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Aliases for DAPK1 Gene

Aliases for DAPK1 Gene

  • Death-Associated Protein Kinase 1 2 3
  • DAP Kinase 1 3 4
  • EC 2.7.11.1 4 63
  • DAPK 3 4
  • EC 2.7.11 63

External Ids for DAPK1 Gene

Summaries for DAPK1 Gene

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. Among its related pathways are Pathways in cancer and Glioma. GO annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is MYLK4.

UniProtKB/Swiss-Prot for DAPK1 Gene

  • 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

  • Isoform 2 cannot induce apoptosis but can induce membrane blebbing

Tocris 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

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for DAPK1 Gene

Genomics for DAPK1 Gene

Genomic Location for DAPK1 Gene

Start:
87,497,228 bp from pter
End:
87,708,651 bp from pter
Size:
211,424 bases
Orientation:
Plus strand

Genomic View for DAPK1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for DAPK1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DAPK1 Gene

Regulatory Elements for DAPK1 Gene

Proteins for DAPK1 Gene

  • Protein details for DAPK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P53355-DAPK1_HUMAN
    Recommended name:
    Death-associated protein kinase 1
    Protein Accession:
    P53355
    Secondary Accessions:
    • B7ZLD2
    • B7ZLE7
    • Q14CQ7
    • Q1W5W0
    • Q68CP8
    • Q6ZRZ3
    • Q9BTL8

    Protein attributes for DAPK1 Gene

    Size:
    1430 amino acids
    Molecular mass:
    160046 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • 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).
    SequenceCaution:
    • Sequence=AAP35581.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305}; Sequence=CAA53712.1; Type=Frameshift; Positions=462, 464; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for DAPK1 Gene

    Alternative splice isoforms for DAPK1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DAPK1 Gene

Proteomics data for DAPK1 Gene at MOPED

Post-translational modifications for DAPK1 Gene

  • 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-308.
  • 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 function.
  • Ubiquitinated by the BCR(KLHL20) E3 ubiquitin ligase complex, leading to its degradation by the proteasome.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for DAPK1 Gene

Domains for DAPK1 Gene

Gene Families for DAPK1 Gene

HGNC:
  • ANKRD :Ankyrin repeat domain containing
IUPHAR :

Suggested Antigen Peptide Sequences for DAPK1 Gene

Graphical View of Domain Structure for InterPro Entry

P53355

UniProtKB/Swiss-Prot:

DAPK1_HUMAN
Domain:
  • The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core:
    • P53355
  • Contains 1 death domain.:
    • P53355
  • Contains 1 protein kinase domain.:
    • P53355
  • Contains 1 Roc domain.:
    • P53355
Family:
  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.:
    • P53355
Similarity:
  • Contains 10 ANK repeats.:
    • P53355
genes like me logo Genes that share domains with DAPK1: view

Function for DAPK1 Gene

Molecular function for DAPK1 Gene

GENATLAS Biochemistry: DAP kinase,160kDa,coupling the control of apoptosis to metastasis,triggered by IFNG,localized to the actin microfilament network
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: 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.
UniProtKB/Swiss-Prot 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
UniProtKB/Swiss-Prot Function: Isoform 2 cannot induce apoptosis but can induce membrane blebbing
UniProtKB/Swiss-Prot Induction: Up-regulated following treatment with IFNG/IFN-gamma.

Enzyme Numbers (IUBMB) for DAPK1 Gene

Gene Ontology (GO) - Molecular Function for DAPK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003824 catalytic activity --
GO:0004672 protein kinase activity IDA 12730201
GO:0004674 protein serine/threonine kinase activity TAS 16756490
GO:0004683 calmodulin-dependent protein kinase activity IDA 10629061
GO:0004713 protein tyrosine kinase activity --
genes like me logo Genes that share ontologies with DAPK1: view
genes like me logo Genes that share phenotypes with DAPK1: view

Animal Models for DAPK1 Gene

MGI Knock Outs for DAPK1:

miRNA for DAPK1 Gene

No data available for Transcription Factor Targeting and HOMER Transcription for DAPK1 Gene

Localization for DAPK1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DAPK1 Gene

