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Symbol DYRK1A contributors: mct/pg/shn - updated : 25-01-2022
HGNC name dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
HGNC id 3091
Corresponding disease
DEL21QD chromosome 21q deletion, including the APP-SOD1 region
MRD7 mental retardation, autosomal dominant 7
TRI21 trisomy 21
Location 21q22.13      Physical location : 38.739.858 - 38.887.678
Synonym name
  • dual specificity YAK1-related kinase
  • dual specificity tyrosine-phosphorylation-regulated kinase 1A
  • minibrain (Drosophila) homolog
  • protein kinase minibrain homolog
  • serine/threonine kinase MNB
  • serine/threonine-specific protein kinase
  • mnb protein kinase homolog hp86
  • MNB/DYRK protein kinase
  • dual-specificity tyrosine-Y-phosphorylation regulated kinase, EC 2.7.19
  • Synonym symbol(s) MNB, MNBH, DYRK1, DYRK, HP86, MRD7
    TYPE functioning gene
    STRUCTURE 160.79 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   HRE
    text structure
  • REST can activate DYRK1A transcription via a neuron-restrictive silencer element at bp &
  • 8722;833 to &
    8722;815 of the promoter
    MAPPING cloned Y linked N status confirmed
    Map cen - D21S1900 - D21S1919 - DYRK1A - D21S1917 - D21S259 - qter
    Authors PMID: 10329007
    regionally located located in the Down syndrome critical region (DCR)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 splicing 5212 85.5 763 - 1998 9784410
    13 splicing 5517 66 584 - 1998 9784410
  • being alternatively spliced in the 5' region and in the 3' part of the coding region compared to variant 1
  • lacking the poly-His domain
  • MNBH, isoform 1, 2, 3, 4 differing by C termini
  • 11 splicing 6580 84.4 754 - 1998 9784410
  • being alternatively spliced in the 5' region and in an internal region of the coding sequence compared to variant 1
  • 10 splicing 5088 60.2 529 - 1998 9784410
  • lacking a 3' coding exon compared to variant 1
  • lacking the poly-His domain
  • 12 - 16281 - 754 - 1998 9784410
    12 - 17024 - 754 - 1998 9784410
    11 - 16938 - 725 - 1998 9784410
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately Homo sapiens
    Digestiveintestinelarge intestinecolon highly Homo sapiens
     liver   lowly Mus musculus
     liver   moderately Homo sapiens
    Endocrineadrenal gland   lowly Mus musculus
     pancreas   lowly Homo sapiens
    Nervousbraindiencephalonamygdala highly Homo sapiens
     brainmidbrainsubstantia nigra lowly Homo sapiens
     brainforebraincerebral cortex moderately Homo sapiens
     brainbasal nucleicorpus callosum moderately Homo sapiens
     brain   highly Homo sapiens
    Reproductivefemale systembreast  lowly Homo sapiens
    Respiratorylung   lowly Mus musculus
     lung   moderately Homo sapiens
    Urinarykidney   highly Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatum  highly Mus musculus
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentkeratinocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period embryo, fetal
    Text brain, liver, lung, heart
  • N-terminal domain, but not the catalytic kinase domain or the C-terminal domain of DYRK1A, was responsible for the WDR68 binding
  • nuclear targeting sequence
  • a putative leucine zipper motif
  • a conserved histidine repeat (13 residues)
  • conjugated PhosphoP
    interspecies ortholog to Dyrk1a, Rattus norvegicus
    ortholog to Dyrk1a, Mus musculus
    ortholog to DYRK1A, Pan troglodytes
    ortholog to dyrk1a, Danio rerio
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • MNB/DYRK subfamily
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
  • coexpressed with Notch in various tissues during embryonic development
  • predominantly localized to the nucleus
  • localizes to mitotic spindles
  • basic FUNCTION
  • serine/threonine and tyrosine kinase involved in post-embryonic neurogenesis
  • putatively involved in cell growth and development
  • playing a role in controlling motor function and may be implicated in Down syndrome motor dysfunction
  • involved in the signaling mechanisms that regulate dendrite differentiation
  • involved with RCAN1 in the cooperative destabilization of a regulatory circuit, leading to reduced NFATc activity
  • may play a role in a signaling pathway regulating nuclear functions of cell proliferaration
  • could be responsible for learning and memory deterioration in Down syndrome and of memory impairment in ALzheimer disease
  • playing a physiological role in the hyperphosphorylation of Tau responsible of insoluble deposits in Alzheimer disease
  • playing an important, but diverse from developmental role in adult central nervous system
  • inhibiting the expression of REST(a key regulator of pluripotency and neuronal differentiation), an alteration that persists in trisomy 21 from undifferentiated embryonic stem (ES) cells to adult brain (deregulation of REST is a very early pathological consequence of trisomy 21 with potential to disturb the development of all embryonic lineages)
  • negative regulator of the intrinsic apoptotic pathway in the developing retina (phosphorylates caspase-9 on threonine residue 125, and this phosphorylation event is crucial to protect retina cells from apoptotic cell death)
  • positively regulates FGF-mitogen-activated protein kinase signaling by phosphorylation-dependent impairment of the inhibitory activity of SPRY2
  • might modulate the hypertrophic response of cardiomyocytes
  • promotes cell survival through phosphorylation and activation of SIRT1 with DYRK3
  • role in controlling synaptic vesicle recycling processes
  • role of DYRK1A in the regulation of neurite formation
  • DYRK1A, DYRK2, and DYRK4 phosphorylate distinct although overlapping sets of the 720 different peptides in the phosphosite array
