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Entry version 177 (23 Feb 2022)
Sequence version 1 (01 Nov 1990)
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Protein

Botulinum neurotoxin type D

Gene

botD

Organism
Clostridium botulinum D phage (Clostridium botulinum D bacteriophage)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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 (PubMed:8175689, PubMed:16252491).

Precursor of botulinum neurotoxin D for which a proteinaceous coreceptor is controversial. In double SV2A/SV2B knockout mice this toxin does not degrade its synaptobrevin target; introducing SV2A, SV2B or SV2C restores target cleavage (PubMed:21483489).

Recognition of SV2 by this toxin does not occur via SV2 glycosylation or its large extracellular loop 4 (PubMed:21483489).

Another group does not find a convincing interaction with SV2 (PubMed:21632541).

Thus a protein receptor for this BoNT serotype has yet to be definitively proven. Recognizes at least 1 complex polysialylated ganglioside found on neural tissue. Electrical stimulation increases uptake of toxin in an ex vivo assay, presumably by transiently exposing a receptor usually found in eukaryotic target synaptic vesicles (PubMed:19650874, PubMed:21483489, PubMed:21632541).

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).

Requires complex eukaryotic host polysialogangliosides for full neurotoxicity and for binding to neurons (PubMed:20704566, PubMed:21483489).

By similarityCurated6 Publications

Has proteolytic activity (PubMed:8175689, PubMed:8197120).

After translocation into the eukaryotic host cytosol, inhibits neurotransmitter release by acting as a zinc endopeptidase that cleaves the '61-Lys-|-Leu-62' bond of synaptobrevin-1 (VAMP1), and the equivalent 'Lys-|-Leu' sites in VAMP2 and VAMP3 (PubMed:8175689).

Cleaves the '49-Lys-|-Ile-50' bond of A.californica synaptobrevin (AC P35589) (PubMed:8197120).

This chain probably has to be partially unfolded to translocate into the eukaryotic host cell cytosol (PubMed:15584922).

1 Publication2 Publications

Responsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of light chain (LC) into eukaryotic host cell 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 eukaryotic target cell surface. 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 (PubMed:17907800).

The TD inserts into synaptic vesicle membrane to allow translocation into the host cytosol (By similarity).

The RBD binds eukaryotic host phosphatidylethanolamine, which may serve as toxin receptor (PubMed:16115873).

Treatment of synaptosomes with proteinase K does not reduce HC binding, suggesting there is no protein receptor or it is protected from extracellular proteases (PubMed:16115873).

HC significantly decreases uptake and toxicity of whole BoNT/D (PubMed:19650874, PubMed:21483489).

HC also interferes with uptake of tetanus toxin (PubMed:19650874).

Has 2 closely located carbohydrate-binding receptor sites and binds at least 1 GT1b ganglioside (PubMed:20704566).

Bind gangliosides in the order GD2 > GT1b > GD1b (PubMed:21632541).

Interacts with eukaryotic target protein SV2B (synaptic vesicle glycoprotein 2B) (PubMed:21483489).

Expression of SV2A, SV2B or SV2C in mice knocked-out for the SV2 proteins restores entry of BoNT/D and cleavage of VAMP2, suggesting SV2 acts as its receptor (PubMed:21483489).

Unlike BoNT/A and BoNT/E, toxin uptake is not mediated by large extracellular loop 4 of SV2 (PubMed:21483489).

Another group finds very poor interaction with SV2 proteins, suggesting the possible protein receptor may not have been identified (PubMed:21632541).

By similarity1 Publication5 Publications

Miscellaneous

There are seven antigenically distinct forms of botulinum neurotoxin: Types A, B, C, D, E, F, and G; new subtypes are quite frequent. Types C and D can undergo domain swapping to create hybrid types.
Botulism poisoning is usually food-borne, either by ingesting toxin or bacterial-contaminated food, or less frequently by inhalation poisoning. In both cases the neurotoxin binds to the apical surface of epithelial cells in the gut or airway. Toxin undergoes receptor-mediated endocytosis (using a different receptor than on target nerve cells), transcytosis across the epithelial cells and release into the general circulation. Once in the general circulation it binds to its target cells.By similarity
Botulinum type D neurotoxin is synthesized by D strains of C.botulinum which carry the appropriate bacteriophage.3 Publications
Botulinum type D South African (D-SA) neurotoxin is released from bacteria as a single chain and presumably cleaved by host proteases into the active dichain (PubMed:2668193). Botulinum type D-1873 neurotoxin is released from bacteria as an already-cleaved dichain (PubMed:16252491). Toxin from strain CB-16 phage d-16 phi is released as an alread-cleaved dichain (PubMed:8569530). Another toxin (possibly from phage CE-beta) is released from over-producing E.coli as a single chain (PubMed:15584922). Type D-4947 is released as a single chain (PubMed:17581814).5 Publications
This protein can also be encoded on a prophage.Curated
BoNT/D causes animal botulism; it is 1,000-fold less toxic in chickens than BoNT/C1 (PubMed:16252491, PubMed:16115873). Cattle botulism is often caused by type D (PubMed:17913314).1 Publication2 Publications

