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Entry version 9 (08 May 2019)
Sequence version 1 (18 Jul 2018)
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Protein

Botulinum neurotoxin type A

Gene

botA

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 A: 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:15394302, PubMed:7578132). Precursor of botulinum neurotoxin A which has 2 coreceptors; complex polysialylated gangliosides found on neural tissue and specific membrane-anchored proteins of 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 (PubMed:17666397, PubMed:19096517). 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. Toxin activity requires polysialylated gangliosides; GT1b supports activity better than GD1a (PubMed:12089155). Binds to host peripheral neuronal presynaptic membranes via the synaptic vesicle glycoproteins SV2A, SV2B and SV2C (PubMed:16543415). It binds directly to the largest lumenal (intravesicular) loop of SV2A, SV2B and SV2C that is transiently exposed outside of cells during exocytosis; gangliosides enhance binding (PubMed:16543415, PubMed:16545378, PubMed:18815274). Recognizes an N-linked glycan on SV2 proteins (PubMed:18815274, PubMed:27294781). May also use FGFR3 as a receptor (PubMed:23696738). Toxin uptake into neural cells requires stimulation (incubation with K+ to stimulate receptor exposure) to be internalized by receptor-mediated endocytosis (PubMed:16543415, PubMed:19650874, PubMed:21632541, PubMed:21832053). Subsequently the toxin colocalizes with its receptor in host cells (PubMed:16543415, PubMed:19650874). Toxin uptake can be blocked by the appropriate SV2 protein fragments in cell culture (PubMed:16543415).13 Publications
Botulinum neurotoxin A light chain: Has proteolytic activity (PubMed:7578132). After translocation into the eukaryotic host cytosol LC hydrolyzes the '197-Gln-|-Arg-198' bond in SNAP25, blocking neurotransmitter release (PubMed:8243676, PubMed:7578132, PubMed:9886085, PubMed:10694409, PubMed:11700044, PubMed:11827515, PubMed:19351593). Recognizes the '146-Met--Gly-155' region of SNAP25, which confers substrate specificity (PubMed:9886085, PubMed:15592454). Hydrolyzes the '202-Thr-|-Arg-203' bond of mouse SNAP23, but not in human which has a different sequence (PubMed:9886085). Reduction of the interchain disulfide bond occurs in the host cytosol and probably prevents retrotranslocation into the synaptic vesicle (PubMed:17666397). Has slow (occurs over 4 weeks) autocatalytic cleavage, however it is not clear if this is physiologically relevant (PubMed:11565902).1 Publication9 Publications
Botulinum neurotoxin A heavy chain: Responsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of botulinum neurotoxin A 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) (PubMed:19096517). The RBD is responsible for binding to host epithelial cells and transcytosis across them; this uses different receptors than those on nerve cells (PubMed:21106906). RBD is also responsible for adherence of toxin to host nerve cell surface; HC alone prevents uptake of whole toxin by neural cells, and delays paralysis onset by 75% (PubMed:6694738, PubMed:10413679). Isolated RBD also delays paralysis onset (PubMed:21106906). The N-terminus of the RBD binds to phosphatidylinositol, which might play a role in membrane-binding (PubMed:19161982). Binds to host protein receptor synaptic vesicle glycoproteins SV2A, SV2B and SV2C via lumenal loop 4 (PubMed:16545378, PubMed:6370252, PubMed:27294781, PubMed:24240280, PubMed:19650874, PubMed:27313224). Binding can be inhibited by protein fragments from either the HC or SV2C (PubMed:24240280). Isolated HC significantly decreases uptake and toxicity of whole BoNT/A, but also interferes with uptake of BoNT/E and to a lesser extent BoNT/F (PubMed:19650874). The RBD recognizes the N-linked glycan on 'Asn-559' of SV2A, SV2B and SV2C; hydrogen-bonding occurs via 10 well-defined water molecules and stacking of hydrophobic residues (PubMed:27294781). Binds one host GT1b ganglioside, which serves as a coreceptor (PubMed:14731268, PubMed:18704164, PubMed:27958736). Modeling shows the HC can bind both coreceptors (a ganglioside and SV2 protein) simultaneously at different sites (PubMed:24240280). Crystals of the RBD with a GT1b analog can be grown at pH 5.5, indicating the toxin-ganglioside complex could be stable within the endosome (PubMed:18704164). Isolated RBD binds NTNHA (a bacterial protein that protects toxin) with high affinity at pH 6.0 but not at pH 7.5 (PubMed:22363010). The N-terminal belt (residues 449-545) wraps around the perimeter of the LC, probably protecting Zn2+ in the active site; it is not required for channel formation by the TD domain but may serve to prevent premature LC dissociation from the translocation channel and to protect toxin prior to translocation (PubMed:22158863, PubMed:17907800, PubMed:19351593). The isolated TD forms transmembrane channels of about 15 Angstroms in the absence of a pH gradient; LC translocation requires a pH and redox gradient (pH 5.0/oxidizing in the cis compartment, pH 7.0/reducing in the trans compartment), LC does not unfold unless the cis pH is 6.0 or less (PubMed:2446925, PubMed:17666397, PubMed:19096517). Pores are presumably made by 1-2 toxin molecules (PubMed:23471747). While interaction with the RBD modulates the pH threshold for membrane insertion, the RBD is not essential for toxin degradation of SNAP25 in neural cells (PubMed:19096517).2 Publications18 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.Curated
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
Neurotoxin type A is released from bacteria in the two-chain form (PubMed:6370252, PubMed:2126206).2 Publications
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.1 Publication

