DYRK1A

Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the "DYRK1A" gene. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode at least five different isoforms.
Function.
DYRK1A is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. This member contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and a highly conservative 13-consecutive-histidine repeat. It catalyzes its autophosphorylation on serine/threonine and tyrosine residues. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. This gene is a homolog of Drosophila mnb (minibrain) gene and rat Dyrk gene.
Dyrk1a has also been shown to modulate plasma homocysteine level in a mouse model of overexpression.
Clinical significance.
DYRK1A is localized in the Down syndrome critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome. In addition, a polymorphism (SNP) in "DYRK1A" was found to be associated with HIV-1 replication in monocyte-derived macrophages, as well as with slower progression to AIDS in two independent cohorts of HIV-1-infected individuals. Mutations in DYRK1A are also associated with Autism spectrum disorder.
Interactions.
DYRK1A has been shown to interact with WDR68. The computational methodologies revealed a unique mechanism of active site binding. The binding interactions within the active site showed that the chosen molecules (Ligand15, Ligand14, and Ligand11) had notable interactions than the co-crystallized molecule 2C3, which could led to the generation of potential compounds to inhibit DYRK1A. 