UniProtKB - P30996 (BXF_CLOBO)
Botulinum neurotoxin type F
botF
Functioni
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. Precursor of botulinum neurotoxin F which may have 2 coreceptors; complex polysialylated gangliosides found on neural tissue and specific membrane-anchored proteins found in synaptic vesicles. Receptor proteins are exposed on host presynaptic cell membrane during neurotransmitter release, when the toxin heavy chain (HC) binds to them. 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 HC forms pores that allows the light chain (LC) to translocate into the cytosol. 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).
Whole toxin only has protease activity after reduction, which releases LC (PubMed:8505288).
Requires complex eukaryotic host polysialogangliosides for full neurotoxicity (By similarity).
It is not clear whether a synaptic vesicle protein acts as its receptor; there is evidence for and against SV2 fulfilling this function (By similarity).
By similarity1 PublicationHas proteolytic activity (PubMed:8505288, PubMed:8175689, PubMed:8197120).
After translocation into the eukaryotic host cytosol, inhibits neurotransmitter release by acting as a zinc endopeptidase that catalyzes the hydrolysis of the '60-Gln-|-Lys-61' bond of synaptobrevin-1/VAMP1 and the equivalent 'Gln-|-Lys' sites in VAMP2 and VAMP3 (PubMed:8505288, PubMed:8175689).
Cleaves the '48-Gln-|-Lys-49' bond of A.californica synaptobrevin (AC P35589) (PubMed:8197120).
1 Publication3 PublicationsResponsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of light chain (LC) into host cytosol. Composed of 3 subdomains; the translocation domain (TD), and N-terminus and C-terminus of the receptor-binding domain (RBD). The RBD is responsible for the adherence of the toxin to the cell surface. It simultaneously recognizes 2 coreceptors; polysialated gangliosides and the receptor protein SV2A, SV2B and SV2C in close proximity on host synaptic vesicles; although not all evidence indicates these are the receptors (By similarity).
The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn2+ in the active site; it may also prevent premature LC dissociation from the translocation channel and protect toxin prior to translocation (By similarity).
The TD inserts into synaptic vesicle membrane to allow translocation into the host cytosol (By similarity).
By similarityMiscellaneous
Caution
Catalytic activityi
- Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on small molecule substrates.2 Publications EC:3.4.24.69
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 227 | Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Active sitei | 228 | PROSITE-ProRule annotation | 1 | |
Metal bindingi | 231 | Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 266 | Zinc; catalyticCombined sources1 Publication | 1 |
GO - Molecular functioni
- lipid binding Source: UniProtKB-KW
- metalloendopeptidase activity Source: UniProtKB-EC
- protein transmembrane transporter activity Source: Reactome
- toxin activity Source: UniProtKB-KW
- zinc ion binding Source: InterPro
GO - Biological processi
- negative regulation of neurotransmitter secretion Source: InterPro
Keywordsi
Molecular function | Hydrolase, Metalloprotease, Neurotoxin, Protease, Toxin |
Biological process | Virulence |
Ligand | Lipid-binding, Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.4.24.69, 1462 |
Reactomei | R-HSA-5250981, Toxicity of botulinum toxin type F (botF) |
Names & Taxonomyi
Protein namesi | Recommended name: Botulinum neurotoxin type FShort name: BoNT/F1 Publication Alternative name(s): Bontoxilysin-F Cleaved into the following 2 chains: |
Gene namesi | Name:botF |
Organismi | Clostridium botulinum |
Taxonomic identifieri | 1491 [NCBI] |
Taxonomic lineagei | Bacteria › Firmicutes › Clostridia › Eubacteriales › Clostridiaceae › Clostridium |
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
Extracellular region or secreted
- Secreted By similarity
Other locations
- host cytosol 2 Publications
Extracellular region or secreted
- Secreted By similarity
Other locations
- host presynaptic cell membrane Curated
- host synaptic vesicle membrane By similarity; Multi-pass membrane protein Curated
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Other locations
- host cell cytoplasmic vesicle Source: UniProtKB-SubCell
- host cell cytosol Source: UniProtKB-SubCell
- host cell junction Source: UniProtKB-KW
- host cell presynaptic membrane Source: UniProtKB-SubCell
- integral component of membrane Source: UniProtKB-KW
Keywords - Cellular componenti
Host cell junction, Host cell membrane, Host cytoplasm, Host cytoplasmic vesicle, Host membrane, Host synapse, Membrane, SecretedPathology & Biotechi
Chemistry databases
ChEMBLi | CHEMBL2007627 |
DrugBanki | DB13901, Equine Botulinum Neurotoxin F Immune FAB2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000444921 | 1 – 1274 | Botulinum neurotoxin type FAdd BLAST | 1274 | |
ChainiPRO_0000029225 | 1 – 436 | Botulinum neurotoxin F light chainAdd BLAST | 436 | |
ChainiPRO_0000029226 | 437 – 1274 | Botulinum neurotoxin F heavy chainAdd BLAST | 838 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 429 ↔ 445 | Interchain (between light and heavy chains)By similarityCurated |
Keywords - PTMi
Disulfide bondInteractioni
Subunit structurei
Heterodimer; disulfide-linked heterodimer of a light chain (LC) and a heavy chain (HC). The LC has the proteolytic/pharmacological activity, while the N- and C-terminal of the HC mediate channel formation and toxin binding, respectively.
