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FLASH GENE
Symbol DAPK2 contributors: mct - updated : 27-04-2017
HGNC name death-associated protein kinase 2
HGNC id 2675
Location 15q22.31      Physical location : 64.199.235 - 64.338.521
Synonym symbol(s) DRP-1
EC.number 2.7.1.37/ 2.7.11.1
DNA
TYPE functioning gene
STRUCTURE 139.29 kb     12 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
text structure
  • E2F1 and Krüppel-like factor 6 (KLF6) strongly activate the DAPK2 promoter (E2F1 and KLF6 responsive elements to a GC-rich region 5' of exon 1 containing several binding sites for KLF6 and Sp1)
    • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 2628 - 370 - 2008 18521079
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
     intestinelarge intestinecolon highly
    Reproductivefemale systembreastmammary gland  
    Respiratorylung   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticeosinophil Homo sapiens
    Blood/Hematopoieticerythroid Homo sapiens
    Blood/Hematopoieticgranulocyte Homo sapiens
    Blood/Hematopoieticneutrophil Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal protein kinase domain, kinase domain of DAPK2 that is important to maintain mitochondrial integrity and, by inference, for cellular metabolism
  • a conserved calmodulin binding kinase domain
  • a C terminal domain required for self-dimerization control of CAM binding and apoptosis
    • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to murine Dapk2
    homolog to rattus LOC503215
    Homologene
    FAMILY
  • family of proapoptotic Ca(2+)/calmodulin-regulated serine/threonine kinases
  • DAP kinase subfamily
    • CATEGORY enzyme , regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    basic FUNCTION
  • preapoptotic Ca2/calmodulin serine/threonine kinase
  • enhancing factor during granulocytic differentiation
  • role for DAPK2 in granulocyte maturation ()
  • contributes to the execution of anoikis of the non-malignant epithelial cells
  • promotes cell death partly through its effect on regulating actin cytoskeletons (
  • molecular link of DAPK to tau phosphorylation, an event associated with Alzheimer disease pathology (
  • calmodulin-dependent protein kinases that are regulated by oligomerization, calmodulin binding, and autophosphorylation
  • Ca(2+)/calmodulin-regulated serine/threonine kinase
  • is a novel regulator of migration in granulocytes
  • DAPK2 is a novel kinase of MTOR and is a potential new member of this multiprotein complex, modulating MTOR activity and autophagy levels under stress and steady-state conditions (
  • new role for DAPK2 in the regulation of mitochondrial integrity
  • Ca(2+)/calmodulin-dependent Ser/Thr kinase that possesses tumor-suppressive functions and regulates programmed cell death, autophagy, oxidative stress, hematopoiesis, and motility
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor,
    magnesium, Mg2+
    protein
  • Ca2+ calmodulin
  • phosphorylating myosin light chain (MLC)
  • E2F1 and KLF6 show cooperation in activating the DAPK2 promoter
  • novel Sp1-dependent target gene for E2F1 and KLF6 in cell death response
  • directly interacts with and phosphorylates MTOR, and has a part in suppressing MTOR activity to promote autophagy induction
  • DAPK2-induced apoptosis is negatively regulated by AKT1 and 14-3-3 proteins
  • interaction of DAPK2 with ACTN1 was localized at the plasma membrane, resulting in massive membrane blebbing and reduced cellular motility, whereas the interaction of DAPK2 with YWHAB was localized to the cytoplasm, with no impact on blebbing, motility, or viability
  • thyroid hormone promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protects hepatocytes from diethylnitrosamine (DEN)-induced hepatotoxicity or carcinogenesis
    • cell & other
    REGULATION
    activated by triggered by IFNG
    Ca2+ calmodulin dependent
    inhibited by autophosphorylated by myosin light chain (MLC)
    Phosphorylated by PRKG1 that phosphorylated DAPK2 at Ser(299), Ser(367) and Ser(368)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    silencing by methylation and histone deacetylation of the 5'CpG island in gastrointestinal malignancies
    constitutional       gain of function
    during late erythropoiesis
    tumoral     --low  
    in acute myeloid leukemia samples, whereas chronic myeloid leukemia samples in chronic phase showed intermediate expression levels
    constitutional     --low  
    associates with attenuated adipocyte autophagic clearance in obesity
    Susceptibility
    Variant & Polymorphism
    Candidate gene new candidate attenuator of stress erythropoiesis (
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    DAPK2 may be a novel target for anti-inflammatory therapies
    ANIMAL & CELL MODELS
  • DAPK(-/-) mice brain displays a reduction of tau phosphorylation and DAPK enhances the effect of MARK2 on regulating polarized neurite outgrowth