Caution

Contradictory results show that only SV2C is the receptor; in these experiments gangliosides do not improve toxin-coreceptor interaction (PubMed:16545378).1 Publication

<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+7 PublicationsNote: Binds 1 zinc ion per subunit (PubMed:1429690, PubMed:11700044, PubMed:15592454, PubMed:19351593, PubMed:22363010).5 Publications

<p>This subsection of the ‘Function’ 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

Toxin internalization is inhibited by azide or dinitrophenol or at 4 degrees Celsius (PubMed:6694738). Dynamin (DNM) inhibitors abolish toxin uptake (PubMed:21832053).2 Publications

<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 140 min(-1) (PubMed:10694409). kcat is 1026 (-1) (PubMed:11827515).2 Publications
  1. KM=41 µM for purified SNAP25 with isolated botulinum neurotoxin A light chain1 Publication
  2. KM=9.8 µM for purified SNAP25 with isolated botulinum neurotoxin A light chain1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Function’ 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 bindingi223Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources2 Publications1
    <p>This subsection of the ‘Function’ 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 sitei224Proton acceptorPROSITE-ProRule annotation1 Publication1
    Metal bindingi227Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources1 Publication2 Publications1
    Metal bindingi262Zinc; catalyticCombined sources1 Publication2 Publications1
    <p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei363Transition state stabilizer1 Publication1
    Sitei366Transition state stabilizer1 Publication1
    <p>This subsection of the ‘Function’ 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 sitei1117Host ganglioside GT1bCombined sources2 Publications1
    Binding sitei1203Host ganglioside GT1bCombined sources1 Publication2 Publications1

    <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

    Reactome - a knowledgebase of biological pathways and processes

    More...
    Reactomei
    R-HSA-5250968 Toxicity of botulinum toxin type A (BoNT/A)

    <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 A
    Short name:
    BoNT/A
    Alternative name(s):
    Bontoxilysin-A
    Short name:
    BOTOX
    Botulinum neurotoxin type A1
    Cleaved into the following 2 chains:
    Botulinum neurotoxin A 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:botA1 Publication
    Synonyms:atx1 Publication, bonT1 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 A :
    • Secreted 1 Publication
    • cell wall 1 Publication
    • host presynaptic cell membrane 1 Publication
    • Note: Whole toxin may be released from the bacteria during cell wall exfoliation (PubMed:7592120). There are estimated to be 150-500 toxin molecules per um2 of non-myelinated mouse hemidiaphragm nerve membrane (PubMed:6694738). In mouse hemidiaphragm binds only to nerve terminals, and not to muscle, blood vessels, connective tissue Schwann cells or myelin, toxin can be internalized by this preparation (PubMed:6694738).2 Publications
    Chain Botulinum neurotoxin A light chain :
    Chain Botulinum neurotoxin A heavy chain :

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei627 – 647HelicalSequence analysisAdd BLAST21
    Transmembranei656 – 676HelicalSequence analysisAdd BLAST21