  • DYRK1A and REST are closely related in neurodevelopment
  • DYRK1A, DYRK3, DYRK4 implicated in the regulation of cytoskeletal organization and process outgrowth in neurons
  • plays a role in many cellular pathways through phosphorylation of diverse substrate proteins
  • implication of DYRK1A overexpression in a developmental alteration of the central nervous system associated with Down syndrome (DS), thereby providing insights into the aetiology of neurosensorial dysfunction in a complex disease
  • DYRK1A controls the transition from proliferation to quiescence during lymphoid development by destabilizing CCND3
  • dose-specific DYRK1A expression and activity appears to be critical for the hyperplastic and hypertrophic growth of the developing heart
  • DYRK1A expression decreases cell survival efficiency in response to DNA damage, suggesting a tumor suppressive role for this kinase
  • is important for both kidney development and function
  • dual kinase that can phosphorylate its own activation loop on tyrosine residue and phosphorylate its substrates on threonine and serine residues
  • DYRK1A and CEP97 coordinate with PLK1 to promote Separase function to properly form multicilia in multiciliated cells (MCCs)
  • involved in many biological processes during development and in adulthood
  • plays a role in major developmental steps of brain development, controlling the proliferation of neural progenitors, the migration of neurons, their dendritogenesis and the function of the synapse
    a component
  • autophosphorylated
    small molecule nucleotide,
  • ATP
  • protein
  • cyclin L2
  • 14-3-3 protein
  • phytanoyl-CoA alpha-hydroxylase associated protein 1, PAHX-AP1
  • SF3B1
  • SPRY2
  • REST/NRSF-SWI/SNF chromatin remodelling complex
  • dynamin 1, endophilin 1
  • SPRED1 and SPRED2
  • DCAF7
  • DYRK1A binds specifically to DCAF7 in cells, and the binding, but not the phosphorylation event, induces the nuclear translocation of DCAF7 5)
  • RCAN1
  • DYRK1A interacts with and phosphorylates STXBP1 at the Thr(479) residue,linking STXBP1 and DYRK1A in synaptic vesicle trafficking and amyloid precursor protein processing
  • DYRK1A restrains CCND3 protein levels by phosphorylating T283 to induce its degradation
  • regulatory role of DYRK1A in controlling MAPT and SNCA
  • DYRK1A may also down-regulate CIC in human cells
  • DYRK1A is a positive kinase in regulation of NFATC1
  • DYRK1A functions in enhancer regulation by interacting with EP300/CREBBP and modulating their activity
  • DYRK1A might be a regulator of MEF2D transcriptional activity and indirectly get involved in regulation of MEF2D target genes
  • DYRK1A activates NFATC1 to increase glioblastoma migration
  • CEP97 interacts with DYRK1A to modulate multiciliogenesis
  • cell & other
    inhibited by RANBP9
    repressed by TFAP4/GMNN complex
    corresponding disease(s) TRI21 , DEL21QD , MRD7
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    significantly elevated in hippocampus of patients with Alzheimer
    constitutional   deletion    
    haploinsufficiency causative for microcephaly observed in partial monosomy 21
    constitutional     --other  
    DYRK1A dosage imbalance perturbs REST levels with decreased REST expression in embryonic neurons and increased expression in adult neurons
    constitutional     --over  
    contributes to neurofibrillary degeneration in Down syndrome more significantly than in subjects with two copies of the DYRK1A gene and sporadic Alzheimer disease)
    constitutional     --over  
    as in Down syndrome could lead to neurofibrillary degeneration by shifting the alternative splicing of MAPT exon 10 to an increase in the ratio of 3R-tau/4R-tau
    tumoral     --over  
    in glioma and glioblastoma cells, and its expression was positively correlated with that of NFATC1
    tumoral     --over  
    in pancreatic ductal adenocarcinoma (PDAC)
    Variant & Polymorphism
    Candidate gene for mental retardation in Down syndrome through deregulation of REST
    Therapy target
    mental retardationtrisomy 
    DYRK1A inhibitor has been proposed as a novel drug to address learning and memory deficit in Down syndrome
    targeting DYRK1A is a potential strategy for management of neurodegenerative disorders
    targeting DYRK1A as a potential strategy for management of cancer
    pharmacological inhibition of DYRK1A by polypeptides could represent a promising therapeutic intervention for GBM
    small molecule inhibition of DYRK1A could thus represent an interesting approach toward the treatment of Alzheimer's and other neurodegenerative disease
    inhibition of DYRK1A could represent a novel therapeutic target for PDAC
  • Dyrk1A Mutant Drosophila minibrain flies have a reduction in both optic lobes and central brain, showing learning deficits and hypoactivity
  • mice overexpressing the full-length cDNA of Dyrk1A exhibit delayed cranio-caudal maturation with functional consequences in neuromotor development, altered motor skill acquisition and hyperactivity, a significant impairment in spatial learning and cognitive flexibility, hippocampal and prefrontal cortex dysfunction
  • Dyrk1A(-/-) mice have a general growth delay and die during midgestation and Dyrk1A(+/-) mice show decreased neonatal viability and a significant body size reduction from birth to adulthood
  • Dyrk1a overexpression in primary mouse cortical neurons induced severe reduction of the dendritic growth and dendritic complexity
  • increased expression of phospho-Thr(192)-RCAN1 was observed in the brains of transgenic mice overexpressing the Dyrk1A protein
  • normalizing Dyrk1A gene expression in the striatum of adult TgDyrk1A mice, by means of AAVshRNA, clearly reverses motor impairment