Neurotoxicity of clostridium toxins (Homo sapiens)

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7, 23, 29, 33, 43...3, 13, 29, 3414, 26, 439, 21, 22, 29, 3229, 32, 51, 552929292921, 29, 322936, 47, 4912, 29, 31, 3221, 29, 3225, 3814, 26, 436, 41, 513319, 47, 495, 29, 31, 3227, 47, 492914, 26, 43, 4516, 5013, 29, 32, 3426, 4324, 30, 402, 488, 2812, 29, 32, 35, 3729, 32, 35, 3743399, 21, 22, 29, 32434310, 30, 42291, 18, 3814, 26, 4316cytosolendocytic vesiclesynaptic vesicle lumensynaptic vesicle lumenclathrin-coated endocytic vesiclecytosolBoNT/A LC:Zn2+Zn2+ SYT1 VAMP2(2-59)GT1bSV2C SNAP25(199-206)BoNT/F LC disulfidebonded VAMP2(2-76)BoNT/C HC:LC dimerNTNHA Zn2+ BoNT/D HC:LC dimerGT1bSV2B Zn2+ SV2B SV2A STX1NTNHABoNT/A LC disulfidebonded BoNT/D LC disulfidebonded BoNT/D:SV2:GD2SYT2 SV2A,B,CBoNT/E LC disulfidebonded Zn2+ Zn2+ SYT1,2TeNT:gangliosidesZn2+ BoNT/B HC:LC dimerSNAP25H+SV2C SV2A Zn2+ GT1b GD3 TeNT HC:LC dimerZn2+ Zn2+ BoNT/E HC disulfidebonded GT1b ha70 BoNT/B LC disulfidebonded Zn2+ BoNT/C LC disulfidebonded GT1b BoNT/D LC disulfidebonded ha33BoNT/C:GT1bVAMP1GT1bBoNT/E:SV2:GT1bBoNT/C HCGT1b SV2A,B,CSNAP25Zn2+ GM1a SV2C STX1(1-?)GD3SV2A,B,CZn2+ GT1bSV2A ha33 Zn2+ ha33 BoNT/G:SYT1:GT1bBoNT/A:SV2:GT1bVAMP2GT1b BoNT/D LC disulfidebonded BoNT/D HC disulfidebonded BoNT/C:GT1bBoNT/A HC disulfidebonded SNAP25GM1aH+BoNT/F HC disulfidebonded Zn2+ BoNT/D LC TeNT HCGT1bBoNT/A:SV2:GT1bSYT1 BoNT/B LC disulfidebonded NTNHA BoNT/E:NTNHASNAP25(198-206)Zn2+ VAMP2GD3 TeNT LC disulfidebonded VAMP2(2-76)SV2A GT1b BoNT/E LC disulfidebonded SV2C VAMP2(2-58)SYT1 SV2B SV2A Zn2+ ha17 Zn2+ SV2A,B,CBoNT/C HC disulfidebonded BoNT/D:SV2:GD2BoNT/F LC BoNT/C HC disulfidebonded BoNT/G LC:Zn2+BoNT/A HC disulfidebonded BoNT/B:SYT:GT1bH+BoNT/D HCSV2A BoNT/B LC GM1a Zn2+ BoNT/G LC GT1b GT1bGD2 GT1b BoNT/A HC:LC dimerSV2A BoNT/B LC disulfidebonded VAMP2(2-81)GT1bVAMP2(60-116)GT1b NTNHA Zn2+ Zn2+ Zn2+ BoNT/E LC disulfidebonded SV2B BoNT/B:NTNHA:HAVAMP2(82-116)BoNT/G LC disulfidebonded BoNT/D HC disulfidebonded SV2B VAMP1(1-61)SV2A,B,CGD2SNAP25(1-197)GT1bZn2+ VAMP1(84-118)TeNT HC disulfidebonded GT1b Zn2+ BoNT/G LC disulfidebonded GD3 BoNT/B HCSV2A,BGD2 BoNT/G:SYT1:GT1bBoNT/E HCha70BoNT/B HC disulfidebonded BoNT/B HC disulfidebonded BoNT/B HC disulfidebonded Zn2+ BoNT/F HC disulfidebonded Zn2+ BoNT/C