| Structural highlights
Function
[DAPK3_HUMAN] Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation, actin cytoskeleton reorganization, cell motility, smooth muscle contraction, and mitosis, particularly cytokinesis. 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. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A, and the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Phosphorylates STAT3 and enhances its transcriptional activity. Positively regulates the canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Can disrupt the NLK-TCF7L2 complex thereby influencing the phosphorylation of TCF7L2 by NLK. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis. Involved in the formation of promyelocytic leukemia protein nuclear body (PML-NB), one of many subnuclear domains in the eukaryotic cell nucleus, and which is involved in oncogenesis and viral infection. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, its association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B.[13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24]
Publication Abstract from PubMed
Automated molecular de novo design led to the discovery of an innovative inhibitor of death-associated protein kinase 3 (DAPK3). An unprecedented crystal structure of the inactive DAPK3 homodimer shows the fragment-like hit bound to the ATP pocket. Target prediction software based on machine learning models correctly identified additional macromolecular targets of the computationally designed compound and the structurally related marketed drug azosemide. The study validates computational de novo design as a prime method for generating chemical probes and starting points for drug discovery.
De Novo Fragment Design for Drug Discovery and Chemical Biology.,Rodrigues T, Reker D, Welin M, Caldera M, Brunner C, Gabernet G, Schneider P, Walse B, Schneider G Angew Chem Int Ed Engl. 2015 Oct 21. doi: 10.1002/anie.201508055. PMID:26486226[25]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Murata-Hori M, Suizu F, Iwasaki T, Kikuchi A, Hosoya H. ZIP kinase identified as a novel myosin regulatory light chain kinase in HeLa cells. FEBS Lett. 1999 May 14;451(1):81-4. PMID:10356987
- ↑ Takamoto N, Komatsu S, Komaba S, Niiro N, Ikebe M. Novel ZIP kinase isoform lacks leucine zipper. Arch Biochem Biophys. 2006 Dec 15;456(2):194-203. Epub 2006 Oct 16. PMID:17126281 doi:S0003-9861(06)00373-0
- ↑ Kawai T, Akira S, Reed JC. ZIP kinase triggers apoptosis from nuclear PML oncogenic domains. Mol Cell Biol. 2003 Sep;23(17):6174-86. PMID:12917339
- ↑ Preuss U, Landsberg G, Scheidtmann KH. Novel mitosis-specific phosphorylation of histone H3 at Thr11 mediated by Dlk/ZIP kinase. Nucleic Acids Res. 2003 Feb 1;31(3):878-85. PMID:12560483
- ↑ Shani G, Marash L, Gozuacik D, Bialik S, Teitelbaum L, Shohat G, Kimchi A. Death-associated protein kinase phosphorylates ZIP kinase, forming a unique kinase hierarchy to activate its cell death functions. Mol Cell Biol. 2004 Oct;24(19):8611-26. PMID:15367680 doi:10.1128/MCB.24.19.8611-8626.2004
- ↑ Mukhopadhyay R, Ray PS, Arif A, Brady AK, Kinter M, Fox PL. DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. Mol Cell. 2008 Nov 7;32(3):371-82. doi: 10.1016/j.molcel.2008.09.019. PMID:18995835 doi:10.1016/j.molcel.2008.09.019
- ↑ Sato N, Kawai T, Sugiyama K, Muromoto R, Imoto S, Sekine Y, Ishida M, Akira S, Matsuda T. Physical and functional interactions between STAT3 and ZIP kinase. Int Immunol. 2005 Dec;17(12):1543-52. Epub 2005 Oct 11. PMID:16219639 doi:10.1093/intimm/dxh331
- ↑ Hagerty L, Weitzel DH, Chambers J, Fortner CN, Brush MH, Loiselle D, Hosoya H, Haystead TA. ROCK1 phosphorylates and activates zipper-interacting protein kinase. J Biol Chem. 2007 Feb 16;282(7):4884-93. Epub 2006 Dec 8. PMID:17158456 doi:10.1074/jbc.M609990200
- ↑ Ohbayashi N, Okada K, Kawakami S, Togi S, Sato N, Ikeda O, Kamitani S, Muromoto R, Sekine Y, Kawai T, Akira S, Matsuda T. Physical and functional interactions between ZIP kinase and UbcH5. Biochem Biophys Res Commun. 2008 Aug 8;372(4):708-12. doi:, 10.1016/j.bbrc.2008.05.113. Epub 2008 Jun 2. PMID:18515077 doi:10.1016/j.bbrc.2008.05.113
