TLK2
Function
Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470, PubMed:9427565). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037).
Involvement in disease
Intellectual developmental disorder, autosomal dominant 57
MRD57
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD57 is characterized by delayed psychomotor development apparent in infancy or early childhood, and a variety of behavioral abnormalities. Affected individuals may have severe gastro-intestinal problems, and facial dysmorphism.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated at Ser-750, probably by CHEK1.
Autophosphorylated; phosphorylation promotes the assembly of higher order oligomers and enzymatic activity.
Sequence Similarities
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
Tissue Specificity
Detected in placenta, fetal liver, kidney, pancreas, heart and skeletal muscle (PubMed:9427565). Highly expressed in testis (PubMed:9427565, PubMed:9662073). Detected in spleen, thymus, colon, ovary, small intestine, prostate and peripheral blood leukocytes (PubMed:9662073). Almost undetectable in liver and lung (PubMed:9662073).
Cellular localization
- Nucleus
- Nucleus
- Nucleoplasm
- Cytoplasm
- Perinuclear region
- Cytoplasm
- Cytoskeleton
- Colocalizes with the cytoplasmic intermediate filament system during the G1 phase of the cell cycle (PubMed:10455159). Present in the perinuclear region at S phase and in the nucleus at late G2 (PubMed:10455159).
Alternative names
Serine/threonine-protein kinase tousled-like 2, HsHPK, PKU-alpha, Tousled-like kinase 2, TLK2