LC disulfidebonded GM1a TeNT HC disulfidebonded BoNT/B:SYT:GT1bBoNT/E HC disulfidebonded BoNT/A LC disulfidebonded BoNT/F:SV2:GT1bZn2+ GT1b SV2B BoNT/G HC disulfidebonded BoNT/F HCBoNT/A LC BoNT/G HC:LC dimerZn2+ BoNT/A HCGD3BoNT/C LC:Zn2+GD2BoNT/C LC TeNT LC disulfidebonded SNAP25(1-198)VAMP1(62-118)BoNT/B LC disulfidebonded TeNT LC:Zn2+BoNT/E LC TeNT:gangliosidesBoNT/A LC disulfidebonded H+BoNT/F LC disulfidebonded BoNT/F:SV2:GT1bSV2A,B,CVAMP1VAMP2Zn2+ GT1bZn2+ BoNT/D HC disulfidebonded BoNT/E LC:Zn2+Zn2+ BoNT/B HC disulfidebonded VAMP2(59-116)NTNHATeNT LC disulfidebonded BoNT/E HC disulfidebonded BoNT/G HC disulfidebonded BoNT/F HC disulfidebonded BoNT/D LC:Zn2+VAMP2(77-116)BoNT/E LC disulfidebonded Zn2+ BoNT/F LC disulfidebonded BoNT/F LC:Zn2+SYT1ha17 GT1bTeNT HC disulfidebonded VAMP1(1-83)BoNT/C LC disulfidebonded BoNT/A HC disulfidebonded H+VAMP1(61-118)SYT1 TeNT LC BoNT/E HC:LC dimerSNAP25(199-206)BoNT/E:SV2:GT1bTeNT:gangliosidesH+BoNT/A LC disulfidebonded SYT1Zn2+ BoNT/G LC disulfidebonded SYT1,2Zn2+ Zn2+ Zn2+ SV2A,BTeNT HC disulfidebonded H+ha70 SYT2 BoNT/F HC:LC dimerZn2+ BoNT/G HCSNAP25(1-198)SV2C GT1b H+GM1aVAMP2(77-116)BoNT/A:NTNHA:HABoNT/C HC disulfidebonded SV2B BoNT/G HC disulfidebonded BoNT/E HC disulfidebonded BoNT/A HC disulfidebonded BoNT/B LC:Zn2+ha17SV2B SV2C VAMP2STX1(?-288)VAMP1(1-60)GT1bSV2A TeNT LC disulfidebonded 1, 1120, 54451, 5520, 544, 6, 5020, 5430, 4053535, 31453272113, 343912, 352111428, 2820, 545, 314, 6111720, 542411175321451, 551744435313, 341751, 55531813, 3411410, 30174, 6, 509, 2194423921241712531720, 54112, 48536, 441220, 54113651, 551153531113, 3420, 549, 21531253531521, 2517420, 541124919111217111712, 35534, 6, 16, 5044


Description

Clostridial neurotoxins, when taken up by human neurons, block synaptic transmission by cleaving proteins required for the fusion of synaptic vesicles with the plasma membrane. They are remarkably efficient so that very small doses cause paralysis of an affected person (Lalli et al. 2003; Turton et al. 2002). All characterized clostridial neurotoxins are synthesized as products of chromosomal, plasmid or prophage-borne bacterial genes. The nascent toxin may be cleaved into light (LC) and heavy (HC) chain moieties that remain attached by noncovalent interactions and a disulfide bond (Turton et al. 2002).

