Neurotoxicity of clostridium toxins (Homo sapiens)

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7, 23, 29, 33, 43...16292, 4814, 26, 432912, 29, 31, 326, 41, 5114, 26, 4326, 432929398, 284329, 32, 35, 3714, 26, 431, 18, 3816, 5029, 32, 51, 553, 13, 29, 349, 21, 22, 29, 3213, 29, 32, 344321, 29, 3221, 29, 3210, 30, 423324, 30, 4025, 385, 29, 31, 3212, 29, 32, 35, 3714, 26, 43, 45299, 21, 22, 29, 322919, 47, 49432936, 47, 4927, 47, 49synaptic vesicle lumensynaptic vesicle lumencytosolclathrin-coated endocytic vesicleendocytic vesiclecytosolZn2+ H+Zn2+ BoNT/G HCBoNT/A LC disulfidebonded SYT2 Zn2+ GD3 SV2A SV2A,B,CTeNT HC disulfidebonded BoNT/E HC disulfidebonded BoNT/B HC disulfidebonded Zn2+ GT1bNTNHAGT1bVAMP1BoNT/C:GT1bBoNT/B LC disulfidebonded GD3ha33BoNT/B HC disulfidebonded GM1a SV2A TeNT HCBoNT/F HC disulfidebonded BoNT/C HC:LC dimerSV2A BoNT/F:SV2:GT1bBoNT/A HC:LC dimerBoNT/F LC disulfidebonded Zn2+ SNAP25(1-198)BoNT/E LC:Zn2+BoNT/E LC disulfidebonded GT1b BoNT/F LC Zn2+ ha17 SNAP25SV2A BoNT/E:NTNHASV2B BoNT/C HC disulfidebonded SYT1VAMP1(61-118)GT1b Zn2+ Zn2+ BoNT/D:SV2:GD2BoNT/C LC:Zn2+BoNT/G LC disulfidebonded GT1b VAMP2(59-116)H+BoNT/F HCBoNT/B:NTNHA:HAH+Zn2+ BoNT/A LC SV2C GM1a BoNT/D LC disulfidebonded TeNT:gangliosidesha70BoNT/E HCSV2C BoNT/A LC disulfidebonded Zn2+ GT1bBoNT/B HC disulfidebonded SYT1,2BoNT/E LC BoNT/A:NTNHA:HABoNT/E LC disulfidebonded BoNT/B LC:Zn2+Zn2+ ha17 SNAP25(198-206)VAMP1(84-118)GD3 BoNT/C LC disulfidebonded BoNT/G HC disulfidebonded BoNT/D LC disulfidebonded NTNHABoNT/F LC disulfidebonded GT1b VAMP1(1-83)SV2A SV2A SNAP25(199-206)VAMP2(77-116)BoNT/C LC VAMP2(60-116)BoNT/E:SV2:GT1bSTX1(1-?)TeNT LC disulfidebonded SYT1 VAMP1(62-118)Zn2+ BoNT/G LC disulfidebonded TeNT:gangliosidesBoNT/F LC disulfidebonded GD2 Zn2+ TeNT LC disulfidebonded BoNT/D HC disulfidebonded Zn2+ GT1bSYT1 SV2B BoNT/F:SV2:GT1bVAMP2(2-76)SNAP25(1-198)Zn2+ BoNT/A:SV2:GT1bZn2+ BoNT/C HCBoNT/A HC disulfidebonded Zn2+ BoNT/E HC:LC dimerZn2+ GM1aBoNT/F LC:Zn2+VAMP2(2-81)Zn2+ ha17SYT1,2Zn2+ SV2A,B,CH+H+SYT2 Zn2+ TeNT HC disulfidebonded SV2A,BGT1bTeNT LC NTNHA BoNT/D HC:LC dimerBoNT/A LC disulfidebonded GD2 BoNT/D HCBoNT/D LC disulfidebonded SV2C GT1b BoNT/D LC Zn2+ SV2A,B,CTeNT LC disulfidebonded SNAP25BoNT/G LC:Zn2+BoNT/B LC disulfidebonded GD2BoNT/D HC disulfidebonded GT1b Zn2+ SV2A,B,CSV2B GD3BoNT/F HC:LC dimerSV2C Zn2+ GT1bGT1bBoNT/C LC disulfidebonded BoNT/G:SYT1:GT1bNTNHA STX1(?-288)BoNT/G:SYT1:GT1bSNAP25GT1b GT1b SV2A SNAP25(1-197)GT1b GT1b Zn2+ VAMP1(1-60)GT1bSV2C BoNT/C HC disulfidebonded NTNHA BoNT/B:SYT:GT1bVAMP2(2-59)GT1b SNAP25(199-206)H+Zn2+ VAMP2(2-58)TeNT LC:Zn2+STX1VAMP2(2-76)ha33 SV2B BoNT/B LC disulfidebonded VAMP2VAMP2(77-116)BoNT/A HC disulfidebonded BoNT/B:SYT:GT1bSV2B BoNT/A:SV2:GT1bBoNT/G LC disulfidebonded BoNT/G HC disulfidebonded BoNT/B HC disulfidebonded GD2BoNT/E HC disulfidebonded BoNT/E HC disulfidebonded BoNT/G HC disulfidebonded SV2A,BBoNT/E LC disulfidebonded TeNT HC disulfidebonded BoNT/F HC disulfidebonded GM1a BoNT/C:GT1bZn2+ Zn2+ GT1bBoNT/B HCH+TeNT:gangliosidesBoNT/B LC disulfidebonded BoNT/D HC disulfidebonded VAMP2(82-116)GD3 Zn2+ SV2A,B,CVAMP2SYT1GT1b SV2A Zn2+ SYT1 ha70 BoNT/A HCZn2+ BoNT/G LC TeNT HC disulfidebonded