Death-associated protein kinase 3

Details

Name
Death-associated protein kinase 3
Synonyms
  • 2.7.11.1
  • DAP kinase 3
  • DAP-like kinase
  • Dlk
  • MYPT1 kinase
  • ZIP-kinase
  • ZIPK
  • Zipper-interacting protein kinase
Gene Name
DAPK3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007267|Death-associated protein kinase 3
MSTFRQEDVEDHYEMGEELGSGQFAIVRKCRQKGTGKEYAAKFIKKRRLSSSRRGVSREE
IEREVNILREIRHPNIITLHDIFENKTDVVLILELVSGGELFDFLAEKESLTEDEATQFL
KQILDGVHYLHSKRIAHFDLKPENIMLLDKNVPNPRIKLIDFGIAHKIEAGNEFKNIFGT
PEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEY
FSNTSELAKDFIRRLLVKDPKRRMTIAQSLEHSWIKAIRRRNVRGEDSGRKPERRRLKTT
RLKEYTIKSHSSLPPNNSYADFERFSKVLEEAAAAEEGLRELQRSRRLCHEDVEALAAIY
EEKEAWYREESDSLGQDLRRLRQELLKTEALKRQAQEEAKGALLGTSGLKRRFSRLENRY
EALAKQVASEMRFVQDLVRALEQEKLQGVECGLR
Number of residues
454
Molecular Weight
52535.165
Theoretical pI
6.87
GO Classification
Functions
ATP binding / cAMP response element binding protein binding / identical protein binding / leucine zipper domain binding / protein homodimerization activity / protein serine/threonine kinase activity / Rho GTPase binding
Processes
apoptotic process / apoptotic signaling pathway / cellular response to interferon-gamma / chromatin modification / cytokinesis / intracellular signal transduction / negative regulation of translation / neuron differentiation / positive regulation of apoptotic process / positive regulation of canonical Wnt signaling pathway / positive regulation of cell migration / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / protein autophosphorylation / protein phosphorylation / regulation of actin cytoskeleton reorganization / regulation of apoptotic process / regulation of autophagy / regulation of cell motility / regulation of cell shape / regulation of focal adhesion assembly / regulation of mitotic cell cycle / regulation of mitotic nuclear division / regulation of myosin II filament organization / regulation of smooth muscle contraction / regulation of transcription, DNA-templated / transcription, DNA-templated
Components
actin filament / cytoplasm / membrane raft / nucleus / PML body
General Function
Rho gtpase binding
Specific Function
Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. 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; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0012644|Death-associated protein kinase 3 (DAPK3)
ATGTCCACGTTCAGGCAGGAGGACGTGGAGGACCATTATGAGATGGGGGAGGAGCTGGGC
AGCGGCCAGTTTGCGATCGTGCGGAAGTGCCGGCAGAAGGGCACGGGCAAGGAGTACGCA
GCCAAGTTCATCAAGAAGCGCCGCCTGTCATCCAGCCGGCGTGGGGTGAGCCGGGAGGAG
ATCGAGCGGGAGGTGAACATCCTGCGGGAGATCCGGCACCCCAACATCATCACCCTGCAC
GACATCTTCGAGAACAAGACGGACGTGGTCCTCATCCTGGAGCTGGTCTCTGGCGGGGAG
CTCTTTGACTTCCTGGCGGAGAAGGAGTCGCTGACGGAGGACGAGGCCACCCAGTTCCTC
AAGCAGATCCTGGACGGCGTTCACTACCTGCACTCTAAGCGCATCGCACACTTTGACCTG
AAGCCGGAAAACATCATGCTGCTGGACAAGAACGTGCCCAACCCACGAATCAAGCTCATC
GACTTCGGCATCGCGCACAAGATCGAGGCGGGGAACGAGTTCAAGAACATCTTCGGCACC
CCGGAGTTTGTGGCCCCAGAGATTGTGAACTATGAGCCGCTGGGCCTGGAGGCGGACATG
TGGAGCATCGGTGTCATCACCTATATCCTCCTGAGCGGTGCATCCCCGTTCCTGGGCGAG
ACCAAGCAGGAGACGCTCACCAACATCTCAGCCGTGAACTACGACTTCGACGAGGAGTAC
TTCAGCAACACCAGCGAGCTGGCCAAGGACTTCATTCGCCGGCTGCTCGTCAAAGATCCC
AAGCGGAGAATGACCATTGCCCAGAGCCTGGAACATTCCTGGATTAAGGCGATCCGGCGG
CGGAACGTGCGTGGTGAGGACAGCGGCCGCAAGCCCGAGCGGCGGCGCCTGAAGACCACG
CGTCTGAAGGAGTACACCATCAAGTCGCACTCCAGCTTGCCGCCCAACAACAGCTACGCC
GACTTCGAGCGCTTCTCCAAGGTGCTGGAGGAGGCGGCGGCCGCCGAGGAGGGCCTGCGC
GAGCTGCAGCGCAGCCGGCGGCTCTGCCACGAGGACGTGGAGGCGCTGGCCGCCATCTAC
GAGGAGAAGGAGGCCTGGTACCGCGAGGAGAGCGACAGCCTGGGCCAGGACCTGCGGAGG
CTACGGCAGGAGCTGCTCAAGACCGAGGCGCTCAAGCGGCAGGCGCAGGAGGAGGCCAAG
GGCGCGCTGCTGGGGACCAGCGGCCTCAAGCGCCGCTTCAGCCGCCTGGAGAACCGCTAC
GAGGCGCTGGCCAAGCAAGTAGCCTCCGAGATGCGCTTCGTGCAGGACCTCGTGCGCGCC
CTGGAGCAGGAGAAGCTGCAGGGCGTGGAGTGCGGGCTGCGCTAG
Chromosome Location
19
Locus
19p13.3
External Identifiers
ResourceLink
UniProtKB IDO43293
UniProtKB Entry NameDAPK3_HUMAN
GenBank Protein ID2911156