Strains of Clostridium botulinum produce seven serologically distinct toxins, BoNT/A, B, C, D, E, F, and G. An eighth toxin, BoNT/H has recently been identified (Barash & Arnon 2014) but its molecular properties have not yet been described. Human poisoning most commonly result from ingestion of toxin contaminated food. More rarely, it is due to wound infection or clostridial colonization of the gut of an infant whose own gut flora have not yet developed or of an older individual whose flora have been suppressed. While all seven characterized toxins can cleave human target proteins, three, BoNT/A, B, and E, are most commonly associated with human disease (Hatheway 1995; Sakaguchi 1982). BoNT/F is also able to cause human botulism.<p>Once ingested, the botulinum toxin must be taken up from the gut lumen into the circulation, a process mediated by four accessory proteins. These proteins form a complex that mediates transcytosis of the toxin molecule across the gut epithelium, allowing its entry into the circulation. The accessory proteins produced by different C. botulinum strains differ in their affinities for polarized epithelia of different species (e.g., human versus canine), and may thus be a key factor in human susceptibility to the toxins of strains A, B, and E and resistance to the others (Simpson 2004).<p>Clostridium tetani produces TeNT toxin. Human poisoning is the result of toxin secretion by bacteria growing in an infected wound and the toxin is released directly into the circulation.<p>Circulating clostridial toxins are taken up by neurons at neuromuscular junctions. They bind to specific gangliosides (BoNT/C, TeNT) or to both gangliosides and synaptic vesicle proteins (BoNT/A, B, D G) exposed on the neuronal plasma membrane during vesicle exocytosis (Montal 2010). All seven characterized forms of BoNT are thought to be taken up into synaptic vesicles as these re-form at the neuromuscular junction. These vesicles remain close to the site of uptake and are rapidly re-loaded with neurotransmitter and acidified (Sudhoff 2004). TeNT, in contrast, is taken up into clathrin coated vesicles that reach the neuron cell body by retrograde transport and then possibly other neurons before undergoing acidification. Vesicle acidification causes a conformational change in the toxin, allowing its HC part to function as a channel through which its LC part is extruded into the neuronal cytosol. The HC - LC disulfide bond is cleaved and the cytosolic LC functions as a zinc metalloprotease to cleave specific bonds in proteins on the cytosolic faces of synaptic vesicles and plasma membranes that normally mediate exocytosis (Lalli et al. 2003; Montal 2010). Source:Reactome.</div>

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Bibliography

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  1. Chen C, Fu Z, Kim JJ, Barbieri JT, Baldwin MR.; ''Gangliosides as high affinity receptors for tetanus neurotoxin.''; PubMed Europe PMC Scholia
  2. Dong M, Liu H, Tepp WH, Johnson EA, Janz R, Chapman ER.; ''Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E into neurons.''; PubMed Europe PMC Scholia
  3. Amatsu S, Sugawara Y, Matsumura T, Kitadokoro K, Fujinaga Y.; ''Crystal structure of Clostridium botulinum whole hemagglutinin reveals a huge triskelion-shaped molecular complex.''; PubMed Europe PMC Scholia