Zn2+ Zn2+ BoNT/A HC disulfidebonded BoNT/F HC disulfidebonded Zn2+ SV2A,B,CBoNT/C HC disulfidebonded BoNT/D LC:Zn2+Zn2+ SV2B H+VAMP1(1-61)GM1aSV2C VAMP1GT1bBoNT/A HC disulfidebonded SV2B BoNT/E HC disulfidebonded ha33 SYT1 TeNT HC:LC dimerBoNT/A LC:Zn2+BoNT/E:SV2:GT1bSV2B TeNT LC disulfidebonded VAMP2GT1bBoNT/B LC ha70 BoNT/A LC disulfidebonded BoNT/E LC disulfidebonded VAMP2BoNT/D:SV2:GD2BoNT/C LC disulfidebonded BoNT/B HC:LC dimerBoNT/G HC:LC dimerZn2+ 30, 405, 3117441920, 542420, 542194320, 5410, 308, 284531820, 54424, 651, 555351, 5512, 3515392, 4817531113, 342753211724111120, 5453171153114, 6, 504, 6, 16, 505353214129, 2113, 3417111241753421120, 541713, 343611116, 4412, 354, 6, 5039945312420, 541721, 25119, 2113, 345, 312151, 55531, 1153244175351, 555320, 5420, 5441117124


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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History

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CompareRevisionActionTimeUserComment
114691view16:16, 25 January 2021ReactomeTeamReactome version 75
113137view11:20, 2 November 2020ReactomeTeamReactome version 74
112368view15:30, 9 October 2020ReactomeTeamReactome version 73
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)ProteinP63027 (Uniprot-TrEMBL)
VAMP2(59-116)ProteinP63027 (Uniprot-TrEMBL)
VAMP2(60-116)ProteinP63027 (Uniprot-TrEMBL)
VAMP2(77-116)ProteinP63027 (Uniprot-TrEMBL)
VAMP2(82-116)ProteinP63027 (Uniprot-TrEMBL)
VAMP2ProteinP63027 (Uniprot-TrEMBL)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
ha17 ProteinQ45878 (Uniprot-TrEMBL)
ha17ProteinQ45878 (Uniprot-TrEMBL)
ha33 ProteinQ57230 (Uniprot-TrEMBL)
ha33ProteinQ57230 (Uniprot-TrEMBL)
ha70 ProteinQ45877 (Uniprot-TrEMBL)
ha70ProteinQ45877 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
BoNT/A HC:LC dimerArrowR-HSA-5228943 (Reactome)
BoNT/A HC:LC dimerR-HSA-5244415 (Reactome)
BoNT/A HCArrowR-HSA-5244428 (Reactome)
BoNT/A LC:Zn2+ArrowR-HSA-5244428 (Reactome)
BoNT/A LC:Zn2+mim-catalysisR-HSA-194818 (Reactome)
BoNT/A:NTNHA:HAR-HSA-5228943 (Reactome)
BoNT/A:SV2:GT1bArrowR-HSA-5244415 (Reactome)
BoNT/A:SV2:GT1bArrowR-HSA-5244424 (Reactome)
BoNT/A:SV2:GT1bR-HSA-5244424 (Reactome)
BoNT/A:SV2:GT1bR-HSA-5244428 (Reactome)
BoNT/A:SV2:GT1bmim-catalysisR-HSA-5244428 (Reactome)
BoNT/B HC:LC dimerArrowR-HSA-5228940 (Reactome)
BoNT/B HC:LC dimerR-HSA-5244397 (Reactome)
BoNT/B HCArrowR-HSA-5244404 (Reactome)
BoNT/B LC:Zn2+ArrowR-HSA-5244404 (Reactome)
BoNT/B LC:Zn2+mim-catalysisR-HSA-194796 (Reactome)
BoNT/B:NTNHA:HAR-HSA-5228940 (Reactome)
BoNT/B:SYT:GT1bArrowR-HSA-5244397 (Reactome)
BoNT/B:SYT:GT1bArrowR-HSA-5244402 (Reactome)
BoNT/B:SYT:GT1bR-HSA-5244402 (Reactome)
BoNT/B:SYT:GT1bR-HSA-5244404 (Reactome)
BoNT/B:SYT:GT1bmim-catalysisR-HSA-5244404 (Reactome)
BoNT/C HC:LC dimerR-HSA-5246506 (Reactome)
BoNT/C HCArrowR-HSA-5246514 (Reactome)
BoNT/C LC:Zn2+ArrowR-HSA-5246514 (Reactome)
BoNT/C LC:Zn2+mim-catalysisR-HSA-181567 (Reactome)
BoNT/C LC:Zn2+mim-catalysisR-HSA-194793 (Reactome)
BoNT/C:GT1bArrowR-HSA-5246506 (Reactome)
BoNT/C:GT1bArrowR-HSA-5246509 (Reactome)
BoNT/C:GT1bR-HSA-5246509 (Reactome)
BoNT/C:GT1bR-HSA-5246514 (Reactome)
BoNT/C:GT1bmim-catalysisR-HSA-5246514 (Reactome)
BoNT/D HC:LC dimerR-HSA-5250607 (Reactome)
