Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 165 (03 Jul 2019)
Sequence version 2 (23 Jan 2007)
Previous versions | rss
Other tutorials and videosHelp videoFeedback
Protein

Botulinum neurotoxin type E

Gene

botE

Organism
Clostridium botulinum
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 neurotoxin type E: Botulinum toxin causes flaccid paralysis by inhibiting neurotransmitter (acetylcholine) release from the presynaptic membranes of nerve terminals of eukaryotic host skeletal and autonomic nervous system, with frequent heart or respiratory failure. Precursor of botulinum neurotoxin E which has 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 (PubMed:19476346, PubMed:19650874). 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 (PubMed:22720883). 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). Electrical stimulation increases uptake of toxin, probably by transiently exposing a receptor found in eukaryotic target synaptic vesicles (PubMed:19476346, PubMed:19650874). Uses the large lumenal domain of synaptic vesicle glycoproteins 2A and 2B (SV2A and SV2B) but not SV2C as receptor; an N-linked glycan of SV2 is essential for receptor function (PubMed:18815274, PubMed:19476346). Host cell gangliosides are also required for neurotoxin uptake and full toxicity (PubMed:18815274, PubMed:19650874). BoNT/E is a 'coincidence detector'; it requires simultaneous binding to coreceptor GT1b and low pH to transform into a membrane-bound, oligomeric channel (PubMed:22720883). Requires trypsinization and reduction before it can be used in assays in vitro (PubMed:8294407).By similarity1 Publication4 Publications
Botulinum neurotoxin E light chain: Has proteolytic activity (PubMed:8243676, PubMed:8294407, PubMed:9886085). After translocation into the eukaryotic host cytosol, inhibits neurotransmitter release by acting as a zinc endopeptidase that catalyzes the hydrolysis of the '180-Arg-|-Ile-181' bond in SNAP25 (PubMed:8243676, PubMed:8294407, PubMed:9886085). Hydrolyzes the '185-Arg-|-Ile-186' bond of mouse SNAP23, but not in human which has a different sequence (PubMed:9886085). Recognizes the '146-Met--Asp-186' region of SNAP25 (PubMed:9886085). The reaction mechanism probably has a nucleophilic water held in place by Glu-213 (PubMed:15157097, PubMed:15938619). Reduction of the interchain disulfide bond occurs in the host cytosol and probably prevents retrotranslocation into the synaptic vesicle (PubMed:17666397).6 Publications
Botulinum neurotoxin E heavy chain: Responsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of light chain (LC) into host cytosol (PubMed:17666397). 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 (PubMed:10413679). It probably simultaneously recognizes 2 coreceptors; polysialated gangliosides and either of the receptor proteins SV2A and SV2B in close proximity on host synaptic vesicles (PubMed:18815274, PubMed:19650874, PubMed:19476346). The N-terminus of the TD wraps an extended belt around the perimeter of the light chain (LC), protecting Zn2+ in the active site (PubMed:19118561). The belt 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). Responsible for adherence of the toxin to the cell surface; HC alone prevents uptake of whole toxin by neural cells, and delays paralysis onset by 154% (PubMed:10413679). Significantly decreases uptake and toxicity of whole BoNT/E, but also interferes with uptake of BoNT/C; binds GT1b in vitro (PubMed:19650874). Binds to synaptic vesicle glycoproteins SV2A and SV2B which serve as coreceptors with gangliosides (PubMed:18815274, PubMed:19650874). Interaction with SV2 proteins requires SV2 glycosylation (PubMed:19476346). HC alone significantly decreases uptake and toxicity of whole BoNT/E (PubMed:19650874). HC is responsible for translocation of LC into the host cytosol; an intact disulfide bond between the 2 subunits is required for translocation, which is reduced upon contact with the host cytosol (PubMed:17666397).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.
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
Types A, B and E are the most frequent cause of adult human foodborne botulism; type A is the most severe, while type E has the shortest incubation period (PubMed:1431246).1 Publication
Unlike botulinum neurotoxin type A, type E is released from bacteria as a single chain and cleaved by host proteases into the active dichain (PubMed:6353669, PubMed:4030755, PubMed:19118561, PubMed:8294407).1 Publication3 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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+4 PublicationsNote: Binds 1 zinc ion per subunit (PubMed:1429690, PubMed:15157097, PubMed:15938619, PubMed:19118561).4 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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

Proteolysis of SNAP25 by whole toxin inhibited by dipicolinic acid, 1,10-phenanthroline and EDTA (PubMed:8294407).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 257 min (-1) with botulinum neurotoxin E light chain.1 Publication
  1. KM=7.9 µM for purified SNAP25 with botulinum neurotoxin E light chain1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 bindingi212Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources1
    <p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 sitei213Proton acceptorPROSITE-ProRule annotation1 Publication1
    Metal bindingi216Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources1
    Metal bindingi251Zinc; catalyticCombined sources1