Isoform 1: Cytoplasm. Cytoplasm, cytoskeleton. Note=Colocalizes with MAP1B in the microtubules and cortical actin fibers.
Isoform 2: Cytoplasm. Cytoplasm, cytoskeleton.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for DAPK1 Gene COMPARTMENTS Subcellular localization image for DAPK1 gene
Compartment Confidence
cytoskeleton 5
cytosol 3
plasma membrane 3
nucleus 1
vacuole 1

Gene Ontology (GO) - Cellular Components for DAPK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 12730201
GO:0005886 plasma membrane IDA 12730201
GO:0015629 actin cytoskeleton IDA 10629061
GO:0016020 membrane --
genes like me logo Genes that share ontologies with DAPK1: view

Pathways for DAPK1 Gene

genes like me logo Genes that share pathways with DAPK1: view

Pathways by source for DAPK1 Gene

1 Sino Biological pathway for DAPK1 Gene
1 Qiagen pathway for DAPK1 Gene
1 Cell Signaling Technology pathway for DAPK1 Gene
1 BioSystems pathway for DAPK1 Gene
2 KEGG pathways for DAPK1 Gene

Gene Ontology (GO) - Biological Process for DAPK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation TAS 16756490
GO:0006915 apoptotic process TAS --
GO:0007165 signal transduction --
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors IEA --
GO:0009103 lipopolysaccharide biosynthetic process --
genes like me logo Genes that share ontologies with DAPK1: view

Compounds for DAPK1 Gene

(5) Tocris Compounds for DAPK1 Gene

Compound Action Cas Number
(5Z)-7-Oxozeaenol Potent and selective TAK1 MAPKKK inhibitor [66018-38-0]
AZ 3146 Potent and selective monopolar spindle 1 (Mps1) kinase inhibitor [1124329-14-1]
CGP 57380 Selective inhibitor of Mnk1 [522629-08-9]
GSK 650394 Serum- and glucocorticoid-regulated kinase (SGK) inhibitor [890842-28-1]
IPA 3 Group I p21-activated kinase (PAK) inhibitor [42521-82-4]

(2) HMDB Compounds for DAPK1 Gene

Compound Synonyms Cas Number PubMed IDs
Calcium
  • Ca
7440-70-2
Magnesium
  • Magnesium
7439-95-4

(11) Novoseek inferred chemical compound relationships for DAPK1 Gene

Compound -log(P) Hits PubMed IDs
o6-methylguanine 70.4 7
5-aza-2deoxycytidine 68 7
sodium bisulfite 63.9 2
threonine 53.3 20
serine 37.1 17
genes like me logo Genes that share compounds with DAPK1: view

Transcripts for DAPK1 Gene

Alternative Splicing Database (ASD) splice patterns (SP) for DAPK1 Gene

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: - -
SP6: - - - -
SP7:
SP8: -

ExUns: 22a · 22b ^ 23 ^ 24 ^ 25 ^ 26a · 26b ^ 27a · 27b ^ 28 ^ 29
SP1: - - -
SP2:
SP3:
SP4: - -
SP5:
SP6:
SP7:
SP8:

Relevant External Links for DAPK1 Gene

GeneLoc Exon Structure for
DAPK1
ECgene alternative splicing isoforms for
DAPK1

Expression for DAPK1 Gene

mRNA expression in normal human tissues for DAPK1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for DAPK1 Gene

SOURCE GeneReport for Unigene cluster for DAPK1 Gene Hs.380277

mRNA Expression by UniProt/SwissProt for DAPK1 Gene

P53355-DAPK1_HUMAN
Tissue specificity: Isoform 2 is expressed in normal intestinal tissue as well as in colorectal carcinomas.
genes like me logo Genes that share expressions with DAPK1: view

No data available for mRNA differential expression in normal tissues for DAPK1 Gene

