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DAPK1 Gene

protein-coding   GIFtS: 75
GCID: GC09P090112

Death-Associated Protein Kinase 1

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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Death-Associated Protein Kinase 11 2
DAPK2 3
DAP Kinase 12 3
EC 2.7.11.13 8
EC 2.7.118

External Ids:    HGNC: 26741   Entrez Gene: 16122   Ensembl: ENSG000001967307   OMIM: 6008315   UniProtKB: P533553   

Export aliases for DAPK1 gene to outside databases

Previous GC identifers: GC09P081156 GC09P081966 GC09P083667 GC09P085569 GC09P087342 GC09P089301 GC09P059938


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for DAPK1 Gene:
Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1
encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats
and 2 putative P-loop consensus sites. It is a tumor suppressor candidate. Alternative splicing results in
multiple transcript variants. (provided by RefSeq, Dec 2013)

GeneCards Summary for DAPK1 Gene:
DAPK1 (death-associated protein kinase 1) is a protein-coding gene. Diseases associated with DAPK1 include pediatric lymphoma, and central nervous system lymphoma. GO annotations related to this gene include protein kinase activity and identical protein binding. An important paralog of this gene is STK17B.

UniProtKB/Swiss-Prot: DAPK1_HUMAN, P53355
Function: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways
that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell
deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is
caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1
resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates
TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its
binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under
oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction
of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth
factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at
extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor
complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels,
resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon
interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition
Function: Isoform 2 cannot induce apoptosis but can induce membrane blebbing

summary for DAPK1 Gene:
Death associated protein kinase (DAPk) is a serine/threonine kinase involved in numerous mechanisms and
pathways linked to cell death and autophagy. Loss of expression of the gene encoding DAPk has been observed
in multiple tumor types, and it has consequently been of interest in cancer research.

Gene Wiki entry for DAPK1 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000009.12  NT_008470.20  NC_018920.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the DAPK1 gene promoter:
         AhR   AML1a   MyoD   AP-2gamma   Egr-4   Arnt   Gfi-1   AP-2beta   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 5): DAPK1 promoter sequence
   Search Chromatin IP Primers for DAPK1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat DAPK1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 9q21.33   Ensembl cytogenetic band:  9q21.33   HGNC cytogenetic band: 9q34.1

DAPK1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
DAPK1 gene location

GeneLoc information about chromosome 9         GeneLoc Exon Structure

GeneLoc location for GC09P090112:  view genomic region     (about GC identifiers)

Start:
90,112,143 bp from pter      End:
90,323,549 bp from pter
Size:
211,407 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: DAPK1_HUMAN, P53355 (See protein sequence)
Recommended Name: Death-associated protein kinase 1  
Size: 1430 amino acids; 160046 Da
Cofactor: Magnesium
Subunit: Interacts with KLHL20. Interacts (via death domain) with MAPK1 and MAPK3. Interacts with MAP1B (via
N-terminus). Interacts (via death domain) with UNC5B (via death domain). Interacts with PRKD1 in an oxidative
stress-regulated manner. Interacts with PIN1, PDCD6, BECN1, GRINB, TSC2 and STX1A. Interacts (via kinase domain)
with DAPK3 (via kinase domain)
Sequence caution: Sequence=AAP35581.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of
unknown origin in the C-terminal part; Sequence=CAA53712.1; Type=Frameshift; Positions=462, 464;
Selected PDB 3D structures from and Proteopedia for DAPK1 (see all 33):
1IG1 (3D)        1JKK (3D)        1JKL (3D)        1JKS (3D)        1JKT (3D)        1P4F (3D)    
Secondary accessions: B7ZLD2 Q14CQ7 Q1W5W0 Q68CP8 Q6ZRZ3 Q9BTL8
Alternative splicing: 3 isoforms:  P53355-1   P53355-2   P53355-3   

Explore the universe of human proteins at neXtProt for DAPK1: NX_P53355

Explore proteomics data for DAPK1 at MOPED

Post-translational modifications: 