  4. Sathyamoorthy V, Dasgupta BR, Foley J, Niece RL.; ''Botulinum neurotoxin type A: cleavage of the heavy chain into two halves and their partial sequences.''; PubMed Europe PMC Scholia
  5. Schiavo G, Malizio C, Trimble WS, Polverino de Laureto P, Milan G, Sugiyama H, Johnson EA, Montecucco C.; ''Botulinum G neurotoxin cleaves VAMP/synaptobrevin at a single Ala-Ala peptide bond.''; PubMed Europe PMC Scholia
  6. Rummel A, Häfner K, Mahrhold S, Darashchonak N, Holt M, Jahn R, Beermann S, Karnath T, Bigalke H, Binz T.; ''Botulinum neurotoxins C, E and F bind gangliosides via a conserved binding site prior to stimulation-dependent uptake with botulinum neurotoxin F utilising the three isoforms of SV2 as second receptor.''; PubMed Europe PMC Scholia
  7. Schiavo G, Rossetto O, Catsicas S, Polverino de Laureto P, DasGupta BR, Benfenati F, Montecucco C.; ''Identification of the nerve terminal targets of botulinum neurotoxin serotypes A, D, and E.''; PubMed Europe PMC Scholia
  8. Foran P, Shone CC, Dolly JO.; ''Differences in the protease activities of tetanus and botulinum B toxins revealed by the cleavage of vesicle-associated membrane protein and various sized fragments.''; PubMed Europe PMC Scholia
  9. Koriazova LK, Montal M.; ''Translocation of botulinum neurotoxin light chain protease through the heavy chain channel.''; PubMed Europe PMC Scholia
  10. Hatheway CL.; ''Botulism: the present status of the disease.''; PubMed Europe PMC Scholia
  11. Montal M.; ''Botulinum neurotoxin: a marvel of protein design.''; PubMed Europe PMC Scholia
  12. Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC.; ''Crystal structure of botulinum neurotoxin type A and implications for toxicity.''; PubMed Europe PMC Scholia
  13. Peng L, Berntsson RP, Tepp WH, Pitkin RM, Johnson EA, Stenmark P, Dong M.; ''Botulinum neurotoxin D-C uses synaptotagmin I and II as receptors, and human synaptotagmin II is not an effective receptor for type B, D-C and G toxins.''; PubMed Europe PMC Scholia
  14. Agarwal R, Eswaramoorthy S, Kumaran D, Binz T, Swaminathan S.; ''Structural analysis of botulinum neurotoxin type E catalytic domain and its mutant Glu212-->Gln reveals the pivotal role of the Glu212 carboxylate in the catalytic pathway.''; PubMed Europe PMC Scholia
  15. Kozaki S, Kamata Y, Watarai S, Nishiki T, Mochida S.; ''Ganglioside GT1b as a complementary receptor component for Clostridium botulinum neurotoxins.''; PubMed Europe PMC Scholia
  16. Fu Z, Chen C, Barbieri JT, Kim JJ, Baldwin MR.; ''Glycosylated SV2 and gangliosides as dual receptors for botulinum neurotoxin serotype F.''; PubMed Europe PMC Scholia
  17. Kroken AR, Karalewitz AP, Fu Z, Kim JJ, Barbieri JT.; ''Novel ganglioside-mediated entry of botulinum neurotoxin serotype D into neurons.''; PubMed Europe PMC Scholia
  18. Simpson LL.; ''Identification of the major steps in botulinum toxin action.''; PubMed Europe PMC Scholia
  19. Lee K, Gu S, Jin L, Le TT, Cheng LW, Strotmeier J, Kruel AM, Yao G, Perry K, Rummel A, Jin R.; ''Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity.''; PubMed Europe PMC Scholia
  20. Schmidt JJ, Sathyamoorthy V, DasGupta BR.; ''Partial amino acid sequence of the heavy and light chains of botulinum neurotoxin type A.''; PubMed Europe PMC Scholia
  21. Dong M, Richards DA, Goodnough MC, Tepp WH, Johnson EA, Chapman ER.; ''Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells.''; PubMed Europe PMC Scholia
  22. Dasgupta BR, Datta A.; ''Botulinum neurotoxin type B (strain 657): partial sequence and similarity with tetanus toxin.''; PubMed Europe PMC Scholia
  23. Henderson I, Whelan SM, Davis TO, Minton NP.; ''Genetic characterisation of the botulinum toxin complex of Clostridium botulinum strain NCTC 2916.''; PubMed Europe PMC Scholia
  24. Montecucco C, Schiavo G.; ''Mechanism of action of tetanus and botulinum neurotoxins.''; PubMed Europe PMC Scholia
  25. Fujinaga Y, Sugawara Y, Matsumura T.; ''Uptake of botulinum neurotoxin in the intestine.''; PubMed Europe PMC Scholia
  26. Deinhardt K, Berninghausen O, Willison HJ, Hopkins CR, Schiavo G.; ''Tetanus toxin is internalized by a sequential clathrin-dependent mechanism initiated within lipid microdomains and independent of epsin1.''; PubMed Europe PMC Scholia
  27. Krieglstein K, Henschen A, Weller U, Habermann E.; ''Arrangement of disulfide bridges and positions of sulfhydryl groups in tetanus toxin.''; PubMed Europe PMC Scholia
  28. Schiavo G, Poulain B, Rossetto O, Benfenati F, Tauc L, Montecucco C.; ''Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc.''; PubMed Europe PMC Scholia
  29. Sudhof TC.; ''The synaptic vesicle cycle.''; PubMed Europe PMC Scholia
  30. Binz T, Blasi J, Yamasaki S, Baumeister A, Link E, Südhof TC, Jahn R, Niemann H.; ''Proteolysis of SNAP-25 by types E and A botulinal neurotoxins.''; PubMed Europe PMC Scholia
  31. Vaidyanathan VV, Yoshino K, Jahnz M, Dörries C, Bade S, Nauenburg S, Niemann H, Binz T.; ''Proteolysis of SNAP-25 isoforms by botulinum neurotoxin types A, C, and E: domains and amino acid residues controlling the formation of enzyme-substrate complexes and cleavage.''; PubMed Europe PMC Scholia
  32. Barash JR, Arnon SS.; ''A novel strain of Clostridium botulinum that produces type B and type H botulinum toxins.''; PubMed Europe PMC Scholia
  33. Lalli G, Bohnert S, Deinhardt K, Verastegui C, Schiavo G.; ''The journey of tetanus and botulinum neurotoxins in neurons.''; PubMed Europe PMC Scholia
  34. Peng L, Tepp WH, Johnson EA, Dong M.; ''Botulinum neurotoxin D uses synaptic vesicle protein SV2 and gangliosides as receptors.''; PubMed Europe PMC Scholia
  35. Blasi J, Chapman ER, Yamasaki S, Binz T, Niemann H, Jahn R.; ''Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin.''; PubMed Europe PMC Scholia
  36. Sun S, Tepp WH, Johnson EA, Chapman ER.; ''Botulinum neurotoxins B and E translocate at different rates and exhibit divergent responses to GT1b and low pH.''; PubMed Europe PMC Scholia
  37. Südhof TC, De Camilli P, Niemann H, Jahn R.; ''Membrane fusion machinery: insights from synaptic proteins.''; PubMed Europe PMC Scholia
  38. Kumaran D, Eswaramoorthy S, Furey W, Navaza J, Sax M, Swaminathan S.; ''Domain organization in Clostridium botulinum neurotoxin type E is unique: its implication in faster translocation.''; PubMed Europe PMC Scholia
  39. Arndt JW, Chai Q, Christian T, Stevens RC.; ''Structure of botulinum neurotoxin type D light chain at 1.65 A resolution: repercussions for VAMP-2 substrate specificity.''; PubMed Europe PMC Scholia
  40. Foran P, Lawrence GW, Shone CC, Foster KA, Dolly JO.; ''Botulinum neurotoxin C1 cleaves both syntaxin and SNAP-25 in intact and permeabilized chromaffin cells: correlation with its blockade of catecholamine release.''; PubMed Europe PMC Scholia
  41. Schiavo G, Santucci A, Dasgupta BR, Mehta PP, Jontes J, Benfenati F, Wilson MC, Montecucco C.; ''Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds.''; PubMed Europe PMC Scholia
