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Eivind A. B. Undheim - One of the best experts on this subject based on the ideXlab platform.
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true lies using proteomics to assess the accuracy of transcriptome based venomics in Centipedes uncovers false positives and reveals startling intraspecific variation in scolopendra subspinipes
Toxins, 2018Co-Authors: Jennifer J Smith, Eivind A. B. UndheimAbstract:Centipede venoms have emerged as a rich source of novel bioactive compounds. However, most Centipede species are commonly considered too small for venom extraction and transcriptomics is likely to be an attractive way of probing the molecular diversity of these venoms. Examining the venom composition of Scolopendra subspinipes, we test the accuracy of this approach. We compared the proteomically determined venom profile with four common toxin transcriptomic toxin annotation approaches: BLAST search against toxins in UniProt, lineage-specific toxins, or species-specific toxins and comparative expression analyses of venom and non-venom producing tissues. This demonstrated that even toxin annotation based on lineage-specific homology searches is prone to substantial errors compared to a proteomic approach. However, combined comparative transcriptomics and phylogenetic analysis of putative toxin families substantially improves annotation accuracy. Furthermore, comparison of the venom composition of S. subspinipes with the closely related S. subspinipes mutilans revealed a surprising lack of overlap. This first insight into the intraspecific venom variability of Centipedes contrasts the sequence conservation expected from previous findings that Centipede toxins evolve under strong negative selection. Our results highlight the importance of proteomic data in studies of even comparably well-characterized venoms and warrants caution when sourcing venom from Centipedes of unknown origin.
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Centipede venoms as a source of drug leads.
Expert opinion on drug discovery, 2016Co-Authors: Eivind A. B. Undheim, Ronald A. Jenner, Glenn F. KingAbstract:ABSTRACTIntroduction: Centipedes are one of the oldest and most successful lineages of venomous terrestrial predators. Despite their use for centuries in traditional medicine, Centipede venoms remain poorly studied. However, recent work indicates that Centipede venoms are highly complex chemical arsenals that are rich in disulfide-constrained peptides that have novel pharmacology and three-dimensional structure.Areas covered: This review summarizes what is currently known about Centipede venom proteins, with a focus on disulfide-rich peptides that have novel or unexpected pharmacology that might be useful from a therapeutic perspective. The authors also highlight the remarkable diversity of constrained three-dimensional peptide scaffolds present in these venoms that might be useful for bioengineering of drug leads.Expert opinion: Like most arthropod predators, Centipede venoms are rich in peptides that target neuronal ion channels and receptors, but it is also becoming increasingly apparent that many of t...
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production and packaging of a biological arsenal evolution of Centipede venoms under morphological constraint
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Eivind A. B. Undheim, Bryan G. Fry, Glenn F. King, Brett Hamilton, Nyoman D Kurniawan, Greg Bowlay, Bronwen W Cribb, David J Merritt, Deon J VenterAbstract:Venom represents one of the most extreme manifestations of a chemical arms race. Venoms are complex biochemical arsenals, often containing hundreds to thousands of unique protein toxins. Despite their utility for prey capture, venoms are energetically expensive commodities, and consequently it is hypothesized that venom complexity is inversely related to the capacity of a venomous animal to physically subdue prey. Centipedes, one of the oldest yet least-studied venomous lineages, appear to defy this rule. Although scutigeromorph Centipedes produce less complex venom than those secreted by scolopendrid Centipedes, they appear to rely heavily on venom for prey capture. We show that the venom glands are large and well developed in both scutigerid and scolopendrid species, but that scutigerid forcipules lack the adaptations that allow scolopendrids to inflict physical damage on prey and predators. Moreover, we reveal that scolopendrid venom glands have evolved to accommodate a much larger number of secretory cells and, by using imaging mass spectrometry, we demonstrate that toxin production is heterogeneous across these secretory units. We propose that the differences in venom complexity between Centipede orders are largely a result of morphological restrictions of the venom gland, and consequently there is a strong correlation between the morphological and biochemical complexity of this unique venom system. The current data add to the growing body of evidence that toxins are not expressed in a spatially homogenous manner within venom glands, and they suggest that the link between ecology and toxin evolution is more complex than previously thought.