BoNT/D HCArrowR-HSA-5250616 (Reactome)
BoNT/D LC:Zn2+ArrowR-HSA-5250616 (Reactome)
BoNT/D LC:Zn2+mim-catalysisR-HSA-194809 (Reactome)
BoNT/D LC:Zn2+mim-catalysisR-HSA-5250606 (Reactome)
BoNT/D:SV2:GD2ArrowR-HSA-5250600 (Reactome)
BoNT/D:SV2:GD2ArrowR-HSA-5250607 (Reactome)
BoNT/D:SV2:GD2R-HSA-5250600 (Reactome)
BoNT/D:SV2:GD2R-HSA-5250616 (Reactome)
BoNT/D:SV2:GD2mim-catalysisR-HSA-5250616 (Reactome)
BoNT/E HC:LC dimerArrowR-HSA-5228941 (Reactome)
BoNT/E HC:LC dimerR-HSA-5244503 (Reactome)
BoNT/E HCArrowR-HSA-5244506 (Reactome)
BoNT/E LC:Zn2+ArrowR-HSA-5244506 (Reactome)
BoNT/E LC:Zn2+mim-catalysisR-HSA-194800 (Reactome)
BoNT/E:NTNHAR-HSA-5228941 (Reactome)
BoNT/E:SV2:GT1bArrowR-HSA-5244500 (Reactome)
BoNT/E:SV2:GT1bArrowR-HSA-5244503 (Reactome)
BoNT/E:SV2:GT1bR-HSA-5244500 (Reactome)
BoNT/E:SV2:GT1bR-HSA-5244506 (Reactome)
BoNT/E:SV2:GT1bmim-catalysisR-HSA-5244506 (Reactome)
BoNT/F HC:LC dimerR-HSA-5250880 (Reactome)
BoNT/F HCArrowR-HSA-5250884 (Reactome)
BoNT/F LC:Zn2+ArrowR-HSA-5250884 (Reactome)
BoNT/F LC:Zn2+mim-catalysisR-HSA-194808 (Reactome)
BoNT/F LC:Zn2+mim-catalysisR-HSA-5250892 (Reactome)
BoNT/F:SV2:GT1bArrowR-HSA-5250875 (Reactome)
BoNT/F:SV2:GT1bArrowR-HSA-5250880 (Reactome)
BoNT/F:SV2:GT1bR-HSA-5250875 (Reactome)
BoNT/F:SV2:GT1bR-HSA-5250884 (Reactome)
BoNT/F:SV2:GT1bmim-catalysisR-HSA-5250884 (Reactome)
BoNT/G HC:LC dimerR-HSA-5250986 (Reactome)
BoNT/G HCArrowR-HSA-5250972 (Reactome)
BoNT/G LC:Zn2+ArrowR-HSA-5250972 (Reactome)
BoNT/G LC:Zn2+mim-catalysisR-HSA-5250962 (Reactome)
BoNT/G LC:Zn2+mim-catalysisR-HSA-5250978 (Reactome)
BoNT/G:SYT1:GT1bArrowR-HSA-5250979 (Reactome)
BoNT/G:SYT1:GT1bArrowR-HSA-5250986 (Reactome)
BoNT/G:SYT1:GT1bR-HSA-5250972 (Reactome)
BoNT/G:SYT1:GT1bR-HSA-5250979 (Reactome)
BoNT/G:SYT1:GT1bmim-catalysisR-HSA-5250972 (Reactome)
GD2ArrowR-HSA-5250616 (Reactome)
GD2R-HSA-5250607 (Reactome)
GD3ArrowR-HSA-5228406 (Reactome)
GD3R-HSA-5228407 (Reactome)
GM1aArrowR-HSA-5228406 (Reactome)
GM1aR-HSA-5228407 (Reactome)
GT1bArrowR-HSA-5244404 (Reactome)
GT1bArrowR-HSA-5244428 (Reactome)
GT1bArrowR-HSA-5244506 (Reactome)
GT1bArrowR-HSA-5246514 (Reactome)
GT1bArrowR-HSA-5250884 (Reactome)
GT1bArrowR-HSA-5250972 (Reactome)
GT1bR-HSA-5244397 (Reactome)
GT1bR-HSA-5244415 (Reactome)
GT1bR-HSA-5244503 (Reactome)
GT1bR-HSA-5246506 (Reactome)
GT1bR-HSA-5250880 (Reactome)
GT1bR-HSA-5250986 (Reactome)
H+ArrowR-HSA-5228406 (Reactome)
H+ArrowR-HSA-5244404 (Reactome)
H+ArrowR-HSA-5244428 (Reactome)
H+ArrowR-HSA-5244506 (Reactome)
H+ArrowR-HSA-5246514 (Reactome)
H+ArrowR-HSA-5250616 (Reactome)
H+ArrowR-HSA-5250884 (Reactome)
H+ArrowR-HSA-5250972 (Reactome)
NTNHAArrowR-HSA-5228940 (Reactome)
NTNHAArrowR-HSA-5228941 (Reactome)
NTNHAArrowR-HSA-5228943 (Reactome)
R-HSA-181567 (Reactome) Botulinum toxin type C light chain (BoNT/C LC), in the cytosol of a target cell, catalyzes the removal of an aminoterminal peptide from syntaxin 1 (STX1). BoNT/C LC is a zinc metalloprotease (Blasi et al. 1993; Foran et al. 1994). STX1 is associated with the cytosolic face of the target cell plasma membrane where it forms part of a complex required for synaptic vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release (Sudhof et al, 1993; Sudhof 2004).
R-HSA-194793 (Reactome) Botulinum toxin type C light chain (BoNT/C LC), in the cytosol of a target cell, catalyzes the removal of a carboxyterminal peptide from synaptosomal associated protein 25 (SNAP25). BoNT/C LC is a zinc metalloprotease (Foran et al. 1994; Vaidyanathan et al. 1999). SNAP25 is associated with the cytosolic face of the target cell plasma membrane where it forms part of a complex required for synaptic vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release (Sudhof et al, 1993; Sudhof 2004).
R-HSA-194796 (Reactome) Botulinum toxin type B light chain (BoNT/B LC), in the cytosol of a target cell, catalyzes the removal of an aminoterminal peptide from vesicle-associated membrane protein 2 (VAMP2). BoNT/B LC is a zinc metalloprotease (Foran et al. 1994; Schiavo et al. 1992). VAMP2 is associated with the cytosolic face of the target cell synaptic vesicle and is required for vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release and in vivo leads to a long lasting flaccid paralysis (Sudhof et al, 1993; Sudhof 2004).
R-HSA-194800 (Reactome) Botulinum toxin type E light chain (BoNT/E LC), in the cytosol of a target cell, catalyzes the removal of a carboxyterminal peptide from synaptosomal-associated protein 25 (SNAP25). BoNT/E LC is a zinc metalloprotease (Binz et al. 1994; Schiavo et al. 1993; Vaidyanathan et al. 1999). SNAP25 is associated with the cytosolic face of the target cell plasma membrane where it forms part of a complex required for synaptic vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release and in vivo leads to a long lasting flaccid paralysis (Sudhof et al, 1993; Sudhof 2004).
R-HSA-194808 (Reactome) Botulinum toxin type F light chain (BoNT/F LC), in the cytosol of a target cell, catalyzes the removal of an aminoterminal peptide from vesicle-associated membrane protein 1 (VAMP1). BoNT/F LC is a zinc metalloprotease (Yamasaki et al. 1994). VAMP1 is associated with the cytosolic face of the target cell synaptic vesicle and is required for vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release (Sudhof et al, 1993; Sudhof 2004).
R-HSA-194809 (Reactome) Botulinum toxin type D light chain (BoNT/D LC), in the cytosol of a target cell, catalyzes the removal of an aminoterminal peptide from vesicle-associated membrane protein 1 (VAMP1). BoNT/D LC is a zinc metalloprotease (Arndt et al. 2006; Schiavo et al. 1993; Yamasaki et al. 1994). VAMP1 is associated with the cytosolic face of the target cell synaptic vesicle and is required for vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release (Sudhof et al, 1993; Sudhof 2004).
R-HSA-194818 (Reactome) Botulinum toxin type A light chain (BoNT/A LC), in the cytosol of a target cell, catalyzes the removal of a carboxyterminal peptide from synaptosomal-associated protein 25 (SNAP25). BoNT/A LC is a zinc metalloprotease (Binz et al. 1994; Schiavo et al. 1993). SNAP25 is associated with the cytosolic face of the target cell plasma membrane where it forms part of a complex required for synaptic vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release and in vivo leads to a long lasting flaccid paralysis (Sudhof et al, 1993; Sudhof 2004).
R-HSA-5228406 (Reactome) Acidification of the vesicle containing tetanus toxin disulfide-bonded heavy chain - light chain dimer (TeNT HC:LC) is inferred to cause a conformational change in the toxin dimer, allowing the HC part of the toxin to function as a channel through which its LC part is extruded into the neuronal cytosol (Montal 2010).
R-HSA-5228407 (Reactome) Tetanus toxin disulfide-bonded heavy chain - light chain dimer (TeNT HC:LC) binds gangliosides on the plasma membrane of a human target cell (Chen et al. 2009; Deinhardt et al. 2006).
R-HSA-5228408 (Reactome) Vesicles containing ganglioside-bound tetanus toxin disulfide-bonded heavy chain - light chain dimer (TeNT HC:LC) are transported in a retrograde fashion away from the target cell synapse where they were formed into the cell body (Lalli et al. 2003).
R-HSA-5228411 (Reactome) Ganglioside-bound tetanus toxin disulfide-bonded heavy chain - light chain dimer (TeNT HC:LC) is taken up into the target cell by clathrin-mediated endocytosis (Deinhardt et al. 2006).
R-HSA-5228578 (Reactome) Tetanus toxin light chain (TeNT LC), in the cytosol of a target cell, catalyzes the removal of an aminoterminal peptide from vesicle-associated membrane protein 2 (VAMP2). TeNT LC is a zinc metalloprotease (Foran et al. 1994; Schiavo et al. 1992). VAMP2 is associated with the cytosolic face of the target cell synaptic vesicle and is required for vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks exocytosis and in vivo leads to a long-lasting spastic paralysis (Link et al. 1992).
R-HSA-5228940 (Reactome) The bacterial BoNT/B:NTNHA:HA complex, consisting of a Botulinum toxin type B (BoNT/B) disulfide bonded heavy chain (HC) - light chain (LC) dimer associated with nontoxic nonhemagglutinin protein (NTNHA), three molecules of hemagglutinin (ha) 17, six of ha33, and three of ha70 (Amatsu et al. 2013), associates with the plasma membrane of a human cell (in vivo, the apical surface of a gut epithelial cell) and undergoes transcytosis. While the molecular details of transcytosis remain to be established definitively, the process enables the toxin heterodimer to cross the epithelial cell layer and enter the circulation (Fujinaga et al. 2013; Simpson 2004).
R-HSA-5228941 (Reactome) The bacterial BoNT/E:NTNHA complex, consisting of a Botulinum toxin type E (BoNT/E) disulfide bonded heavy chain (HC) - light chain (LC) heterodimer (“dichain”) associated with nontoxic nonhemagglutinin protein (NTNHA) (Benefield et al. 2013), associates with the plasma membrane of a human cell (in vivo, the apical surface of a gut epithelial cell) and undergoes transcytosis. While the molecular details of transcytosis remain to be established definitively, the process enables the toxin heterodimer to cross the epithelial cell layer and enter the circulation (Fujinaga et al. 2013; Simpson 2004).
R-HSA-5228943 (Reactome) The bacterial BoNT/A:NTNHA:HA complex, consisting of a Botulinum toxin type A (BoNT/A) disulfide bonded heavy chain (HC) - light chain (LC) heterodimer ("dichain") associated with nontoxic nonhemagglutinin protein (NTNHA), three molecules of hemagglutinin (ha) 17, six of ha33, and three of ha70 (Lee et al. 2013), associates with the plasma membrane of a human cell (in vivo, the apical surface of a gut epithelial cell) and undergoes transcytosis. While the molecular details of transcytosis remain to be established definitively, the process enables the toxin heterodimer to cross the epithelial cell layer and enter the circulation (Fujinaga et al. 2013; Simpson 2004).
R-HSA-5244397 (Reactome) The Botulinum toxin type B disulfide-bonded heavy chain - light chain dimer (BoNT/B HC:LC, encoded by the C. botulinum botB gene) (Swaminathan & Eswaramoorthy 2000) binds ganglioside GT1b and syntagmin 1 or 2 (SYT1 or 2) on the plasma membrane of a human target cell. In vivo, this process specifically targets synapses at neuromuscular junctions, where toxin association with ganglioside may position it to bind efficiently to SYT1 or 2 when those proteins are exposed at the cell surface by exocytosis (Dong et al. 2003). In vitro, BoNT/B HC:LC can bind gangliosides in addition to GT1b but with lower affinity (Kozaki et al. 1998). Only GT1b binding is annotated here.
R-HSA-5244402 (Reactome) Synaptic vesicles re-form rapidly after exocytosis, carrying vesicle membrane proteins that had been exposed on the cell surface by exocytosis back into the cell (Sudhoff 2004). The botulinum toxin type B disulfide bonded heavy chain - light chain heterodimer (BoNT/B) bound to ganglioside GT1b and syntagmin 1 or 2 (SYT) is inferred to be taken up as well, delivering it to the re-formed synaptic vesicle.
R-HSA-5244404 (Reactome) By analogy to the process described for botulinum toxin type A (Koriazova and Montal 2003; Montal 2010), acidification, a normal step in synaptic vesicle recycling, is inferred to cause a conformational change in the botulinum toxin type B disulfide bonded heavy chain - light chain dimer (BoNT/B HC:LC) it contains, allowing the HC part of the toxin to function as a channel through which its LC part is extruded into the neuronal cytosol. The HC - LC disulfide bond is cleaved. Recent studies in vitro suggest that GT1b ganglioside associated with the toxin may play a role in this process (Sun et al. 2011, 2012).
R-HSA-5244415 (Reactome) The Botulinum toxin type A disulfide bonded heavy chain - light chain heterodimer (BoNT/A HC:LC, encoded by the C. botulinum botA gene) (Lacy et al. 1998) binds ganglioside GT1b and synaptic vesicle protein 2A (SV2A) on the plasma membrane of a human target cell. In vivo, this process specifically targets synapses at neuromuscular junctions, where toxin association with ganglioside may position it to bind efficiently to SV2A, SV2B, or SV2C when those proteins are exposed at the cell surface by exocytosis (Dong et al. 2006). In vitro, BoNT/A HC:LC can bind gangliosides in addition to GT1b but with lower affinity (Kozaki et al. 1998). Only GT1b binding is annotated here.
R-HSA-5244424 (Reactome) Synaptic vesicles re form rapidly after exocytosis, carrying vesicle membrane proteins that had been exposed on the cell surface by exocytosis back into the cell (Sudhoff 2004). The botulinum toxin type A disulfide bonded heavy chain - light chain heterodimer (“dichain”) (BoNT/A HC:LC) bound to ganglioside GT1b and synaptic vesicle protein 2A, 2B, or 2C (SV2A, B, or C) is inferred to be taken up as well, delivering it to the re-formed synaptic vesicle.
R-HSA-5244428 (Reactome) Acidification, a normal step in endocytosis causes a conformational change in the botulinum toxin type A disulfide bonded heavy chain - light chain heterodimer (“dichain”) (BoNT/A HC:LC) it contains, allowing the HC part of the toxin to function as a channel through which its LC part is extruded into the neuronal cytosol. The HC - LC disulfide bond is cleaved (Koriazova & Montal 2003; Montal 2010). Recent studies in vitro suggest that GT1b ganglioside associated with the toxin may play a role in this process (Sun et al. 2012).
R-HSA-5244500 (Reactome) Synaptic vesicles re-form rapidly after exocytosis, carrying vesicle membrane proteins that had been exposed on the cell surface by exocytosis back into the cell (Sudhoff 2004). The botulinum toxin type E disulfide bonded heavy chain - light chain heterodimer (BoNT/E HC:LC) bound to ganglioside GT1b and synaptic vesicle protein 2A (SV2A) or 2B (SV2B) is inferred to be taken up as well, delivering it to the re-formed synaptic vesicle.
R-HSA-5244503 (Reactome) The Botulinum toxin type E disulfide bonded heavy chain - light chain heterodimer (BoNT/E HC:LC, encoded by the C. botulinum botE gene) (Kumaran et al. 2009) binds ganglioside GT1b and synaptic vesicle protein 2A (SV2A) or 2B (SV2B) on the plasma membrane of a human target cell. In vivo, this process specifically targets synapses at neuromuscular junctions, where toxin association with ganglioside may position it to bind efficiently to SV2A or B when those proteins are exposed at the cell surface by exocytosis (Dong et al. 2008; Rummel et al. 2009).
R-HSA-5244506 (Reactome) By analogy to the process described for botulinum toxin type A (Koriazova and Montal 2003; Montal 2010), acidification, a normal step in synaptic vesicle recycling, is inferred to cause a conformational change in the botulinum toxin type E disulfide bonded heavy chain - light chain dimer (BoNT/E HC:LC) it contains, allowing the HC part of the toxin to function as a channel through which its LC part is extruded into the neuronal cytosol. The HC - LC disulfide bond is cleaved. Recent studies in vitro suggest that GT1b ganglioside associated with the toxin may play a role in this process (Sun et al. 2012).
R-HSA-5246506 (Reactome) The botulinum toxin type C disulfide-bonded heavy chain - light chain heterodimer (“dichain”) (BoNT/C HC:LC, encoded by the C. botulinum botC1 gene) binds two molecules of GT1b ganglioside on the plasma membrane of a human target cell (Karalewitz et al. 2012).
R-HSA-5246509 (Reactome) Synaptic vesicles re-form rapidly after exocytosis, carrying vesicle membrane proteins that had been exposed on the cell surface by exocytosis back into the cell (Sudhoff 2004). The botulinum toxin type C disulfide-bonded heavy chain - light chain heterodimer (BoNT/C HC:LC) bound to ganglioside GT1b is inferred to be taken up as well, delivering it to the re-formed synaptic vesicle.
R-HSA-5246514 (Reactome) By analogy to the process described for botulinum toxin type A (Koriazova and Montal 2003; Montal 2010), acidification, a normal step in synaptic vesicle recycling, is inferred to cause a conformational change in the botulinum toxin type C disulfide-bonded heavy chain - light chain dimer (BoNT/C HC:LC) it contains, allowing the HC part of the toxin to function as a channel through which its LC part is extruded into the neuronal cytosol. The HC - LC disulfide bond is cleaved. Recent studies in vitro suggest that GT1b ganglioside associated with the toxin may play a role in this process (Sun et al. 2012).
R-HSA-5250600 (Reactome) Synaptic vesicles re-form rapidly after exocytosis, carrying vesicle membrane proteins that had been exposed on the cell surface by exocytosis back into the cell (Sudhoff 2004). The botulinum toxin type D disulfide-bonded heavy chain - light chain heterodimer (BoNT/D HC:LC) bound to ganglioside GD2 and synaptic vesicle protein 2A, 2B, or 2C (SV2A, B, or C) is inferred to be taken up as well, delivering it to the re-formed synaptic vesicle.
R-HSA-5250606 (Reactome) Botulinum toxin type D light chain (BoNT/D LC), in the cytosol of a target cell, catalyzes the removal of an aminoterminal peptide from vesicle-associated membrane protein 2 (VAMP2). BoNT/D LC is a zinc metalloprotease (Arndt et al. 2006; Schiavo et al. 1993; Yamasaki et al. 1994). VAMP2 is associated with the cytosolic face of the target cell synaptic vesicle and is required for vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release (Sudhof et al, 1993; Sudhof 2004).