  • Ubiquitinated by the BCR(KLHL20) E3 ubiquitin ligase complex, leading to its degradation by the proteasome1
  • Removal of the C-terminal tail of isoform 2 (corresponding to amino acids 296-337 of isoform 2) by proteolytic
    cleavage stimulates maximally its membrane-blebbing function1
  • In response to mitogenic stimulation (PMA or EGF), phosphorylated at Ser-289; phosphorylation suppresses DAPK1
    pro-apoptotic function. Autophosphorylation at Ser-308 inhibits its catalytic activity. Phosphorylation at
    Ser-734 by MAPK1 increases its catalytic activity and promotes cytoplasmic retention of MAPK1. Endoplasmic-stress
    can cause dephosphorylation at Ser-3081
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for DAPK1 (P53355) (see all 9)
     GDTKQET  IIDFGLA  IRRLLVKD  GVITYILL 


    See DAPK1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (4 alternative transcripts): 
    NP_001275658.1  NP_001275659.1  NP_001275660.1  NP_004929.2  

    ENSEMBL proteins: 
     ENSP00000350785   ENSP00000417076   ENSP00000386135   ENSP00000419026   ENSP00000417746  
     ENSP00000418885  
    Reactome Protein details: P53355

    DAPK1 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant DAPK1 Protein
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for DAPK1
    OriGene Protein Over-expression Lysate for DAPK1
    OriGene MassSpec for DAPK1
    OriGene Custom Protein Services for DAPK1
    GenScript Custom Purified and Recombinant Proteins Services for DAPK1
    Novus Biologicals DAPK1 Proteins
    Novus Biologicals DAPK1 Lysate
    Sino Biological Recombinant Protein for DAPK1
    Sino Biological Cell Lysate for DAPK1
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for DAPK1

    DAPK1 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of DAPK1
    Browse R&D Systems for Antibodies
    Cell Signaling Technology (CST) Antibodies for DAPK1 
    OriGene Antibodies for DAPK1
    OriGene Custom Antibody Services for DAPK1
    Novus Biologicals DAPK1 Antibodies
    Abcam antibodies for DAPK1
    Cloud-Clone Corp. Antibodies for DAPK1
    ThermoFisher Antibodies for DAPK1
    LSBio Antibodies in human, mouse, rat for DAPK1

    DAPK1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for DAPK1
    Browse R&D Systems for biochemical assays
    GenScript DAPK1-Activity-based Kinase Assay for Compound Screening
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for DAPK1
    Cloud-Clone Corp. CLIAs for DAPK1


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    ANKRD: Ankyrin repeat domain containing

    IUPHAR Guide to PHARMACOLOGY protein family classification: death-associated protein kinase 1
    Death-associated kinase (DAPK) family

    Selected InterPro protein domains (see all 11):
     IPR017441 Protein_kinase_ATP_BS
     IPR002290 Ser/Thr_dual-sp_kinase_dom
     IPR011029 DEATH-like_dom
     IPR011009 Kinase-like_dom
     IPR008271 Ser/Thr_kinase_AS

    Graphical View of Domain Structure for InterPro Entry P53355

    ProtoNet protein and cluster: P53355

    1 Blocks protein domain: IPB000488 Death domain

    UniProtKB/Swiss-Prot: DAPK1_HUMAN, P53355
    Domain: The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic
    and electrostatic contacts with the kinase core
    Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily
    Similarity: Contains 10 ANK repeats
    Similarity: Contains 1 death domain
    Similarity: Contains 1 protein kinase domain


    DAPK1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: DAPK1_HUMAN, P53355
    Function: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways
    that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell
    deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is
    caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1
    resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates
    TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its
    binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under
    oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction
    of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth
    factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at
    extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor
    complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels,
    resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon
    interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition
    Function: Isoform 2 cannot induce apoptosis but can induce membrane blebbing
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: Activated by Ca(2+)/calmodulin. Regulated by a locking mechanism, involving autophosphorylation
    at Ser-308 and calmodulin binding. In the inactive state, Ser-308 is phosphorylated. Activation involves its
    dephosphorylation and a release-of-autoinhibition mechanism where binding of calmodulin induces a conformational
    change that relieves the steric block of the active site by the autoinhibitory domain. Activity is modulated by
    UNC5B and NTN1. UNC5B activates it by inhibiting the phosphorylation at Ser-308, whereas NTN1 inhibits
    UNC5B-mediated activation of DAPK1. Endoplasmic-stress activates by causing Ser-308 dephosphorylation
    Induction: Up-regulated following treatment with IFNG/IFN-gamma