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Centipede venom: recent discoveries and current state of knowledge.
Toxins, 2015Co-Authors: Eivind A. B. Undheim, Bryan G. Fry, Glenn F. KingAbstract:Centipedes are among the oldest extant venomous predators on the planet. Armed with a pair of modified, venom-bearing limbs, they are an important group of predatory arthropods and are infamous for their ability to deliver painful stings. Despite this, very little is known about Centipede venom and its composition. Advances in analytical tools, however, have recently provided the first detailed insights into the composition and evolution of Centipede venoms. This has revealed that Centipede venom proteins are highly diverse, with 61 phylogenetically distinct venom protein and peptide families. A number of these have been convergently recruited into the venoms of other animals, providing valuable information on potential underlying causes of the occasionally serious complications arising from human Centipede envenomations. However, the majority of venom protein and peptide families bear no resemblance to any characterised protein or peptide family, highlighting the novelty of Centipede venoms. This review highlights recent discoveries and summarises the current state of knowledge on the fascinating venom system of Centipedes.
Wallace Arthur - One of the best experts on this subject based on the ideXlab platform.
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prey orientation and the role of venom availability in the predatory behaviour of the Centipede scolopendra subspinipes mutilans arthropoda chilopoda
Journal of Insect Physiology, 2012Co-Authors: Michel M Dugon, Wallace ArthurAbstract:Many animal phyla contain clades in which most or all species are venom-injecting predators. An example, in the arthropods, is the class Chilopoda, containing the approximately 3500 species of Centipedes. Very little ecological or behavioural work yielding quantitative data has been conducted on Centipede predation. Here, we describe a study of this kind. Our experiments employed one Centipede species – a large tropical one, Scolopendra subspinipes mutilans – and two species of prey – a cricket, Gryllus assimilis, and a locust, Schistocerca gregaria. We conducted two experiments. The first was aimed at investigating the extent to which the Centipedes attacked prey in particular tagmata as opposed to at random over the whole body surface. The results showed that the Centipedes were highly selective, preferring to attack the head or thorax rather than the abdomen; indeed, they often reoriented the prey in order to achieve this. A possible explanation of this behaviour is to maximize the speed with which the neurotoxins in the venom reach either the brain or the thoracic ganglia that control limb movement. The second experiment was aimed at investigating the effect of venom-extraction on the attack rate, and specifically at testing if the magnitude of any such effect differed between the two types of prey, which differ considerably in size. The results showed a major effect of venom extraction in relation to both types of prey, but with the time taken to return to a ‘normal’ attack rate being longer in the case of the larger prey-type, namely the locust. We discuss these results in relation to the ‘venom optimization hypothesis’ and, more generally, to the principle of minimizing the production/use of venom, which is an energetically expensive resource. 2012 Elsevier Ltd. All rights reserved.
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an early temperature sensitive period for the plasticity of segment number in the Centipede strigamia maritima
Evolution & Development, 2010Co-Authors: Vincent Vedel, Wallace Arthur, Michael Akam, Zivkos Apostolou, Carlo BrenaAbstract:SUMMARY Geophilomorph Centipedes show variation in segment number (a) between closely related species and (b) within and between populations of the same species. We have previously shown for a Scottish population of the coastal Centipede Strigamia maritima that the temperature of embryonic development is one of the factors that affects the segment number of hatchlings, and hence of adults, as these animals grow epimorphically—that is, without postembryonic addition of segments. Here, we show, using temperature-shift experiments, that the main developmental period during which embryos are sensitive to environmental temperature is surprisingly early, during blastoderm formation and before, or very shortly after, the onset of segmentation.
