Dual specificity tyrosine-phosphorylation-regulated kinase 1A (EC 2.7.12.2; UniProt Q63470; also known as Dual specificity YAK1-related kinase, MNBH, Protein kinase minibrain homolog, RP86) is encoded by the Dyrk1a (also known as Dyrk) gene (Gene ID 25255) in rat species. DYRK1A belongs to a family of conserved dual-specificity tyrosine-phosphorylated and regulated kinases (DYRKs) within the CMGC (CDK, MAPK, GSK, and CLK) group of eukaryote kinome. DYRK family members share a conserved kinase domain and an adjacent DYRK-homology domain or DH-box (DDDNXDY), wihile differing in their N- and C-terminal regions. DYRK1A is regulated by autophosphorylation on Ser, Thr and Tyr residues, but catalyzes phosphorylation of a broad-range of substrates only on Ser/Thr residues within the RPX(S/T)P motif with a preference for Pro at the +1 position (X). Known DYRK1A substrates include transcription factors (e.g. FKHR, CREB, Gli1, NFAT), splicing factors (e.g. cycling L2, SF3b/SAP155), glycogen synthase, as well as multiple proteins engaged in endocytosis in neurons, including dynamin and synaptojanin 1. DYRK1A is also implicated in promoting the formation of neurotoxic Aβ peptides by phosphorylating APP and presenilin-1. Human DYRK1A gene is located in the Down syndrome critical region of chromosome 21 and the protein plays an essential role in the development of the central nervous system. DYRK1A haploinsufficiency and mutations are the causes of intellectual disability (ID), microcephaly and dysmorphic features in human, while transgenic mice carrying extra copies of the gene exhibit learning defects and motor abnormalities.
Synonyms: Dual specificity tyrosine-phosphorylation-regulated kinase 1A
Application: Research CategoryNeuroscience
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