Caution

The existence of a proteinaceous coreceptor is unclear. In double SV2A/SV2B knockout mice this toxin does not degrade its VAMP target; introducing SV2A, SV2B or SV2C restores target cleavage (PubMed:21483489). However another group does not find a convincing interaction with SV2 (PubMed:21632541).2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Zn2+2 PublicationsNote: Binds 1 zinc ion per subunit (PubMed:16519520, PubMed:26324071).2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Inhibited by dipicolinic acid, captopril, 1,10-phenanthroline and EDTA.1 Publication

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

kcat is 0.59, 146.60 and 113.41 sec(-1) for over-expressed human VAMP1, VAMP2 and VAMP3 respectively.1 Publication
  1. KM=28.9 µM for over-expressed human VAMP11 Publication
  2. KM=28.0 µM for over-expressed human VAMP21 Publication
  3. KM=11.1 µM for over-expressed human VAMP31 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi229Zinc; via tele nitrogen; catalyticCombined sources2 Publications1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei230PROSITE-ProRule annotation1
Metal bindingi233Zinc; via tele nitrogen; catalyticCombined sources2 Publications1
Metal bindingi269Zinc; catalyticCombined sources2 Publications1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei1192N-acetyl-beta-neuraminic acidCombined sources1 Publication1
Binding sitei1239N-acetyl-beta-neuraminic acidCombined sources1 Publication1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase, Metalloprotease, Neurotoxin, Protease, Toxin
Biological processVirulence
LigandLipid-binding, Metal-binding, Zinc

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...
BRENDAi
3.4.24.69, 1462

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-5250955, Toxicity of botulinum toxin type D (botD)

Protein family/group databases

UniLectin database of carbohydrate-binding proteins

More...
UniLectini
P19321

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Botulinum neurotoxin type D
Short name:
BoNT/D
Alternative name(s):
Bontoxilysin-D
Cleaved into the following 2 chains:
Botulinum neurotoxin D light chain (EC:3.4.24.691 Publication)
Short name:
LC
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:botD
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiClostridium botulinum D phage (Clostridium botulinum D bacteriophage)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri29342 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiVirusesDuplodnaviriaHeunggongviraeUroviricotaCaudoviricetesCaudoviralesSiphoviridae
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section only exists in viral entries and indicates the host(s) either as a specific organism or taxonomic group of organisms that are susceptible to be infected by a virus.<p><a href='/help/virus_host' target='_top'>More...</a></p>Virus hostiClostridium botulinum [TaxID: 1491]

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section describes the use of a specific protein in the biotechnological industry.<p><a href='/help/biotechnological_use' target='_top'>More...</a></p>Biotechnological usei

