DYRK1A
DYRK1A (dual specificity tyrosine phosphorylation regulated kinase 1A, also known as DYRK1, DYRK or MNBH) is a nuclear kinase with both serine/threonine and tyrosine kinase activity. It acts in DNA repair, transcription, splicing and cell survival. Browse Assay Genie's current range of DYRK1A research reagents below, or read on for the biology behind the target.
DYRK1A is a dual-specificity kinase that phosphorylates serine/threonine and tyrosine residues. It shows a substrate preference for proline at position P+1 and arginine at position P-3. It catalyses its own autophosphorylation on serine/threonine and tyrosine residues. In the nucleus it has several roles. It supports double-strand break repair after DNA damage by phosphorylating RNF169, which increases the ability of RNF169 to block TP53BP1 accumulation at break sites and so promotes homologous recombination repair. It also positively regulates transcription as a CTD kinase, phosphorylating the C-terminal domain of the large subunit of RNA polymerase II (POLR2A).
DYRK1A also modulates alternative splicing by phosphorylating the splice factor SRSF6, and it phosphorylates SF3B1 at Thr-434, along with SEPTIN4 and SEPTIN5. It has a pro-survival function and negatively regulates apoptosis. After genotoxic stress it phosphorylates SIRT1, which inhibits p53/TP53 activity and apoptosis. It may also act in a signalling pathway that regulates nuclear functions in cell proliferation.
The DYRK1A gene encodes a member of the DYRK family, which belongs to the CMGC Ser/Thr protein kinase family and the MNB/DYRK subfamily. The protein contains a nuclear targeting signal, a protein kinase domain, a leucine zipper motif and a highly conserved run of 13 consecutive histidines. It is a homologue of the Drosophila minibrain (mnb) gene and the rat Dyrk gene, which explains the MNBH alias. The gene lies in the Down syndrome critical region of chromosome 21 and is considered a strong candidate for the learning defects associated with Down syndrome. It may also be involved in brain development. Alternative splicing produces several transcript variants that encode at least five isoforms.
DYRK1A phosphorylates RNF169 to limit TP53BP1 accumulation at double-strand breaks, promoting homologous recombination repair.
It phosphorylates the RNA polymerase II C-terminal domain, SRSF6 and SF3B1, linking one kinase to transcription and splicing control.
DYRK1A promotes survival after genotoxic stress by phosphorylating SIRT1, which inhibits p53 activity and apoptosis.
The gene sits in the Down syndrome critical region and is a candidate for learning defects and a possible contributor to brain development.
DYRK1A is a nuclear dual-specificity kinase. It phosphorylates RNF169 to aid homologous recombination repair, phosphorylates the RNA polymerase II C-terminal domain to promote transcription, modulates splicing through SRSF6, and supports cell survival by phosphorylating SIRT1 and limiting p53 activity.
DYRK1A is also called DYRK1, DYRK and MNBH, and was previously named dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A. Alternative splicing of the DYRK1A gene gives several transcript variants that encode at least five different isoforms.
DYRK1A is a homologue of Drosophila minibrain (mnb) and rat Dyrk, and mouse and rat both carry a Dyrk1a ortholog. It lies in the Down syndrome critical region of chromosome 21 and is a strong candidate gene for Down syndrome learning defects. Check the datasheet of any product for its validated reactivity.
Other DYRK family kinases, DNA repair factors, splicing regulators and survival pathway partners connected to DYRK1A.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13627; product specifications from Assay Genie datasheets.