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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
General
nuclear protein
protein kinase CLK (cdc-like kinase)
Properties
SIZE: entity length = 638 aa
MW = 74 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: Tyr phosphorylation site {Y155}
Ser phosphorylation site {S157}
arginine-rich region {167-264}
MOTIF: arginine residue (SEVERAL)
Ser phosphorylation site {S197}
Ser phosphorylation site {S199}
Ser phosphorylation site {S215}
Ser phosphorylation site {S224}
Ser phosphorylation site {S226}
Ser phosphorylation site {S283}
kinase domain
SITE: 304-620
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 310-318
ATP-binding site
NAME: ATP-binding site
SITE: 334-334
aspartate residue {D431}
STATE: active state
Database Correlations
OMIM 602990
UniProt P49761
Pfam PF00069
Entrez Gene 1198
Kegg hsa:1198
ENZYME 2.7.12.1
References
UniProt :accession P49761