor

Related proteins · sequence + function similarity

• Wee1-like protein kinase 0.97
• Wee1-like protein kinase 0.97
• Wee1-like protein kinase 1-A 0.87
• Wee1-like protein kinase 1-B 0.84
• Wee1-like protein kinase 2 0.73
• Wee1-like protein kinase 2-C 0.72
• Wee1-like protein kinase 2 0.72
• Wee1-like protein kinase 2-B 0.72
• Wee1-like protein kinase 2-A 0.71
• Wee1-like protein kinase 2 0.68
• Wee1-like protein kinase 2 0.68
• Wee1-like protein kinase 2 0.68

Co-cited proteins · studied together in the literature

• Serine/threonine-protein kinase BRSK1 2 shared papers
• RNA polymerase II subunit A C-terminal domain phosphatase 1 shared papers
• PPP2R1A-PPP2R2A-interacting phosphatase regulator 1 1 shared papers
• Wee1-like protein kinase 1 shared papers
• Rhombotin-1 1 shared papers
• Rhombotin-1 1 shared papers
• Serine/threonine-protein kinase BRSK1 1 shared papers
• Serine/threonine-protein kinase PLK1 1 shared papers
• Ubiquitin carboxyl-terminal hydrolase 44 1 shared papers
• Serine/threonine-protein kinase BRSK2 1 shared papers
• M-phase inducer phosphatase 2 1 shared papers
• M-phase inducer phosphatase 3 1 shared papers

Literature · 19 cited papers

• CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress. Mol. Cell · 2020
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit. Nat. Commun. · 2012
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Persistence of the cell-cycle checkpoint kinase Wee1 in SadA- and SadB-deficient neurons disrupts neuronal polarity. J. Cell Sci. · 2010
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
• Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J. Proteome Res. · 2008
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
• Structure and inhibition of the human cell cycle checkpoint kinase, Wee1A kinase: an atypical tyrosine kinase with a key role in CDK1 regulation. Structure · 2005
• Human SAD1 kinase is involved in UV-induced DNA damage checkpoint function. J. Biol. Chem. · 2004
• … and 7 more in the literature graph