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FLASH GENE
Symbol DYRK2 contributors: mct/npt/pgu - updated : 28-02-2018
HGNC name dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2
HGNC id 3093
Location 12q15      Physical location : 68.042.511 - 68.056.443
Synonym symbol(s) FLJ21365, FLJ21217
EC.number 2.7.12.1
DNA
TYPE functioning gene
STRUCTURE 13.93 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
2 - 6010 - 528 - 2007 17349958
3 initiation site 6159 - 601 - 2007 17349958
5' insertion
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon highly
 stomach    
Endocrinepancreas    
Lymphoid/Immunelymph node    
 thymus    
Nervousnerve   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  highly
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • functional nuclear localization signal at N-terminal domain, domain that is critical for its nuclear targeting in the apoptotic response to DNA damage
  • HOMOLOGY
    interspecies homolog to Drosophila smi35a
    intraspecies homolog to DYRK3
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • CMGC (cyclin-dependent kinases, mitogen-activated protein kinases, GSK and CDK-like kinases) family of protein kinases
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    text translocates from the cytoplasm to the nucleus in response to DNA damage
    basic FUNCTION
  • serine/threonine and tyrosine kinase, phosphorylating histone H2B
  • putatively involved in cell growth and development
  • could be novel and essential regulatory molecules for the regulation of cell fate including apoptosis
  • having an unexpected role as a scaffold for an E3 ubiquitin ligase complex, its kinase activity is required for the phosphorylation and subsequent degradation of the substrate, katanin p60
  • presumed to be involved in regulating key developmental and cellular processes such as neurogenesis, cell proliferation, cytokinesis, and cellular differentiation
  • has unexpected role as a scaffold for an E3 ubiquitin ligase complex
  • involved in the response to DNA damage through TP53 phosphorylation
  • DYRK1A, DYRK2, and DYRK4 phosphorylate distinct although overlapping sets of the 720 different peptides in the phosphosite array
  • zinc finger transcriptional repressor, and an important regulator of epithelial-mesenchymal transition (EMT)
  • is a novel negative regulator of cardiomyocyte growth
  • expression is associated with lymph node involvement and is a possible predictive factor of breast cancer recurrence
  • DYRK2 down-regulates key molecules on cell cycle control and has functions during cell division
  • DYRK2 controls neddylation and is necessary for maintaining genome stability
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with ATM (essential role for ATM in the intracellular control of DYRK2)
  • stable complex of DYRK2 with MDM2 at the nucleus (nuclear and not cytoplasmic DYRK2 is ubiquitinated by MDM2, resulting in its constitutive degradation)
  • regulates tumor progression through modulation of JUN and MYC
  • is a SIAH2 interaction partner that phosphorylates SIAH2 at five residues (Ser16, Thr26, Ser28, Ser68, and Thr119)
  • during the cell cycle, DYRK2 interacts with TERT at the G2/M phase and induces degradation
  • DYRK2-associated DDB1-UBR5-VPRBP E3 ligase inhibits telomerase by TERT degradation
  • DYRK2 regulates cancer invasion and metastasis by degrading SNAI1
  • interaction of GSK3B and its priming kinase DYRK2 regulate the activity of EIF2B in cardiac myocytes
  • post-translational regulation of NR1I2 via phosphorylation-facilitated ubiquitination by DYRK2 and UBR5
  • DYRK2 phosphorylated Ser527 of TBK1, which is essential for the recruitment of NLRP4 and for the E3 ubiquitin ligase DTX4 to degrade TBK1
  • RNF8 is a binding partner of dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2)
  • DYRK2 promotes neddylation through forming a complex with NAE1, which is a component of NEDD8-activating enzyme E1, and maintaining its protein level by suppressing polyubiquitylation
  • cell & other
    REGULATION
    activated by ATM and induces apoptosis by phosphorylating TP53 at Ser46
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification --over  
    in esophageal and lung adenocarcinoma
    tumoral     --over  
    in gastric cancer
    tumoral     --low  
    was a strong predictor of disease progression in non-small cell lung cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascular  
    could serve as a therapeutic option to regulate myocardial growth
    ANIMAL & CELL MODELS