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

More general terms

• serine/threonine kinase
• nuclear protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9874
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9874
• OMIM: https://mirror.omim.org/entry/608438
• UniProt: http://www.uniprot.org/uniprot/Q9UKI8.html