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early development and segment formation in the Centipede strigamia maritima geophilomorpha
Evolution & Development, 2004Co-Authors: Ariel D Chipman, Wallace Arthur, Michael AkamAbstract:Summary Geophilomorph Centipedes exhibit a number of unique characteristics that make them of particular developmental and evolutionary interest. Segment numbers in geophilomorphs are higher than in any other Centipedes, ranging from 27 to 191. They may be constant within a species, presenting in extreme form the “counting” problem in development, or they may vary—a situation that provides us with the opportunity to study naturally occurring variation in segment numbers. All their segments are generated during embryogenesis, a situation unlike that in the more basal Centipede orders, which generate only a fraction of their 15 trunk segments in the embryo and develop the rest postembryonically. Here we provide a foundation for further developmental studies of the Geophilomorpha, building on the one study that has been conducted to date, on the coastal species Strigamia maritima. Development begins with the migration of nuclei to the surface of the egg, which then condense to form an embryonic rudiment of more than 20,000 cells, covering an entire hemisphere. During early development, the embryo can be divided into two distinct areas: a large terminal disc of apparently undifferentiated tissue and the germ-band, which has a clear anteroposterior axis and differentiated segments. The germ-band forms from the anterior of the terminal disc and extends anteriorly as the disc contracts. New segments are formed at the posterior margin of the germ-band. Once the process of segmentation ends, the germ-band folds and sinks into the yolk. We note that the classic description of Centipede development, by Heymons more than a century ago, contains a fundamental error in the identification of the axes and hence in the interpretation of early segmentation.
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Homeotic transformation in a Centipede.
Trends in genetics : TIG, 1999Co-Authors: Chris Kettle, Wallace Arthur, Trevor Jowett, Alessandro MinelliAbstract:The suggested involvement of homeotic mutations in evolution1xHomeotic mutatants and evolution. Goldschmidt, R. Acta Biotheoretica. 1952; 10: 87–104Crossref | Scopus (15)See all References1 is controversial, and is rejected by most evolutionary biologists. However, an acknowledged difficulty is that these mutations are best known in Drosophila, which is a highly derived arthropod. Perhaps the severe fitness depression accompanying homeotic transformation would have been less pronounced, even absent, in a primitive arthropod with many similar segments. Centipedes provide a model for studying the effects of homeotic transformation as they might have been manifested in an ancient arthropod stem species. This is not to say that their particular body plan is not highly derived – it clearly is – but, rather, that it retains the feature of many broadly similar segments that characterized the first arthropods. The key question, then, is whether homeotic transformation in a system of this kind would be radically different in effect to its Drosophila counterpart.Despite more than a century of study of the morphology of Centipedes, and the existence of at least 3000 species, there has until now been no observed case of homeotic transformation of a segment in any Centipede. However, we have recently found a case of this in an adult male Strigamia maritima – a geophilomorph species of intermediate length – collected at Whitburn on the coast of NE England (grid ref. NZ 412615). This specimen (see Fig. 1Fig. 1) exhibits transformation of the most anterior of the normally legless terminal segments (the ‘intermediate’ segment) into a repeat of the posteriormost leg-bearing segment, giving it two pairs of specialized rear legs (male sexual characters) instead of one. This makes it the first Centipede ever discovered with an even number of leg-bearing segments (48; normally only uneven numbers between 15 and 191 are observed).FIGURE 1Homeotic transformation in a Centipede. (a) Normal and (b) transformed morphologies of the Centipede Strigamia maritima. In the normal arrangement, there is a single segment with multiple coxal pores and with special rearward-pointing legs that are swollen in the male (pictured) but slender in the female. In the mutant Centipede there are two such segments, the second deriving from the transformation of the normally legless ‘intermediate segment’.View Large Image | Download PowerPoint SlideThe symmetry of the transformed segment suggests a hereditary origin, perhaps involving a mutation of the Abdominal-B gene. [A homologue of this Drosophila gene was detected in one recent Centipede study (M.L. Smith, PhD thesis, University of Cambridge, 1998) but not in another2xEvolution of the entire arthropod Hox gene set predated the origin and radiation of the onychophoran/arthropod clade. Grenier, J.K. et al. Curr. Biol. 1997; 7: 547–553Abstract | Full Text | Full Text PDF | PubMedSee all References2.] The mutant individual was viable under natural conditions: it had reached adulthood, and so must have been at least two years old3xThe life history and ecology of the littoral Centipede Strigamia (= Scolioplanes) maritima (Leach). Lewis, J.G.E. Proc. Zool. Soc. London. 1961; 137: 221–248CrossrefSee all References3. Its fertility is unknown, although the genital segments, immediately posterior to the transformed one, appear normal. Although these observations appear to argue for an evolutionary role of homeotic mutation in this kind of body plan, there is a more pressing counter-argument. The homeotic Centipede shares with the four-winged fly a morphological shift that appears never to have happened in evolution. Relative to the realized direction of evolutionary change, homeotic transformations seem to be always either ‘backwards’ (two-wings-to-four as opposed to four-wings-to-two) or ‘dead-ends’ (our Centipede). So, even if the fitness problem is overcome, morphology itself argues against an evolutionary role for these mutations. However, in a final twist to the story, there is now evidence4xA role of Ultrabithorax in morphological differences between Drosophila species. Stern, D.L. Nature. 1998; 396: 463–466Crossref | PubMed | Scopus (174)See all References, 5xHox genes, homeosis and the evolution of segment identity: no need for hopeless monsters. Akam, M. Int. J. Dev. Biol. 1998; 42: 445–451PubMedSee all References that other (lesser) mutations of the Hox genes are involved in arthropod morphological evolution.