    GO - Cellular componenti

    Keywords - Cellular componenti

    Cell wall, 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

    Dynamin inhibitors slow toxin uptake by nerve cells, and might be used to prolong the treatment window for antitoxins.1 Publication
    Replacement of the RBD by other proteins (such as wheat germ agglutinin) allows the rest of the toxin to be taken up by other cell types, and can be used for investigating synaptic vesicle docking-dependent processes in BoNT resistant cells (PubMed:10768948). LC retains protease activity (PubMed:10768948, PubMed:19351593).2 Publications
    Isolated receptor-binding domain (RBD) can be used as a vaccine; a mutated form that is transcytosed into the general circulation but does not enter nerve cells (Leu-1266-1267-Ser) is as efficient as wild-type RBD (PubMed:21106906).1 Publication

    <p>This subsection of the ‘Pathology and Biotech’ section describes the use of a protein as a pharmaceutical drug. It indicates the name of the drug, the name of the firm that commercializes it and explains in a few words in which context the drug is used. In some cases, drugs that are under development are also described.<p><a href='/help/pharmaceutical_use' target='_top'>More...</a></p>Pharmaceutical usei

    Available under the name Botox (onabotulinumtoxinA, Allergan), Dysport (abobotulinumtoxinA, Ipsen Biopharmaceuticals) and Xeomin (incobotulinumtoxinA, Merz Pharmaceuticals) for the treatment of strabismus and blepharospasm associated with dystonia and cervical dystonia. Also used for the treatment of hemifacial spasm and a number of other neurological disorders characterized by abnormal muscle contraction. It is also used cosmetically to smooth facial wrinkles.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>Mutagenesisi224E → D: Light chain has 5% cleavage activity on SNAP25. KM for SNAP25 is nearly wild-type. 1 Publication1
    Mutagenesisi224E → Q: Light chain no longer cleaves SNAP25, no effect on substrate or Zn(2+) binding. 1 Publication1
    Mutagenesisi227H → Y: Light chain no longer cleaves SNAP25, not toxic in vitro or in vivo when reconstituted with heavy chain. 1 Publication1
    Mutagenesisi262E → A: Light chain has 20% cleavage activity on SNAP25, 40% decrease in Zn(2+). 1 Publication1
    Mutagenesisi266F → A: Light chain has 50% cleavage activity on SNAP25, no effect on Zn(2+) binding. 1 Publication1
    Mutagenesisi351E → A or Q: Wild-type KM for SNAP25, no protease activity, about 30% less Zn(2+). 1 Publication1
    Mutagenesisi363R → A, H or K: Wild-type KM for SNAP25, about 75-fold decrease in kcat, no effect on Zn(2+) binding. 1 Publication1
    Mutagenesisi366Y → A: Light chain has 40% cleavage activity on SNAP25, 30% decrease in Zn(2+). 1 Publication1
    Mutagenesisi366Y → F: About wild-type KM for SNAP25, 35-fold decrease in kcat, no effect on Zn(2+) binding. 1 Publication1
    Mutagenesisi861 – 871RLLSTFTEYIK → ALLSTFTPYIP: Reduced toxicity. 1 PublicationAdd BLAST11
    Mutagenesisi862 – 867LLSTFT → KESTFK: Reduced toxicity. 1 Publication6
    Mutagenesisi953F → G: Whole toxin has 50-fold reduction in toxicity, almost no binding of RBD to neurons. 1 Publication1
    Mutagenesisi953F → R: Whole toxin is non-toxic, almost no binding of RBD to neurons. 1 Publication1
    Mutagenesisi982E → A or Q: Decreased binding of NTNHA by receptor-binding domain (RBD) at pH 7.5. 1 Publication1
    Mutagenesisi1000K → A: Decreased binding of NTNHA by RBD at pH 6.0, none at pH 7.5. 1 Publication1
    Mutagenesisi1037D → A or N: Decreased binding of NTNHA by RBD at pH 7.5. 1 Publication1
    Mutagenesisi1064H → G or R: Whole toxin has reduced toxicity, dramatically reduced binding of RBD to neurons. 1 Publication1
    Mutagenesisi1118D → A: Decreased binding of NTNHA by RBD at pH 7.5. 1 Publication1
    Mutagenesisi1145 – 1146TT → AA: No binding of RBD to neurons. Loss of binding to SV2C. 2 Publications2
    Mutagenesisi1156R → E: Decreased binding of RBD to SV2C, substantial binding to neurons. 2 Publications1
    Mutagenesisi1171D → A: Decreased binding of NTNHA by RBD at pH 7.5. 1 Publication1
    Mutagenesisi1203E → L: Strongly reduced toxicity, heavy chain has very strongly reduced binding to synaptosomes, decreased binding to gangioside GT1b. 1 Publication1
    Mutagenesisi1253H → A: Strongly reduced toxicity, heavy chain has very strongly reduced binding to synaptosomes, decrease in ganglioside GT1b binding. 1 Publication1
    Mutagenesisi1253H → W: Heavy chain has very strongly reduced binding to synaptosomes, binds much less GT1b. RBD protects against neurotoxin less well than wild-type. 2 Publications1
    Mutagenesisi1264S → A: Reduced toxicity, heavy chain has strongly reduced binding to synaptosomes, heavy chain binds less GT1b. 1 Publication1
    Mutagenesisi1266 – 1267WY → LS: Whole RBD does not protect against neurotoxin, no effect on epithelial cell passage; can be used as a vaccine. 1 Publication2
    Mutagenesisi1266W → L: Nearly complete loss of toxicity, heavy chain has very strongly reduced binding to synaptosomes, binds much less GT1b. Heavy chain no longer inhibits whole-toxin uptake and toxicity. RBD protects against neurotoxin considerably less well than wild-type. 3 Publications1
    Mutagenesisi1267Y → F: Nearly complete loss of toxicity, heavy chain has very strongly reduced binding to synaptosomes, binds much less GT1b. 1 Publication1
    Mutagenesisi1267Y → S: Nearly complete loss of toxicity, heavy chain has very strongly reduced binding to synaptosomes, binds much less GT1b. RBD protects against neurotoxin considerably less well than wild-type. 2 Publications1
    Mutagenesisi1292G → Q: Whole toxin has very strongly reduced toxicity, almost no binding of RBD to neurons. 1 Publication1
    Mutagenesisi1292G → R: Nearly complete loss of toxicity, almost no binding of RBD to neurons. 1 Publication1
    Mutagenesisi1294R → A: Decreased binding of RBD to SV2C, substantial binding to neurons. 1 Publication1
    Mutagenesisi1294R → S: Decreased binding of RBD to SV2C, substantial binding to neurons. 1 Publication1

