Gene Symbol: nec
Description: necrotic
Alias: CG1857, Dmel\CG1857, NEC, Nec, SER3, Ser3, Spn43Ac, anon-WO0118057.3, necrotic, CG1857-PA, nec-PA, necrotic serpin, serine protease inhibitor 3, serpin43Ac
Species: fruit fly

Top Publications

  1. Carrell R, Corral J. What can Drosophila tell us about serpins, thrombosis and dementia?. Bioessays. 2004;26:1-5 pubmed
    ..1 They show that the mutations causing a necrotic disease phenotype in Drosophila, precisely mirror those resulting in a group of well-studied but perplexing ..
  2. Scherfer C, Tang H, Kambris Z, Lhocine N, Hashimoto C, Lemaitre B. Drosophila Serpin-28D regulates hemolymph phenoloxidase activity and adult pigmentation. Dev Biol. 2008;323:189-96 pubmed publisher
    ..The Drosophila genome encodes 29 serpins, of which only two, Serpin-27A (Spn27A) and Necrotic, have been analyzed in detail...
  3. Goto A, Blandin S, Royet J, Reichhart J, Levashina E. Silencing of Toll pathway components by direct injection of double-stranded RNA into Drosophila adult flies. Nucleic Acids Res. 2003;31:6619-23 pubmed
  4. Robertson A, Belorgey D, Lilley K, Lomas D, Gubb D, Dafforn T. Characterization of the necrotic protein that regulates the Toll-mediated immune response in Drosophila. J Biol Chem. 2003;278:6175-80 pubmed
    b>Necrotic (Nec) is an important component of the proteolytic cascade that activates the Toll-mediated immune response in Drosophila...
  5. Crowther D, Kinghorn K, Miranda E, Page R, Curry J, Duthie F, et al. Intraneuronal Abeta, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimer's disease. Neuroscience. 2005;132:123-35 pubmed
    ..Moreover it provides a platform to dissect the pathways of neurodegeneration in Alzheimer's disease and to develop novel therapeutic interventions. ..
  6. Green C, Levashina E, McKimmie C, Dafforn T, Reichhart J, Gubb D. The necrotic gene in Drosophila corresponds to one of a cluster of three serpin transcripts mapping at 43A1.2. Genetics. 2000;156:1117-27 pubmed
    Mutants of the necrotic (nec) gene in Drosophila melanogaster die in the late pupal stage as pharate adults, or hatch as weak, but relatively normal-looking, flies...
  7. Green C, Brown G, Dafforn T, Reichhart J, Morley T, Lomas D, et al. Drosophila necrotic mutations mirror disease-associated variants of human serpins. Development. 2003;130:1473-8 pubmed
    ..The Drosophila serpin Necrotic controls the innate immune response and is homologous to human alpha(1)-antitrypsin...
  8. Pelte N, Robertson A, Zou Z, Belorgey D, Dafforn T, Jiang H, et al. Immune challenge induces N-terminal cleavage of the Drosophila serpin Necrotic. Insect Biochem Mol Biol. 2006;36:37-46 pubmed
    The Drosophila Necrotic protein is a serine proteinase inhibitor, which regulates the Toll-mediated innate immune response...
  9. Gubb D, Green C, Huen D, Coulson D, Johnson G, Tree D, et al. The balance between isoforms of the prickle LIM domain protein is critical for planar polarity in Drosophila imaginal discs. Genes Dev. 1999;13:2315-27 pubmed
    ..Lack of both pk and sple transcripts gives a phenotype affecting the whole body surface that is similar to those of dishevelled and frizzled (fz) suggesting a functional relationship between pk and fz signaling. ..

More Information


  1. Levashina E, Langley E, Green C, Gubb D, Ashburner M, Hoffmann J, et al. Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila. Science. 1999;285:1917-9 pubmed
    ..Here, a loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to lead to constitutive expression of the antifungal peptide drosomycin, and this effect was mediated ..
  2. Govind S, Nehm R. Innate immunity in fruit flies: a textbook example of genomic recycling. PLoS Biol. 2004;2:E276 pubmed
  3. Robertson A, Belorgey D, Gubb D, Dafforn T, Lomas D. Inhibitory activity of the Drosophila melanogaster serpin Necrotic is dependent on lysine residues in the D-helix. J Biol Chem. 2006;281:26437-43 pubmed
    b>Necrotic is a member of the serine protease inhibitor or serpin superfamily. It is a potent inhibitor of elastase and chymotrypsin type proteases and is responsible for regulating the anti-fungal response in Drosophila melanogaster...
  4. Soukup S, Culi J, Gubb D. Uptake of the necrotic serpin in Drosophila melanogaster via the lipophorin receptor-1. PLoS Genet. 2009;5:e1000532 pubmed publisher
    ..conclusion, we identify the cells and the receptor molecule responsible for the uptake and degradation of the Necrotic serpin in Drosophila melanogaster...