R-HSA-5250607 (Reactome) The botulinum toxin type D disulfide-bonded heavy chain - light chain heterodimer ("dichain") (BoNT/D HC:LC, encoded by the C. botulinum botD gene) binds ganglioside GD2 and synaptic vesicle proteins 2A (SV2A), 2B (SV2B), or 2C (SV2C) on the plasma membrane of a human target cell. In vivo, this process specifically targets synapses at neuromuscular junctions, where toxin association with ganglioside may position it to bind efficiently to SV2A, SV2B, or SV2C when those proteins are exposed at the cell surface by exocytosis (Kroken et al. 2011; Peng et al. 2011).
R-HSA-5250616 (Reactome) By analogy to the process described for botulinum toxin type A (Koriazova and Montal 2003; Montal 2010), acidification, a normal step in synaptic vesicle recycling, is inferred to cause a conformational change in the botulinum toxin type D disulfide-bonded heavy chain - light chain dimer (BoNT/D HC:LC) it contains, allowing the HC part of the toxin to function as a channel through which its LC part is extruded into the neuronal cytosol where the HC - LC disulfide bond is cleaved.
R-HSA-5250875 (Reactome) Synaptic vesicles re-form rapidly after exocytosis, carrying vesicle membrane proteins that had been exposed on the cell surface by exocytosis back into the cell (Sudhoff 2004). The botulinum toxin type D disulfide-bonded heavy chain - light chain heterodimer ("dichain") (BoNT/F HC:LC) bound to ganglioside GT1b and synaptic vesicle protein 2A (SV2A), 2B (SV2B), or 2C (SV2C) is inferred to be taken up as well, delivering it to the re-formed synaptic vesicle.
R-HSA-5250880 (Reactome) The botulinum toxin type F disulfide-bonded heavy chain - light chain heterodimer ("dichain") (BoNT/F HC:LC, encoded by the C. botulinum botF gene) binds ganglioside GT1b and synaptic vesicle protein 2A (SV2A), B (SV2B), or C (SV2C) on the plasma membrane of a human target cell. In vivo, this process specifically targets synapses at neuromuscular junctions, where toxin association with ganglioside may position it to bind efficiently to SV2A, B, or C when those proteins are exposed at the cell surface by exocytosis (Fu et al. 2009; Rummel et al. 2009).
R-HSA-5250884 (Reactome) By analogy to the process described for botulinum toxin type A (Koriazova and Montal 2003; Montal 2010), acidification, a normal step in synaptic vesicle recycling, is inferred to cause a conformational change in the botulinum toxin type F disulfide-bonded heavy chain - light chain heterodimer (BoNT/F HC:LC) it contains, allowing the HC part of the toxin to function as a channel through which its LC part is extruded into the neuronal cytosol.The HC - LC disulfide bond is cleaved. Recent studies in vitro suggest that GT1b ganglioside associated with the toxin may play a role in this process (Sun et al. 2012).
R-HSA-5250892 (Reactome) Botulinum toxin type F light chain (BoNT/F LC), in the cytosol of a target cell, catalyzes the removal of an aminoterminal peptide from vesicle-associated membrane protein 2 (VAMP2). BoNT/F LC is a zinc metalloprotease (Yamasaki et al. 1994). VAMP2 is associated with the cytosolic face of the target cell synaptic vesicle and is required for vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release (Sudhof et al, 1993; Sudhof 2004).
R-HSA-5250962 (Reactome) Botulinum toxin type G light chain (BoNT/G LC), in the cytosol of a target cell, catalyzes the removal of an aminoterminal peptide from vesicle-associated membrane protein 2 (VAMP2). BoNT/G LC is a zinc metalloprotease (Schiavo et al. 1994; Yamasaki et al. 1994). VAMP2 is associated with the cytosolic face of the target cell synaptic vesicle and is required for vesicle docking and exocytosis. Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release (Sudhof et al, 1993; Sudhof 2004).
R-HSA-5250972 (Reactome) By analogy to the process described for botulinum toxin type A (Koriazova and Montal 2003; Montal 2010), acidification, a normal step in synaptic vesicle recycling, is inferred to cause a conformational change in the botulinum toxin type G disulfide-bonded heavy chain - light chain dimer (BoNT/G HC:LC) it contains, allowing the HC part of the toxin to function as a channel through which its LC part is extruded into the neuronal cytosol. The HC - LC disulfide bond is cleaved. Recent studies in vitro suggest that GT1b ganglioside associated with the toxin may play a role in this process (Sun et al. 2012).
R-HSA-5250978 (Reactome) Botulinum toxin type G light chain (BoNT/G LC), in the cytosol of a target cell, catalyzes the removal of an aminoterminal peptide from vesicle-associated membrane protein 1 (VAMP1). BoNT/G LC is a zinc metalloprotease (Schiavo et al. 1994; Yamasaki et al. 1994). VAMP1 is associated with the cytosolic face of the target cell synaptic vesicle and is required for vesicle docking and exocytosis.Its cleavage by botulinum toxin blocks synaptic vesicle fusion with the plasma membrane and neurotransmitter release (Sudhof et al, 1993; Sudhof 2004).