         Genatlas biochemistry entry for DAPK1:
    DAP kinase,160kDa,coupling the control of apoptosis to metastasis,triggered by IFNG,localized to the actin
    microfilament network

         Enzyme Numbers (IUBMB): EC 2.7.11.11 2 EC 2.7.112

         Gene Ontology (GO): Selected molecular function terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003824catalytic activity ----
    GO:0004672protein kinase activity IDA7828849
    GO:0004674protein serine/threonine kinase activity TAS16756490
    GO:0004683calmodulin-dependent protein kinase activity IDA10629061
    GO:0004713protein tyrosine kinase activity ----
         
    DAPK1 for ontologies           About GeneDecksing


    Phenotypes:
         5 GenomeRNAi human phenotypes for DAPK1:
     Decreased focal adhesion (FA)   Decreased substrate adherent c  Decreased viability with RAF26  Increased cell death in HCC-19 
     PARP inhibitor sensitization 

         4 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Dapk1):
     cellular  homeostasis/metabolism  nervous system  renal/urinary system 

    DAPK1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for DAPK1: Dapk1tm1Akc Dapk1tm1Yuk

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for DAPK1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for DAPK1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for DAPK1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for DAPK1

    miRNA
    Products:
        
    miRTarBase miRNAs that target DAPK1:
    hsa-mir-107 (MIRT006691), hsa-mir-124-3p (MIRT022627), hsa-mir-103a-3p (MIRT006690), hsa-mir-214-3p (MIRT004738)

    Block miRNA regulation of human, mouse, rat DAPK1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate DAPK1 (see all 37):
    hsa-miR-1321 hsa-let-7d hsa-miR-200a hsa-miR-16-1* hsa-miR-877* hsa-miR-141 hsa-let-7g hsa-miR-124
    SwitchGear 3'UTR luciferase reporter plasmidDAPK1 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for DAPK1
    Predesigned siRNA for gene silencing in human, mouse, rat DAPK1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for DAPK1

    Clone
    Products:
         
    OriGene clones in human, mouse for DAPK1 (see all 8)
    OriGene ORF clones in mouse, rat for DAPK1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: DAPK1 (NM_004938)
    Sino Biological Human cDNA Clone for DAPK1
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for DAPK1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat DAPK1

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for DAPK1
    Browse ESI BIO Cell Lines and PureStem Progenitors for DAPK1 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for DAPK1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    DAPK1_HUMAN, P53355: Isoform 1: Cytoplasm. Cytoplasm, cytoskeleton. Note=Colocalizes with MAP1B in the
    microtubules and cortical actin fibers
    DAPK1_HUMAN, P53355: Isoform 2: Cytoplasm. Cytoplasm, cytoskeleton
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    cytosol3
    plasma membrane3
    nucleus1
    vacuole1

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm IEA--
    GO:0015629actin cytoskeleton IDA10629061
    GO:0016020membrane ----

    DAPK1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for DAPK1 About   (see all 9)                                                                                              See pathways by source

    SuperPathContained pathways About
    1CDK-mediated phosphorylation and removal of Cdc6
    Regulation of Apoptosis0.82
    Role of DCC in regulating apoptosis0.00
    Apoptosis0.38
    2TNF Signaling
    Death Receptor Signaling0.50
    3Immune response IFN gamma signaling pathway
    IFN-gamma pathway0.43
    4TWEAK Pathway
    Apoptosis through Death Receptors0.42
    5Glioma
    Bladder cancer0.31

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for DAPK1
        Apoptosis through Death Receptors

