This entry represents the serine/threonine-protein kinase TOUSLED- like 2 (TLK2) protein (). TLK2 is involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation. It phosphorylates the chromatin assembly factors ASF1A AND ASF1B. Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly. It acts as a negative regulator of amino acid starvation-induced autophagy [].
The HirA B (Histone regulatory homologue A binding) motif is the essential binding interface between and ASF1a, of approx. 40 residues. It forms an antiparallel β-hairpin that binds perpendicular to the strands of the β-sandwich of ASF1a N-terminal core domain, via β-sheet, salt bridge and van der Waals interactions []. The two histone chaperone proteins, HIRA and ASF1a, form a heterodimer with histones H3 and H4. HIRA is the human orthologue of Hir proteins known to silence histone gene expression and create transcriptionally silent heterochromatin in yeast, flies, plants and humans. The HIR complex is composed of HIR1, HIR2, HIR3 and HPC2, and interacts with ASF1. The HIR complex cooperates with ASF1 to promote replication-independent chromatin assembly. The HIR complex is also required for the periodic repression of three of the four histone gene loci during cell cycle as well as for autogenous regulation of the HTA1-HTB1 locus by H2A and H2B. DNA-binding by the HIR complex may repress transcription by inhibiting nucleosome remodeling by the SWI/SNF complex. The HIR complex may also be required for transcriptional silencing of centromeric, telomeric and mating-type loci in the absence of CAF-1.