Feng Zhao - One of the best experts on this subject based on the ideXlab platform.
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comparative analysis of diverse toxins from a new pharmaceutical Centipede scolopendra mojiangica
Zoological Research, 2020Co-Authors: Jinyang Liang, Yun Zhang, Tao Li, Jiarui Zhang, Fang Zhao, Geng Li, Peiyi Chen, Feng ZhaoAbstract:As the oldest venomous animals, Centipedes use their venom as a weapon to attack prey and for protection. Centipede venom, which contains many bioactive and pharmacologically active compounds, has been used for centuries in Chinese medicine, as shown by ancient records. Based on comparative analysis, we revealed the diversity of and differences in Centipede toxin-like molecules between Scolopendra mojiangica, a substitute pharmaceutical material used in China, and S. subspinipes mutilans. More than 6 000 peptides isolated from the venom were identified by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) and inferred from the transcriptome. As a result, in the proteome of S. mojiangica, 246 unique proteins were identified: one in five were toxin-like proteins or putative toxins with unknown function, accounting for a lower percentage of total proteins than that in S. mutilans. Transcriptome mining identified approximately 10 times more toxin-like proteins, which can characterize the precursor structures of mature toxin-like peptides. However, the constitution and quantity of the toxin transcripts in these two Centipedes were similar. In toxicity assays, the crude venom showed strong insecticidal and hemolytic activity. These findings highlight the extensive diversity of toxin-like proteins in S. mojiangica and provide a new foundation for the medical-pharmaceutical use of Centipede toxin-like proteins.
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proteotranscriptomic analysis and discovery of the profile and diversity of toxin like proteins in Centipede
Molecular & Cellular Proteomics, 2018Co-Authors: Yun Zhang, Feng Zhao, Fang Zhao, Xinqiang Lan, Yang Xiang, Wenhui LeeAbstract:Centipedes are one of the oldest venomous animals and use their venoms as weapons to attack prey or protect themselves. Their venoms contain various components with different biomedical and pharmacological properties. However, little attention has been paid to the profiles and diversity of their toxin-like proteins/peptides. In this study, we used a proteotranscriptomic approach to uncover the diversity of Centipede toxin-like proteins in Scolopendra subspinipes mutilans. Nine hundred twenty-three and 6,736 peptides, which were separately isolated from venom and torso tissues, respectively, were identified by ESI-MS/MS and deduced from their transcriptomes. Finally, 1369 unique proteins were identified in the proteome, including 100 proteins that exhibited overlapping expression in venom and torso tissues. Of these proteins, at least 40 proteins were identified as venom toxin-like proteins. Meanwhile, transcriptome mining identified ∼10-fold more toxin-like proteins and enabled the characterization of the precursor architecture of mature toxin-like peptides. Importantly, combined with proteomic and transcriptomic analyses, 25 toxin-like proteins/peptides (neurotoxins accounted for 50%) were expressed outside the venom gland and involved in gene recruitment processes. These findings highlight the extensive diversity of Centipede toxin-like proteins and provide a new foundation for the medical-pharmaceutical use of Centipede toxin-like proteins. Moreover, we are the first group to report the gene recruitment activity of venom toxin-like proteins in Centipede, similar to snakes.