  42. Giménez JA, DasGupta BR.; ''Botulinum neurotoxin type E fragmented with endoproteinase Lys-C reveals the site trypsin nicks and homology with tetanus neurotoxin.''; PubMed Europe PMC Scholia
  43. Sakaguchi G.; ''Clostridium botulinum toxins.''; PubMed Europe PMC Scholia
  44. Benefield DA, Dessain SK, Shine N, Ohi MD, Lacy DB.; ''Molecular assembly of botulinum neurotoxin progenitor complexes.''; PubMed Europe PMC Scholia
  45. Sun S, Suresh S, Liu H, Tepp WH, Johnson EA, Edwardson JM, Chapman ER.; ''Receptor binding enables botulinum neurotoxin B to sense low pH for translocation channel assembly.''; PubMed Europe PMC Scholia
  46. Turton K, Chaddock JA, Acharya KR.; ''Botulinum and tetanus neurotoxins: structure, function and therapeutic utility.''; PubMed Europe PMC Scholia
  47. Mochida S, Poulain B, Weller U, Habermann E, Tauc L.; ''Light chain of tetanus toxin intracellularly inhibits acetylcholine release at neuro-neuronal synapses, and its internalization is mediated by heavy chain.''; PubMed Europe PMC Scholia
  48. Dong M, Yeh F, Tepp WH, Dean C, Johnson EA, Janz R, Chapman ER.; ''SV2 is the protein receptor for botulinum neurotoxin A.''; PubMed Europe PMC Scholia
  49. Swaminathan S, Eswaramoorthy S.; ''Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B.''; PubMed Europe PMC Scholia
  50. Willjes G, Mahrhold S, Strotmeier J, Eichner T, Rummel A, Binz T.; ''Botulinum neurotoxin G binds synaptotagmin-II in a mode similar to that of serotype B: tyrosine 1186 and lysine 1191 cause its lower affinity.''; PubMed Europe PMC Scholia
  51. Schiavo G, Benfenati F, Poulain B, Rossetto O, Polverino de Laureto P, DasGupta BR, Montecucco C.; ''Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin.''; PubMed Europe PMC Scholia
  52. Yamasaki S, Baumeister A, Binz T, Blasi J, Link E, Cornille F, Roques B, Fykse EM, Südhof TC, Jahn R.; ''Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin.''; PubMed Europe PMC Scholia
  53. Link E, Edelmann L, Chou JH, Binz T, Yamasaki S, Eisel U, Baumert M, Südhof TC, Niemann H, Jahn R.; ''Tetanus toxin action: inhibition of neurotransmitter release linked to synaptobrevin proteolysis.''; PubMed Europe PMC Scholia
  54. Karalewitz AP, Fu Z, Baldwin MR, Kim JJ, Barbieri JT.; ''Botulinum neurotoxin serotype C associates with dual ganglioside receptors to facilitate cell entry.''; PubMed Europe PMC Scholia
  55. Yamasaki S, Binz T, Hayashi T, Szabo E, Yamasaki N, Eklund M, Jahn R, Niemann H.; ''Botulinum neurotoxin type G proteolyses the Ala81-Ala82 bond of rat synaptobrevin 2.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
101270view11:16, 1 November 2018ReactomeTeamreactome version 66
100808view20:44, 31 October 2018ReactomeTeamreactome version 65
100349view19:21, 31 October 2018ReactomeTeamreactome version 64
99894view16:04, 31 October 2018ReactomeTeamreactome version 63
99451view14:38, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99115view12:40, 31 October 2018ReactomeTeamreactome version 62
93784view13:36, 16 August 2017ReactomeTeamreactome version 61
93317view11:20, 9 August 2017ReactomeTeamreactome version 61
87757view09:56, 25 July 2016RyanmillerOntology Term : 'disease pathway' added !
87755view09:56, 25 July 2016RyanmillerOntology Term : 'infectious disease pathway' added !
87752view09:53, 25 July 2016RyanmillerOntology Term : 'bacterial infectious disease' added !
