The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

DAPK3  -  death-associated protein kinase 3

Homo sapiens

Synonyms: DAP kinase 3, DAP-like kinase, DLK, Death-associated protein kinase 3, Dlk, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of DAPK3

  • A total of 528 men, including 214 treated for clinically localized prostate cancer (41 with evidence of metastatic disease were excluded from this analysis) and 273 age-matched, ZIP code-matched comparison patients without prostate cancer [1].
  • PARTICIPANTS--A total of 2.1 million adults residing within the boundaries of the Maryland Regional ESRD Registry, grouped by race and ZIP code into 26 subpopulations [2].
  • RESULTS: Compared with whites, blacks were less likely to complete steps B (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.61-0.76), C (OR, 0.56; 95% CI, 0.48-0.65), and D (OR, 0.50; 95% CI, 0.40-0.62) after adjustment for age, sex, cause of renal failure, years receiving dialysis, and median income of patient ZIP code [3].
  • Vietnam service and military service experiences of 281 men with sarcomas of soft tissues were compared in this epidemiologic study to a control group of men derived from driver's license files and matched on 5-year period of birth and ZIP code of residence [4].
  • Examination of the Blast Bank samples from 22 patients with MDS, 31 with AML, and 8 with chronic myeloid leukemia confirmed the highly selective expression of the Dlk gene in the individuals with MDS [5].

Psychiatry related information on DAPK3

  • The authors used ZIP codes to designate rural or urban residence and categorized outpatient utilization into primary care, individual mental health care, non-mental health specialty care, or emergency room care [6].

High impact information on DAPK3


Chemical compound and disease context of DAPK3


Biological context of DAPK3

  • ZIP kinase (ZIPK) is a proapoptotic protein kinase with homology to DAP kinase, a protein kinase implicated in apoptosis [14].
  • The down-regulated genes include IL8, IL10RA, DAPK3, and those involved in nuclear factor of activated T cells (NFAT) signal pathway and endocrine responsiveness [15].
  • High stringency screening of a human aortic cDNA library for the SMPP-1M-associated kinase identified 18 positive clones, all of which proved to be clones of hZIPK [16].
  • C-terminal truncation of Dlk/ZIP kinase leads to abrogation of nuclear transport and high apoptotic activity [17].
  • Taken together, these data strongly suggest a functional role for Dlk in control of cell survival which is dependent on its subcellular localization [17].

Anatomical context of DAPK3

  • Here we show that only native hZIPK mRNA and protein are detectable in human vascular smooth muscle cells (VSMCs) [16].
  • ZIP kinase identified as a novel myosin regulatory light chain kinase in HeLa cells [18].
  • In this model, ZIP potentiated the inhibitory action of Grb14 on insulin-induced oocyte maturation [19].
  • To this end, we have cloned smooth muscle zipper-interacting protein (ZIP) kinase cDNA [20].
  • Abrogation of phosphorylation of Thr299, Thr306, and Ser311 had little effect on enzyme activity, but mutation of Thr299 and Thr300 to alanine resulted in redistribution of ZIPK from the cytosol to the nucleus [21].

Associations of DAPK3 with chemical compounds

  • Arsenic trioxide (As(2)O(3)) and gamma interferon (IFN-gamma), which accentuate POD formation, increased the association of ZIPK with PODs [14].
  • Dlk (also termed ZIP kinase) is a novel serine/threonine kinase with a unique C-terminal domain that is rich in arginine and contains three putative NLS motifs and a functional lecuine zipper [17].
  • Here we found that HeLa ZIPK phosphorylated the regulatory light chain of myosin II (MRLC) at both serine 19 and threonine 18 in a Ca2+/calmodulin independent manner [18].
  • The interaction domain within Dlk was mapped to an arginine-rich region between residues 338 - 417, rather than to the leucine zipper [22].
  • A mutant ZIP kinase construct, in which the six serine/threonine residues were mutated to aspartic acid to mimic the phosphorylated state, was found predominantly in the cytoplasm as a trimer and possessed greater cell death-inducing potency [23].