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venomic and transcriptomic analysis of Centipede scolopendra subspinipes dehaani
Journal of Proteome Research, 2012Co-Authors: Rong Zhang, Yong Q Zhang, Jiuping Ding, Zhongming Chen, Ping Jiang, Yanjie Wang, Feng Zhao, Yun ZhangAbstract:Centipedes have venom glands in their first pair of limbs, and their venoms contain a large number of components with different biochemical and pharmacological properties. However, information about the compositions and functions of their venoms is largely unknown. In this study, Scolopendra subspinipes dehaani venoms were systematically investigated by transcriptomic and proteomic analysis coupled with biological function assays. After random screening approximately 1500 independent clones, 1122 full length cDNA sequences, which encode 543 different proteins, were cloned from a constructed cDNA library using a pair of venom glands from a single Centipede species. Neurotoxins, ion channel acting components and venom allergens were the main fractions of the crude venom as revealed by transcriptomic analysis. Meanwhile, 40 proteins/peptides were purified and characterized from crude venom of S. subspinipes dehaani. The N-terminal amino acid sequencing and mass spectrum results of 29 out of these 40 proteins...
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venomic and transcriptomic analysis of Centipede scolopendra subspinipes dehaani
Journal of Proteome Research, 2012Co-Authors: Zichao Liu, Jiuping Ding, Zhongming Chen, Ping Jiang, Yanjie Wang, Rong Zhang, Feng Zhao, Haowen Liu, Yong Zhang, Wenhui LeeAbstract:Centipedes have venom glands in their first pair of limbs, and their venoms contain a large number of components with different biochemical and pharmacological properties. However, information about the compositions and functions of their venoms is largely unknown. In this study, Scolopendra subspinipes dehaani venoms were systematically investigated by transcriptomic and proteomic analysis coupled with biological function assays. After random screening approximately 1500 independent clones, 1122 full length cDNA sequences, which encode 543 different proteins, were cloned from a constructed cDNA library using a pair of venom glands from a single Centipede species. Neurotoxins, ion channel acting components and venom allergens were the main fractions of the crude venom as revealed by transcriptomic analysis. Meanwhile, 40 proteins/peptides were purified and characterized from crude venom of S. subspinipes dehaani. The N-terminal amino acid sequencing and mass spectrum results of 29 out of these 40 proteins or peptides matched well with their corresponding cDNAs. The purified proteins/peptides showed different pharmacological properties, including the following: (1) platelet aggregating activity; (2) anticoagulant activity; (3) phospholipase A(2) activity; (4) trypsin inhibiting activity; (5) voltage-gated potassium channel activities; (6) voltage-gated sodium channel activities; (7) voltage-gated calcium channel activities. Most of them showed no significant similarity to other protein sequences deposited in the known public database. This work provides the largest number of protein or peptide candidates with medical-pharmaceutical significance and reveals the toxin nature of Centipede S. subspinipes dehaani venom.
Ui-wook Hwang - One of the best experts on this subject based on the ideXlab platform.
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Antimicrobial peptides in the Centipede Scolopendra subspinipes mutilans
Functional & Integrative Genomics, 2014Co-Authors: Younhee Shin, Jae-young Shim, Byeong-chul Kang, Jaedon Oh, Jiyeon Seong, Hong Sik Kong, Ki-duk Song, Myunghee Jung, Young-nam Kwon, Ui-wook HwangAbstract:The Centipede Scolopendra subspinipes mutilans is an environmentally beneficial and medically important arthropod species. Although this species is increasingly applied as a reliable source of new antimicrobial peptides, the transcriptome of this species is a prerequisite for more rational selection of antimicrobial peptides. In this report, we isolated total RNA from the whole body of adult Centipedes, S. subspinipes mutilans , that were nonimmunized and immunized against Escherichia coli , and we generated a total of 77,063 pooled contigs and singletons using high-throughput sequencing. To screen putative antimicrobial peptides, in silico analyses of the S. subspinipes mutilans transcriptome were performed based on the physicochemical evidence of length, charge, isoelectric point, and in vitro and in vivo aggregation scores together with the existence of continuous antimicrobial peptide stretches. Moreover, we excluded some transcripts that showed similarity with both previously known antimicrobial peptides and the human proteome, had a proteolytic cleavage site, and had downregulated expression compared with the nonimmunized sample. As a result, we selected 17 transcripts and tested their antimicrobial activity with a radial diffusion assay. Among them, ten synthetic peptides experimentally showed antimicrobial activity against microbes and no toxicity to mouse erythrocytes. Our results provide not only a useful set of antimicrobial peptide candidates and an efficient strategy for novel antimicrobial peptide development but also the transcriptome data of a big Centipede as a valuable resource.
