Death-associated protein kinase 2

Details

Name
Death-associated protein kinase 2
Synonyms
  • 2.7.11.1
  • DAP kinase 2
  • DAP-kinase-related protein 1
  • DRP-1
Gene Name
DAPK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051734|Death-associated protein kinase 2
MFQASMRSPNMEPFKQQKVEDFYDIGEELGSGQFAIVKKCREKSTGLEYAAKFIKKRQSR
ASRRGVSREEIEREVSILRQVLHHNVITLHDVYENRTDVVLILELVSGGELFDFLAQKES
LSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPIPHIKLIDFGLAHEIED
GVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANIT
AVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWITPVDNQQAMVRRESV
VNLENFRKQYVRRRWKLSFSIVSLCNHLTRSLMKKVHLRPDEDLRNCESDTEEDIARRKA
LHPRRRSSTS
Number of residues
370
Molecular Weight
42897.685
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / calmodulin binding / identical protein binding / protein serine/threonine kinase activity
Processes
anoikis / apoptotic process / intracellular signal transduction / neutrophil migration / peptidyl-serine phosphorylation / peptidyl-threonine phosphorylation / positive regulation of eosinophil chemotaxis / positive regulation of neutrophil chemotaxis / protein autophosphorylation / protein phosphorylation / regulation of apoptotic process / regulation of autophagy / regulation of intrinsic apoptotic signaling pathway
Components
autophagosome lumen / cytoplasm / cytoplasmic vesicle / Golgi apparatus / intracellular membrane-bounded organelle
General 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 death signals, 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. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (PubMed:17347302). Regulates granulocytic motility by controlling cell spreading and polarization (PubMed:24163421).
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051735|Death-associated protein kinase 2 (DAPK2)
ATGTTCCAGGCCTCAATGAGGAGTCCAAACATGGAGCCATTCAAGCAGCAGAAGGTGGAG
GACTTTTATGACATCGGAGAGGAGCTGGGGAGTGGCCAGTTTGCCATCGTGAAGAAGTGC
CGGGAGAAGAGCACGGGGCTTGAGTATGCAGCCAAGTTCATCAAGAAGCGGCAGAGCCGG
GCGAGCCGGCGCGGTGTGAGCCGGGAGGAGATCGAGCGGGAGGTGAGCATCCTGCGGCAG
GTGCTGCACCACAATGTCATCACGCTGCACGACGTCTATGAGAACCGCACCGACGTGGTG
CTCATCCTTGAGCTAGTGTCTGGAGGAGAGCTCTTCGATTTCCTGGCCCAGAAGGAGTCA
CTGAGTGAGGAGGAGGCCACCAGCTTCATTAAGCAGATCCTGGATGGGGTGAACTACCTT
CACACAAAGAAAATTGCTCACTTTGATCTCAAGCCAGAAAACATTATGTTGTTAGACAAG
AATATTCCCATTCCACACATCAAGCTGATTGACTTTGGTCTGGCTCACGAAATAGAAGAT
GGAGTTGAATTTAAGAATATTTTTGGGACGCCGGAATTTGTTGCTCCAGAAATTGTGAAC
TACGAGCCCCTGGGTCTGGAGGCTGACATGTGGAGCATAGGCGTCATCACCTACATCCTC
TTAAGTGGAGCATCCCCTTTCCTGGGAGACACGAAGCAGGAAACACTGGCAAATATCACA
GCAGTGAGTTACGACTTTGATGAGGAATTCTTCAGCCAGACGAGCGAGCTGGCCAAGGAC
TTTATTCGGAAGCTTCTGGTTAAAGAGACCCGGAAACGGCTCACAATCCAAGAGGCTCTC
AGACACCCCTGGATCACGCCGGTGGACAACCAGCAAGCCATGGTGCGCAGGGAGTCTGTG
GTCAATCTGGAGAACTTCAGGAAGCAGTATGTCCGCAGGCGGTGGAAGCTTTCCTTCAGC
ATCGTGTCCCTGTGCAACCACCTCACCCGCTCGCTGATGAAGAAGGTGCACCTGAGGCCG
GATGAGGACCTGAGGAACTGTGAGAGTGACACTGAGGAGGACATCGCCAGGAGGAAAGCC
CTCCACCCACGGAGGAGGAGCAGCACCTCCTAA
Chromosome Location
15
Locus
15q22.31
External Identifiers
ResourceLink
UniProtKB IDQ9UIK4
UniProtKB Entry NameDAPK2_HUMAN
HGNC IDHGNC:2675
General References
  1. Kawai T, Nomura F, Hoshino K, Copeland NG, Gilbert DJ, Jenkins NA, Akira S: Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity. Oncogene. 1999 Jun 10;18(23):3471-80. [Article]
  2. Inbal B, Shani G, Cohen O, Kissil JL, Kimchi A: Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis. Mol Cell Biol. 2000 Feb;20(3):1044-54. [Article]
  3. 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]
  4. Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. [Article]
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  6. Shani G, Henis-Korenblit S, Jona G, Gileadi O, Eisenstein M, Ziv T, Admon A, Kimchi A: Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding. EMBO J. 2001 Mar 1;20(5):1099-113. [Article]
  7. Shohat G, Shani G, Eisenstein M, Kimchi A: The DAP-kinase family of proteins: study of a novel group of calcium-regulated death-promoting kinases. Biochim Biophys Acta. 2002 Nov 4;1600(1-2):45-50. [Article]
  8. Inbal B, Bialik S, Sabanay I, Shani G, Kimchi A: DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J Cell Biol. 2002 Apr 29;157(3):455-68. Epub 2002 Apr 29. [Article]
  9. Bialik S, Kimchi A: The death-associated protein kinases: structure, function, and beyond. Annu Rev Biochem. 2006;75:189-210. [Article]
  10. Rizzi M, Tschan MP, Britschgi C, Britschgi A, Hugli B, Grob TJ, Leupin N, Mueller BU, Simon HU, Ziemiecki A, Torbett BE, Fey MF, Tobler A: The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells. J Leukoc Biol. 2007 Jun;81(6):1599-608. Epub 2007 Mar 8. [Article]
  11. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  12. Li H, Ray G, Yoo BH, Erdogan M, Rosen KV: Down-regulation of death-associated protein kinase-2 is required for beta-catenin-induced anoikis resistance of malignant epithelial cells. J Biol Chem. 2009 Jan 23;284(4):2012-22. doi: 10.1074/jbc.M805612200. Epub 2008 Oct 27. [Article]
  13. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
  14. Geering B, Stoeckle C, Rozman S, Oberson K, Benarafa C, Simon HU: DAPK2 positively regulates motility of neutrophils and eosinophils in response to intermediary chemoattractants. J Leukoc Biol. 2014 Feb;95(2):293-303. doi: 10.1189/jlb.0813462. Epub 2013 Oct 25. [Article]
  15. Yuasa K, Ota R, Matsuda S, Isshiki K, Inoue M, Tsuji A: Suppression of death-associated protein kinase 2 by interaction with 14-3-3 proteins. Biochem Biophys Res Commun. 2015 Aug 14;464(1):70-5. doi: 10.1016/j.bbrc.2015.05.105. Epub 2015 Jun 3. [Article]
  16. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails