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A5HZZ9 (BXA1_CLOBH) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 57. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Botulinum neurotoxin type A

Short name=BoNT/A
EC=3.4.24.69
Alternative name(s):
Bontoxilysin-A
Short name=BOTOX
Gene names
Name:botA
Ordered Locus Names:CBO0806, CLC_0862
OrganismClostridium botulinum (strain Hall / ATCC 3502 / NCTC 13319 / Type A) [Reference proteome] [HAMAP]
Taxonomic identifier441771 [NCBI]
Taxonomic lineageBacteriaFirmicutesClostridiaClostridialesClostridiaceaeClostridium

Protein attributes

Sequence length1296 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

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

Cofactor

Binds 1 zinc ion per subunit.

Subunit structure

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

Subcellular location

Botulinum neurotoxin A light chain: Secreted. Host cytoplasmhost cytosol.

Botulinum neurotoxin A heavy chain: Secreted. Host cell junctionhost synapsehost presynaptic cell membrane; Multi-pass membrane protein Potential.

Pharmaceutical use

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.

Miscellaneous

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

Sequence similarities

Belongs to the peptidase M27 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 448447Botulinum neurotoxin A light chain
PRO_0000308906
Chain449 – 1296848Botulinum neurotoxin A heavy chain
PRO_0000308907

Regions

Transmembrane627 – 64721Helical; Potential
Transmembrane656 – 67621Helical; Potential

Sites

Active site2241 By similarity
Metal binding2231Zinc; catalytic By similarity
Metal binding2271Zinc; catalytic By similarity
Metal binding2621Zinc; catalytic By similarity

Amino acid modifications

Disulfide bond430 ↔ 454Interchain (between light and heavy chains) By similarity
Disulfide bond1235 ↔ 1280 By similarity

Experimental info

Sequence conflict12181S → Y AA sequence Ref.4

Secondary structure

................................................................................................................................................... 1296
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
A5HZZ9 [UniParc].

Last modified June 26, 2007. Version 1.
Checksum: DEA8CF2754AE43E6

FASTA1,296149,426
        10         20         30         40         50         60 
MPFVNKQFNY KDPVNGVDIA YIKIPNAGQM QPVKAFKIHN KIWVIPERDT FTNPEEGDLN 

        70         80         90        100        110        120 
PPPEAKQVPV SYYDSTYLST DNEKDNYLKG VTKLFERIYS TDLGRMLLTS IVRGIPFWGG 

       130        140        150        160        170        180 
STIDTELKVI DTNCINVIQP DGSYRSEELN LVIIGPSADI IQFECKSFGH EVLNLTRNGY 

       190        200        210        220        230        240 
GSTQYIRFSP DFTFGFEESL EVDTNPLLGA GKFATDPAVT LAHELIHAGH RLYGIAINPN 

       250        260        270        280        290        300 
RVFKVNTNAY YEMSGLEVSF EELRTFGGHD AKFIDSLQEN EFRLYYYNKF KDIASTLNKA 

       310        320        330        340        350        360 
KSIVGTTASL QYMKNVFKEK YLLSEDTSGK FSVDKLKFDK LYKMLTEIYT EDNFVKFFKV 

       370        380        390        400        410        420 
LNRKTYLNFD KAVFKINIVP KVNYTIYDGF NLRNTNLAAN FNGQNTEINN MNFTKLKNFT 

       430        440        450        460        470        480 
GLFEFYKLLC VRGIITSKTK SLDKGYNKAL NDLCIKVNNW DLFFSPSEDN FTNDLNKGEE 

       490        500        510        520        530        540 
ITSDTNIEAA EENISLDLIQ QYYLTFNFDN EPENISIENL SSDIIGQLEL MPNIERFPNG 

       550        560        570        580        590        600 
KKYELDKYTM FHYLRAQEFE HGKSRIALTN SVNEALLNPS RVYTFFSSDY VKKVNKATEA 

       610        620        630        640        650        660 
AMFLGWVEQL VYDFTDETSE VSTTDKIADI TIIIPYIGPA LNIGNMLYKD DFVGALIFSG 

       670        680        690        700        710        720 
AVILLEFIPE IAIPVLGTFA LVSYIANKVL TVQTIDNALS KRNEKWDEVY KYIVTNWLAK 

