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serine/threonine protein kinase tousled-like 1; PKU-beta; Tousled-like kinase 1 (TLK1, KIAA0137)
Function:
- rapidly & transiently inhibited by phosphorylation following generation of DNA double-stranded breaks during S-phase
- this is cell cycle checkpoint & ATM-pathway dependent & appears to regulate processes involved in chromatin assembly
- isoform 3
- phosphorylates & enhances stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin
- protects cells from ionizing radiation by faciliting repair of DNA double-stranded breaks
- in vitro, phosphorylates histone H3 at Ser-10
- cell-cycle regulated, maximal activity in S-phase
- inactivated by phosphorylation at Ser-743, potentially by CHK1
- heterodimerizes with TLK2
- interacts with ASF1A & ASF1B
Cofactor: Mg+2
Structure:
- belongs to the protein kinase superfamily, Ser/Thr protein kinase family
- contains 1 protein kinase domain
Compartment: nucleus
Alternative splicing: named isoforms=3
Expression:
- widely expressed
- present in fetal placenta, liver, kidney & pancreas but not heart or skeletal muscle
- also found in adult cell lines
- isoform 3 is ubiquitously expressed in all tissues examined
General
nuclear protein
serine/threonine kinase
Properties
SIZE: entity length = 766 aa
MW = 87 kD
COMPARTMENT: cell nucleus
MOTIF: Ser phosphorylation site {S74}
Thr phosphorylation site {T75}
Ser phosphorylation site {S77}
Thr phosphorylation site {T78}
Ser phosphorylation site {S80}
Ser phosphorylation site {S133}
Ser phosphorylation site {S138}
Ser phosphorylation site {S158}
Ser phosphorylation site {S159}
Thr phosphorylation site {T179}
Ser phosphorylation site {S190}
coiled coil {230-281}
coiled coil {397-445}
kinase domain
SITE: 456-734
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 462-470
ATP-binding site
NAME: ATP-binding site
SITE: 485-485
aspartate residue {D586}
Ser phosphorylation site {S741}
Ser phosphorylation site {S743}
STATE: active state
Database Correlations
OMIM 608438
UniProt Q9UKI8
Pfam PF00069
Entrez Gene 9874
Kegg hsa:9874
ENZYME 2.7.11.1
References
UniProt :accession Q9UKI8