GenBank Gene IDAB007144
HGNC IDHGNC:2676
General References
  1. Kawai T, Matsumoto M, Takeda K, Sanjo H, Akira S: ZIP kinase, a novel serine/threonine kinase which mediates apoptosis. Mol Cell Biol. 1998 Mar;18(3):1642-51. [Article]
  2. 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. [Article]
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  5. 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. [Article]
  6. Niiro N, Ikebe M: Zipper-interacting protein kinase induces Ca(2+)-free smooth muscle contraction via myosin light chain phosphorylation. J Biol Chem. 2001 Aug 3;276(31):29567-74. Epub 2001 May 30. [Article]
  7. Murata-Hori M, Fukuta Y, Ueda K, Iwasaki T, Hosoya H: HeLa ZIP kinase induces diphosphorylation of myosin II regulatory light chain and reorganization of actin filaments in nonmuscle cells. Oncogene. 2001 Dec 13;20(57):8175-83. [Article]
  8. Kawai T, Akira S, Reed JC: ZIP kinase triggers apoptosis from nuclear PML oncogenic domains. Mol Cell Biol. 2003 Sep;23(17):6174-86. [Article]
  9. Endo A, Surks HK, Mochizuki S, Mochizuki N, Mendelsohn ME: Identification and characterization of zipper-interacting protein kinase as the unique vascular smooth muscle myosin phosphatase-associated kinase. J Biol Chem. 2004 Oct 1;279(40):42055-61. Epub 2004 Jul 30. [Article]
  10. Komatsu S, Ikebe M: ZIP kinase is responsible for the phosphorylation of myosin II and necessary for cell motility in mammalian fibroblasts. J Cell Biol. 2004 Apr 26;165(2):243-54. Epub 2004 Apr 19. [Article]
  11. 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. [Article]
  12. 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. [Article]
  13. Yu H, Jiang D, Guo Z, Saiyin H, Guo J, Wang X, Yu L: TCP10L is expressed specifically in spermatogenic cells and binds to death associated protein kinase-3. Int J Androl. 2005 Jun;28(3):163-70. [Article]
  14. Graves PR, Winkfield KM, Haystead TA: Regulation of zipper-interacting protein kinase activity in vitro and in vivo by multisite phosphorylation. J Biol Chem. 2005 Mar 11;280(10):9363-74. Epub 2004 Dec 20. [Article]
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  17. Shoval Y, Pietrokovski S, Kimchi A: ZIPK: a unique case of murine-specific divergence of a conserved vertebrate gene. PLoS Genet. 2007 Oct;3(10):1884-93. Epub 2007 Sep 7. [Article]
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  19. 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. [Article]
  20. Brognard J, Zhang YW, Puto LA, Hunter T: Cancer-associated loss-of-function mutations implicate DAPK3 as a tumor-suppressing kinase. Cancer Res. 2011 Apr 15;71(8):3152-61. doi: 10.1158/0008-5472.CAN-10-3543. Epub 2011 Apr 12. [Article]
  21. Weitzel DH, Chambers J, Haystead TA: Phosphorylation-dependent control of ZIPK nuclear import is species specific. Cell Signal. 2011 Jan;23(1):297-303. doi: 10.1016/j.cellsig.2010.09.016. Epub 2010 Sep 18. [Article]
  22. Tang HW, Wang YB, Wang SL, Wu MH, Lin SY, Chen GC: Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy. EMBO J. 2011 Feb 16;30(4):636-51. doi: 10.1038/emboj.2010.338. Epub 2010 Dec 17. [Article]
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  24. 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. [Article]
  25. Nehru V, Almeida FN, Aspenstrom P: Interaction of RhoD and ZIP kinase modulates actin filament assembly and focal adhesion dynamics. Biochem Biophys Res Commun. 2013 Apr 5;433(2):163-9. doi: 10.1016/j.bbrc.2013.02.046. Epub 2013 Feb 26. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB071254-(6-{[(1R)-1-(hydroxymethyl)propyl]amino}imidazo[1,2-b]pyridazin-3-yl)benzoic acidexperimentalunknownDetails
DB07242(4R)-7,8-dichloro-1',9-dimethyl-1-oxo-1,2,4,9-tetrahydrospiro[beta-carboline-3,4'-piperidine]-4-carbonitrileexperimentalunknownDetails
DB047162-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-oneexperimentalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails