The Protein Journal

, Volume 36, Issue 2, pp 77–97 | Cite as

Analysis of Pelagia noctiluca proteome Reveals a Red Fluorescent Protein, a Zinc Metalloproteinase and a Peroxiredoxin

  • Bárbara Frazão
  • Alexandre Campos
  • Hugo Osório
  • Benjamin Thomas
  • Sérgio Leandro
  • Alexandre Teixeira
  • Vitor Vasconcelos
  • Agostinho AntunesEmail author


Pelagia noctiluca is the most venomous jellyfish in the Mediterranean Sea where it forms dense blooms. Although there is several published research on this species, until now none of the works has been focused on a complete protein profile of the all body constituents of this organism. Here, we have performed a detailed proteomics characterization of the major protein components expressed by P. noctiluca. With that aim, we have considered the study of jellyfish proteins involved in defense, body constituents and metabolism, and furthered explore the significance and potential application of such bioactive molecules. P. noctiluca body proteins were separated by1D SDS–PAGE and 2DE followed by characterization by nanoLC-MS/MS and MALDI-TOF/TOF techniques. Altogether, both methods revealed 68 different proteins, including a Zinc Metalloproteinase, a Red Fluorescent Protein (RFP) and a Peroxiredoxin. These three proteins were identified for the first time in P. noctiluca. Zinc Metalloproteinase was previously reported in the venom of other jellyfish species. Besides the proteins described above, the other 65 proteins found in P. noctiluca body content were identified and associated with its clinical significance. Among all the proteins identified in this work we highlight: Zinc metalloproteinase, which has a ShK toxin domain and therefore should be implicated in the sting toxicity of P. noctiluca.; the RFP which are a very important family of proteins due to its possible application as molecular markers; and last but not least the discovery of a Peroxiredoxin in this organism makes it a new natural resource of antioxidant and anti-UV radiation agents.