Enzymatic interactions of DAPK3

  • ZIPK also binds and phosphorylates proapoptotic protein Par-4 [14].
  • Furthermore, DAP kinase phosphorylates ZIP kinase at six specific sites within its extracatalytic C-terminal domain [23].

Regulatory relationships of DAPK3


Other interactions of DAPK3

  • We show here that ZIPK is present in PODs, where it colocalizes with and binds to proapoptotic protein Daxx [14].
  • Association of ZIPK with Daxx was enhanced by coexpression of Par-4 [14].
  • Therefore, both ZIP and DAP kinases represent a novel kinase family, which mediates apoptosis through their catalytic activities [25].
  • HeLa ZIPK is the first non-muscle MLCK that phosphorylates MRLC at two sites [18].
  • Expression of various deletion and point mutations of Dlk as GFP fusion proteins revealed that the leucine zipper is required for association with speckles and the most C-terminal NLS is necessary and sufficient for nuclear transport [17].

Analytical, diagnostic and therapeutic context of DAPK3


  1. Quality-of-life outcomes in men treated for localized prostate cancer. Litwin, M.S., Hays, R.D., Fink, A., Ganz, P.A., Leake, B., Leach, G.E., Brook, R.H. JAMA (1995) [Pubmed]
  2. The excess incidence of diabetic end-stage renal disease among blacks. A population-based study of potential explanatory factors. Brancati, F.L., Whittle, J.C., Whelton, P.K., Seidler, A.J., Klag, M.J. JAMA (1992) [Pubmed]
  3. Barriers to cadaveric renal transplantation among blacks, women, and the poor. Alexander, G.C., Sehgal, A.R. JAMA (1998) [Pubmed]
  4. Sarcomas of soft tissues after Vietnam service. Greenwald, P., Kovasznay, B., Collins, D.N., Therriault, G. J. Natl. Cancer Inst. (1984) [Pubmed]
  5. Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction. Miyazato, A., Ueno, S., Ohmine, K., Ueda, M., Yoshida, K., Yamashita, Y., Kaneko, T., Mori, M., Kirito, K., Toshima, M., Nakamura, Y., Saito, K., Kano, Y., Furusawa, S., Ozawa, K., Mano, H. Blood (2001) [Pubmed]
  6. Veterans Health Administration and Medicare outpatient health care utilization by older rural and urban New England veterans. Weeks, W.B., Bott, D.M., Lamkin, R.P., Wright, S.M. The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association. (2005) [Pubmed]
  7. Identification of an amino acid-base contact in the GCN4-DNA complex by bromouracil-mediated photocrosslinking. Blatter, E.E., Ebright, Y.W., Ebright, R.H. Nature (1992) [Pubmed]
  8. Signaling for contraction and relaxation in smooth muscle of the gut. Murthy, K.S. Annu. Rev. Physiol. (2006) [Pubmed]
  9. ZIP kinase is responsible for the phosphorylation of myosin II and necessary for cell motility in mammalian fibroblasts. Komatsu, S., Ikebe, M. J. Cell Biol. (2004) [Pubmed]
  10. Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Beeton, C., Wulff, H., Standifer, N.E., Azam, P., Mullen, K.M., Pennington, M.W., Kolski-Andreaco, A., Wei, E., Grino, A., Counts, D.R., Wang, P.H., Leehealey, C.J., S Andrews, B., Sankaranarayanan, A., Homerick, D., Roeck, W.W., Tehranzadeh, J., Stanhope, K.L., Zimin, P., Havel, P.J., Griffey, S., Knaus, H.G., Nepom, G.T., Gutman, G.A., Calabresi, P.A., Chandy, K.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Translocation of FGF2 to the cell surface without release into conditioned media. Trudel, C., Faure-Desire, V., Florkiewicz, R.Z., Baird, A. J. Cell. Physiol. (2000) [Pubmed]