    <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-5250992 Toxicity of botulinum toxin type E (BoNT/E)

    Protein family/group databases

    MEROPS protease database

    More...
    MEROPSi
    M27.002

    Transport Classification Database

    More...
    TCDBi
    1.C.8.1.3 the botulinum and tetanus toxin (btt) family

    <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_and_taxonomy_section">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 E
    Short name:
    BoNT/E1 Publication
    Alternative name(s):
    Bontoxilysin-E
    Cleaved into the following 2 chains:
    Botulinum neurotoxin E light chain (EC:3.4.24.691 Publication)
    Short name:
    LC
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:botE1 Publication
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 identifieri1491 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 lineageiBacteriaFirmicutesClostridiaClostridialesClostridiaceaeClostridium

    <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

    Botulinum neurotoxin type E :
    Chain Botulinum neurotoxin E light chain :
    Chain Botulinum neurotoxin E heavy chain :

    GO - Cellular componenti

    Keywords - Cellular componenti

    Host cell junction, Host cell membrane, Host cytoplasm, Host cytoplasmic vesicle, Host membrane, Host synapse, Membrane, 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

    Double mutants Gln-213/Gln-336 or Gln-213/Ala-351 might be suitable as vaccine candiates (PubMed:15938619).1 Publication

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'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>Mutagenesisi159 – 161ETN → AAA: KM for SNAP25 unchanged, kcat 10-fold reduced. 1 Publication3
    Mutagenesisi213E → Q: No cleavage of SNAP25. 1 Publication1
    Mutagenesisi250E → A: KM unchanged, kcat 10-fold reduced. 1 Publication1
    Mutagenesisi336E → A: KM unchanged, kcat 30-fold reduced, binds zinc in crystal. 1 Publication1
    Mutagenesisi336E → Q: No cleavage of SNAP25. KM unchanged, kcat 5700-fold reduced, zinc replaced by H(2)O in crystal. 2 Publications1
    Mutagenesisi348R → A: KM unchanged, kcat 700-fold reduced. 1 Publication1
    Mutagenesisi351Y → A: No cleavage of SNAP25. 1 Publication1
    Mutagenesisi1172E → A: Significantly decreased toxicity, dramatically decreased binding of heavy chain to synaptosomes, significantly decreased binding to ganglioside GT1b. 1 Publication1
    Mutagenesisi1223W → L: Dramatically decreased toxicity, dramatically decreased binding of heavy chain to synaptosomes, dramatically decreased binding to ganglioside GT1b. 1 Publication1

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules

    More...
    ChEMBLi
    CHEMBL1697662

    <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_processing_section">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 methionineiRemoved1 Publication
    <p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00004449072 – 1251Botulinum neurotoxin type EAdd BLAST1250
    ChainiPRO_00000292212 – 422Botulinum neurotoxin E light chainAdd BLAST421
    ChainiPRO_0000029222423 – 1251Botulinum neurotoxin E heavy chainAdd BLAST829

    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 bondi412 ↔ 426Interchain (between light and heavy chains)Combined sources1 Publication1 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_section">'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_section">'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); cleavage occurs after bacterial export by host proteases (PubMed:6353669, PubMed:4030755, PubMed:19118561). The LC has the proteolytic/pharmacological activity, while the N- and C-terminal of the HC mediate channel formation and toxin binding, respectively. Oligomerizes in the presence of coreceptor ganglioside GT1b between pH 4.4 and 8.0; it might oligomerize on host cell surface (PubMed:22720883).

    Interacts with host synaptic vesicle glycoproteins SV2A and SV2B (PubMed:18815274, PubMed:19650874). HC interacts with a complex including at least host SV2 and synaptotagmin-1 (SYT1); copurification depends on glycosylation of SV2 (PubMed:19476346).

    7 Publications

    Protein-protein interaction databases

    Database of interacting proteins

    More...
    DIPi
    DIP-46083N

    Protein interaction database and analysis system

    More...
    IntActi
    Q00496, 4 interactors

    Molecular INTeraction database

    More...
    MINTi
    Q00496

    Chemistry databases

    BindingDB database of measured binding affinities

    More...
    BindingDBi
    Q00496

    <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

    11251
    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

    More...
    SMRi
    Q00496

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    Miscellaneous databases

    Relative evolutionary importance of amino acids within a protein sequence

    More...
    EvolutionaryTracei
    Q00496

    <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>Regioni423 – 819Translocation domain (TD)1 PublicationAdd BLAST397
    Regioni466 – 515Belt1 PublicationAdd BLAST50
    Regioni845 – 1067N-terminus of receptor binding domain (N-RBD)1 PublicationAdd BLAST223
    Regioni850 – 1251Receptor-binding domain (TD)1 PublicationAdd BLAST402
    Regioni1068 – 1251C-terminus of receptor binding domain (C-RBD)1 PublicationAdd BLAST184

    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>Motifi1221 – 1224Host 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

    Botulinum neurotoxin E light chain: Has protease activity (PubMed:8243676, PubMed:8294407, PubMed:9886085).3 Publications
    Botulinum neurotoxin E heavy chain: 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) (PubMed:19118561). In BoNT/E the domains are arranged differently than BoNT/A and BoNT/B; in BoNT/E the LC and RBD are on the same side of the TD and are in contact, whereas in BoNT/A and BoNT/B the LC is separated from the RBD by the TD (PubMed:19118561). The putative transmembrane region is closer to the receptor-binding regions in this toxin, which may explain why it acts faster than BoNT/A and BoNT/B (PubMed:19118561). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, partially protecting Zn2+ in the active site (PubMed:19118561). The belt may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol (PubMed:17907800). The RBD binds transiently exposed coreceptors on the host presynaptic cell membrane (PubMed:18815274, PubMed:19650874, PubMed:19476346).1 Publication4 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

    Keywords - Domaini

    Transmembrane

    Phylogenomic databases

    KEGG Orthology (KO)

    More...
    KOi
    K06011

    Family and domain databases

    Database of protein disorder

    More...
    DisProti
    DP00732

    Gene3D Structural and Functional Annotation of Protein Families

    More...
    Gene3Di
    1.20.1120.10, 1 hit

    Integrated resource of protein families, domains and functional sites

    More...
    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

    More...
    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

    More...
    PRINTSi
    PR00760 BONTOXILYSIN

    Superfamily database of structural and functional annotation

    More...
    SUPFAMi
    SSF49899 SSF49899, 1 hit
    SSF50386 SSF50386, 1 hit
    SSF58091 SSF58091, 1 hit

    PROSITE; a protein domain and family database

    More...
    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_length">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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.

    Q00496-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MPKINSFNYN DPVNDRTILY IKPGGCQEFY KSFNIMKNIW IIPERNVIGT
    60 70 80 90 100
    TPQDFHPPTS LKNGDSSYYD PNYLQSDEEK DRFLKIVTKI FNRINNNLSG
    110 120 130 140 150
    GILLEELSKA NPYLGNDNTP DNQFHIGDAS AVEIKFSNGS QDILLPNVII
    160 170 180 190 200
    MGAEPDLFET NSSNISLRNN YMPSNHRFGS IAIVTFSPEY SFRFNDNCMN
    210 220 230 240 250
    EFIQDPALTL MHELIHSLHG LYGAKGITTK YTITQKQNPL ITNIRGTNIE
    260 270 280 290 300
    EFLTFGGTDL NIITSAQSND IYTNLLADYK KIASKLSKVQ VSNPLLNPYK
    310 320 330 340 350
    DVFEAKYGLD KDASGIYSVN INKFNDIFKK LYSFTEFDLR TKFQVKCRQT
    360 370 380 390 400
    YIGQYKYFKL SNLLNDSIYN ISEGYNINNL KVNFRGQNAN LNPRIITPIT
    410 420 430 440 450
    GRGLVKKIIR FCKNIVSVKG IRKSICIEIN NGELFFVASE NSYNDDNINT
    460 470 480 490 500
    PKEIDDTVTS NNNYENDLDQ VILNFNSESA PGLSDEKLNL TIQNDAYIPK
    510 520 530 540 550
    YDSNGTSDIE QHDVNELNVF FYLDAQKVPE GENNVNLTSS IDTALLEQPK
    560 570 580 590 600
    IYTFFSSEFI NNVNKPVQAA LFVSWIQQVL VDFTTEANQK STVDKIADIS
    610 620 630 640 650
    IVVPYIGLAL NIGNEAQKGN FKDALELLGA GILLEFEPEL LIPTILVFTI
    660 670 680 690 700
    KSFLGSSDNK NKVIKAINNA LKERDEKWKE VYSFIVSNWM TKINTQFNKR
    710 720 730 740 750
    KEQMYQALQN QVNAIKTIIE SKYNSYTLEE KNELTNKYDI KQIENELNQK
    760 770 780 790 800
    VSIAMNNIDR FLTESSISYL MKIINEVKIN KLREYDENVK TYLLNYIIQH
    810 820 830 840 850
    GSILGESQQE LNSMVTDTLN NSIPFKLSSY TDDKILISYF NKFFKRIKSS
    860 870 880 890 900
    SVLNMRYKND KYVDTSGYDS NININGDVYK YPTNKNQFGI YNDKLSEVNI
    910 920 930 940 950
    SQNDYIIYDN KYKNFSISFW VRIPNYDNKI VNVNNEYTII NCMRDNNSGW
    960 970 980 990 1000
    KVSLNHNEII WTFEDNRGIN QKLAFNYGNA NGISDYINKW IFVTITNDRL
    1010 1020 1030 1040 1050
    GDSKLYINGN LIDQKSILNL GNIHVSDNIL FKIVNCSYTR YIGIRYFNIF
    1060 1070 1080 1090 1100
    DKELDETEIQ TLYSNEPNTN ILKDFWGNYL LYDKEYYLLN VLKPNNFIDR
    1110 1120 1130 1140 1150
    RKDSTLSINN IRSTILLANR LYSGIKVKIQ RVNNSSTNDN LVRKNDQVYI
    1160 1170 1180 1190 1200
    NFVASKTHLF PLYADTATTN KEKTIKISSS GNRFNQVVVM NSVGNCTMNF
    1210 1220 1230 1240 1250
    KNNNGNNIGL LGFKADTVVA STWYYTHMRD HTNSNGCFWN FISEEHGWQE

