Dual specificity protein kinase CLK2

Function

Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Phosphorylates PAGE4 at several serine and threonine residues and this phosphorylation attenuates the ability of PAGE4 to potentiate the transcriptional activator activity of JUN.

Classification

Family (Pfam)

PF00069 Pkinase

InterPro

CLK_kinases, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS

Functional cluster

RRM RNA-Binding & Protein Kinases

Experimental structures · PDB · 6

• 3NR9 X-ray 2.89A
• 5UNP X-ray 2.92A
• 6FYI X-ray 2.60A
• 6FYK X-ray 2.39A
• 6FYL X-ray 1.95A
• 6KHE X-ray 2.80A

A predicted model is available from AlphaFold.

Gene Ontology · 15

• GO:0016604 nuclear body
• GO:0016607 nuclear speck
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005524 ATP binding
• GO:0042802 identical protein binding
• GO:0106310 protein serine kinase activity
• GO:0004674 protein serine/threonine kinase activity
• GO:0004712 protein serine/threonine/tyrosine kinase activity
• GO:0004713 protein tyrosine kinase activity
• GO:0045721 negative regulation of gluconeogenesis
• GO:0046777 protein autophosphorylation
• GO:0006468 protein phosphorylation
• GO:0043484 regulation of RNA splicing
• GO:0010212 response to ionizing radiation

Drugs targeting this protein · 1

• LORECIVIVINT inhibitor

Related proteins · sequence + function similarity

• Dual specificity protein kinase CLK2 1.00
• Dual specificity protein kinase CLK1 0.94
• Dual specificity protein kinase CLK4 0.93
• Dual specificity protein kinase CLK1 0.93
• Dual specificity protein kinase CLK4 0.93
• Dual specificity protein kinase CLK3 0.92
• Dual specificity protein kinase CLK3 0.92
• Dual specificity protein kinase CLK3 0.92
• Dual specificity protein kinase CLK3 0.92
• Serine/threonine-protein kinase AFC3 0.71
• Cyclin-dependent kinase 11.2 0.71
• Transformer-2 sex-determining protein 0.70

Co-cited proteins · studied together in the literature

• Dual specificity protein kinase CLK3 3 shared papers
• Dual specificity protein kinase CLK1 4 shared papers
• Tyrosine-protein phosphatase 1 1 shared papers
• Dual specificity protein kinase CLK4 2 shared papers
• Dual specificity protein kinase KNS1 1 shared papers
• P antigen family member 4 1 shared papers
• Serine/threonine-protein kinase Doa 1 shared papers
• Thrombospondin-3 1 shared papers
• Dual specificity protein kinase CLK1 1 shared papers
• Homeodomain-interacting protein kinase 1 1 shared papers
• Ubiquitin-like protein 5 1 shared papers
• Protein ENTREP3 1 shared papers

Literature · 17 cited papers

• Phosphorylation-induced conformational dynamics in an intrinsically disordered protein and potential role in phenotypic heterogeneity. Proc. Natl. Acad. Sci. U.S.A. · 2017
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell survival after ionizing radiation. J. Biol. Chem. · 2010
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Heterogeneous nuclear ribonucleoprotein G regulates splice site selection by binding to CC(A/C)-rich regions in pre-mRNA. J. Biol. Chem. · 2009
• Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. Circ. Res. · 2009
• Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• An unappreciated role for RNA surveillance. Genome Biol. · 2004
• Beacon interacts with cdc2/cdc28-like kinases. Biochem. Biophys. Res. Commun. · 2003
• … and 5 more in the literature graph