- ↑ Leister P, Felten A, Chasan AI, Scheidtmann KH. ZIP kinase plays a crucial role in androgen receptor-mediated transcription. Oncogene. 2008 May 22;27(23):3292-300. Epub 2007 Dec 17. PMID:18084323 doi:10.1038/sj.onc.1210995
- ↑ Togi S, Ikeda O, Kamitani S, Nakasuji M, Sekine Y, Muromoto R, Nanbo A, Oritani K, Kawai T, Akira S, Matsuda T. Zipper-interacting protein kinase (ZIPK) modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-like kinase and T-cell factor 4 (NLK/TCF4). J Biol Chem. 2011 May 27;286(21):19170-7. doi: 10.1074/jbc.M110.189829. Epub 2011, Mar 30. PMID:21454679 doi:10.1074/jbc.M110.189829
- ↑ Shoval Y, Berissi H, Kimchi A, Pietrokovski S. New modularity of DAP-kinases: alternative splicing of the DRP-1 gene produces a ZIPk-like isoform. PLoS One. 2011 Mar 8;6(2):e17344. doi: 10.1371/journal.pone.0017344. PMID:21408167 doi:10.1371/journal.pone.0017344
- ↑ Murata-Hori M, Suizu F, Iwasaki T, Kikuchi A, Hosoya H. ZIP kinase identified as a novel myosin regulatory light chain kinase in HeLa cells. FEBS Lett. 1999 May 14;451(1):81-4. PMID:10356987
- ↑ Takamoto N, Komatsu S, Komaba S, Niiro N, Ikebe M. Novel ZIP kinase isoform lacks leucine zipper. Arch Biochem Biophys. 2006 Dec 15;456(2):194-203. Epub 2006 Oct 16. PMID:17126281 doi:S0003-9861(06)00373-0
- ↑ Kawai T, Akira S, Reed JC. ZIP kinase triggers apoptosis from nuclear PML oncogenic domains. Mol Cell Biol. 2003 Sep;23(17):6174-86. PMID:12917339
- ↑ Preuss U, Landsberg G, Scheidtmann KH. Novel mitosis-specific phosphorylation of histone H3 at Thr11 mediated by Dlk/ZIP kinase. Nucleic Acids Res. 2003 Feb 1;31(3):878-85. PMID:12560483
- ↑ Shani G, Marash L, Gozuacik D, Bialik S, Teitelbaum L, Shohat G, Kimchi A. Death-associated protein kinase phosphorylates ZIP kinase, forming a unique kinase hierarchy to activate its cell death functions. Mol Cell Biol. 2004 Oct;24(19):8611-26. PMID:15367680 doi:10.1128/MCB.24.19.8611-8626.2004
- ↑ Mukhopadhyay R, Ray PS, Arif A, Brady AK, Kinter M, Fox PL. DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. Mol Cell. 2008 Nov 7;32(3):371-82. doi: 10.1016/j.molcel.2008.09.019. PMID:18995835 doi:10.1016/j.molcel.2008.09.019
- ↑ Sato N, Kawai T, Sugiyama K, Muromoto R, Imoto S, Sekine Y, Ishida M, Akira S, Matsuda T. Physical and functional interactions between STAT3 and ZIP kinase. Int Immunol. 2005 Dec;17(12):1543-52. Epub 2005 Oct 11. PMID:16219639 doi:10.1093/intimm/dxh331
- ↑ Hagerty L, Weitzel DH, Chambers J, Fortner CN, Brush MH, Loiselle D, Hosoya H, Haystead TA. ROCK1 phosphorylates and activates zipper-interacting protein kinase. J Biol Chem. 2007 Feb 16;282(7):4884-93. Epub 2006 Dec 8. PMID:17158456 doi:10.1074/jbc.M609990200
- ↑ Ohbayashi N, Okada K, Kawakami S, Togi S, Sato N, Ikeda O, Kamitani S, Muromoto R, Sekine Y, Kawai T, Akira S, Matsuda T. Physical and functional interactions between ZIP kinase and UbcH5. Biochem Biophys Res Commun. 2008 Aug 8;372(4):708-12. doi:, 10.1016/j.bbrc.2008.05.113. Epub 2008 Jun 2. PMID:18515077 doi:10.1016/j.bbrc.2008.05.113
- ↑ Leister P, Felten A, Chasan AI, Scheidtmann KH. ZIP kinase plays a crucial role in androgen receptor-mediated transcription. Oncogene. 2008 May 22;27(23):3292-300. Epub 2007 Dec 17. PMID:18084323 doi:10.1038/sj.onc.1210995
- ↑ Togi S, Ikeda O, Kamitani S, Nakasuji M, Sekine Y, Muromoto R, Nanbo A, Oritani K, Kawai T, Akira S, Matsuda T. Zipper-interacting protein kinase (ZIPK) modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-like kinase and T-cell factor 4 (NLK/TCF4). J Biol Chem. 2011 May 27;286(21):19170-7. doi: 10.1074/jbc.M110.189829. Epub 2011, Mar 30. PMID:21454679 doi:10.1074/jbc.M110.189829
- ↑ Shoval Y, Berissi H, Kimchi A, Pietrokovski S. New modularity of DAP-kinases: alternative splicing of the DRP-1 gene produces a ZIPk-like isoform. PLoS One. 2011 Mar 8;6(2):e17344. doi: 10.1371/journal.pone.0017344. PMID:21408167 doi:10.1371/journal.pone.0017344
- ↑ Rodrigues T, Reker D, Welin M, Caldera M, Brunner C, Gabernet G, Schneider P, Walse B, Schneider G. De Novo Fragment Design for Drug Discovery and Chemical Biology. Angew Chem Int Ed Engl. 2015 Oct 21. doi: 10.1002/anie.201508055. PMID:26486226 doi:http://dx.doi.org/10.1002/anie.201508055
|