    1 Cell Signaling Technology (CST) Pathway for DAPK1
        Apoptosis and Autophagy

    1 BioSystems Pathway for DAPK1
        IFN-gamma pathway

    1 Sino Biological Pathway for DAPK1
        Death Receptor Signaling

    1 Reactome Pathway for DAPK1
        Role of DCC in regulating apoptosis


    2 Kegg Pathways  (Kegg details for DAPK1):
        Pathways in cancer
    Bladder cancer


    DAPK1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including DAPK1 (see all 7): 
              Leukemia in human mouse rat
              p53 Signaling Pathway in human mouse rat
              Neurotoxicity in human mouse rat
              Lymphoma in human mouse rat
              Autophagy in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for DAPK1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for DAPK1 (P533551, 2, 3 ENSP000003507854) via UniProtKB, MINT, STRING, and/or I2D (see all 60)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TSC2P498152, 3, ENSP000002194764MINT-8057232 MINT-8057213 I2D: score=2 STRING: ENSP00000219476
    DAPK1P533551, 2EBI-358616,EBI-358616 MINT-7014515 MINT-8204891 MINT-8204873
    MAPK3P273611, 3, ENSP000002630254EBI-358616,EBI-73995 I2D: score=5 STRING: ENSP00000263025
    CUL3Q136182, 3, ENSP000002644144MINT-7900697 I2D: score=2 STRING: ENSP00000264414
    KLHL20Q9Y2M51, 3, ENSP000002098844EBI-358616,EBI-7904035 I2D: score=2 STRING: ENSP00000209884
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 16):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006468protein phosphorylation TAS16756490
    GO:0006915apoptotic process TAS--
    GO:0007165signal transduction ----
    GO:0008625extrinsic apoptotic signaling pathway via death domain receptors IEA--
    GO:0009103lipopolysaccharide biosynthetic process ----

    DAPK1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Compounds for DAPK1 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    (5Z)-7-OxozeaenolPotent and selective TAK1 MAPKKK inhibitor[66018-38-0]
    GSK 650394Serum- and glucocorticoid-regulated kinase (SGK) inhibitor[890842-28-1]
    IPA 3Group I p21-activated kinase (PAK) inhibitor[42521-82-4]
    CGP 57380Selective inhibitor of Mnk1[522629-08-9]
    AZ 3146Potent and selective monopolar spindle 1 (Mps1) kinase inhibitor[1124329-14-1]

    2 HMDB Compounds for DAPK1    About this table
    CompoundSynonyms CAS #PubMed Ids
    CalciumCa (see all 2)7440-70-2--
    MagnesiumMagnesium (see all 2)7439-95-4--

    3 DrugBank Compounds for DAPK1    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    5,6-Dihydro-Benzo[H]Cinnolin-3-Ylamine-- --target--17139284 17016423 10592235
    Phosphoaminophosphonic Acid-Adenylate Ester-- --target--17139284 17016423
    6-(3-AMINOPROPYL)-4,9-DIMETHYLPYRROLO[3,4-C]CARBAZOLE-1,3(2H,6H)-DIONE-- --target--10592235

    Selected Novoseek inferred chemical compound relationships for DAPK1 gene (see all 11)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    o6-methylguanine 70.4 7 12845678 (1), 19513524 (1), 19302404 (1), 15068392 (1) (see all 7)
    5-aza-2'deoxycytidine 68 12 19778817 (3), 16094112 (1), 12912953 (1), 16520653 (1) (see all 5)
    sodium bisulfite 63.9 2 17898258 (1), 18026971 (1)
    threonine 53.3 21 18583991 (1), 19878310 (1), 20206532 (1), 16204252 (1) (see all 20)
    serine 37.1 18 18583991 (1), 20206532 (1), 16204252 (1), 16476779 (1) (see all 17)
    retinoic acid 36.6 14 12845678 (1), 17285579 (1), 17696735 (1), 15797047 (1) (see all 12)
    crcs 31.4 1 16819711 (1)
    5-methylcytosine 30.3 1 12154064 (1)
    calcium 0 8 16204252 (2), 14505650 (1), 16213824 (1), 19022289 (1) (see all 5)
    methionine 0 1 15589597 (1)