86402view09:17, 11 July 2016ReactomeTeamreactome version 56
83321view10:46, 18 November 2015ReactomeTeamVersion54
81748view09:47, 26 August 2015ReactomeTeamVersion53
76848view08:07, 17 July 2014ReactomeTeamFixed remaining interactions
76552view11:53, 16 July 2014ReactomeTeamFixed remaining interactions
75885view09:54, 11 June 2014ReactomeTeamRe-fixing comment source
75585view10:42, 10 June 2014ReactomeTeamReactome 48 Update
74940view13:46, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74584view08:37, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
BoNT/A HC disulfide bonded ProteinP10845 (Uniprot-TrEMBL)
BoNT/A HC:LC dimerComplexR-CBO-5228590 (Reactome)
BoNT/A HCProteinP10845 (Uniprot-TrEMBL)
BoNT/A LC ProteinP10845 (Uniprot-TrEMBL)
BoNT/A LC disulfide bonded ProteinP10845 (Uniprot-TrEMBL)
BoNT/A LC:Zn2+ComplexR-CBO-190017 (Reactome)
BoNT/A:NTNHA:HAComplexR-CBO-5228604 (Reactome)
BoNT/A:SV2:GT1bComplexR-NUL-5244411 (Reactome)
BoNT/A:SV2:GT1bComplexR-NUL-5244507 (Reactome)
BoNT/B HC disulfide bonded ProteinP10844 (Uniprot-TrEMBL)
BoNT/B HC:LC dimerComplexR-CBO-5228599 (Reactome)
BoNT/B HCProteinP10844 (Uniprot-TrEMBL)
BoNT/B LC ProteinP10844 (Uniprot-TrEMBL)
BoNT/B LC disulfide bonded ProteinP10844 (Uniprot-TrEMBL)
BoNT/B LC:Zn2+ComplexR-CBO-190016 (Reactome)
BoNT/B:NTNHA:HAComplexR-CBO-5228681 (Reactome)
BoNT/B:SYT:GT1bComplexR-NUL-5244408 (Reactome)
BoNT/B:SYT:GT1bComplexR-NUL-5244502 (Reactome)
BoNT/C HC disulfide bonded ProteinP18640 (Uniprot-TrEMBL)
BoNT/C HC:LC dimerComplexR-CBO-5246516 (Reactome)
BoNT/C HCProteinP18640 (Uniprot-TrEMBL)
BoNT/C LC ProteinP18640 (Uniprot-TrEMBL)
BoNT/C LC disulfide bonded ProteinP18640 (Uniprot-TrEMBL)
BoNT/C LC:Zn2+ComplexR-CBO-190018 (Reactome)
BoNT/C:GT1bComplexR-CBO-5246508 (Reactome)
BoNT/C:GT1bComplexR-CBO-5246513 (Reactome)
BoNT/D HC disulfide bonded ProteinP19321 (Uniprot-TrEMBL)
BoNT/D HC:LC dimerComplexR-CBO-5250523 (Reactome)
BoNT/D HCProteinP19321 (Uniprot-TrEMBL)
BoNT/D LC ProteinP19321 (Uniprot-TrEMBL)
BoNT/D LC disulfide bonded ProteinP19321 (Uniprot-TrEMBL)
BoNT/D LC:Zn2+ComplexR-CBO-190038 (Reactome)
BoNT/D:SV2:GD2ComplexR-NUL-5250603 (Reactome)
BoNT/D:SV2:GD2ComplexR-NUL-5250612 (Reactome)
BoNT/E HC disulfide bonded ProteinQ00496 (Uniprot-TrEMBL)
BoNT/E HC:LC dimerComplexR-CBO-5228686 (Reactome)
BoNT/E HCProteinQ00496 (Uniprot-TrEMBL)
BoNT/E LC ProteinQ00496 (Uniprot-TrEMBL)
BoNT/E LC disulfide bonded ProteinQ00496 (Uniprot-TrEMBL)
BoNT/E LC:Zn2+ComplexR-CBO-190047 (Reactome)
BoNT/E:NTNHAComplexR-CBO-5228688 (Reactome)
BoNT/E:SV2:GT1bComplexR-NUL-5244509 (Reactome)
BoNT/E:SV2:GT1bComplexR-NUL-5244512 (Reactome)
BoNT/F HC disulfide bonded ProteinP30996 (Uniprot-TrEMBL)