  5. Agnes F, Suzanne M, Noselli S. The Drosophila JNK pathway controls the morphogenesis of imaginal discs during metamorphosis. Development. 1999;126:5453-62 pubmed
    ..We discuss a general model whereby the JNK pathway regulates morphogenesis of epithelia with differentiated edges. ..
  6. De Gregorio E, Han S, Lee W, Baek M, Osaki T, Kawabata S, et al. An immune-responsive Serpin regulates the melanization cascade in Drosophila. Dev Cell. 2002;3:581-92 pubmed
    ..Our data demonstrate that Serpin-27A is required to restrict the phenoloxidase activity to the site of injury or infection, preventing the insect from excessive melanization. ..
  7. Kambris Z, Brun S, Jang I, Nam H, Romeo Y, Takahashi K, et al. Drosophila immunity: a large-scale in vivo RNAi screen identifies five serine proteases required for Toll activation. Curr Biol. 2006;16:808-13 pubmed
    ..These results demonstrate the existence of a common cascade of SPs upstream of Spz, integrating signals sent by various secreted recognition molecules via more specialized SPs. ..
  8. Heitzler P, Coulson D, Saenz Robles M, Ashburner M, Roote J, Simpson P, et al. Genetic and cytogenetic analysis of the 43A-E region containing the segment polarity gene costa and the cellular polarity genes prickle and spiny-legs in Drosophila melanogaster. Genetics. 1993;135:105-15 pubmed
    ..In addition 19 novel lethal complementation groups and two semi-lethal complementation groups with morphogenetic escaper phenotypes are described. ..
  9. Moreno E, Yan M, Basler K. Evolution of TNF signaling mechanisms: JNK-dependent apoptosis triggered by Eiger, the Drosophila homolog of the TNF superfamily. Curr Biol. 2002;12:1263-8 pubmed
    ..A direct mode of action via the apical FADD/caspase-8 pathway may have been coopted by some TNF signaling systems only at subsequent stages of evolution. ..
  10. Ahmad S, Sweeney S, Lee J, Sweeney N, Gao F. Genetic screen identifies serpin5 as a regulator of the toll pathway and CHMP2B toxicity associated with frontotemporal dementia. Proc Natl Acad Sci U S A. 2009;106:12168-73 pubmed publisher
    ..This fly model will be useful to further dissect genetic pathways that are potentially relevant to the pathogenesis and treatment of FTD. ..
  11. Easow G, Teleman A, Cohen S. Isolation of microRNA targets by miRNP immunopurification. RNA. 2007;13:1198-204 pubmed
    ..This approach provides a means to identify functional miRNA targets based on their physical interaction in vivo. ..
  12. Michel T, Reichhart J, Hoffmann J, Royet J. Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature. 2001;414:756-9 pubmed
    ..Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway...
  13. McEwen D, Cox R, Peifer M. The canonical Wg and JNK signaling cascades collaborate to promote both dorsal closure and ventral patterning. Development. 2000;127:3607-17 pubmed
    ..Together, these results demonstrate that MAP-Kinase and Wingless signaling cooperate in both the dorsal and ventral epidermis, and suggest that Wingless may activate both the Wingless and the Jun N-terminal kinase signaling cascades. ..
  14. Ulevitch R. Toll gates for pathogen selection. Nature. 1999;401:755-6 pubmed
  15. Stronach B, Perrimon N. Activation of the JNK pathway during dorsal closure in Drosophila requires the mixed lineage kinase, slipper. Genes Dev. 2002;16:377-87 pubmed
    ..Furthermore, our results show that other putative JNKKKs cannot compensate for the loss of slpr function and, thus, may regulate other JNK or MAPK-dependent processes. ..
  16. Adachi Yamada T, O Connor M. Morphogenetic apoptosis: a mechanism for correcting discontinuities in morphogen gradients. Dev Biol. 2002;251:74-90 pubmed
    ..This phenomenon is likely related to the process of cell competition, and we suggest that it is an evolutionarily important mechanism that helps prevent abnormal tissue specification and growth during development. ..
  17. Yang L, Keyhani N, Tang G, Tian C, Lu R, Wang X, et al. Expression of a toll signaling regulator serpin in a mycoinsecticide for increased virulence. Appl Environ Microbiol. 2014;80:4531-9 pubmed
    ..The Drosophila melanogaster serpin Spn43Ac negatively controls the Toll pathway that is activated in response to fungal infection...
  18. Yan H, Venkatesan K, Beaver J, Klitgord N, Yildirim M, Hao T, et al. A genome-wide gene function prediction resource for Drosophila melanogaster. PLoS ONE. 2010;5:e12139 pubmed publisher
    ..The resulting resource of prioritized associations between Drosophila genes and their potential functions offers a guide for experimental investigations. ..