    DAPK1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for DAPK1 gene (4 alternative transcripts): 
    NM_001288729.1  NM_001288730.1  NM_001288731.1  NM_004938.3  

    Unigene Cluster for DAPK1:

    Death-associated protein kinase 1
    Hs.380277  [show with all ESTs]
    Unigene Representative Sequence: NM_004938
    18 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000358077 ENST00000472284(uc004apc.3) ENST00000469067(uc004ape.3)
    ENST00000495182 ENST00000408954 ENST00000470267 ENST00000496522 ENST00000472344
    ENST00000491893(uc004apf.1) ENST00000489291 ENST00000463069 ENST00000475804
    ENST00000495281 ENST00000494010 ENST00000466188 ENST00000497743 ENST00000468482
    ENST00000469640(uc004apd.3 uc011ltg.2 uc011lth.2)

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    hsa-miR-1321 hsa-let-7d hsa-miR-200a hsa-miR-16-1* hsa-miR-877* hsa-miR-141 hsa-let-7g hsa-miR-124
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    OriGene ORF clones in mouse, rat for DAPK1
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    GenScript: all cDNA clones in your preferred vector: DAPK1 (NM_004938)
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      QuantiFast Probe-based Assays in human, mouse, rat DAPK1

    Additional mRNA sequence: 

    AB208871.1 AK127855.1 AK295119.1 AK296839.1 BC113660.1 BC143730.1 BC143733.1 BC143759.1 
    BT006935.1 CR749834.1 X76104.1 

    14 DOTS entries:

    DT.449320  DT.92433148  DT.40121399  DT.95229766  DT.75124125  DT.97813727  DT.97810796  DT.121189199 
    DT.91839838  DT.91862442  DT.97773110  DT.100658969  DT.102839048  DT.92433149 

    Selected AceView cDNA sequences (see all 217):

    AI378628 AL708910 W60210 BE302335 F04423 AI690993 AL531618 AA455493 
    CR626501 CB121221 CK904559 BM682968 T17329 AI969709 T29354 AW072599 
    AI655412 BG620709 BG413577 AI371096 BE502994 AW674416 AI679983 AW513135 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for DAPK1 (see all 8)    About this scheme

    ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^
    SP1:                    -           -     -                                                                             -                                       
    SP2:                                                                                                                                                            
    SP3:                                -     -                                                                                                                     
    SP4:                                                                                                                                                            
    SP5:                    -           -                                                                                                                           

    ExUns: 22a · 22b ^ 23 ^ 24 ^ 25 ^ 26a · 26b ^ 27a · 27b ^ 28 ^ 29
    SP1:        -     -                 -                                 
    SP2:                                                                  
    SP3:                                                                  
    SP4:                          -     -                                 
    SP5:                                                                  


    ECgene alternative splicing isoforms for DAPK1

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    DAPK1 expression in normal human tissues (normalized intensities)      DAPK1 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TAATGTTAAT
    DAPK1 Expression
    About this image


    DAPK1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Inner Cell Mass (Early Embryonic Tissues)    fully expand to see all 2 entries
             Human embryonic stem cells (family)
     
     Umbilical Cord (Extraembryonic Tissues)
             Wharton's jelly-derived stem cells
     
     Placenta (Extraembryonic Tissues)
    DAPK1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    DAPK1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.380277

    UniProtKB/Swiss-Prot: DAPK1_HUMAN, P53355
    Tissue specificity: Isoform 2 is expressed in normal intestinal tissue as well as in colorectal carcinomas

        Pathway & Disease-focused RT2 Profiler PCR Arrays including DAPK1 (see all 7): 
              Leukemia in human mouse rat
              p53 Signaling Pathway in human mouse rat
              Neurotoxicity in human mouse rat
              Lymphoma in human mouse rat
              Autophagy in human mouse rat