Wenhui Lee - One of the best experts on this subject based on the ideXlab platform.
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proteotranscriptomic analysis and discovery of the profile and diversity of toxin like proteins in Centipede
Molecular & Cellular Proteomics, 2018Co-Authors: Yun Zhang, Feng Zhao, Fang Zhao, Xinqiang Lan, Yang Xiang, Wenhui LeeAbstract:Centipedes are one of the oldest venomous animals and use their venoms as weapons to attack prey or protect themselves. Their venoms contain various components with different biomedical and pharmacological properties. However, little attention has been paid to the profiles and diversity of their toxin-like proteins/peptides. In this study, we used a proteotranscriptomic approach to uncover the diversity of Centipede toxin-like proteins in Scolopendra subspinipes mutilans. Nine hundred twenty-three and 6,736 peptides, which were separately isolated from venom and torso tissues, respectively, were identified by ESI-MS/MS and deduced from their transcriptomes. Finally, 1369 unique proteins were identified in the proteome, including 100 proteins that exhibited overlapping expression in venom and torso tissues. Of these proteins, at least 40 proteins were identified as venom toxin-like proteins. Meanwhile, transcriptome mining identified ∼10-fold more toxin-like proteins and enabled the characterization of the precursor architecture of mature toxin-like peptides. Importantly, combined with proteomic and transcriptomic analyses, 25 toxin-like proteins/peptides (neurotoxins accounted for 50%) were expressed outside the venom gland and involved in gene recruitment processes. These findings highlight the extensive diversity of Centipede toxin-like proteins and provide a new foundation for the medical-pharmaceutical use of Centipede toxin-like proteins. Moreover, we are the first group to report the gene recruitment activity of venom toxin-like proteins in Centipede, similar to snakes.
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venomic and transcriptomic analysis of Centipede scolopendra subspinipes dehaani
Journal of Proteome Research, 2012Co-Authors: Zichao Liu, Jiuping Ding, Zhongming Chen, Ping Jiang, Yanjie Wang, Rong Zhang, Feng Zhao, Haowen Liu, Yong Zhang, Wenhui LeeAbstract:Centipedes have venom glands in their first pair of limbs, and their venoms contain a large number of components with different biochemical and pharmacological properties. However, information about the compositions and functions of their venoms is largely unknown. In this study, Scolopendra subspinipes dehaani venoms were systematically investigated by transcriptomic and proteomic analysis coupled with biological function assays. After random screening approximately 1500 independent clones, 1122 full length cDNA sequences, which encode 543 different proteins, were cloned from a constructed cDNA library using a pair of venom glands from a single Centipede species. Neurotoxins, ion channel acting components and venom allergens were the main fractions of the crude venom as revealed by transcriptomic analysis. Meanwhile, 40 proteins/peptides were purified and characterized from crude venom of S. subspinipes dehaani. The N-terminal amino acid sequencing and mass spectrum results of 29 out of these 40 proteins or peptides matched well with their corresponding cDNAs. The purified proteins/peptides showed different pharmacological properties, including the following: (1) platelet aggregating activity; (2) anticoagulant activity; (3) phospholipase A(2) activity; (4) trypsin inhibiting activity; (5) voltage-gated potassium channel activities; (6) voltage-gated sodium channel activities; (7) voltage-gated calcium channel activities. Most of them showed no significant similarity to other protein sequences deposited in the known public database. This work provides the largest number of protein or peptide candidates with medical-pharmaceutical significance and reveals the toxin nature of Centipede S. subspinipes dehaani venom.