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FLASH GENE
Symbol DAPK1 contributors: mct/pgu - updated : 31-08-2009
HGNC name death-associated protein kinase 1
HGNC id 2674
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal protein-kinase domain followed by a conserved calmodulin binding domain
  • eight ankyrin repeats
  • two P-loops
  • a death domain
  • a functional ROC (Ras of complex proteins) domain that mediates homo-oligomerization and GTP binding through a defined P-loop motif (GTP binding regulates its function through intramolecular signalling)
  • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • serine/threonine protein kinase family
  • ROCO family of proteins
  • CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microfilament
    basic FUNCTION
  • adhesion inhibitory effect, inducing death coupling the control of apoptosis to metastasis
  • calcium/calmodulin serine/threonine kinase, which positively mediates programmed cell death in a variety of systems
  • involved in Fas-induced extrinsic apoptosis in lymphoid cells
  • phosphorylates BECN1 on Thr 119 located at a crucial position within its BH3 domain, and thus promotes the dissociation of BECN1 from BCL2L1 and the induction of autophagy
  • phosphorylates tropomyosin-1 in response to ERK activation by hydrogen peroxide (H(2)O(2), and regulates the formation of stress fibers in response to oxidative stress
  • modulation of DAPK1 activities is critical for regulation of apoptosis and cellular homeostasis
  • phosphorylating GRIN2B and in turn enhancing the NR1/NR2B receptor channel conductance
  • 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
  • inhibits the ability of PIN1 to induce centrosome amplification and cell transformation
  • calmodulin-dependent protein kinases that are regulated by oligomerization, calmodulin binding, and autophosphorylation
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • constituent of the actin microfilament network
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • suppressing integrin activity and disrupting matrix survival signals thereby activating a p53 dependent apoptotic pathway
  • interaction with GRIN2B mediating brain damage in stroke
  • KLHL20-CUL3-RBX1 E3 ligase complex promotes DAPK1 polyubiquitination, thereby inducing the proteasomal degradation of DAPK1, and controling interferon response
  • interacting with PIN1 (phosphorylates PIN1 and inhibits its prolyl isomerase activity and cellular function)
  • interacting with UNC5B (triggers cell death through the activation of the serine-threonine protein kinase DAPK1)
  • ATF6 in association with the transcription factor CEBPB, regulates IFNG-induced expression of DAPK1
  • cell & other
    REGULATION
    repressed by HOXB7
    Other calcium Ca2+/calmodulin-regulated
    triggered by IFNG
    regulated by CEBPB (CEBPB binds to the promoter of DAPK1 and is required for the regulation of DAPK1)
    regulated by RGM/neogenin that regulates cell fate by controlling the DAPK1 activity
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    by hypermethylation in head and neck carcinomas
    tumoral     --low  
    by promoter methylation in B cell chronic lymphocytic leukemia and chronic myeloid leukemia (promoter methylation might play a significant role in the progression of CML)
    Susceptibility
  • to late-onset Alzheimer's disease
  • to chronic lymphocytic leukemia
  • Variant & Polymorphism SNP
  • significantly associated with late-onset Alzheimer's disease
  • downregulation in familial chronic lymphocytic leukemia
  • Candidate gene for sensitive detection in plasma or serum of cancer gastric, lung cancer, head and neck cancer, by DNA methylation markers
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    for the development of novel treatment regimens in chronic lymphocytic leukemia involving epigenetic therapies for gene reactivation
    ANIMAL & CELL MODELS