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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for DAPK1 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Dapk11 , 5 death associated protein kinase 11, 5 87.67(n)1
    95.1(a)1
      13 (32.53 cM)5
    696351  NM_134062.21  NP_598823.11 
     606019475 
    chicken
    (Gallus gallus)
    Aves DAPK11 death-associated protein kinase 1 78.55(n)
    90.42(a)
      431670  NM_001278031.1  NP_001264960.1 
    lizard
    (Anolis carolinensis)
    Reptilia DAPK16
    death-associated protein kinase 1
    89(a)
    1 ↔ 1
    2(40963821-41082749)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia dapk11 death-associated protein kinase 1 74.7(n)
    86.62(a)
      100144678  NM_001123439.1  NP_001116911.1 
    zebrafish
    (Danio rerio)
    Actinopterygii dapk11 death-associated protein kinase 1 68.86(n)
    74.7(a)
      558314  NM_001099990.2  NP_001093460.1 
    worm
    (Caenorhabditis elegans)
    Secernentea ZC373.43
    dapk-11
    calcium/calmodulin dependent protein
    kinase3
    dapk-11
    38(a)
    (best of 2)3
    46.21(n)1
    36.22(a)1
      X(10098022-10105019)3
    1873221  NM_058439.41  NP_490840.21 


    ENSEMBL Gene Tree for DAPK1 (if available)
    TreeFam Gene Tree for DAPK1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for DAPK1 gene
    STK17B2  DAPK22  MYLK22  TTN2  STK17A2  MYLK32  OBSCN2  DAPK32  
    SPEG2  MYLK42  MYLK2  
    Selected SIMAP similar genes for DAPK1 using alignment to 5 protein entries:     DAPK1_HUMAN (see all proteins) (see all similar genes):
    DAPK3    DAPK2    STK17A    BRSK2    RPS6KA4    STK17B
    MYLK4    NUAK1    PRKAA1    PHKG2    KIAA0999    MARK4
    STK36    RPS6KA1    CAMKV    PNCK    SIK3    STK32A

    DAPK1 for paralogs           About GeneDecksing


    1 Pseudogenes.org Pseudogene for DAPK1
    PGOHUM00000236238


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for DAPK1 (see all 4968)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 9 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs108686121,2
    C,F,A--59958546(+) TTTTGG/TATTTT 1 -- int14Minor allele frequency- T:0.25NA CSA 8
    rs341665751,2
    C--59959800(+) GGATT-/GGGGCT 1 -- int10--------
    rs2005281401,2
    C--59974371(-) CAAAAA/TTAAAA 1 -- int10--------
    rs736544661,2
    C--60062070(+) TTTTTT/ATTTCT 1 -- int11Minor allele frequency- A:0.50WA 2
    rs2009792551,2
    --60108695(+) GGGGG-/GTCACTG 1 -- int10--------
    rs713547791,2
    C--60113885(+) AAAAA-/A/AA  
            
    GTAGT
    1 -- int11NA 2
    rs1138486901,2
    F--60115253(+) CACACC/ACCCTT 1 -- int11Minor allele frequency- A:0.00CSA 1
    rs105970201,2
    C--60142818(+) AGTCT-/GTTA  
            
    GTTTG
    1 -- int11Minor allele frequency- GTTA:0.00CSA 2
    rs19649111,2
    C,F,A,H--89990243(-) ATCCTA/CGTCTT 1 -- us2k121Minor allele frequency- C:0.43NS EA NA WA CSA 2342
    rs1888904991,2
    --89990311(+) GAGGAA/TCACCT 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for DAPK1 (90112143 - 90323549 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for DAPK1 (see all 15):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv1345777CNV Deletion17803354
    esv1024641CNV Deletion17803354
    esv1463209CNV Deletion17803354
    esv2738709CNV Deletion23290073
    esv1009206CNV Deletion20482838
    esv2738708CNV Deletion23290073
    esv28714CNV Loss19812545
    esv21629CNV Loss19812545
    nsv893546CNV Gain21882294
    nsv893548CNV Gain21882294

    Human Gene Mutation Database (HGMD): DAPK1
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing DAPK1
    DNA2.0 Custom Variant and Variant Library Synthesis for DAPK1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600831    OMIM disorders: --