Cargo proteins fused to the N-terminus of whole toxin are imported into neurons; stabilized cargo proteins are poorer substrates, suggesting partial unfolding of the cargo protein is necessary for import (PubMed:15584922).1 Publication
Can be used for targeted secretion inhibition in eukaryotic cells. A construct with a mammalian growth hormone-releasing factor ligand domain (GHRH) inserted between the LC and TD, when injected into rats, leads to decreased growth hormone production. The GHRH ligand domain binds to the GHRH receptor on somatotrophs where it is taken up into endosomes. There the TD inserts into the membrane, releasing LC which cleaves synaptobrevin and inhibits growth hormone exocytosis (PubMed:24029240, PubMed:26324071).1 Publication1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi1192K → A: Decreased binding of heavy chain (HC) to synaptosomes. Significantly decreased HC binding, whole toxin is dramatically less neurotoxic; when associated with A-1239. 1 Publication1
Mutagenesisi1233D → A: Significantly decreased binding of heavy chain (HC) to synaptosomes, whole toxin is significantly less neurotoxic. Dramatically decreased HC binding, whole toxin is dramatically less neurotoxic; when associated with A-1239. 1 Publication1
Mutagenesisi1235Y → A: Significantly decreased binding of heavy chain to synaptosomes, whole toxin is significantly less neurotoxic. 1 Publication1
Mutagenesisi1235Y → W: Increased binding of heavy chain to synaptosomes, whole toxin has half neurotoxicity. 1 Publication1
Mutagenesisi1238W → A: Dramatically decreased binding of heavy chain (HC) to synaptosomes, whole toxin is dramatically less neurotoxic. Loss of HC binding to GD1b, GT1b, GD2 and synaptic vesicles, ganglioside-binding loop is disordered in crystal. 2 Publications1
Mutagenesisi1238W → F or Y: Decreased binding of heavy chain to synaptosomes, whole toxin is significantly less neurotoxic. 1 Publication1
Mutagenesisi1238W → L: Significantly decreased binding of heavy chain to synaptosomes, whole toxin is dramatically less neurotoxic. 1 Publication1
Mutagenesisi1239R → A: Significantly decreased binding of heavy chain (HC) to synaptosomes, whole toxin is dramatically less neurotoxic. Dramatically decreased HC binding, whole toxin is dramatically less neurotoxic; when associated with A-1192. Significantly decreased HC binding, whole toxin is dramatically less neurotoxic; when associated with A-1233. Decrease in HC binding to GD1b, GT1b, GD2 and synaptic vesicles. 2 Publications1
Mutagenesisi1239R → Y: Significantly decreased binding of heavy chain to synaptosomes, whole toxin is dramatically less neurotoxic. 1 Publication1
Mutagenesisi1240F → A: Significantly decreased binding of heavy chain to synaptosomes, whole toxin is dramatically less neurotoxic. Significant decrease in HC binding to GD1b, GT1b, GD2 and synaptic vesicles, GBL is well ordered in crystal. 1 Publication1
Mutagenesisi1240F → W: Increased binding of heavy chain (HC) to synaptosomes, whole toxin is slightly less neurotoxic. Slightly greater than wild-type HC binding to GT1b. 2 Publications1
Mutagenesisi1242F → S: Significantly decreased binding of heavy chain to synaptosomes, whole toxin is dramatically less neurotoxic. 1 Publication1
Mutagenesisi1242F → W: No effect on heavy chain binding to synaptosomes, whole toxin is slightly less neurotoxic. 1 Publication1
Mutagenesisi1244N → A: Significantly decreased binding of heavy chain to synaptosomes, whole toxin is significantly less neurotoxic. 1 Publication1
Mutagenesisi1246Y → A, S or W: Significantly decreased binding of heavy chain to synaptosomes, whole toxin is significantly less neurotoxic. 1 Publication1
Mutagenesisi1251V → F: Significantly decreased binding of heavy chain to synaptosomes, whole toxin is significantly less neurotoxic. 1 Publication1
Mutagenesisi1253N → A: Significantly decreased binding of heavy chain to synaptosomes. 1 Publication1
Mutagenesisi1257K → A: Decreased binding of heavy chain to synaptosomes. 1 Publication1
Mutagenesisi1262S → F: Decreased binding of heavy chain to synaptosomes. 1 Publication1

Chemistry databases

Drug and drug target database

More...
DrugBanki
DB13902, Equine Botulinum Neurotoxin D Immune FAB2

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemoved3 Publications
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00004449062 – 1276Botulinum neurotoxin type DAdd BLAST1275
ChainiPRO_00000292192 – 442Botulinum neurotoxin D light chainAdd BLAST441
ChainiPRO_0000029220443 – 1276Botulinum neurotoxin D heavy chain1 Publication1 PublicationAdd BLAST834

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi437 ↔ 450Interchain (between light and heavy chains)Combined sources1 Publication

Keywords - PTMi

Disulfide bond

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Heterodimer; disulfide-linked heterodimer of a light chain (LC) and a heavy chain (HC) (PubMed:26324071). The LC has the proteolytic/pharmacological activity (PubMed:8175689, PubMed:8197120). The N- and C-termini of the HC mediate channel formation and eukaryotic host cell binding, respectively. Can also be purified in complex with a non-toxic component that is larger than the HC (PubMed:16252491). Single chain toxin from strain D-4947 copurifies with NTHNA, and in complexes that include NTNHA, HA-70, HA-33 and HA-17 (PubMed:11713244, PubMed:17581814). Dichain toxin from strain CB-16 phage d-16 phi copurifies with NTHNA, and in complexes that include NTNHA, HA-55, HA-33, HA-22 and HA-17 (PubMed:8569530). The stoichiometry of the whole complex has been modeled as one BoNT/D, one NTNHA, three HA-70, six HA-33 and three HA-17 (PubMed:17581814). HC interacts with eukaryotic protein synaptic vesicle glycoprotein 2B (SV2B), which may serve as its receptor (PubMed:21483489). Another group does not find a convincing interaction with SV2 (PubMed:21632541).

1 Publication9 Publications

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11276
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P19321

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P19321

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni443 – 862Translocation domain (TD)2 PublicationsAdd BLAST420
Regioni458 – 547Belt1 PublicationAdd BLAST90
Regioni863 – 1082N-terminus of receptor binding domain (N-RBD), Hcn2 PublicationsAdd BLAST220
Regioni1083 – 1276C-terminus of receptor binding domain (C-RBD), Hcc2 PublicationsAdd BLAST194
Regioni1172 – 1173N-acetyl-beta-neuraminic acidCombined sources1 Publication2
Regioni1235 – 1245Ganglioside-binding loop1 PublicationAdd BLAST11

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi1252 – 1255Host ganglioside-binding motifBy similarity1 Publication4

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

Has protease activity (PubMed:8175689, PubMed:8197120).2 Publications
Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD, also called Hcn and Hcc) (PubMed:20731382, PubMed:20704566). The N-terminus of the TD wraps an extended belt around the perimeter of the LC which occludes the catalytic pocket (PubMed:26324071). The belt region may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol (PubMed:17907800).1 Publication3 Publications

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the peptidase M27 family.Curated

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.20.1120.10, 1 hit

Integrated resource of protein families, domains and functional sites

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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

Pfam protein domain database

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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

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00760, BONTOXILYSIN

Superfamily database of structural and functional annotation

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SUPFAMi
SSF49899, SSF49899, 1 hit
SSF50386, SSF50386, 1 hit
SSF58091, SSF58091, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00142, ZINC_PROTEASE, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

