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A5HZZ9

- BXA1_CLOBH

UniProt

A5HZZ9 - BXA1_CLOBH

Protein

Botulinum neurotoxin type A

Gene

botA

Organism
Clostridium botulinum (strain Hall / ATCC 3502 / NCTC 13319 / Type A)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 60 (01 Oct 2014)
      Sequence version 1 (26 Jun 2007)
      Previous versions | rss
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    Functioni

    Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure.

    Catalytic activityi

    Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on small molecule substrates.

    Cofactori

    Binds 1 zinc ion per subunit.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi223 – 2231Zinc; catalyticPROSITE-ProRule annotation
    Active sitei224 – 2241PROSITE-ProRule annotation
    Metal bindingi227 – 2271Zinc; catalyticPROSITE-ProRule annotation
    Metal bindingi262 – 2621Zinc; catalyticPROSITE-ProRule annotation

    GO - Molecular functioni

    1. metalloendopeptidase activity Source: InterPro
    2. zinc ion binding Source: InterPro

    GO - Biological processi

    1. inhibition of neurotransmitter uptake Source: InterPro
    2. pathogenesis Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Neurotoxin, Protease, Toxin

    Keywords - Biological processi

    Virulence

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciCBOT413999:GJ72-872-MONOMER.
    CBOT441771:GIWX-833-MONOMER.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Botulinum neurotoxin type A (EC:3.4.24.69)
    Short name:
    BoNT/A
    Alternative name(s):
    Bontoxilysin-A
    Short name:
    BOTOX
    Cleaved into the following 2 chains:
    Gene namesi
    Name:botA
    Ordered Locus Names:CBO0806, CLC_0862
    OrganismiClostridium botulinum (strain Hall / ATCC 3502 / NCTC 13319 / Type A)
    Taxonomic identifieri441771 [NCBI]
    Taxonomic lineageiBacteriaFirmicutesClostridiaClostridialesClostridiaceaeClostridium
    ProteomesiUP000001986: Chromosome, UP000002409: Chromosome

    Subcellular locationi

    GO - Cellular componenti

    1. host cell cytosol Source: UniProtKB-SubCell
    2. host cell junction Source: UniProtKB-KW
    3. host cell presynaptic membrane Source: UniProtKB-SubCell
    4. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Host cell junction, Host cell membrane, Host cytoplasm, Host membrane, Host synapse, Membrane, Secreted

    Pathology & Biotechi

    Pharmaceutical usei

    Available under the name BOTOX (Allergan) 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.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 448447Botulinum neurotoxin A light chainPRO_0000308906Add
    BLAST
    Chaini449 – 1296848Botulinum neurotoxin A heavy chainPRO_0000308907Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi430 ↔ 454Interchain (between light and heavy chains)By similarity
    Disulfide bondi1235 ↔ 1280By similarity

    Keywords - PTMi

    Disulfide bond

    Interactioni

    Subunit structurei

    Disulfide-linked heterodimer of a light chain (L) and a heavy chain (H).

    Protein-protein interaction databases

    STRINGi413999.CBO0806.