Pelagia noctiluca Jellyfish Proteomic Toxin 





Colloidal Coomassie Brilliant Blue


3[(3-cholamidopropyl) dimethylammonio]-1-propane sulfonate


Cytochrome oxidase subunit I


Cetyl trimethylammonium bromide


Desoxyribonucleic acid


Green fluorescent protein


Human immunodeficiency virus


High Preformence Liquid Chromatography


Isoelectric focusing


Liquid chromatography mass spectrometry


Matrix-assisted laser desorption/ionization Time-of-Flight


National Center for Biotechnology Information


Polymerase Chain Reaction


Phospholipase A2


Ref fluorescent protein


Ribonucleic acid


Reactive oxygen species




Sodium dodecyl sulfate polyacrylamide gel


Tris (2-Carboxyethyl) phosphine Hydrochloride




Yellow fluorescent protein


α-cyano-4-hydroxycinnamic acid



BF was funded by a PhD grant (SFRH/BD/48184/2008) from the Foundation for Science and Technology “Fundação para a Ciência e a Tecnologia” (FCT). AA was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT and the European Regional Development Fund (ERDF) in the framework of the program PT2020, by the European Structural and Investment Funds (ESIF) through the Competitiveness and Internationalization Operational Program - COMPETE 2020 and by National Funds through the FCT under the projects PTDC/AAG-GLO/6887/2014 (POCI-01-0124-FEDER-016845) and PTDC/MAR-BIO/0440/2014 (POCI-01-0145-FEDER-016772), and by the Structured Program of R&D&I INNOVMAR - Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, Research Line NOVELMAR) and CORAL NORTE (NORTE-01-0145-FEDER-000036), funded by the Northern Regional Operational Program (NORTE2020) through the ERDF.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Tibballs J (2006) Australian venomous jellyfish, envenomation syndromes, toxins and therapy. Toxicon 48:830–859CrossRefGoogle Scholar
  2. 2.
    Marino A, Valveri V, Muia C, Crupi R, Rizzo G, Musci G, La Spada G (2004) Cytotoxicity of the nematocyst venom from the sea anemone Aiptasia mutabilis. Comp Biochem Physiol C Toxicol Pharmacol 139:295–301CrossRefGoogle Scholar
  3. 3.
    Mariottini GL, Giacco E, Pane L (2008) The mauve stinger Pelagia noctiluca (Forsskål, 1775). Distribution, ecology, toxicity and epidemiology of stings. A review. Mar Drugs 6:496–513Google Scholar
  4. 4.
    Del Pozo LJ, Knopfel N, Martin-Santiago A, Escudero-Gongora MM, Saus C, Izquierdo-Herce N, Bauza-Alonso A (2016) Dermoscopic Findings of Jellyfish Stings Caused by Pelagia noctiluca. Actas DermosifiliogrGoogle Scholar
  5. 5.
    Burnett JW (2009) Treatment of Atlantic cnidarian envenomations. Toxicon 54:1201–1205CrossRefGoogle Scholar
  6. 6.
    Andras CD, Albert C, Salamon S, Galicza J, Andras R, Andras E (2011) Conus magus vs. Irukandji syndrome: a computational approach of a possible new therapy. Brain Res Bull 10:195–201CrossRefGoogle Scholar
  7. 7.
    Morabito R, Marino A, Lauf PK, Adragna NC, La Spada G, Cell Physiol B (2013) Sea water acidification affects osmotic swelling, regulatory volume decrease and discharge in nematocytes of the jellyfish Pelagia noctiluca. Cell Physiol Biochem 32:77–85CrossRefGoogle Scholar
  8. 8.
    Morabito R, Dossena S, La Spada G, Marino A, Cell Physiol B (2014) Heavy metals affect nematocysts discharge response and biological activity of crude venom in the jellyfish Pelagia noctiluca (Cnidaria, Scyphozoa). Cell Physiol Biochem 34:244–254CrossRefGoogle Scholar
  9. 9.
    Zimmer M, Chem Soc R (2009) GFP: from jellyfish to the Nobel prize and beyond. Chem Soc Rev 38:2823–2832CrossRefGoogle Scholar
  10. 10.
    Fradkov AF, Chen Y, Ding L, Barsova EV, Matz MV, Lukyanov SA, Lett F (2000) Novel fluorescent protein from Discosoma coral and its mutants possesses a unique far-red fluorescence. FEBS Lett 479:127–130CrossRefGoogle Scholar
  11. 11.
    Hoi H, Howe ES, Ding Y, Zhang W, Baird MA, Sell BR, Allen JR, Davidson MW, Campbell RE (2013) An engineered monomeric Zoanthus sp. yellow fluorescent protein. Chem Biol 20:1296–1304CrossRefGoogle Scholar
  12. 12.
    Chudakov DM, Matz MV, Lukyanov S, Lukyanov KA (2010) Fluorescent proteins and their applications in imaging living cells and tissues. Physiol Rev 90:1103–1163CrossRefGoogle Scholar
  13. 13.
    Licandro P, Conway DVP, Daly Yahia MN, Fernandez de Puelles ML, Gasparini S, Hecq JH, Tranter P, Kirby RR (2010) A blooming jellyfish in the northeast Atlantic and Mediterranean. Biol Lett 6:688–691CrossRefGoogle Scholar
  14. 14.
    Bosch-Belmar M, M’Rabet C, Dhaouadi R, Chalghaf M, Daly Yahia MN, Fuentes V, Piraino S, Kefi-Daly Yahia O (2016) Jellyfish stings trigger gill disorders and increased mortality in farmed Sparus aurata (Linnaeus, 1758) in the Mediterranean Sea. PLoS ONE 11:e0154239CrossRefGoogle Scholar
  15. 15.
    Milisenda G, Rosa S, Fuentes VL, Boero F, Guglielmo L, Purcell JE, Piraino S (2014) Jellyfish as prey: frequency of predation and selective foraging of Boops boops (Vertebrata, Actinopterygii) on the mauve stinger Pelagia noctiluca (Cnidaria, Scyphozoa). PLoS ONE 9:1932–6203CrossRefGoogle Scholar
  16. 16.
    Mariottini GL, Sottofattori E, Mazzei M, Robbiano L, Carli A (2002) Cytotoxicity of the venom of Pelagia noctiluca forskål (Cnidaria: Scyphozoa). Toxicon 40:695–698CrossRefGoogle Scholar
  17. 17.
    Morabito R, La Spada G, Crupi R, Esposito E, Marino A (2015) Crude venom from nematocysts of the jellyfish Pelagia noctiluca as a tool to study cell physiology. Cent Nerv Syst Agents Med Chem 15:68–73CrossRefGoogle Scholar
  18. 18.
    Ayed Y, Boussabbeh M, Zakhama W, Bouaziz C, Abid S, Bacha H (2011) Induction of cytotoxicity of Pelagia noctiluca venom causes reactive oxygen species generation, lipid peroxydation induction and DNA damage in human colon cancer cells. Lipids Health Dis 10:1–10CrossRefGoogle Scholar
  19. 19.
    Ayed Y, Chayma B, Hayla A, Abid S, Bacha H (2013) Is cell death induced by nematocysts extract of medusa Pelagia noctiluca related to oxidative stress?. Env Toxicol 28:498–506.CrossRefGoogle Scholar
  20. 20.
    Salleo A, La Spada G, Barbera R (1994) Gadolinium is a powerful blocker of the activation of nematocytes of Pelagia noctiluca. J Exp Biol 187:201–206Google Scholar
  21. 21.
    Ovchinnikova TV, Balandin SV, Aleshina GM, Tagaev AA, Leonova YF, Krasnodembsky ED, Men’shenin AV, Kokryakov VN (2006) Aurelin, a novel antimicrobial peptide from jellyfish Aurelia aurita with structural features of defensins and channel-blocking toxins. Biochem Biophys Res Commun 348:514–523CrossRefGoogle Scholar
  22. 22.
    Ávila-Soria G (2009) Molecular characterization of Carukia barnesi and Malo kingi, Cnidaria; Cubozoa; Carybdeidae. PhD thesis:192.Google Scholar
  23. 23.
    Nagai H, Takuwa K, Nakao M, Sakamoto B, Crow GL, Nakajima T (2000) Isolation and characterization of a novel protein toxin from the Hawaiian box jellyfish (sea wasp) Carybdea alata. Biochem Biophys Res Commun 275:589–594CrossRefGoogle Scholar
  24. 24.
    Nagai H, Takuwa K, Nakao M, Ito E, Miyake M, Noda M, Nakajima T (2000) Novel proteinaceous toxins from the box jellyfish (sea wasp) Carybdea rastoni. Biochem Biophys Res Commun 275:582–588CrossRefGoogle Scholar
  25. 25.
    Brinkman D, Burnell J (2007) Identification, cloning and sequencing of two major venom proteins from the box jellyfish, Chironex fleckeri. Toxicon 50:850–860CrossRefGoogle Scholar
  26. 26.
    Brinkman D, Burnell J (2008) Partial purification of cytolytic venom proteins from the box jellyfish, Chionex fleckeri. Toxicon 51:853–863CrossRefGoogle Scholar
  27. 27.
    Brinkman DL, Konstantakopoulos N, McInerney BV, Mulvenna J, Seymour JE, Isbister GK, Hodgson WC (2014) Chironex fleckeri (box jellyfish) venom proteins: expansion of a cnidarian toxin family that elicits variable cytolytic and cardiovascular effects. J Biol Chem 289:4798–4812CrossRefGoogle Scholar
  28. 28.
    Nagai H, Takuwa-Kuroda K, Nakao M, Oshiro N, Iwanaga S, Nakajima T (2002) A novel protein toxin from the deadly box jellyfish (Sea Wasp, Habu-kurage) Chiropsalmus quadrigatus. Biosci Biotechnol Biochem 66:97–102CrossRefGoogle Scholar
  29. 29.
    Lassen S, Helmholz H, Ruhnau C, Prange A (2011) A novel proteinaceous cytotoxin from the northern Scyphozoa Cyanea capillata (L.) with structural homology to cubozoan haemolysins. Toxicon 57:721–729CrossRefGoogle Scholar
  30. 30.
    Lassen S, Wiebring A, Helmholz H, Ruhnau C, Prange A (2012) Isolation of a Nav channel blocking polypeptide from Cyanea capillata medusae- a neurotoxin contained in fishing tentacle isorhizas. Toxicon 59:610–616CrossRefGoogle Scholar
  31. 31.
    Carneiro RF, Nascimento NR, Costa PP, Gomes VM, de Souza AJ, de Oliveira SC, Dos Santos Diz Filho EB, Zara FJ, Fonteles MC, de Oliveira Toyama D, Toyama MH, Santos CF, Toxicol JA (2011) The extract of the jellyfish Phyllorhiza punctata promotes neurotoxic effects. J Appl Toxicol 31:720–729.Google Scholar
  32. 32.
    Tamkun MM, Hessinger DA, Biochim Biophys A (1981) Isolation and partial characterization of a hemolytic and toxic protein from the nematocyst venom of the Portuguese Man-of-War, Physalia physalis. Biochim Biophys Acta 667:87–98CrossRefGoogle Scholar
  33. 33.
    Menendez R, Mas R, Garateix A, Garcia M, Chavez M (1990) Effects of a high molecular weight polypeptidic toxin from Physalia physalis (Portuguese man-of-war) on cholinergic responses. Comp Biochem Physiol C 95:63–69CrossRefGoogle Scholar
  34. 34.
    Mas R, Menendez R, Garateix A, Garcia M, Chavez M (1989) Effects of a high molecular weight toxin from Physalia physalis on glutamate responses. Neuroscience 33:269–273CrossRefGoogle Scholar
  35. 35.
    Diaz-Garcia CM, Fuentes-Silva D, Sanchez-Soto C, Dominguez-Perez D, Garcia-Delgado N, Varela C, Mendoza-Hernandez G, Rodriguez-Romero A, Castaneda O, Hiriart M (2012) Toxins from Physalia physalis (Cnidaria) raise the intracellular Ca2+ of beta-cells and promote insulin secretion. Curr Med Chem 19:5414–5423CrossRefGoogle Scholar
  36. 36.
    Li R, Yu H, Xing R, Liu S, Qing Y, Li K, Li B, Meng X, Cui J, Li P (2012) Application of nanoLC-MS/MS to the shotgun proteomic analysis of the nematocyst proteins from jellyfish Stomolophus meleagris. J Chromatogr B Anal Technol Biomed. Life Sci 899:86–95Google Scholar
  37. 37.
    Stopar K, Ramsak A, Trontelj P, Malej A (2010) Lack of genetic structure in the jellyfish Pelagia noctiluca (Cnidaria: Scyphozoa: Semaeostomeae) across European seas. Mol Phylogenet Evol 57:417–428CrossRefGoogle Scholar
  38. 38.
    Rocha J, Peixe L, Gomes NCM, Calado R (2011) Cnidarians as a source of new marine bioactive compounds–an overview of the last decade and future steps for bioprospecting. Mar Drugs 9:1860–1886CrossRefGoogle Scholar
  39. 39.
    Ruan Z, Liu G, Wang B, Zhou Y, Lu J, Wang Q, Zhao J, Zhang L (2014) First report of a peroxiredoxin homologue in jellyfish: molecular cloning, expression and functional characterization of CcPrx4 from Cyanea capillata. Mar Drugs 12:214–231CrossRefGoogle Scholar
  40. 40.
    Pierce J (2009) Prediction, location, collection and transport of jellyfish (Cnidaria) and their polyps. Zoo Biol 28:163–176CrossRefGoogle Scholar
  41. 41.
    Maisano M, Trapani MR, Parrino V, Parisi MG, Cappello T, D’Agata A, Benenati G, Natalotto A, Mauceri A, Cammarata M (2013) Haemolytic activity and characterization of nematocyst venom from Pelagia noctiluca (Cnidaria: Scyphozoa). Ital J Zool 80:168–176CrossRefGoogle Scholar
  42. 42.
    Santos R, da Costa G, Franco C, Gomes-Alves P, Flammang P, Coelho AV (2009) First insights into the biochemistry of tube foot adhesive from the sea urchin Paracentrotus lividus (Echinoidea Echinodermata). Mar Biotechnol 11:686–698CrossRefGoogle Scholar
  43. 43.
    Neuhoff V, Arold N, Taube D, Ehrhardt W, (1988) Improved staining of proteins in polyacrylamide gels including isoelectric focusing gels with clear background at nanogram sensitivity using Coomassie Brilliant Blue G-250 and R-250. Electrophoresis 9:255–262CrossRefGoogle Scholar
  44. 44.
    Raposo R, Thomas B, Ridlova G, James W (2011) Proteomic-Based Identification of CD4-Interacting Proteins in Human Primary Macrophages. PLoS ONE 6:e18690CrossRefGoogle Scholar
  45. 45.
    Puerto M, Campos A, Prieto A, Cameán A, Almeida AM, Coelho AV, Vasconcelos V (2011) Differential protein expression in two bivalve species; Mytilus galloprovincialis and Corbicula fluminea; exposed to Cylindrospermopsis raciborskii cells. Aquat Toxicol 101:109–116CrossRefGoogle Scholar
  46. 46.
    Neves J, Campos A, Osório H, Antunes A, Vasconcelos V (2013) Conopeptides from Cape Verde Conus crotchii. Mar Drugs 11:2203–2215CrossRefGoogle Scholar
  47. 47.
    Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer ELL, Tate J, Punta M The Pfam protein families database. Available online: (Accessed 15 March 2015).
  48. 48.
    Consortium TU (2014) Activities at the Universal Protein Resource (UniProt). Nucleic Acids Res. 42Google Scholar
  49. 49.
    Geller JB, Walton ED (2001) Breaking up and getting together: evolution of symbiosis and cloning by fission in sea anemones (Genus Anthopleura). Evolution (N Y) 55:1781–1794.CrossRefGoogle Scholar
  50. 50.
    Bridge D, Cunningham CW, Schierwater B, Desalle R, Buss L (1992) Class-level relationships in the phylum Cnidaria: Evidence from mitochondrial genome structure. Proc Natl Acad Sci 89:8750–8753.CrossRefGoogle Scholar
  51. 51.
    Meyer CP, Geller JB, Paulay G (2005) Fine scale endemism on coral reefs: archipelagic differentiation in turbinid gastropods. Evolution (N Y) 59:113.CrossRefGoogle Scholar
  52. 52.
    Kearse M, Moir R, Wilson A, Stones-Havas S, Cheung M, Sturrock S, Buxton S, Cooper A, Markowitz S, Duran C, Thierer T, Ashton B, Meintjes P, Drummond A (2012) Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28:1647–1649CrossRefGoogle Scholar
  53. 53.
    Kawabata T, Lindsay D, Kitamura M, Konishi S, Nishikawa J, Nishida S, Kamio M, Nagai H (2013) Evaluation of the bioactivities of water-soluble extracts from twelve deep-sea jellyfish species. Fish Sci 79:487–494.CrossRefGoogle Scholar
  54. 54.
    Brinkman DL, Aziz A, Loukas A, Potriquet J, Seymour J, Mulvenna J (2012) Venom proteome of the box jellyfish Chironex fleckeri. PLoS ONE 7:e47866CrossRefGoogle Scholar
  55. 55.
    Weston AJ, Chung R, Dunlap WC, Morandini AC, Marques AC, Moura-da-Silva AM, Ward M, Padilla G, da Silva LLF, Andreakis N, Long PF (2013) Proteomic characterisation of toxins isolated from nematocysts of the South Atlantic jellyfish Olindias sambaquiensis. Toxicon 71:11–17CrossRefGoogle Scholar
  56. 56.
    Kang C, Han DY, Park KI, Pyo MJ, Heo Y, Lee H, Kim GS, Kim E, (2014) Characterization and neutralization of Nemopilema nomurai (Scyphozoa: Rhizostomeae) jellyfish venom using polyclonal antibody. Toxicon 86:116–125CrossRefGoogle Scholar
  57. 57.
    Li R, Yu H, Xue W, Yue Y, Liu S, Xing R, Li P (2014) Jellyfish venomics and venom gland transcriptomics analysis of Stomolophus meleagris to reveal the toxins associated with sting. J Proteomics 106:17–29CrossRefGoogle Scholar
  58. 58.
    Letunic I, Doerks T, Bork P (2015) SMART: recent updates, new developments and status in 2015. Nucleic Acids Res 43:D257–D260CrossRefGoogle Scholar
  59. 59.
    Lee H, Jung E sun, Kang C, Yoon WD, Kim JS, Kim E (2011) Scyphozoan jellyfish venom metalloproteinases and their role in the cytotoxicity. Toxicon 58:277–284CrossRefGoogle Scholar
  60. 60.
    Pan T, Groger H, Schmid V, Spring J, Dev Genes E, Gröger H, Schmid V, Spring J (1998) A toxin homology domain in an astacin-like metalloproteinase of the jellyfish Podocoryne carnea with a dual role in digestion and development. Dev Genes Evol 208:259–266CrossRefGoogle Scholar
  61. 61.
    Sánchez–Rodríguez J, Lucio–Martínez NL (2011) Isolation and prepurification of active compounds in venom from Pelagia noctiluca (Scyphozoa: Pelagiidae). Ciencias Mar 37:369–377.CrossRefGoogle Scholar
  62. 62.
    Marino A, Crupi R, Rizzo G, Morabito R, Musci G, La Spada G (2007) The unusual toxicity and stability properties of crude venom from isolated nematocysts of Pelagia noctiluca (Cnidaria, Scyphozoa). Cell Mol Biol 53:Suppl:OL994–1002.Google Scholar
  63. 63.
    Marino A, Morabito R, Pizzata T, La Spada G (2008) Effect of various factors on Pelagia noctiluca (Cnidaria, Scyphozoa) crude venom-induced haemolysis. Comp Biochem Physiol A Mol Integr Physiol 151:144–149CrossRefGoogle Scholar
  64. 64.
    Ayed Y, Bouaziz C, Brahmi D, Zaid C, Abid S, Bacha H (2014) Cell death in relation to DNA damage after exposure to the jellyfish Pelagia noctiluca nematocysts. Env Toxicol 29:337–344.CrossRefGoogle Scholar
  65. 65.
    Morabito R, Condello S, Curro M, Marino A, Ientile R, La Spada G (2012) Oxidative stress induced by crude venom from the jellyfish Pelagia noctiluca in neuronal-like differentiated SH-SY5Y cells. Toxicol Vitr 26:694–699.CrossRefGoogle Scholar
  66. 66.
    Ayed Y, Bousabbeh M, Mabrouk HB, Morjen M, Marrakchi N, Bacha H (2012) Impairment of the cell-to-matrix adhesion and cytotoxicity induced by the Mediterranean jellyfish Pelagia noctiluca venom and its fractions in cultured glioblastoma cells. Lipids Health Dis 11:1–9CrossRefGoogle Scholar
  67. 67.
    Santoro MG (2000) Heat shock factors and the control of the stress response. Biochem Pharmacol 59:55–63CrossRefGoogle Scholar
  68. 68.
    Matz MV, Fradkov AF, Labas YA, Savitsky AP, Zaraisky AG, Markelov MI, Lukyanov SA (1999) Fluorescent proteins from nonbioluminescent Anthozoa species. Nat Biotechnol 17:969–973CrossRefGoogle Scholar
  69. 69.
    Shrestha S, Deo SK (2006) Anthozoa red fluorescent protein in biosensing. Anal Bioanal Chem 386:515–524CrossRefGoogle Scholar
  70. 70.
    Zhuang Y, Hou H, Zhao X, Zhang Z, Li B (2009) Effects of collagen and collagen hydrolysate from jellyfish (Rhopilema esculentum) on mice skin photoaging induced by UV irradiation. J Food Sci 74:H183–H188CrossRefGoogle Scholar
  71. 71.
    Desvignes T, Pontarotti P, Bobe J (2010) Nme gene family evolutionary history reveals pre-metazoan origins and high conservation between humans and the sea anemone, Nematostella vectensis. PLoS ONE 5:e15506CrossRefGoogle Scholar
  72. 72.
    Bubka M, Link-Lenczowski P, Janik M, Pochec E, Litynska A (2014) Overexpression of N-acetylglucosaminyltransferases III and V in human melanoma cells. Implications for MCAM N-glycosylation. Biochimie 103:37–49CrossRefGoogle Scholar
  73. 73.
    Bierbaum S, Nickel R, Koch A, Lau S, Deichmann KA, Wahn U, Superti-Furga A, Heinzmann A (2005) Polymorphisms and Haplotypes of Acid Mammalian Chitinase Are Associated with Bronchial Asthma. Am J Respir Crit Care Med 172:1505–1509CrossRefGoogle Scholar
  74. 74.
    Ikeda N, Nakajima Y, Tokuhara T, Hattori N, Sho M, Kanehiro H, Miyake M (2003) Clinical significance of aminopeptidase N/CD13 expression in human pancreatic carcinoma. Clin Cancer Res 9:1503–1508Google Scholar
  75. 75.
    Tomita H, Sato S, Matsuda R, Sugiura Y, Kawaguchi H, Niimi T, Yoshida S, Morishita M (1999) Serum lysozyme levels and clinical features of sarcoidosis. Lung 177:161–167CrossRefGoogle Scholar
  76. 76.
    Lamballe F, Maniey D, Boscher MY, Fauchet R, le Prise PY, David JC (1988) Effects of clinical combinations of antileukemic drugs on DNA ligase from human thymocytes and normal, stimulated, or leukemic lymphocytes. Leukemia 2:363–370Google Scholar
  77. 77.
    Martinon F, Gaide O, Petrilli V, Mayor A, Tschopp J (2007) NALP inflammasomes: a central role in innate immunity. Semin Immunopathol 29:213–229CrossRefGoogle Scholar
  78. 78.
    Khan KN, Nakata K, Kusumoto Y, Nakao K, Kato Y, Nagataki S (1998) Use of fructose 1,6-diphosphate aldolase to detect tumour necrosis after transcatheter arterial embolization of hepatocellular carcinoma. J Gastroenterol Hepatol 13:192–196CrossRefGoogle Scholar
  79. 79.
    Gonzalez D, Elias M, Chabriere E (2014) The DING family of phosphate binding proteins in inflammatory diseases. Adv Exp Med Biol 824:27–32CrossRefGoogle Scholar
  80. 80.
    Tian X, Zhang S, Liu HM, Zhang YB, Blair CA, Mercola D, Sassone-Corsi P, Zi X (2013) Histone lysine-specific methyltransferases and demethylases in carcinogenesis: new targets for cancer therapy and prevention. Curr Cancer Drug Targets 13:558–579CrossRefGoogle Scholar
  81. 81.
    Muscoli C, Cuzzocrea S, Riley DP, Zweier JL, Thiemermann C, Wang ZQ, Salvemini D (2003) On the selectivity of superoxide dismutase mimetics and its importance in pharmacological studies. Br J Pharmacol 140:445–460CrossRefGoogle Scholar
  82. 82.
    Sinicrope FA, Sargent DJ (2012) Molecular pathways: microsatellite instability in colorectal cancer: prognostic, predictive, and therapeutic implications. Clin Cancer Res 18:1506–1512CrossRefGoogle Scholar
  83. 83.
    Goffin J, Eisenhauer E (2002) DNA methyltransferase inhibitors-state of the art. Ann Oncol 13:1699–1716CrossRefGoogle Scholar
  84. 84.
    Satish L, Gallo P, Baratz M, Johnson S, Kathju S (2011) Reversal of TGF-beta1 stimulation of alpha-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren’s - derived fibroblasts. BMC Musculoskelet Disord 12:113CrossRefGoogle Scholar
  85. 85.
    Nishikawa Y, Miyazaki T, Nakashiro K, Yamagata H, Isokane M, Goda H, Tanaka H, Oka R, Hamakawa H (2011) Human FAT1 cadherin controls cell migration and invasion of oral squamous cell carcinoma through the localization of beta-catenin. Oncol Rep 26:587–592Google Scholar