P19321-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTWPVKDFNY SDPVNDNDIL YLRIPQNKLI TTPVKAFMIT QNIWVIPERF
60 70 80 90 100
SSDTNPSLSK PPRPTSKYQS YYDPSYLSTD EQKDTFLKGI IKLFKRINER
110 120 130 140 150
DIGKKLINYL VVGSPFMGDS STPEDTFDFT RHTTNIAVEK FENGSWKVTN
160 170 180 190 200
IITPSVLIFG PLPNILDYTA SLTLQGQQSN PSFEGFGTLS ILKVAPEFLL
210 220 230 240 250
TFSDVTSNQS SAVLGKSIFC MDPVIALMHE LTHSLHQLYG INIPSDKRIR
260 270 280 290 300
PQVSEGFFSQ DGPNVQFEEL YTFGGLDVEI IPQIERSQLR EKALGHYKDI
310 320 330 340 350
AKRLNNINKT IPSSWISNID KYKKIFSEKY NFDKDNTGNF VVNIDKFNSL
360 370 380 390 400
YSDLTNVMSE VVYSSQYNVK NRTHYFSRHY LPVFANILDD NIYTIRDGFN
410 420 430 440 450
LTNKGFNIEN SGQNIERNPA LQKLSSESVV DLFTKVCLRL TKNSRDDSTC
460 470 480 490 500
IKVKNNRLPY VADKDSISQE IFENKIITDE TNVQNYSDKF SLDESILDGQ
510 520 530 540 550
VPINPEIVDP LLPNVNMEPL NLPGEEIVFY DDITKYVDYL NSYYYLESQK
560 570 580 590 600
LSNNVENITL TTSVEEALGY SNKIYTFLPS LAEKVNKGVQ AGLFLNWANE
610 620 630 640 650
VVEDFTTNIM KKDTLDKISD VSVIIPYIGP ALNIGNSALR GNFNQAFATA
660 670 680 690 700
GVAFLLEGFP EFTIPALGVF TFYSSIQERE KIIKTIENCL EQRVKRWKDS
710 720 730 740 750
YQWMVSNWLS RITTQFNHIN YQMYDSLSYQ ADAIKAKIDL EYKKYSGSDK
760 770 780 790 800
ENIKSQVENL KNSLDVKISE AMNNINKFIR ECSVTYLFKN MLPKVIDELN
810 820 830 840 850
KFDLRTKTEL INLIDSHNII LVGEVDRLKA KVNESFENTM PFNIFSYTNN
860 870 880 890 900
SLLKDIINEY FNSINDSKIL SLQNKKNALV DTSGYNAEVR VGDNVQLNTI
910 920 930 940 950
YTNDFKLSSS GDKIIVNLNN NILYSAIYEN SSVSFWIKIS KDLTNSHNEY
960 970 980 990 1000
TIINSIEQNS GWKLCIRNGN IEWILQDVNR KYKSLIFDYS ESLSHTGYTN
1010 1020 1030 1040 1050
KWFFVTITNN IMGYMKLYIN GELKQSQKIE DLDEVKLDKT IVFGIDENID
1060 1070 1080 1090 1100
ENQMLWIRDF NIFSKELSNE DINIVYEGQI LRNVIKDYWG NPLKFDTEYY
1110 1120 1130 1140 1150
IINDNYIDRY IAPESNVLVL VQYPDRSKLY TGNPITIKSV SDKNPYSRIL
1160 1170 1180 1190 1200
NGDNIILHML YNSRKYMIIR DTDTIYATQG GECSQNCVYA LKLQSNLGNY
1210 1220 1230 1240 1250
GIGIFSIKNI VSKNKYCSQI FSSFRENTML LADIYKPWRF SFKNAYTPVA
1260 1270
VTNYETKLLS TSSFWKFISR DPGWVE
Length:1,276
Mass (Da):146,872
Last modified:November 1, 1990 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iC1EC50F46C8233E2
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural varianti15 – 16ND → PV in strain: D-SA. 2
Natural varianti17 – 18ND → LQ in strain: D-1873. 2
Natural varianti452K → Q in strain: D-SA and D-4947. 1
Natural varianti457R → F in strain: D-1873. 1
Natural varianti457R → T in strain: D-SA. 1
Natural varianti462A → D in strain: D-1873. 1
Natural varianti489K → N in strain: CB16. 1
Natural varianti644N → K in strain: CB16. 1
Natural varianti1122Q → R in strain: CB16. 1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
X54254 Genomic DNA Translation: CAA38175.1
S49407 Genomic DNA Translation: AAB24244.1

Protein sequence database of the Protein Information Resource

More...
PIRi
S11455

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

BotDB - A Database Resource for Clostridial Neurotoxins

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54254 Genomic DNA Translation: CAA38175.1
S49407 Genomic DNA Translation: AAB24244.1
PIRiS11455

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FPQX-ray1.65A1-436[»]
3N7JX-ray2.00A862-1276[»]
3OBRX-ray1.72A863-1276[»]
3OBTX-ray2.00A863-1276[»]
3OGGX-ray1.65A863-1276[»]
3RMXX-ray2.75A/B/C/D862-1276[»]
3RMYX-ray2.30A/B/C/D862-1276[»]
5BQMX-ray3.10A/C1-437[»]
B/D450-861[»]
5BQNX-ray2.30A1-437[»]
A450-862[»]
SMRiP19321
ModBaseiSearch...
PDBe-KBiSearch...

Chemistry databases

DrugBankiDB13902, Equine Botulinum Neurotoxin D Immune FAB2

Protein family/group databases

UniLectiniP19321

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...
ABCDi
P19321, 36 sequenced antibodies

Enzyme and pathway databases

BRENDAi3.4.24.69, 1462
ReactomeiR-HSA-5250955, Toxicity of botulinum toxin type D (botD)

Miscellaneous databases

EvolutionaryTraceiP19321

Family and domain databases

Gene3Di1.20.1120.10, 1 hit
InterProiView 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
PfamiView 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
PRINTSiPR00760, BONTOXILYSIN
SUPFAMiSSF49899, SSF49899, 1 hit
SSF50386, SSF50386, 1 hit
SSF58091, SSF58091, 1 hit
PROSITEiView protein in PROSITE
PS00142, ZINC_PROTEASE, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiBXD_CBDP
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P19321
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: February 23, 2022
This is version 177 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
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