BoNT/F HC:LC dimerComplexR-CBO-5250693 (Reactome)
BoNT/F HCProteinP30996 (Uniprot-TrEMBL)
BoNT/F LC ProteinP30996 (Uniprot-TrEMBL)
BoNT/F LC disulfide bonded ProteinP30996 (Uniprot-TrEMBL)
BoNT/F LC:Zn2+ComplexR-CBO-190042 (Reactome)
BoNT/F:SV2:GT1bComplexR-NUL-5250879 (Reactome)
BoNT/F:SV2:GT1bComplexR-NUL-5250883 (Reactome)
BoNT/G HC disulfide bonded ProteinQ60393 (Uniprot-TrEMBL)
BoNT/G HC:LC dimerComplexR-CBO-5250691 (Reactome)
BoNT/G HCProteinQ60393 (Uniprot-TrEMBL)
BoNT/G LC ProteinQ60393 (Uniprot-TrEMBL)
BoNT/G LC disulfide bonded ProteinQ60393 (Uniprot-TrEMBL)
BoNT/G LC:Zn2+ComplexR-CBO-190032 (Reactome)
BoNT/G:SYT1:GT1bComplexR-NUL-5250975 (Reactome)
BoNT/G:SYT1:GT1bComplexR-NUL-5250976 (Reactome)
GD2 MetaboliteCHEBI:28648 (ChEBI)
GD2MetaboliteCHEBI:28648 (ChEBI)
GD3 MetaboliteCHEBI:28424 (ChEBI)
GD3MetaboliteCHEBI:28424 (ChEBI)
GM1a MetaboliteCHEBI:18216 (ChEBI)
GM1aMetaboliteCHEBI:18216 (ChEBI)
GT1b MetaboliteCHEBI:60913 (ChEBI)
GT1bMetaboliteCHEBI:60913 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
NTNHA ProteinQ9LBS8 (Uniprot-TrEMBL)
NTNHAProteinQ9LBS8 (Uniprot-TrEMBL)
SNAP25(1-197)ProteinP60880 (Uniprot-TrEMBL)
SNAP25(1-198)ProteinP60880 (Uniprot-TrEMBL)
SNAP25(198-206)ProteinP60880 (Uniprot-TrEMBL)
SNAP25(199-206)ProteinP60880 (Uniprot-TrEMBL)
SNAP25ProteinP60880 (Uniprot-TrEMBL)
STX1(1-?)R-HSA-5250515 (Reactome)
STX1(?-288)R-HSA-5250513 (Reactome)
STX1R-HSA-5250514 (Reactome)
SV2A ProteinQ7L0J3 (Uniprot-TrEMBL)
SV2A,B,CR-HSA-5324682 (Reactome)
SV2A,B,CR-HSA-5324684 (Reactome)
SV2A,BR-HSA-5324689 (Reactome)
SV2A,BR-HSA-5324690 (Reactome)
SV2B ProteinQ7L1I2 (Uniprot-TrEMBL)
SV2C ProteinQ496J9 (Uniprot-TrEMBL)
SYT1 ProteinP21579 (Uniprot-TrEMBL)
SYT1,2R-HSA-5324683 (Reactome)
SYT1,2R-HSA-5324686 (Reactome)
SYT1ProteinP21579 (Uniprot-TrEMBL)
SYT2 ProteinQ8N9I0 (Uniprot-TrEMBL)
TeNT HC disulfide bonded ProteinP04958 (Uniprot-TrEMBL)
TeNT HC:LC dimerComplexR-CTE-5228372 (Reactome)
TeNT HCProteinP04958 (Uniprot-TrEMBL)
TeNT LC ProteinP04958 (Uniprot-TrEMBL)
TeNT LC disulfide bonded ProteinP04958 (Uniprot-TrEMBL)
TeNT LC:Zn2+ComplexR-CTE-5228371 (Reactome)
TeNT:gangliosidesComplexR-CTE-5228368 (Reactome)
TeNT:gangliosidesComplexR-CTE-5228374 (Reactome)
TeNT:gangliosidesComplexR-CTE-5228403 (Reactome)
VAMP1(1-60)ProteinP23763 (Uniprot-TrEMBL)
VAMP1(1-61)ProteinP23763 (Uniprot-TrEMBL)
VAMP1(1-83)ProteinP23763 (Uniprot-TrEMBL)
VAMP1(61-118)ProteinP23763 (Uniprot-TrEMBL)
VAMP1(62-118)ProteinP23763 (Uniprot-TrEMBL)
VAMP1(84-118)ProteinP23763 (Uniprot-TrEMBL)
VAMP1ProteinP23763 (Uniprot-TrEMBL)
VAMP2(2-58)ProteinP63027 (Uniprot-TrEMBL)
VAMP2(2-59)ProteinP63027 (Uniprot-TrEMBL)
VAMP2(2-76)ProteinP63027 (Uniprot-TrEMBL)
VAMP2(2-81)