  86. 86.
    Roberts SJ, Owen HC, Farquharson C (2008) Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1. Biochem Biophys Res Commun 371:872–876CrossRefGoogle Scholar
  87. 87.
    Hoffman RM (2005) The multiple uses of fluorescent proteins to visualize cancer in vivo. Nat Rev Cancer 5:796–806CrossRefGoogle Scholar
  88. 88.
    Knudson CB, Knudson W (2001) Cartilage proteoglycans. Semin Cell Dev Biol 12:69–78CrossRefGoogle Scholar
  89. 89.
    Nash JW, Morrison C, Frankel WL (2003) The utility of estrogen receptor and progesterone receptor immunohistochemistry in the distinction of metastatic breast carcinoma from other tumors in the liver. Arch Pathol Lab Med 127:1591–1595Google Scholar
  90. 90.
    Fiedler J, Stove J, Heber F, Brenner RE (2002) Clinical phenotype and molecular diagnosis of multiple epiphyseal dysplasia with relative hip sparing during childhood (EDM2). Am J Med Genet 112:144–153CrossRefGoogle Scholar
  91. 91.
    Kim J, Park RY, Chen JK, Jeong S, Ohn T (2014) Splicing factor SRSF3 represses the translation of programmed cell death 4 mRNA by associating with the 5´-UTR region. Cell Death Differ 21:481–490CrossRefGoogle Scholar
  92. 92.
    Zhou B, Yuan T, Liu M, Liu H, Xie J, Shen Y, Chen P (2012) Overexpression of the structural maintenance of chromosome 4 protein is associated with tumor de-differentiation, advanced stage and vascular invasion of primary liver cancer. Oncol Rep 28:1263–1268Google Scholar
  93. 93.
    Yadav S, Sehrawat A, Eroglu Z, Somlo G, Hickey R, Yadav S, Liu X, Awasthi YC, Awasthi S (2013) Role of SMC1 in overcoming drug resistance in triple negative breast cancer. PLoS ONE 8:e64338CrossRefGoogle Scholar
  94. 94.
    Stabler SM, Ostrowski LL, Janicki SM, Monteiro MJ (1999) A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer’s disease presenilin 2 protein. J Cell Biol 145:1277–1292CrossRefGoogle Scholar
  95. 95.
    Ogawa M, Watanabe M, Mitsuyama Y, Anan T, Ohkuma M, Kobayashi T, Eto K, Yanaga K (2014) Thymidine phosphorylase mRNA expression may be a predictor of response to post-operative adjuvant chemotherapy with S-1 in patients with stage III colorectal cancer. Oncol Lett 8:2463–2468.Google Scholar
  96. 96.
    Adav SS, Qian J, Ang YL, Kalaria RN, Lai MK, Chen CP, Sze SK, Res JP (2014) iTRAQ quantitative clinical proteomics revealed role of Na+ K+ -ATPase and its correlation with deamidation in vascular dementia. J Proteome Res 13:4635–4646CrossRefGoogle Scholar
  97. 97.
    Krizkova S, Zitka O, Masarik M, Adam V, Stiborova M, Eckschlager T, Hubalek J, Kizek R (2011) Clinical importance of matrix metalloproteinases. Bratisl Lek List 112:435–440.Google Scholar
  98. 98.
    Chiabrando D, Marro S, Mercurio S, Giorgi C, Petrillo S, Vinchi F, Fiorito V, Fagoonee S, Camporeale A, Turco E, Merlo GR, Silengo L, Altruda F, Pinton P, Tolosano E (2012) The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation. J Clin Invest 122:4569–4579CrossRefGoogle Scholar
  99. 99.
    Flaumenhaft R, Furie B, Zwicker JI (2015) Therapeutic implications of protein disulfide isomerase inhibition in thrombotic disease. Arter Thromb Vasc Biol 35:16–23.CrossRefGoogle Scholar
  100. 100.
    Wolny M, Wroblewska AM, Machnicka B, Sikorski AF (2012) Spectrin–variety of functions hidden in the structure. Postep Biochem 58:245–254.Google Scholar
  101. 101.
    Valdes-Mas R, Gutierrez-Fernandez A, Gomez J, Coto E, Astudillo A, Puente DA, Reguero JR, Alvarez V, Moris C, Leon D, Martin M, Puente XS, Lopez-Otin C (2014) Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy. Nat Commun 5:5326CrossRefGoogle Scholar
  102. 102.
    Chua E, Clague JE, Sharma AK, Horan MA, Lombard M (1999) Serum transferrin receptor assay in iron deficiency anaemia and anaemia of chronic disease in the elderly. QJM 92:587–594CrossRefGoogle Scholar
  103. 103.
    Maksimenko A V, Vavaev A V (2012) Antioxidant enzymes as potential targets in cardioprotection and treatment of cardiovascular diseases. Enzyme antioxidants: the next stage of pharmacological counterwork to the oxidative stress. Hear Int 7:e3.Google Scholar
  104. 104.
    Klug A (2005) Towards therapeutic applications of engineered zinc finger proteins. FEBS Lett 579:892–894CrossRefGoogle Scholar
  105. 105.