       730        740        750        760        770        780 
VNTQIDLIRK KMKEALENQA EATKAIINYQ YNQYTEEEKN NINFNIDDLS SKLNESINKA 

       790        800        810        820        830        840 
MININKFLNQ CSVSYLMNSM IPYGVKRLED FDASLKDALL KYIYDNRGTL IGQVDRLKDK 

       850        860        870        880        890        900 
VNNTLSTDIP FQLSKYVDNQ RLLSTFTEYI KNIINTSILN LRYESNHLID LSRYASKINI 

       910        920        930        940        950        960 
GSKVNFDPID KNQIQLFNLE SSKIEVILKN AIVYNSMYEN FSTSFWIRIP KYFNSISLNN 

       970        980        990       1000       1010       1020 
EYTIINCMEN NSGWKVSLNY GEIIWTLQDT QEIKQRVVFK YSQMINISDY INRWIFVTIT 

      1030       1040       1050       1060       1070       1080 
NNRLNNSKIY INGRLIDQKP ISNLGNIHAS NNIMFKLDGC RDTHRYIWIK YFNLFDKELN 

      1090       1100       1110       1120       1130       1140 
EKEIKDLYDN QSNSGILKDF WGDYLQYDKP YYMLNLYDPN KYVDVNNVGI RGYMYLKGPR 

      1150       1160       1170       1180       1190       1200 
GSVMTTNIYL NSSLYRGTKF IIKKYASGNK DNIVRNNDRV YINVVVKNKE YRLATNASQA 

      1210       1220       1230       1240       1250       1260 
GVEKILSALE IPDVGNLSQV VVMKSKNDQG ITNKCKMNLQ DNNGNDIGFI GFHQFNNIAK 

      1270       1280       1290 
LVASNWYNRQ IERSSRTLGC SWEFIPVDDG WGERPL 

« Hide

References

« Hide 'large scale' references
[1]"Genome sequence of a proteolytic (Group I) Clostridium botulinum strain Hall A and comparative analysis of the clostridial genomes."
Sebaihia M., Peck M.W., Minton N.P., Thomson N.R., Holden M.T.G., Mitchell W.J., Carter A.T., Bentley S.D., Mason D.R., Crossman L., Paul C.J., Ivens A., Wells-Bennik M.H.J., Davis I.J., Cerdeno-Tarraga A.M., Churcher C., Quail M.A., Chillingworth T. expand/collapse author list , Feltwell T., Fraser A., Goodhead I., Hance Z., Jagels K., Larke N., Maddison M., Moule S., Mungall K., Norbertczak H., Rabbinowitsch E., Sanders M., Simmonds M., White B., Whithead S., Parkhill J.
Genome Res. 17:1082-1092(2007) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AM412317 Genomic DNA. Translation: CAL82360.1.
CP000727 Genomic DNA. Translation: ABS38337.1.
PIRBTCLAB. A35294.
RefSeqYP_001253342.1. NC_009495.1.
YP_001386738.1. NC_009698.1.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalA5HZZ9.
SMRA5HZZ9. Positions 1-423.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING413999.CBO0806.

Chemistry

BindingDBA5HZZ9.
ChEMBLCHEMBL5344.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaABS38337; ABS38337; CLC_0862.
GeneID5185061.
5398487.
KEGGcbh:CLC_0862.
cbo:CBO0806.
PATRIC19363717. VBICloBot22612_0802.

Phylogenomic databases

HOGENOMHOG000234384.
KOK06011.
OMADFWGNYL.
OrthoDBEOG67T5DS.
ProtClustDBCLSK912378.

Enzyme and pathway databases

BioCycCBOT413999:GJ72-872-MONOMER.
CBOT441771:GIWX-833-MONOMER.

Family and domain databases

Gene3D2.60.120.200. 1 hit.
3.90.1240.10. 1 hit.
InterProIPR008985. 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]
PfamPF01742. 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]
PRINTSPR00760. BONTOXILYSIN.
SUPFAMSSF49899. SSF49899. 1 hit.
SSF50386. SSF50386. 1 hit.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceA5HZZ9.

Entry information

Entry nameBXA1_CLOBH
AccessionPrimary (citable) accession number: A5HZZ9
Secondary accession number(s): A7G1U9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: June 26, 2007
Last modified: February 19, 2014
This is version 57 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references