Orthologs for DAPK1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for DAPK1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia DAPK1 35
  • 99.21 (n)
  • 99.86 (a)
DAPK1 36
  • 98 (a)
OneToOne
cow
(Bos Taurus)
Mammalia DAPK1 35
  • 90.77 (n)
  • 95.8 (a)
DAPK1 36
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia DAPK1 35
  • 89.77 (n)
  • 95.52 (a)
DAPK1 36
  • 96 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Dapk1 35
  • 87.67 (n)
  • 95.1 (a)
Dapk1 16
Dapk1 36
  • 95 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia DAPK1 36
  • 94 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia DAPK1 36
  • 63 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Dapk1 35
  • 87.6 (n)
  • 95.03 (a)
chicken
(Gallus gallus)
Aves DAPK1 35
  • 78.55 (n)
  • 90.42 (a)
DAPK1 36
  • 90 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia DAPK1 36
  • 89 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia dapk1 35
  • 74.7 (n)
  • 86.62 (a)
zebrafish
(Danio rerio)
Actinopterygii dapk1 35
  • 68.86 (n)
  • 74.7 (a)
dapk1 36
  • 74 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG1776 37
  • 43 (a)
worm
(Caenorhabditis elegans)
Secernentea dapk-1 35
  • 46.21 (n)
  • 36.22 (a)
dapk-1 36
  • 35 (a)
OneToMany
ZC373.4 37
  • 38 (a)
K12C11.4 37
  • 34 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MBP1 38
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 46 (a)
OneToMany
Species with no ortholog for DAPK1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for DAPK1 Gene

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

Paralogs for DAPK1 Gene

Paralogs for DAPK1 Gene

Pseudogenes.org Pseudogenes for DAPK1 Gene

genes like me logo Genes that share paralogs with DAPK1: view

Variants for DAPK1 Gene

Sequence variations from dbSNP and Humsavar for DAPK1 Gene

SNP ID Clin Chr 09 pos Sequence Context AA Info Type MAF
rs1554 -- 87,518,811(-) TGGGC(A/G)CGGGC intron-variant
rs1556 -- 87,518,758(-) AGACA(C/T)TGATA intron-variant
rs3028 -- 87,536,447(-) AATCA(A/G)TACAG intron-variant
rs12821 -- 87,554,052(+) CCCCT(C/T)TTCAG intron-variant
rs721936 -- 87,668,234(+) CACCT(A/G)ATGAG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for DAPK1 Gene

Variant ID Type Subtype PubMed ID
dgv2396e1 CNV Complex 17122850
nsv893546 CNV Gain 21882294
esv21629 CNV Loss 19812545
esv22121 CNV Gain 19812545
nsv483067 CNV Gain 15286789
nsv8545 CNV Gain 18304495
esv28714 CNV Loss 19812545
esv2738708 CNV Deletion 23290073
esv1463209 CNV Deletion 17803354
esv1345777 CNV Deletion 17803354
esv1009206 CNV Deletion 20482838
esv2738709 CNV Deletion 23290073
esv1024641 CNV Deletion 17803354
nsv893547 CNV Gain 21882294
nsv893548 CNV Gain 21882294

Relevant External Links for DAPK1 Gene

HapMap Linkage Disequilibrium report
DAPK1
Human Gene Mutation Database (HGMD)
DAPK1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DAPK1 Gene

Disorders for DAPK1 Gene

(1) University of Copenhagen DISEASES for DAPK1 Gene

(56) Novoseek inferred disease relationships for DAPK1 Gene

Disease -log(P) Hits PubMed IDs
tumors 59.8 121
cancer 54.8 28
nsclc 51.9 22
bladder cancer 48 12
cervical cancer 47.9 27

Relevant External Links for DAPK1

Genetic Association Database (GAD)
DAPK1
Human Genome Epidemiology (HuGE) Navigator
DAPK1
genes like me logo Genes that share disorders with DAPK1: view

No data available for UniProtKB/Swiss-Prot for DAPK1 Gene

Publications for DAPK1 Gene

  1. Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK. (PMID: 15616583) Chen C.H. … Chen R.H. (EMBO J. 2005) 3 4 23
  2. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. (PMID: 16213824) Anjum R. … Blenis J. (Curr. Biol. 2005) 3 4 23
  3. Control of death-associated protein kinase (DAPK) activity by phosphorylation and proteasomal degradation. (PMID: 17056602) Jin Y. … Gallagher P.J. (J. Biol. Chem. 2006) 3 4 23
  4. An alternative transcript from the death-associated protein kinase 1 locus encoding a small protein selectively mediates membrane blebbing. (PMID: 18422656) Lin Y. … Hupp T. (FEBS J. 2008) 3 4 23
  5. DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. (PMID: 19180116) Zalckvar E. … Kimchi A. (EMBO Rep. 2009) 3 4 23

Products for DAPK1 Gene

  • Addgene plasmids for DAPK1

Sources for DAPK1 Gene

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