    Pajares MA, Perez-Sala D (2006) Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism?. Cell Mol Life Sci 63:2792–2803CrossRefGoogle Scholar
  106. 106.
    Neri D, de Lalla C, Petrul H, Neri P, Winter G (1995) Calmodulin as a versatile tag for antibody fragments. Biotechnol (N Y) 13:373–377.CrossRefGoogle Scholar
  107. 107.
    Ellis TM, Atkinson MA (1996) The clinical significance of an autoimmune response against glutamic acid decarboxylase. Nat Med 2:148–153CrossRefGoogle Scholar
  108. 108.
    Muller CE, Schiedel AC, Baqi Y (2012) Allosteric modulators of rhodopsin-like G protein-coupled receptors: opportunities in drug development. Pharmacol Ther 135:292–315CrossRefGoogle Scholar
  109. 109.
    Matsuo M (2010) ATP-binding cassette proteins involved in glucose and lipid homeostasis. Biosci Biotechnol Biochem 74:899–907CrossRefGoogle Scholar
  110. 110.
    Rosewell K, Al-Alem L, Li F, Kelty B, Curry TE Jr (2011) Identification of hepsin and protein disulfide isomerase A3 as targets of gelatinolytic action in rat ovarian granulosa cells during the periovulatory period. Biol Reprod 85:858–866CrossRefGoogle Scholar
  111. 111.
    Ferguson MA, Brimacombe JS, Brown JR, Crossman A, Dix A, Field RA, Guther ML, Milne KG, Sharma DK, Smith TK (1999) The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness. Biochim Biophys Acta 1455:327–340CrossRefGoogle Scholar
  112. 112.
    Ding Y, Zhang L, Goodwin JS, Wang Z, Liu B, Zhang J, Fan GH (2008) Plectin regulates the signaling and trafficking of the HIV-1 co-receptor CXCR4 and plays a role in HIV-1 infection. Exp Cell Res 314:590–602CrossRefGoogle Scholar
  113. 113.
    Soti C, Nagy E, Giricz Z, Vigh L, Csermely P, Ferdinandy P (2005) Heat shock proteins as emerging therapeutic targets. Br J Pharmacol 146:769–780CrossRefGoogle Scholar
  114. 114.
    Yokoyama M, Mori H, Sato H (2010) Allosteric regulation of HIV-1 reverse transcriptase by ATP for nucleotide selection. PLoS ONE 5:e8867CrossRefGoogle Scholar
  115. 115.
    Yang S, Wang C (2012) The intraflagellar transport protein IFT80 is required for cilia formation and osteogenesis. Bone 51:407–417CrossRefGoogle Scholar
  116. 116.
    Li H, Zhang L, Yin D, Zhang Y, Miao J (2010) Targeting phosphatidylcholine-specific phospholipase C for atherogenesis therapy. Trends Cardiovasc Med 20:172–176CrossRefGoogle Scholar
  117. 117.
    Ramadan WM, Kashir J, Jones C, Coward K (2012) Oocyte activation and phospholipase C zeta (PLCzeta): diagnostic and therapeutic implications for assisted reproductive technology. Cell Commun Signal 10:1–20.CrossRefGoogle Scholar
  118. 118.
    Bhaskar, Kumari N, Goyal N (2012) Cloning, characterization and sub-cellular localization of gamma subunit of T-complex protein-1 (chaperonin) from Leishmania donovani. Biochem Biophys Res Commun 429:70–74CrossRefGoogle Scholar
  119. 119.
    Ivics Z, Izsvak Z (2006) Transposons for gene therapy! Curr Gene Ther 6:593–607CrossRefGoogle Scholar
  120. 120.
    Xu G, Jaffrey SR (2013) Proteomic identification of protein ubiquitination events. Biotechnol Genet Eng Rev 29:73–109CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Bárbara Frazão
    • 1
    • 2
  • Alexandre Campos
    • 1
  • Hugo Osório
    • 3
    • 4
  • Benjamin Thomas
    • 5
  • Sérgio Leandro
    • 6
  • Alexandre Teixeira
    • 7
    • 8
  • Vitor Vasconcelos
    • 1
    • 2
  • Agostinho Antunes
    • 1
    • 2
    Email author
  1. 1.CIIMAR/CIMAR, Interdisciplinary Centre of Marine and Environmental ResearchUniversity of PortoPortoPortugal
  2. 2.Department of Biology, Faculty of SciencesUniversity of PortoPortoPortugal
  3. 3.IPATIMUPInstitute of Molecular Pathology and Immunology of the University of PortoPortoPortugal
  4. 4.Faculty of Medicine of the University of PortoPortoPortugal
  5. 5.Proteomics Facility, Sir William Dunn School of PathologyUniversity of OxfordOxfordUK
  6. 6.MARE – Marine and Environmental Sciences Centre, ESTMPolytechnic Institute of LeiriaPenichePortugal
  7. 7.Department of Human GeneticsNational Health Institute Dr. Ricardo JorgeLisbonPortugal
  8. 8.Department of Genetics, Faculty of Medical Sciences, Human Molecular Genetics Research Center (CIGMH)Universidade Nova de LisboaLisbonPortugal

Personalised recommendations