dual specificity protein kinase CLK3; CDC-like kinase 3 (CLK3)

Function

• dual specificity protein kinase
• phosphorylates both Ser/Thr & Tyr-containing substrates
• phosphorylates Ser- & Arg-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
• role in redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution
• phosphorylates SRSF1 & SRSF3
• regulates alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells
• autophosphorylates on Ser, Thr & Tyr

Inhibition:

• leucettine L41 inhibits CLK3 kinase activity & affects regulation of alternative splicing mediated by phosphorylation of SR proteins

Structure

• belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, lammer subfamily
• contains 1 protein kinase domain

Compartment

• isoform 1:
  • nucleus, cytoplasm
  • cytoplasmic vesicle, secretory vesicle, acrosome
• isoform 2:
  • nuclear speckle
  • co localizes with Ser- & Arg-rich (SR) proteins in the nuclear speckles

Alternative splicing

• named isoforms=4
• at least one isoform lacks the kinase domain
• at least one isoform may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay

Expression

endothelial cells

More general terms

• protein kinase CLK (cdc-like kinase)
• nuclear protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1198
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1198
• OMIM: https://mirror.omim.org/entry/602990
• UniProt: http://www.uniprot.org/uniprot/P49761.html