    Selected diseases for DAPK1 (see all 80):    About MalaCards
    pediatric lymphoma    central nervous system lymphoma    choroid plexus papilloma    cervical squamous cell carcinoma
    lichen sclerosus    h. pylori infection    adenoiditis    silicosis
    ependymoma    cervicitis    cervical adenocarcinoma    kidney cancer
    malt lymphoma    choroiditis    thyroid cancer    pilocytic astrocytoma
    familial adenomatous polyposis    endometrial adenocarcinoma    bladder carcinoma    nasopharyngitis

    1 disease from the University of Copenhagen DISEASES database for DAPK1:
    Carcinoma

    DAPK1 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for DAPK1 gene (see all 56)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tumors 59.8 161 16476779 (6), 15099958 (4), 16094112 (4), 17803936 (3) (see all 79)
    cancer 54.8 39 19878310 (3), 16256792 (2), 16142356 (2), 16928264 (2) (see all 23)
    nsclc 51.9 30 19926549 (3), 19795445 (3), 19653236 (2), 15797047 (2) (see all 13)
    bladder cancer 48 14 19778817 (5), 11839665 (2), 15569975 (2), 18070176 (1) (see all 6)
    cervical cancer 47.9 29 18425396 (5), 18799028 (4), 16803511 (4), 16928264 (3) (see all 12)
    primary tumor 47.5 5 12684406 (2), 17570703 (1), 11309270 (1), 12684420 (1)
    cervical squamous cell carcinoma 45.8 3 18799028 (1), 16142356 (1)
    carcinoma squamous cell 41.2 6 19926549 (1), 15099958 (1), 16142356 (1), 11448914 (1) (see all 6)
    cancer lung 40 25 20360646 (6), 12912953 (4), 19781081 (2), 15709192 (1) (see all 10)
    pleural effusion malignant 37.1 4 17285579 (1), 17696735 (1)

    Genetic Association Database (GAD): DAPK1
    Human Genome Epidemiology (HuGE) Navigator: DAPK1 (14 documents)

    Export disorders for DAPK1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for DAPK1 gene, integrated from 10 sources (see all 382):
    (articles sorted by number of sources associating them with DAPK1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses. (PubMed id 20389280)1, 2, 9 Lee Y.R.... Chen R.H. (EMBO J. 2010)
    2. Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK. (PubMed id 15616583)1, 2, 9 Chen C.H....Chen R.H. (EMBO J. 2005)
    3. Control of death-associated protein kinase (DAPK) activity by phosphorylation and proteasomal degradation. (PubMed id 17056602)1, 2, 9 Jin Y.... Gallagher P.J. (J. Biol. Chem. 2006)
    4. An alternative transcript from the death-associated protein kinase 1 locus encoding a small protein selectively mediates membrane blebbing. (PubMed id 18422656)1, 2, 9 Lin Y.... Hupp T. (FEBS J. 2008)
    5. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. (PubMed id 16213824)1, 2, 9 Anjum R.... Blenis J. (Curr. Biol. 2005)
    6. DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. (PubMed id 19180116)1, 2, 9 Zalckvar E.... Kimchi A. (EMBO Rep. 2009)
    7. DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. (PubMed id 18995835)1, 2, 9 Mukhopadhyay R.... Fox P.L. (Mol. Cell 2008)
    8. A genome-wide association study identifies four genetic markers for hematological toxicities in cancer patients receiving gemcitabine therapy. (PubMed id 22293537)1, 4 Kiyotani K....Zembutsu H. (Pharmacogenet. Genomics 2012)
    9. Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function. (PubMed id 21497122)1, 2 Lee T.H.... Lu K.P. (Mol. Cell 2011)
    10. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (Mol. Med. 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 1612 HGNC: 2674 AceView: DAPK1 Ensembl:ENSG00000196730 euGenes: HUgn1612
    ECgene: DAPK1 Kegg: 1612 H-InvDB: DAPK1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for DAPK1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for DAPK1 Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPshttp://egp.gs.washington.edu/data/dapk1/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for DAPK1 gene:
    Search GeneIP for patents involving DAPK1

    Licensable Technologies for DAPK1 gene:
    Weizmann Institute:DAP Kinase Gene Family: A Novel Target for Treatment of Neurodegenerative Disorders and Cancer    (see all 2)
    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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