    <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 Publication3 Publications
    <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_00004449022 – 1296Botulinum neurotoxin type AAdd BLAST1295
    ChainiPRO_00000292112 – 448Botulinum neurotoxin A light chain1 PublicationAdd BLAST447
    ChainiPRO_0000029212449 – 1296Botulinum neurotoxin A heavy chain1 PublicationAdd BLAST848

    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 bondi430 ↔ 454Interchain (between light and heavy chains)Combined sources1 Publication2 Publications
    Disulfide bondi1235 ↔ 1280Combined sources

    <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

    Botulinum neurotoxin A light chain: Has slow autocatalytic activity, cleaves 250-Tyr-Tyr-251, 266-Phe-Gly-267, 419-Phe-Thr-420, 423-Phe-Glu-424, 430-Cys-Val-431, 432-Arg-Gly-433, 438-Lys-Thr-439, and probably 429-Leu-Cys-430 over a period of 4 weeks. Catalysis of the '197-Gln-|-Arg-198' bond in SNAP25 is estimated to be 105 more efficient than autocatalysis, leaving the physiological importance of autocatalysis in doubt (PubMed:11565902).1 Publication

    Keywords - PTMi

    Disulfide bond

    <p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

    <p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

    In cultured bacteria, first detected in late exponential growth (17 hours), reaches maximal levels at 24-25 hours and remains nearly constant for 5 days (at protein level).1 Publication

    <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 heavy chain (HC) (PubMed:7578132). Interacts with glycosylated host synaptic vesicle glycoproteins SV2A, SV2B and SV2C which serve as coreceptors (PubMed:16543415, PubMed:18815274, PubMed:19650874, PubMed:24240280, PubMed:27313224). Glycosylation of 'Asn-559' in SV2C contributes a 12-fold increase in affinity to this interaction (PubMed:27313224). Depolarization of target tissue with high levels of K+ leads to greater levels of receptor exposure (PubMed:16543415). In vitro addition of gangliosides increases SV2-toxin interaction (PubMed:16543415). Forms a highly interlocked heterodimer with NTNHA at pH 6.0 but not at pH 7.5 called the minimally functional progenitor toxin complex (M-PTC) (PubMed:22363010). The PTC is thought to protect toxin in the host acidic gastrointestinal tract, facilitate transcytosis across the intestinal barrier and release at neutral pH as is found in the bloodstream (PubMed:22363010).1 Publication8 Publications

