dual specificity protein kinase CLK1; CDC-like kinase 1 (CLK1, CLK)

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
• phosphorylates SRSF1, SRSF3 & PTPN1
• regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells & adenovirus E1A pre-mRNA
• regulates splicing of its own pre-mRNA according to its kinase activity
  • increased expression of the catalytically active form influences splicing to generate the catalytically inactive splicing variant lacking the kinase domain
• autophosphorylates on Ser, Thr & Tyr
• interacts with PPIG & UBL5

Inhibition:

• leucettine L41 inhibits its kinase activity & affects the regulation of alternative splicing mediated by phosphorylation of SR proteins (putative)

Structure

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

Compartment

nucleus

Alternative splicing

• named isoforms=2
• 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)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1195
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1195
• OMIM: https://mirror.omim.org/entry/601951
• UniProt: http://www.uniprot.org/uniprot/P49759.html