R-HSA-5250979 (Reactome) Synaptic vesicles re-form rapidly after exocytosis, carrying vesicle membrane proteins that had been exposed on the cell surface by exocytosis back into the cell (Sudhoff 2004). The botulinum toxin type G disulfide-bonded heavy chain - light chain heterodimer (BoNT/G HC:LC) bound to ganglioside GT1b and syntagmin 1 (SYT1) is inferred to be taken up as well, delivering it to the re-formed synaptic vesicle.
R-HSA-5250986 (Reactome) The botulinum toxin type G disulfide-bonded heavy chain - light chain heterodimer ("dichain") (BoNT/G HC:LC) binds ganglioside GT1b and synaptotagmin-1 (SYT1) on the plasma membrane of a human target cell. In vivo, this process specifically targets synapses at neuromuscular junctions, where toxin association with ganglioside may position it to bind efficiently to SYT1 when that protein is exposed at the cell surface by exocytosis (Peng et al. 2012; Willjes et al. 2013).
SNAP25(1-197)ArrowR-HSA-194818 (Reactome)
SNAP25(1-198)ArrowR-HSA-194793 (Reactome)
SNAP25(1-198)ArrowR-HSA-194800 (Reactome)
SNAP25(198-206)ArrowR-HSA-194818 (Reactome)
SNAP25(199-206)ArrowR-HSA-194793 (Reactome)
SNAP25(199-206)ArrowR-HSA-194800 (Reactome)
SNAP25R-HSA-194793 (Reactome)
SNAP25R-HSA-194800 (Reactome)
SNAP25R-HSA-194818 (Reactome)
STX1(1-?)ArrowR-HSA-181567 (Reactome)
STX1(?-288)ArrowR-HSA-181567 (Reactome)
STX1R-HSA-181567 (Reactome)
SV2A,B,CArrowR-HSA-5244428 (Reactome)
SV2A,B,CArrowR-HSA-5250616 (Reactome)
SV2A,B,CArrowR-HSA-5250884 (Reactome)
SV2A,B,CR-HSA-5244415 (Reactome)
SV2A,B,CR-HSA-5250607 (Reactome)
SV2A,B,CR-HSA-5250880 (Reactome)
SV2A,BArrowR-HSA-5244506 (Reactome)
SV2A,BR-HSA-5244503 (Reactome)
SYT1,2ArrowR-HSA-5244404 (Reactome)
SYT1,2R-HSA-5244397 (Reactome)
SYT1ArrowR-HSA-5250972 (Reactome)
SYT1R-HSA-5250986 (Reactome)
TeNT HC:LC dimerR-HSA-5228407 (Reactome)
TeNT HCArrowR-HSA-5228406 (Reactome)
TeNT LC:Zn2+ArrowR-HSA-5228406 (Reactome)
TeNT LC:Zn2+mim-catalysisR-HSA-5228578 (Reactome)
TeNT:gangliosidesArrowR-HSA-5228407 (Reactome)
TeNT:gangliosidesArrowR-HSA-5228408 (Reactome)
TeNT:gangliosidesArrowR-HSA-5228411 (Reactome)
TeNT:gangliosidesR-HSA-5228406 (Reactome)
TeNT:gangliosidesR-HSA-5228408 (Reactome)
TeNT:gangliosidesR-HSA-5228411 (Reactome)
TeNT:gangliosidesmim-catalysisR-HSA-5228406 (Reactome)
VAMP1(1-60)ArrowR-HSA-194808 (Reactome)
VAMP1(1-61)ArrowR-HSA-194809 (Reactome)
VAMP1(1-83)ArrowR-HSA-5250978 (Reactome)
VAMP1(61-118)ArrowR-HSA-194808 (Reactome)
VAMP1(62-118)ArrowR-HSA-194809 (Reactome)
VAMP1(84-118)ArrowR-HSA-5250978 (Reactome)
VAMP1R-HSA-194808 (Reactome)
VAMP1R-HSA-194809 (Reactome)
VAMP1R-HSA-5250978 (Reactome)
VAMP2(2-58)ArrowR-HSA-5250892 (Reactome)
VAMP2(2-59)ArrowR-HSA-5250606 (Reactome)
VAMP2(2-76)ArrowR-HSA-194796 (Reactome)
VAMP2(2-76)ArrowR-HSA-5228578 (Reactome)
VAMP2(2-81)ArrowR-HSA-5250962 (Reactome)
VAMP2(59-116)ArrowR-HSA-5250892 (Reactome)
VAMP2(60-116)ArrowR-HSA-5250606 (Reactome)
VAMP2(77-116)ArrowR-HSA-194796 (Reactome)
VAMP2(77-116)ArrowR-HSA-5228578 (Reactome)
VAMP2(82-116)ArrowR-HSA-5250962 (Reactome)
VAMP2R-HSA-194796 (Reactome)
VAMP2R-HSA-5228578 (Reactome)
VAMP2R-HSA-5250606 (Reactome)
VAMP2R-HSA-5250892 (Reactome)
VAMP2R-HSA-5250962 (Reactome)
ha17ArrowR-HSA-5228940 (Reactome)
ha17ArrowR-HSA-5228943 (Reactome)
ha33ArrowR-HSA-5228940 (Reactome)
ha33ArrowR-HSA-5228943 (Reactome)
ha70ArrowR-HSA-5228940 (Reactome)
ha70ArrowR-HSA-5228943 (Reactome)

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