    <p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

    Protein-protein interaction databases

    Protein interaction database and analysis system

    More...
    IntActi
    P0DPI0, 4 interactors

    Molecular INTeraction database

    More...
    MINTi
    P0DPI0

    <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

    11296
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    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
    1UEEmodel-A2-545[»]
    1XTFX-ray2.20A/B2-420[»]
    1XTGX-ray2.10A2-420[»]
    2ILPX-ray1.90A/B3-424[»]
    2IMAX-ray1.94A/B1-424[»]
    2IMBX-ray2.41A/B3-424[»]
    2IMCX-ray2.00A/B3-424[»]
    2ISEX-ray2.20A/B1-420[»]
    2ISGX-ray2.00A/B1-420[»]
    2ISHX-ray2.00A/B1-420[»]
    2VU9X-ray1.60A876-1296[»]
    2VUAX-ray1.70A876-1296[»]
    2W2DX-ray2.59A/C3-442[»]
    B/D447-877[»]
    3BOKX-ray1.25A3-425[»]
    3BONX-ray1.20A3-425[»]
    3BOOX-ray1.40A3-425[»]
    3V0AX-ray2.70A1-1296[»]
    3V0BX-ray3.90A1-1296[»]
    3V0CX-ray4.30A1-1296[»]
    3ZURX-ray2.71A/B3-430[»]
    A/B454-865[»]
    3ZUSX-ray2.95A/B/C/D3-431[»]
    A/B/C/D454-865[»]
    4HEVX-ray2.50A/B1-425[»]
    4IQPX-ray2.30A871-1296[»]
    4JRAX-ray2.30A/B871-1296[»]
    5JLVX-ray2.00A/B872-1296[»]
    5JMCX-ray2.64A/C/E/G872-1296[»]
    5MK6X-ray1.45A871-1296[»]
    5MK7X-ray1.80A871-1296[»]
    5TPBX-ray2.60A/B876-1296[»]
    5TPCX-ray2.00A876-1296[»]
    5V8PX-ray2.50A/B1-424[»]
    5V8RX-ray1.90A/B1-424[»]
    5V8UX-ray2.05A/B1-424[»]
    5VGVX-ray2.60A1-425[»]
    5VGXX-ray2.15A1-425[»]
    6DKKX-ray2.70A/B547-871[»]
    6MHJX-ray3.02A547-871[»]

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

    More...
    SMRi
    P0DPI0

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    MobiDB: a database of protein disorder and mobility annotations

    More...
    MobiDBi
    Search...

    <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>Regioni449 – 870Translocation domain (TD); not required to bind NTNHA1 Publication1 PublicationAdd BLAST422
    Regioni492 – 545Belt; not required for channel formation1 PublicationAdd BLAST54
    Regioni871 – 1092N-terminus of receptor binding domain (N-RBD)1 PublicationAdd BLAST222
    Regioni1093 – 1296C-terminus of receptor binding domain (C-RBD)1 PublicationAdd BLAST204
    Regioni1252 – 1253Interaction with host ganglioside GT1bCombined sources1 Publication2 Publications2

    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>Motifi1264 – 1267Host ganglioside-binding motif; interacts with GT1bCombined sources2 Publications2 Publications4

    <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 A light chain: Has protease activity (PubMed:7578132).1 Publication
    Botulinum neurotoxin A 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). Upon trypsin digestion the isolated TD forms channels in bilayers when the cis side is acidic/oxidizing and the trans side is pH 7.0/reducing (PubMed:2446925, PubMed:17666397, PubMed:19096517). The RBD rotates 140 degrees around the TD in the presence of NTNHA (PubMed:22363010). The 3 major domains each serve as a chaperone for the other 2 to ensure they act only in the correct host cell context (PubMed:19096517). In BoNT/A structures the LC is separated from the RBD by the TD; the belt wraps around the perimeter of the LC, protecting Zn2+ in the active site (PubMed:18032388, PubMed:19351593, PubMed:22363010). The belt region (449-545) 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 Publication6 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, Transmembrane helix

    Family and domain databases

    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>.<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.