  12. Adjuvant goserelin in pre-menopausal patients with early breast cancer: Results from the ZIPP study. Baum, M., Hackshaw, A., Houghton, J., Rutqvist, n.u.l.l., Fornander, T., Nordenskjold, B., Nicolucci, A., Sainsbury, R. Eur. J. Cancer (2006) [Pubmed]
  13. Pancreatic cancer mortality and organochlorine pesticide exposure in California, 1989-1996. Clary, T., Ritz, B. Am. J. Ind. Med. (2003) [Pubmed]
  14. ZIP kinase triggers apoptosis from nuclear PML oncogenic domains. Kawai, T., Akira, S., Reed, J.C. Mol. Cell. Biol. (2003) [Pubmed]
  15. Silencing of DNA-PKcs alters the transcriptional profile of certain signal transduction genes related to proliferation and differentiation in HeLa cells. An, J., Xu, Q.Z., Sui, J.L., Bai, B., Zhou, P.K. Int. J. Mol. Med. (2005) [Pubmed]
  16. Identification and characterization of zipper-interacting protein kinase as the unique vascular smooth muscle myosin phosphatase-associated kinase. Endo, A., Surks, H.K., Mochizuki, S., Mochizuki, N., Mendelsohn, M.E. J. Biol. Chem. (2004) [Pubmed]
  17. C-terminal truncation of Dlk/ZIP kinase leads to abrogation of nuclear transport and high apoptotic activity. Kögel, D., Bierbaum, H., Preuss, U., Scheidtmann, K.H. Oncogene (1999) [Pubmed]
  18. ZIP kinase identified as a novel myosin regulatory light chain kinase in HeLa cells. Murata-Hori, M., Suizu, F., Iwasaki, T., Kikuchi, A., Hosoya, H. FEBS Lett. (1999) [Pubmed]
  19. The adapter protein ZIP binds Grb14 and regulates its inhibitory action on insulin signaling by recruiting protein kinase Czeta. Cariou, B., Perdereau, D., Cailliau, K., Browaeys-Poly, E., Béréziat, V., Vasseur-Cognet, M., Girard, J., Burnol, A.F. Mol. Cell. Biol. (2002) [Pubmed]
  20. Zipper-interacting protein kinase induces Ca(2+)-free smooth muscle contraction via myosin light chain phosphorylation. Niiro, N., Ikebe, M. J. Biol. Chem. (2001) [Pubmed]
  21. Regulation of zipper-interacting protein kinase activity in vitro and in vivo by multisite phosphorylation. Graves, P.R., Winkfield, K.M., Haystead, T.A. J. Biol. Chem. (2005) [Pubmed]
  22. Interaction partners of Dlk/ZIP kinase: co-expression of Dlk/ZIP kinase and Par-4 results in cytoplasmic retention and apoptosis. Page, G., Kögel, D., Rangnekar, V., Scheidtmann, K.H. Oncogene (1999) [Pubmed]
  23. Death-associated protein kinase phosphorylates ZIP kinase, forming a unique kinase hierarchy to activate its cell death functions. Shani, G., Marash, L., Gozuacik, D., Bialik, S., Teitelbaum, L., Shohat, G., Kimchi, A. Mol. Cell. Biol. (2004) [Pubmed]
  24. TCP10L is expressed specifically in spermatogenic cells and binds to death associated protein kinase-3. Yu, H., Jiang, D., Guo, Z., Saiyin, H., Guo, J., Wang, X., Yu, L. Int. J. Androl. (2005) [Pubmed]
  25. ZIP kinase, a novel serine/threonine kinase which mediates apoptosis. Kawai, T., Matsumoto, M., Takeda, K., Sanjo, H., Akira, S. Mol. Cell. Biol. (1998) [Pubmed]
  26. Assignment of the ZIP kinase gene to human chromosome 19p13.3 by somatic hybrid analysis and fluorescence in-situ hybridization. Saito, T., Seki, N., Ohira, M., Hayashi, A., Kozuma, S., Hattori, A., Hori, T. J. Hum. Genet. (1998) [Pubmed]
  27. Guidelines and realities of asthma management. The Philadelphia story. Lang, D.M., Sherman, M.S., Polansky, M. Arch. Intern. Med. (1997) [Pubmed]
WikiGenes - Universities