    K
    Length:1,251
    Mass (Da):143,844
    Last modified:January 23, 2007 - v2
    <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:iB05AA65FF1B30362
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti177R → G in CAA44558 (PubMed:1541280).Curated1
    Sequence conflicti198C → S in CAA44558 (PubMed:1541280).Curated1
    Sequence conflicti198C → S no nucleotide entry (PubMed:2160960).Curated1
    Sequence conflicti340R → A in CAA44558 (PubMed:1541280).Curated1
    Sequence conflicti773I → L in CAA44558 (PubMed:1541280).Curated1
    Sequence conflicti773I → L in CAA50146 (PubMed:8408542).Curated1
    Sequence conflicti963 – 964FE → LQ in CAA44558 (PubMed:1541280).Curated2
    Sequence conflicti963 – 964FE → LQ in CAA50146 (PubMed:8408542).Curated2
    Sequence conflicti967R → A in CAA44558 (PubMed:1541280).Curated1
    Sequence conflicti967R → A in CAA50146 (PubMed:8408542).Curated1
    Sequence conflicti1195N → NN in CAA44558 (PubMed:1541280).Curated1

    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
    X62089 Genomic DNA Translation: CAA43999.1
    X62683 Genomic DNA Translation: CAA44558.1
    X70815 Genomic DNA Translation: CAA50146.1

    Protein sequence database of the Protein Information Resource

    More...
    PIRi
    S08575
    S21178

    NCBI Reference Sequences

    More...
    RefSeqi
    WP_003372387.1, NZ_LHUM01000023.1

    Genome annotation databases

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...
    KEGGi
    ag:CAA43999

    <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_references_section">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
    X62089 Genomic DNA Translation: CAA43999.1
    X62683 Genomic DNA Translation: CAA44558.1
    X70815 Genomic DNA Translation: CAA50146.1
    PIRiS08575
    S21178
    RefSeqiWP_003372387.1, NZ_LHUM01000023.1

    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
    1T3AX-ray2.16A/B2-422[»]
    1T3CX-ray1.90A/B2-422[»]
    1ZKWX-ray2.17A/B2-421[»]
    1ZKXX-ray2.52A/B2-421[»]
    1ZL5X-ray2.60A/B2-421[»]
    1ZL6X-ray2.40A/B2-421[»]
    1ZN3X-ray2.60A/B2-421[»]
    3FFZX-ray2.65A/B1-1251[»]
    SMRiQ00496
    ModBaseiSearch...

    Protein-protein interaction databases

    DIPiDIP-46083N
    IntActiQ00496, 4 interactors
    MINTiQ00496

    Chemistry databases

    BindingDBiQ00496
    ChEMBLiCHEMBL1697662

    Protein family/group databases

    MEROPSiM27.002
    TCDBi1.C.8.1.3 the botulinum and tetanus toxin (btt) family

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    KEGGiag:CAA43999

    Phylogenomic databases

    KOiK06011

    Enzyme and pathway databases

    BRENDAi3.4.24.69 1462
    ReactomeiR-HSA-5250992 Toxicity of botulinum toxin type E (BoNT/E)

    Miscellaneous databases

    EvolutionaryTraceiQ00496

    Family and domain databases

    DisProtiDP00732
    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

    ProtoNet; Automatic hierarchical classification of proteins

    More...
    ProtoNeti
    Search...

    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 nameiBXE_CLOBO
    <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: Q00496
    Secondary accession number(s): Q45862
    <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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: January 23, 2007
    Last modified: July 3, 2019
    This is version 165 of the entry and version 2 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 programProkaryotic 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families
    3. Peptidase families
      Classification of peptidase families and list of entries
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

    We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

    Do not show this banner again