    P0DPI0-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MPFVNKQFNY KDPVNGVDIA YIKIPNVGQM QPVKAFKIHN KIWVIPERDT
    60 70 80 90 100
    FTNPEEGDLN PPPEAKQVPV SYYDSTYLST DNEKDNYLKG VTKLFERIYS
    110 120 130 140 150
    TDLGRMLLTS IVRGIPFWGG STIDTELKVI DTNCINVIQP DGSYRSEELN
    160 170 180 190 200
    LVIIGPSADI IQFECKSFGH EVLNLTRNGY GSTQYIRFSP DFTFGFEESL
    210 220 230 240 250
    EVDTNPLLGA GKFATDPAVT LAHELIHAGH RLYGIAINPN RVFKVNTNAY
    260 270 280 290 300
    YEMSGLEVSF EELRTFGGHD AKFIDSLQEN EFRLYYYNKF KDIASTLNKA
    310 320 330 340 350
    KSIVGTTASL QYMKNVFKEK YLLSEDTSGK FSVDKLKFDK LYKMLTEIYT
    360 370 380 390 400
    EDNFVKFFKV LNRKTYLNFD KAVFKINIVP KVNYTIYDGF NLRNTNLAAN
    410 420 430 440 450
    FNGQNTEINN MNFTKLKNFT GLFEFYKLLC VRGIITSKTK SLDKGYNKAL
    460 470 480 490 500
    NDLCIKVNNW DLFFSPSEDN FTNDLNKGEE ITSDTNIEAA EENISLDLIQ
    510 520 530 540 550
    QYYLTFNFDN EPENISIENL SSDIIGQLEL MPNIERFPNG KKYELDKYTM
    560 570 580 590 600
    FHYLRAQEFE HGKSRIALTN SVNEALLNPS RVYTFFSSDY VKKVNKATEA
    610 620 630 640 650
    AMFLGWVEQL VYDFTDETSE VSTTDKIADI TIIIPYIGPA LNIGNMLYKD
    660 670 680 690 700
    DFVGALIFSG AVILLEFIPE IAIPVLGTFA LVSYIANKVL TVQTIDNALS
    710 720 730 740 750
    KRNEKWDEVY KYIVTNWLAK VNTQIDLIRK KMKEALENQA EATKAIINYQ
    760 770 780 790 800
    YNQYTEEEKN NINFNIDDLS SKLNESINKA MININKFLNQ CSVSYLMNSM
    810 820 830 840 850
    IPYGVKRLED FDASLKDALL KYIYDNRGTL IGQVDRLKDK VNNTLSTDIP
    860 870 880 890 900
    FQLSKYVDNQ RLLSTFTEYI KNIINTSILN LRYESNHLID LSRYASKINI
    910 920 930 940 950
    GSKVNFDPID KNQIQLFNLE SSKIEVILKN AIVYNSMYEN FSTSFWIRIP
    960 970 980 990 1000
    KYFNSISLNN EYTIINCMEN NSGWKVSLNY GEIIWTLQDT QEIKQRVVFK
    1010 1020 1030 1040 1050
    YSQMINISDY INRWIFVTIT NNRLNNSKIY INGRLIDQKP ISNLGNIHAS
    1060 1070 1080 1090 1100
    NNIMFKLDGC RDTHRYIWIK YFNLFDKELN EKEIKDLYDN QSNSGILKDF
    1110 1120 1130 1140 1150
    WGDYLQYDKP YYMLNLYDPN KYVDVNNVGI RGYMYLKGPR GSVMTTNIYL
    1160 1170 1180 1190 1200
    NSSLYRGTKF IIKKYASGNK DNIVRNNDRV YINVVVKNKE YRLATNASQA
    1210 1220 1230 1240 1250
    GVEKILSALE IPDVGNLSQV VVMKSKNDQG ITNKCKMNLQ DNNGNDIGFI
    1260 1270 1280 1290
    GFHQFNNIAK LVASNWYNRQ IERSSRTLGC SWEFIPVDDG WGERPL
    Length:1,296
    Mass (Da):149,454
    Last modified:July 18, 2018 - 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:iB731EF5BA5E62FDA
    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 conflicti2P → Q in CAA36289 (PubMed:2185020).Curated1
    Sequence conflicti480E → P AA sequence (PubMed:3896784).Curated1

