DYRK1A : dual specificity tyrosine phosphorylation regulated kinase 1A
Description
The DYRK1A (dual specificity tyrosine phosphorylation regulated kinase 1A) is a protein-coding gene located on chromosome 21.
The DYRK1A gene provides instructions for making an enzyme that is important in the development of the nervous system. The DYRK1A enzyme is a kinase, which means that it adds a cluster of oxygen and phosphorus atoms (a phosphate group) to other proteins through a process called phosphorylation. Phosphorylation of proteins helps to control (regulate) their activity. The proteins whose activity the DYRK1A enzyme helps regulate are involved in various processes in cells, including cell growth and division (proliferation) and the process by which cells mature to carry out specific functions (differentiation). In nerve cells (neurons), the DYRK1A enzyme is involved in the formation and maturation of dendritic spines from dendrites. Dendrites are specialized extensions from neurons that are essential for the transmission of nerve impulses. Dendritic spines are small outgrowths from dendrites that further help transmit nerve impulses and increase communication between neurons.
DYRK1A is a dual-specificity kinase, meaning it can add phosphate groups to both serine/threonine and tyrosine amino acids within proteins. This activity is essential for various cellular processes, including DNA damage repair and transcription regulation. DYRK1A preferentially targets proteins with proline at the +1 position and arginine at the -3 position relative to the phosphorylation site. Following DNA damage, DYRK1A plays a crucial role in repairing double-strand breaks (DSBs). It does this by phosphorylating RNF169, which then blocks the accumulation of TP53BP1 at the DSB site, promoting homologous recombination repair (HRR). DYRK1A also acts as a positive regulator of transcription, functioning as a CTD kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (RNAP II), specifically POLR2A. DYRK1A may participate in a signaling pathway controlling nuclear functions related to cell proliferation. It is also known to influence alternative splicing by phosphorylating the splice factor SRSF6. Furthermore, DYRK1A promotes cell survival under genotoxic stress by phosphorylating SIRT1, which in turn inhibits p53/TP53 activity and apoptosis. DYRK1A has been observed to phosphorylate SEPTIN4, SEPTIN5, and SF3B1 at Thr-434. Interactions have been reported between DYRK1A and several other proteins, including RAD54L2/ARIP4, CRY2, RANBP9, WDR68, and SIRT1. In the context of microbial infection, DYRK1A interacts with the human adenovirus 5 E1A protein.
DYRK1A is also known as DYRK, DYRK1, HP86, MNB, MNBH, MRD7.
Associated Diseases
- Intellectual disability syndrome due to a DYRK1A point mutation
- DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion
- Intellectual developmental disorder, autosomal dominant 7
- Autism spectrum disorder