Interacts with host synaptic vesicle glycoproteins SV2A, SV2B and SV2C (By similarity).
By similarityProtein-protein interaction databases
IntActi | P30996, 2 interactors |
MINTi | P30996 |
Chemistry databases
BindingDBi | P30996 |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P30996 |
SMRi | P30996 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P30996 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 440 – 862 | Translocation domain (TD)By similarityAdd BLAST | 423 | |
Regioni | 485 – 534 | BeltBy similarityAdd BLAST | 50 | |
Regioni | 863 – 1087 | N-terminus of receptor binding domain (N-RBD)By similarityAdd BLAST | 225 | |
Regioni | 1088 – 1274 | C-terminus of receptor binding domain (C-RBD)By similarityAdd BLAST | 187 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 1245 – 1248 | Host ganglioside-binding motifBy similarity | 4 |
Domaini
Sequence similaritiesi
Keywords - Domaini
TransmembraneFamily and domain databases
DisProti | DP03019 |
Gene3Di | 1.20.1120.10, 1 hit |
InterProi | View protein in InterPro IPR000395, Bot/tetX_LC IPR036248, Clostridium_toxin_transloc IPR013320, ConA-like_dom_sf IPR011065, Kunitz_inhibitor_STI-like_sf IPR013104, Toxin_rcpt-bd_C IPR012928, Toxin_rcpt-bd_N IPR012500, Toxin_trans |
Pfami | View protein in Pfam PF01742, Peptidase_M27, 1 hit PF07951, Toxin_R_bind_C, 1 hit PF07953, Toxin_R_bind_N, 1 hit PF07952, Toxin_trans, 1 hit |
PRINTSi | PR00760, BONTOXILYSIN |
SUPFAMi | SSF49899, SSF49899, 1 hit SSF50386, SSF50386, 1 hit SSF58091, SSF58091, 1 hit |
PROSITEi | View protein in PROSITE PS00142, ZINC_PROTEASE, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MPVAINSFNY NDPVNDDTIL YMQIPYEEKS KKYYKAFEIM RNVWIIPERN
60 70 80 90 100
TIGTNPSDFD PPASLKNGSS AYYDPNYLTT DAEKDRYLKT TIKLFKRINS
110 120 130 140 150
NPAGKVLLQE ISYAKPYLGN DHTPIDEFSP VTRTTSVNIK LSTNVESSML
160 170 180 190 200
LNLLVLGAGP DIFESCCYPV RKLIDPDVVY DPSNYGFGSI NIVTFSPEYE
210 220 230 240 250
YTFNDISGGH NSSTESFIAD PAISLAHELI HALHGLYGAR GVTYEETIEV
260 270 280 290 300
KQAPLMIAEK PIRLEEFLTF GGQDLNIITS AMKEKIYNNL LANYEKIATR
310 320 330 340 350
LSEVNSAPPE YDINEYKDYF QWKYGLDKNA DGSYTVNENK FNEIYKKLYS
360 370 380 390 400
FTESDLANKF KVKCRNTYFI KYEFLKVPNL LDDDIYTVSE GFNIGNLAVN
410 420 430 440 450
NRGQSIKLNP KIIDSIPDKG LVEKIVKFCK SVIPRKGTKA PPRLCIRVNN
460 470 480 490 500
SELFFVASES SYNENDINTP KEIDDTTNLN NNYRNNLDEV ILDYNSQTIP
510 520 530 540 550
QISNRTLNTL VQDNSYVPRY DSNGTSEIEE YDVVDFNVFF YLHAQKVPEG
560 570 580 590 600
ETNISLTSSI DTALLEESKD IFFSSEFIDT INKPVNAALF IDWISKVIRD
610 620 630 640 650
FTTEATQKST VDKIADISLI VPYVGLALNI IIEAEKGNFE EAFELLGVGI
660 670 680 690 700
LLEFVPELTI PVILVFTIKS YIDSYENKNK AIKAINNSLI EREAKWKEIY
710 720 730 740 750
SWIVSNWLTR INTQFNKRKE QMYQALQNQV DAIKTAIEYK YNNYTSDEKN
760 770 780 790 800
RLESEYNINN IEEELNKKVS LAMKNIERFM TESSISYLMK LINEAKVGKL
810 820 830 840 850
KKYDNHVKSD LLNYILDHRS ILGEQTNELS DLVTSTLNSS IPFELSSYTN
860 870 880 890 900
DKILIIYFNR LYKKIKDSSI LDMRYENNKF IDISGYGSNI SINGNVYIYS
910 920 930 940 950
TNRNQFGIYN SRLSEVNIAQ NNDIIYNSRY QNFSISFWVR IPKHYKPMNH
960 970 980 990 1000
NREYTIINCM GNNNSGWKIS LRTVRDCEII WTLQDTSGNK ENLIFRYEEL
1010 1020 1030 1040 1050
NRISNYINKW IFVTITNNRL GNSRIYINGN LIVEKSISNL GDIHVSDNIL
1060 1070 1080 1090 1100
FKIVGCDDET YVGIRYFKVF NTELDKTEIE TLYSNEPDPS ILKNYWGNYL
1110 1120 1130 1140 1150
LYNKKYYLFN LLRKDKYITL NSGILNINQQ RGVTEGSVFL NYKLYEGVEV
1160 1170 1180 1190 1200
IIRKNGPIDI SNTDNFVRKN DLAYINVVDR GVEYRLYADT KSEKEKIIRT
1210 1220 1230 1240 1250
SNLNDSLGQI IVMDSIGNNC TMNFQNNNGS NIGLLGFHSN NLVASSWYYN
1260 1270
NIRRNTSSNG CFWSSISKEN GWKE
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M92906 Genomic DNA Translation: AAA23263.1 S73676 Genomic DNA Translation: AAC60475.1 X70820 Genomic DNA Translation: CAA50151.1 X70816 Genomic DNA Translation: CAA50147.1 |
PIRi | I40813 S48109 |
Similar proteinsi
Cross-referencesi
Web resourcesi
BotDB - A Database Resource for Clostridial Neurotoxins |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M92906 Genomic DNA Translation: AAA23263.1 S73676 Genomic DNA Translation: AAC60475.1 X70820 Genomic DNA Translation: CAA50151.1 X70816 Genomic DNA Translation: CAA50147.1 |
PIRi | I40813 S48109 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2A8A | X-ray | 2.00 | A | 1-439 | [»] | |
2A97 | X-ray | 1.80 | A/B | 1-439 | [»] | |
AlphaFoldDBi | P30996 | |||||
SMRi | P30996 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
IntActi | P30996, 2 interactors |
MINTi | P30996 |
Chemistry databases
BindingDBi | P30996 |
ChEMBLi | CHEMBL2007627 |
DrugBanki | DB13901, Equine Botulinum Neurotoxin F Immune FAB2 |
Protocols and materials databases
ABCDi | P30996, 10 sequenced antibodies |
Enzyme and pathway databases
BRENDAi | 3.4.24.69, 1462 |
Reactomei | R-HSA-5250981, Toxicity of botulinum toxin type F (botF) |
Miscellaneous databases
EvolutionaryTracei | P30996 |
Family and domain databases
DisProti | DP03019 |
Gene3Di | 1.20.1120.10, 1 hit |
InterProi | View protein in InterPro IPR000395, Bot/tetX_LC IPR036248, Clostridium_toxin_transloc IPR013320, ConA-like_dom_sf IPR011065, Kunitz_inhibitor_STI-like_sf IPR013104, Toxin_rcpt-bd_C IPR012928, Toxin_rcpt-bd_N IPR012500, Toxin_trans |
Pfami | View protein in Pfam PF01742, Peptidase_M27, 1 hit PF07951, Toxin_R_bind_C, 1 hit PF07953, Toxin_R_bind_N, 1 hit PF07952, Toxin_trans, 1 hit |
PRINTSi | PR00760, BONTOXILYSIN |
SUPFAMi | SSF49899, SSF49899, 1 hit SSF50386, SSF50386, 1 hit SSF58091, SSF58091, 1 hit |
PROSITEi | View protein in PROSITE PS00142, ZINC_PROTEASE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | BXF_CLOBO | |
Accessioni | P30996Primary (citable) accession number: P30996 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1993 |
Last sequence update: | July 1, 1993 | |
Last modified: | May 25, 2022 | |
This is version 162 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structureDocuments
- Peptidase families
Classification of peptidase families and list of entries - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families