    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 varianti27V → A in strain 62A. 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
    X52066 Genomic DNA Translation: CAA36289.1
    M30196 Genomic DNA Translation: AAA23262.1
    X92973 Genomic DNA Translation: CAA63551.1
    D67030 Genomic DNA Translation: BAA11051.1

    Protein sequence database of the Protein Information Resource

    More...
    PIRi
    A35294 BTCLAB

    NCBI Reference Sequences

    More...
    RefSeqi
    WP_003356619.1, NZ_LFOS01000037.1
    WP_011948511.1, NZ_LHUL01000004.1

    <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

    BOTOX product information Web site
    Protein Spotlight

    From sausages to wrinkles - Issue 19 of February 2002

    BotDB - A Database Resource for Clostridial Neurotoxins

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X52066 Genomic DNA Translation: CAA36289.1
    M30196 Genomic DNA Translation: AAA23262.1
    X92973 Genomic DNA Translation: CAA63551.1
    D67030 Genomic DNA Translation: BAA11051.1
    PIRiA35294 BTCLAB
    RefSeqiWP_003356619.1, NZ_LFOS01000037.1
    WP_011948511.1, NZ_LHUL01000004.1

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1UEEmodel-A2-545[»]
    1XTFX-ray2.20A/B2-420[»]
    1XTGX-ray2.10A2-420[»]
    2ILPX-ray1.90A/B3-424[»]
    2IMAX-ray1.94A/B1-424[»]
    2IMBX-ray2.41A/B3-424[»]
    2IMCX-ray2.00A/B3-424[»]
    2ISEX-ray2.20A/B1-420[»]
    2ISGX-ray2.00A/B1-420[»]
    2ISHX-ray2.00A/B1-420[»]
    2VU9X-ray1.60A876-1296[»]
    2VUAX-ray1.70A876-1296[»]
    2W2DX-ray2.59A/C3-442[»]
    B/D447-877[»]
    3BOKX-ray1.25A3-425[»]
    3BONX-ray1.20A3-425[»]
    3BOOX-ray1.40A3-425[»]
    3V0AX-ray2.70A1-1296[»]
    3V0BX-ray3.90A1-1296[»]
    3V0CX-ray4.30A1-1296[»]
    3ZURX-ray2.71A/B3-430[»]
    A/B454-865[»]
    3ZUSX-ray2.95A/B/C/D3-431[»]
    A/B/C/D454-865[»]
    4HEVX-ray2.50A/B1-425[»]
    4IQPX-ray2.30A871-1296[»]
    4JRAX-ray2.30A/B871-1296[»]
    5JLVX-ray2.00A/B872-1296[»]
    5JMCX-ray2.64A/C/E/G872-1296[»]
    5MK6X-ray1.45A871-1296[»]
    5MK7X-ray1.80A871-1296[»]
    5TPBX-ray2.60A/B876-1296[»]
    5TPCX-ray2.00A876-1296[»]
    5V8PX-ray2.50A/B1-424[»]
    5V8RX-ray1.90A/B1-424[»]
    5V8UX-ray2.05A/B1-424[»]
    5VGVX-ray2.60A1-425[»]
    5VGXX-ray2.15A1-425[»]
    6DKKX-ray2.70A/B547-871[»]
    6MHJX-ray3.02A547-871[»]
    SMRiP0DPI0
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiP0DPI0, 4 interactors
    MINTiP0DPI0

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Enzyme and pathway databases

    ReactomeiR-HSA-5250968 Toxicity of botulinum toxin type A (BoNT/A)

    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

    ProtoNet; Automatic hierarchical classification of proteins

    More...
    ProtoNeti
    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 nameiBXA1_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: P0DPI0
    Secondary accession number(s): A5HZZ9
    , A7G1U9, P01561, P10845, P18639
    <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 18, 2018
    Last sequence update: July 18, 2018
    Last modified: May 8, 2019
    This is version 9 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 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, Pharmaceutical

    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
    4. Protein Spotlight
      Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
    UniProt is an ELIXIR core data resource
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