  19. Yamamoto Hino M, Muraoka M, Kondo S, Ueda R, Okano H, Goto S. Dynamic regulation of innate immune responses in Drosophila by Senju-mediated glycosylation. Proc Natl Acad Sci U S A. 2015;112:5809-14 pubmed publisher
  20. Martin Blanco E, Gampel A, Ring J, Virdee K, Kirov N, Tolkovsky A, et al. puckered encodes a phosphatase that mediates a feedback loop regulating JNK activity during dorsal closure in Drosophila. Genes Dev. 1998;12:557-70 pubmed
  21. Ligoxygakis P, Pelte N, Hoffmann J, Reichhart J. Activation of Drosophila Toll during fungal infection by a blood serine protease. Science. 2002;297:114-6 pubmed
    ..We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection. ..
  22. Sanyal S, Sandstrom D, Hoeffer C, Ramaswami M. AP-1 functions upstream of CREB to control synaptic plasticity in Drosophila. Nature. 2002;416:870-4 pubmed
  23. Martin Blanco E. Regulatory control of signal transduction during morphogenesis in Drosophila. Int J Dev Biol. 1998;42:363-8 pubmed
    ..The negative regulatory control of signal transduction pathways could be a general mechanism regulating differentiation and morphogenesis. ..
  24. Weber U, Paricio N, Mlodzik M. Jun mediates Frizzled-induced R3/R4 cell fate distinction and planar polarity determination in the Drosophila eye. Development. 2000;127:3619-29 pubmed
  25. Tateno M, Nishida Y, Adachi Yamada T. Regulation of JNK by Src during Drosophila development. Science. 2000;287:324-7 pubmed
    ..Thus, activation of the Bsk pathway is required downstream of Src42A in epidermal closure. This work confirms mammalian studies that demonstrated a physiological link between Src and JNK. ..
  26. Adachi Yamada T, Fujimura Kamada K, Nishida Y, Matsumoto K. Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing. Nature. 1999;400:166-9 pubmed
  27. Shin S, Kokoza V, Bian G, Cheon H, Kim Y, Raikhel A. REL1, a homologue of Drosophila dorsal, regulates toll antifungal immune pathway in the female mosquito Aedes aegypti. J Biol Chem. 2005;280:16499-507 pubmed
    ..bassiana. These results indicate that the homologue of Dl, but not that of Dif, is a key regulator of the Toll antifungal immune pathway in A. aegypti female mosquitoes. ..
  28. Gritzan U, Weiss C, Brennecke J, Bohmann D. Transrepression of AP-1 by nuclear receptors in Drosophila. Mech Dev. 2002;115:91-100 pubmed
    ..A potential role of nuclear receptors in setting a threshold of AP-1 activity required for the manifestation of a cellular response is discussed. ..
  29. Janssens S, Beyaert R. Role of Toll-like receptors in pathogen recognition. Clin Microbiol Rev. 2003;16:637-46 pubmed
    ..The fact that TLR expression is regulated in both a cell type- and stimulus-dependent fashion further contributes to the complexity. ..
  30. Matskevich A, Quintin J, Ferrandon D. The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll-pathway activation function. Eur J Immunol. 2010;40:1244-54 pubmed publisher
    ..Finally, we show that GNBP3 assembles "attack complexes", which comprise phenoloxidase and the necrotic serpin. We propose that Drosophila GNBP3 targets fungi immediately at the inception of the infection by bringing ..
  31. Ramet M, Lanot R, Zachary D, Manfruelli P. JNK signaling pathway is required for efficient wound healing in Drosophila. Dev Biol. 2002;241:145-56 pubmed
    ..In addition, Drosophila appears as a good in vivo model to study morphogenetic processes requiring epithelial regeneration such as wound healing in vertebrates. ..
  32. Luheshi L, Hoyer W, de Barros T, van Dijk Härd I, Brorsson A, Macao B, et al. Sequestration of the Abeta peptide prevents toxicity and promotes degradation in vivo. PLoS Biol. 2010;8:e1000334 pubmed publisher
  33. Zeitlinger J, Bohmann D. Thorax closure in Drosophila: involvement of Fos and the JNK pathway. Development. 1999;126:3947-56 pubmed
  34. Williams J, Sathyanarayanan S, Hendricks J, Sehgal A. Interaction between sleep and the immune response in Drosophila: a role for the NFkappaB relish. Sleep. 2007;30:389-400 pubmed
    ..These results demonstrate a conserved interaction between sleep and the immune system. Genetic manipulation of an immune component alters sleep, and likewise, acute sleep deprivation alters the immune response. ..
  35. Khush R, Leulier F, Lemaitre B. Immunology. Pathogen surveillance--the flies have it. Science. 2002;296:273-5 pubmed
  36. Moreno E, Basler K, Morata G. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature. 2002;416:755-9 pubmed
    ..This sequence of events might represent a general mechanism by which weaker cells are eliminated from a growing population, and might serve as a method of controlling cell number and optimizing tissue fitness and hence organ function. ..
  37. Reichhart J, Ligoxygakis P, Naitza S, Woerfel G, Imler J, Gubb D. Splice-activated UAS hairpin vector gives complete RNAi knockout of single or double target transcripts in Drosophila melanogaster. Genesis. 2002;34:160-4 pubmed