TLK1

TLK1 is rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by faciliting the repair of DSBs. In vitro, TLK1 phosphorylates histone H3 at 'Ser-10'.

TLK1 Related Areas

Enzyme>>Protein Kinase>>Intracellular Kinase>>TLK1

Signal Transduction>>Protein Kinase>>Intracellular Kinase>>TLK1

TLK1 Alternative Names

TLK1, KIAA0137, PKU-beta [Homo sapiens]

Tlk1, RP23-428O15.2, 4930545J15Rik [Mus musculus]

Summaries for TLK1

Entrez Gene summary for TLK1:

The protein encoded by TLK1 gene is a serine/threonine kinase that may be involved in the regulation of chromatin assembly. The encoded protein is only active when it is phosphorylated, and this phosphorylation is cell cycle-dependent, with the maximal activity of this protein coming during S phase. The catalytic activity of this protein is diminished by DNA damage and by blockage of DNA replication. Three transcript variants encoding different isoforms have been found for TLK1 gene. [provided by RefSeq, Nov 2011]

OMIM - description for TLK1:

The Tousled-like kinases, first described in Arabidopsis, are nuclear serine/threonine kinases that are potentially involved in the regulation of chromatin assembly.

Wikipedia summary for TLK1:

Serine/threonine-protein kinase tousled-like 1 is an enzyme that in humans is encoded by the TLK1 gene.
The Tousled-like kinases, first described in Arabadopsis, are nuclear serine/threonine kinases that are potentially involved in the regulation of chromatin assembly.[supplied by OMIM]

Human TLK1 Protein General Information

 

• Protein names: Tousled-like kinase 1
  Short name=TLK1
• Sequence length: 766 AA.
• Domain: Coiled coil
• Sequence similarities: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
  Contains 1 protein kinase domain.
• Enzyme regulation: Cell-cycle regulated, maximal activity in S-phase. Inactivated by phosphorylation at Ser-743, potentially by CHEK1.
• Subunit structure: Heterodimerizes with TLK2. Interacts with ASF1A and ASF1B.
• Subcellular location: Nucleus
• Tissue specificity: Widely expressed. Present in fetal placenta, liver, kidney and pancreas but not heart or skeletal muscle. Also found in adult cell lines. Isoform 3 is ubiquitously expressed in all tissues examined.
• Cofactor: Magnesium.
• Catalytic activity: ATP + a protein = ADP + a phosphoprotein.
• Sequence caution: The sequence AAF03094.1 differs from that shown. Reason: Erroneous initiation.
  The sequence BAA09486.2 differs from that shown. Reason: Erroneous initiation.

General information above from UniProt

Function for TLK1 Protein

UniProtKB:

TLK1 is rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by faciliting the repair of DSBs. In vitro, TLK1 phosphorylates histone H3 at 'Ser-10'.

Genatlas:

• TLK1 is potentially involved in the regulation of chromatin assembly
• TLK1 might participate in diverse biologic functions like cell growth and differentiation, pre-mRNA splicing, and transcriptional coactivation (Kodym 2005)
• TLK1 cooperates with Aurora kinase to regulate spindle assembly and chromosome segregation (Li (2007)
• TLK1 plays important roles in DNA repair, not only by modulation of chromatin assembly via ASF1A, but also by a more direct function in processing the ends of a DSB via interaction with Rad9 (Canfield 2009)
• TLK1 is involved in chromatin dynamics, including DNA replication and repair, transcription, and chromosome segregation (De Benedetti 2010)
• TLK1 mediates chromatin assembly in conjunction with ASF1A, ASF1B regardless of its kinase activity (De Benedetti 2010)

Homology for human TLK1

• homolog to Arabidopsis thaliana