Protein: Botulinum neurotoxin type C (BoNT/C) (Bontoxilysin-C1) (BoNT/C1) (Botulinum neurotoxin type C1) [Cleaved into: Botulinum neurotoxin C light chain (LC) (EC 3.4.24.69); Botulinum neurotoxin C heavy chain (HC)] (P18640)
Organism: Clostridium botulinum C phage (Clostridium botulinum C bacteriophage)
Function: Botulinum toxin causes flaccid paralysis by inhibiting neurotransmitter (acetylcholine) release from the presynaptic membranes of nerve terminals of the eukaryotic host skeletal and autonomic nervous system, with frequent heart or respiratory failure. Is unique among characterized BoNTs in having 2 substrates, syntaxin (STX) and SNAP25. Precursor of botulinum neurotoxin C which unlike most BoNTs seems not to have a proteinaceous coreceptor, and instead recognizes 2 different complex polysialylated gangliosides found on neural tissue probably found in synaptic vesicles. Upon synaptic vesicle recycling the toxin is taken up via the endocytic pathway. When the pH of the toxin-containing endosome drops a structural rearrangement occurs so that the N-terminus of the heavy chain (HC) forms pores that allows the light chain (LC) to translocate into the cytosol (By similarity). Once in the cytosol the disulfide bond linking the 2 subunits is reduced and LC cleaves its target protein on synaptic vesicles, preventing their fusion with the cytoplasmic membrane and thus neurotransmitter release (By similarity). In vitro the whole toxin only has protease activity after reduction. Electrical stimulation increases uptake of toxin, presumably by transiently exposing a receptor usually found in eukaryotic target synaptic vesicles. Forms ion-conducting channels at around pH 6.1. Requires complex eukaryotic host polysialogangliosides for full neurotoxicity. Synaptic vesicle glycoproteins (SV2) do not seem to act as its receptor.
Subcellular location: [Botulinum neurotoxin type C]: Secreted {ECO:0000269|PubMed:16252491}.; SUBCELLULAR LOCATION: [Botulinum neurotoxin C light chain]: Secreted {ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:7802661}. Note=In animals that have ingested BoNT/C the LC acts in the eukaryotic host cytosol (PubMed:17718519, PubMed:7737992, PubMed:7901002, PubMed:8611567, PubMed:9886085). {ECO:0000305|PubMed:17718519, ECO:0000305|PubMed:7737992, ECO:0000305|PubMed:7901002, ECO:0000305|PubMed:8611567, ECO:0000305|PubMed:9886085}.; SUBCELLULAR LOCATION: [Botulinum neurotoxin C heavy chain]: Secreted {ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:7802661}. Note=Upon incubation with cultured neurons the HC is detected in a synaptophysin-positive intracellular compartment (probably host synaptic vesicles) (PubMed:23027864). It probably integrates into the eukaryotic host synaptic vesicle membrane (PubMed:2424493). {ECO:0000269|PubMed:23027864, ECO:0000305|PubMed:2424493}.
Interaction partners:
Sequence:
MPITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCHKAIDGRSLYNKTLDCRELLVKNTDLPFIGDISDVKTDIFLRKDINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQNVDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQFNNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDIINEYFNNINDSKILSLQNRKNTLVDTSGYNAEVSEEGDVQLNPIFPFDFKLGSSGEDRGKVIVTQNENIVYNSMYESFSISFWIRINKWVSNLPGYTIIDSVKNNSGWSIGIISNFLVFTLKQNEDSEQSINFSYDISNNAPGYNKWFFVTVTNNMMGNMKIYINGKLIDTIKVKELTGINFSKTITFEINKIPDTGLITSDSDNINMWIRDFYIFAKELDGKDINILFNSLQYTNVVKDYWGNDLRYNKEYYMVNIDYLNRYMYANSRQIVFNTRRNNNDFNEGYKIIIKRIRGNTNDTRVRGGDILYFDMTINNKAYNLFMKNETMYADNHSTEDIYAIGLREQTKDINDNIIFQIQPMNNTYYYASQIFKSNFNGENISGICSIGTYRFRLGGDWYRHNYLVPTVKQGNYASLLESTSTHWGFVPVSE