    Structurei

    Secondary structure

    1
    1296
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi4 – 63
    Beta strandi16 – 238
    Beta strandi26 – 283
    Beta strandi33 – 397
    Beta strandi42 – 487
    Beta strandi51 – 533
    Helixi54 – 563
    Beta strandi63 – 653
    Turni68 – 703
    Turni75 – 784
    Helixi81 – 9919
    Helixi102 – 11312
    Beta strandi126 – 1283
    Helixi131 – 1333
    Beta strandi134 – 1385
    Beta strandi144 – 1485
    Beta strandi150 – 1556
    Beta strandi164 – 1663
    Beta strandi171 – 1733
    Turni175 – 1773
    Beta strandi184 – 1874
    Beta strandi192 – 1965
    Helixi200 – 2034
    Beta strandi211 – 2144
    Helixi217 – 23216
    Beta strandi242 – 2443
    Helixi249 – 2524
    Turni253 – 2553
    Beta strandi257 – 2593
    Helixi260 – 2667
    Helixi268 – 2736
    Helixi276 – 29924
    Beta strandi302 – 3087
    Helixi310 – 32112
    Beta strandi323 – 3253
    Beta strandi327 – 3293
    Beta strandi331 – 3333
    Helixi335 – 34713
    Helixi351 – 3588
    Beta strandi366 – 3683
    Beta strandi372 – 3754
    Turni381 – 3833
    Turni386 – 3883
    Beta strandi393 – 3953
    Helixi396 – 3983
    Turni400 – 4045
    Turni406 – 4094
    Helixi410 – 4123
    Beta strandi414 – 4185
    Turni420 – 4223
    Beta strandi425 – 4317
    Beta strandi453 – 4586
    Helixi459 – 4613
    Helixi468 – 4703
    Beta strandi479 – 4813
    Helixi496 – 5049
    Beta strandi542 – 5476
    Helixi550 – 5567
    Beta strandi568 – 5725
    Helixi573 – 5753
    Beta strandi581 – 5833
    Helixi588 – 5958
    Turni600 – 6023
    Helixi603 – 61816
    Beta strandi625 – 6295
    Helixi637 – 6415
    Turni642 – 6443
    Helixi649 – 65911
    Helixi660 – 6634
    Beta strandi679 – 6813
    Helixi688 – 72033
    Helixi722 – 75231
    Helixi758 – 7625
    Helixi766 – 79934
    Helixi801 – 82525
    Turni826 – 8294
    Helixi834 – 84512
    Helixi853 – 8553
    Helixi860 – 87011

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1XTFX-ray2.20A/B2-420[»]
    1XTGX-ray2.10A2-422[»]
    2W2DX-ray2.59A/C1-442[»]
    B/D447-877[»]
    3DSEX-ray1.90A1-417[»]
    3K3QX-ray2.60B3-250[»]
    C251-425[»]
    3QIXX-ray2.41A/B3-424[»]
    3QIYX-ray2.30A3-424[»]
    3QIZX-ray2.00A3-424[»]
    3QJ0X-ray2.30A3-424[»]
    3QW5X-ray1.60A1-424[»]
    3QW6X-ray1.60A1-424[»]
    3QW7X-ray1.50A1-424[»]
    3QW8X-ray1.60A1-424[»]
    ProteinModelPortaliA5HZZ9.
    SMRiA5HZZ9. Positions 1-423.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiA5HZZ9.

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei627 – 64721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei656 – 67621HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase M27 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    HOGENOMiHOG000234384.
    KOiK06011.
    OMAiHASNKIM.
    OrthoDBiEOG67T5DS.

    Family and domain databases

    Gene3Di2.60.120.200. 1 hit.
    3.90.1240.10. 1 hit.
    InterProiIPR008985. ConA-like_lec_gl_sf.
    IPR013320. ConA-like_subgrp.
    IPR011065. Kunitz_inhibitor_ST1-like.
    IPR000395. Neurotox_Zn_protease.
    IPR013104. Toxin_rcpt-bd_C.
    IPR012928. Toxin_rcpt-bd_N.
    IPR012500. Toxin_trans.
    [Graphical view]
    PfamiPF01742. Peptidase_M27. 1 hit.
    PF07951. Toxin_R_bind_C. 1 hit.
    PF07953. Toxin_R_bind_N. 1 hit.
    PF07952. Toxin_trans. 1 hit.
    [Graphical view]
    PRINTSiPR00760. BONTOXILYSIN.
    SUPFAMiSSF49899. SSF49899. 1 hit.
    SSF50386. SSF50386. 1 hit.
    PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    A5HZZ9-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPFVNKQFNY KDPVNGVDIA YIKIPNAGQM QPVKAFKIHN KIWVIPERDT     50
    FTNPEEGDLN PPPEAKQVPV SYYDSTYLST DNEKDNYLKG VTKLFERIYS 100
    TDLGRMLLTS IVRGIPFWGG STIDTELKVI DTNCINVIQP DGSYRSEELN 150
    LVIIGPSADI IQFECKSFGH EVLNLTRNGY GSTQYIRFSP DFTFGFEESL 200
    EVDTNPLLGA GKFATDPAVT LAHELIHAGH RLYGIAINPN RVFKVNTNAY 250
    YEMSGLEVSF EELRTFGGHD AKFIDSLQEN EFRLYYYNKF KDIASTLNKA 300
    KSIVGTTASL QYMKNVFKEK YLLSEDTSGK FSVDKLKFDK LYKMLTEIYT 350
    EDNFVKFFKV LNRKTYLNFD KAVFKINIVP KVNYTIYDGF NLRNTNLAAN 400
    FNGQNTEINN MNFTKLKNFT GLFEFYKLLC VRGIITSKTK SLDKGYNKAL 450
    NDLCIKVNNW DLFFSPSEDN FTNDLNKGEE ITSDTNIEAA EENISLDLIQ 500
    QYYLTFNFDN EPENISIENL SSDIIGQLEL MPNIERFPNG KKYELDKYTM 550
    FHYLRAQEFE HGKSRIALTN SVNEALLNPS RVYTFFSSDY VKKVNKATEA 600
    AMFLGWVEQL VYDFTDETSE VSTTDKIADI TIIIPYIGPA LNIGNMLYKD 650
    DFVGALIFSG AVILLEFIPE IAIPVLGTFA LVSYIANKVL TVQTIDNALS 700
    KRNEKWDEVY KYIVTNWLAK VNTQIDLIRK KMKEALENQA EATKAIINYQ 750
    YNQYTEEEKN NINFNIDDLS SKLNESINKA MININKFLNQ CSVSYLMNSM 800
    IPYGVKRLED FDASLKDALL KYIYDNRGTL IGQVDRLKDK VNNTLSTDIP 850
    FQLSKYVDNQ RLLSTFTEYI KNIINTSILN LRYESNHLID LSRYASKINI 900
    GSKVNFDPID KNQIQLFNLE SSKIEVILKN AIVYNSMYEN FSTSFWIRIP 950
    KYFNSISLNN EYTIINCMEN NSGWKVSLNY GEIIWTLQDT QEIKQRVVFK 1000
    YSQMINISDY INRWIFVTIT NNRLNNSKIY INGRLIDQKP ISNLGNIHAS 1050
    NNIMFKLDGC RDTHRYIWIK YFNLFDKELN EKEIKDLYDN QSNSGILKDF 1100
    WGDYLQYDKP YYMLNLYDPN KYVDVNNVGI RGYMYLKGPR GSVMTTNIYL 1150
    NSSLYRGTKF IIKKYASGNK DNIVRNNDRV YINVVVKNKE YRLATNASQA 1200
    GVEKILSALE IPDVGNLSQV VVMKSKNDQG ITNKCKMNLQ DNNGNDIGFI 1250
    GFHQFNNIAK LVASNWYNRQ IERSSRTLGC SWEFIPVDDG WGERPL 1296
    Length:1,296
    Mass (Da):149,426
    Last modified:June 26, 2007 - v1
    Checksum:iDEA8CF2754AE43E6
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti1218 – 12181S → Y AA sequence (PubMed:8397793)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AM412317 Genomic DNA. Translation: CAL82360.1.
    CP000727 Genomic DNA. Translation: ABS38337.1.
    PIRiA35294. BTCLAB.
    RefSeqiWP_011948511.1. NC_009698.1.
    YP_001253342.1. NC_009495.1.
    YP_001386738.1. NC_009698.1.

    Genome annotation databases

    EnsemblBacteriaiABS38337; ABS38337; CLC_0862.
    GeneIDi5185061.
    5398487.
    KEGGicbh:CLC_0862.
    cbo:CBO0806.
    PATRICi19363717. VBICloBot22612_0802.

    Cross-referencesi

    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AM412317 Genomic DNA. Translation: CAL82360.1 .
    CP000727 Genomic DNA. Translation: ABS38337.1 .
    PIRi A35294. BTCLAB.
    RefSeqi WP_011948511.1. NC_009698.1.
    YP_001253342.1. NC_009495.1.
    YP_001386738.1. NC_009698.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1XTF X-ray 2.20 A/B 2-420 [» ]
    1XTG X-ray 2.10 A 2-422 [» ]
    2W2D X-ray 2.59 A/C 1-442 [» ]
    B/D 447-877 [» ]
    3DSE X-ray 1.90 A 1-417 [» ]
    3K3Q X-ray 2.60 B 3-250 [» ]
    C 251-425 [» ]
    3QIX X-ray 2.41 A/B 3-424 [» ]
    3QIY X-ray 2.30 A 3-424 [» ]
    3QIZ X-ray 2.00 A 3-424 [» ]
    3QJ0 X-ray 2.30 A 3-424 [» ]
    3QW5 X-ray 1.60 A 1-424 [» ]
    3QW6 X-ray 1.60 A 1-424 [» ]
    3QW7 X-ray 1.50 A 1-424 [» ]
    3QW8 X-ray 1.60 A 1-424 [» ]
    ProteinModelPortali A5HZZ9.
    SMRi A5HZZ9. Positions 1-423.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 413999.CBO0806.

    Chemistry

    BindingDBi A5HZZ9.
    ChEMBLi CHEMBL5344.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblBacteriai ABS38337 ; ABS38337 ; CLC_0862 .
    GeneIDi 5185061.
    5398487.
    KEGGi cbh:CLC_0862.
    cbo:CBO0806.
    PATRICi 19363717. VBICloBot22612_0802.

    Phylogenomic databases

    HOGENOMi HOG000234384.
    KOi K06011.
    OMAi HASNKIM.
    OrthoDBi EOG67T5DS.

    Enzyme and pathway databases

    BioCyci CBOT413999:GJ72-872-MONOMER.
    CBOT441771:GIWX-833-MONOMER.

    Miscellaneous databases

    EvolutionaryTracei A5HZZ9.

    Family and domain databases

    Gene3Di 2.60.120.200. 1 hit.
    3.90.1240.10. 1 hit.
    InterProi IPR008985. ConA-like_lec_gl_sf.
    IPR013320. ConA-like_subgrp.
    IPR011065. Kunitz_inhibitor_ST1-like.
    IPR000395. Neurotox_Zn_protease.
    IPR013104. Toxin_rcpt-bd_C.
    IPR012928. Toxin_rcpt-bd_N.
    IPR012500. Toxin_trans.
    [Graphical view ]
    Pfami PF01742. Peptidase_M27. 1 hit.
    PF07951. Toxin_R_bind_C. 1 hit.
    PF07953. Toxin_R_bind_N. 1 hit.
    PF07952. Toxin_trans. 1 hit.
    [Graphical view ]
    PRINTSi PR00760. BONTOXILYSIN.
    SUPFAMi SSF49899. SSF49899. 1 hit.
    SSF50386. SSF50386. 1 hit.
    PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Hall / ATCC 3502 / NCTC 13319 / Type A.
    2. "Analysis of the neurotoxin complex genes in Clostridium botulinum A1-A4 and B1 strains: BoNT/A3, /Ba4 and /B1 clusters are located within plasmids."
      Smith T.J., Hill K.K., Foley B.T., Detter J.C., Munk A.C., Bruce D.C., Doggett N.A., Smith L.A., Marks J.D., Xie G., Brettin T.S.
      PLoS ONE 2:E1271-E1271(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Hall / ATCC 3502 / NCTC 13319 / Type A.
    3. "Characterization of botulinum type A neurotoxin gene: delineation of the N-terminal encoding region."
      Betley M.J., Somers E., Dasgupta B.R.
      Biochem. Biophys. Res. Commun. 162:1388-1395(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
    4. "Botulinum type A neurotoxin digested with pepsin yields 132, 97, 72, 45, 42, and 18 kD fragments."
      Gimenez J.A., DasGupta B.R.
      J. Protein Chem. 12:351-363(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 867-880 AND 1148-1219.
    5. "Proteolysis of SNAP-25 by types E and A botulinal neurotoxins."
      Binz T., Blasi J., Yamasaki S., Baumeister A., Link E., Suedhof T.C., Jahn R., Niemann H.
      J. Biol. Chem. 269:1617-1620(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION OF SUBSTRATE.

    Entry informationi

    Entry nameiBXA1_CLOBH
    AccessioniPrimary (citable) accession number: A5HZZ9
    Secondary accession number(s): A7G1U9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 13, 2007
    Last sequence update: June 26, 2007
    Last modified: October 1, 2014
    This is version 60 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    There are seven antigenically distinct forms of botulinum neurotoxin: Types A, B, C1, D, E, F, and G.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. Protein Spotlight
      Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3