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Protein

Botulinum neurotoxin type A

Gene

botA

Organism
Clostridium botulinum (strain Hall / ATCC 3502 / NCTC 13319 / Type A)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Zn2+Note: Binds 1 zinc ion per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi223Zinc; catalyticPROSITE-ProRule annotation1
Active sitei224PROSITE-ProRule annotation1
Metal bindingi227Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi262Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Neurotoxin, Protease, Toxin

Keywords - Biological processi

Virulence

Keywords - Ligandi

Metal-binding, Zinc

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
Proteomesi
  • UP000001986 Componenti: Chromosome

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei627 – 647HelicalSequence analysisAdd BLAST21
Transmembranei656 – 676HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

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.

Chemistry databases

ChEMBLiCHEMBL5344.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00003089062 – 448Botulinum neurotoxin A light chainAdd BLAST447
ChainiPRO_0000308907449 – 1296Botulinum neurotoxin A heavy chainAdd BLAST848

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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

DIPiDIP-61682N.

Chemistry databases

BindingDBiA5HZZ9.

Structurei

Secondary structure

11296
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 6Combined sources3
Beta strandi16 – 23Combined sources8
Beta strandi26 – 28Combined sources3
Beta strandi33 – 39Combined sources7
Beta strandi42 – 48Combined sources7
Beta strandi50 – 52Combined sources3
Helixi54 – 56Combined sources3
Beta strandi63 – 65Combined sources3
Turni68 – 70Combined sources3
Turni75 – 78Combined sources4
Helixi81 – 99Combined sources19
Helixi102 – 113Combined sources12
Beta strandi126 – 128Combined sources3
Helixi131 – 133Combined sources3
Beta strandi134 – 138Combined sources5
Beta strandi144 – 148Combined sources5
Beta strandi150 – 155Combined sources6
Beta strandi164 – 166Combined sources3
Beta strandi169 – 171Combined sources3
Turni175 – 177Combined sources3
Beta strandi184 – 187Combined sources4
Beta strandi192 – 196Combined sources5
Helixi200 – 203Combined sources4
Beta strandi211 – 214Combined sources4
Helixi217 – 232Combined sources16
Beta strandi242 – 244Combined sources3
Helixi249 – 252Combined sources4
Turni253 – 255Combined sources3
Beta strandi257 – 259Combined sources3
Helixi260 – 266Combined sources7
Helixi268 – 273Combined sources6
Helixi276 – 299Combined sources24
Beta strandi302 – 308Combined sources7
Helixi310 – 321Combined sources12
Beta strandi323 – 325Combined sources3
Beta strandi327 – 329Combined sources3
Beta strandi331 – 333Combined sources3
Helixi335 – 347Combined sources13
Helixi351 – 358Combined sources8
Beta strandi366 – 368Combined sources3
Beta strandi372 – 375Combined sources4
Turni381 – 383Combined sources3
Turni386 – 388Combined sources3
Beta strandi393 – 395Combined sources3
Helixi396 – 398Combined sources3
Turni400 – 404Combined sources5
Turni406 – 409Combined sources4
Helixi410 – 412Combined sources3
Beta strandi414 – 418Combined sources5
Turni420 – 422Combined sources3
Beta strandi425 – 431Combined sources7
Beta strandi453 – 458Combined sources6
Helixi459 – 461Combined sources3
Helixi468 – 470Combined sources3
Beta strandi479 – 481Combined sources3
Helixi496 – 504Combined sources9
Beta strandi542 – 547Combined sources6
Helixi550 – 556Combined sources7
Beta strandi568 – 572Combined sources5
Helixi573 – 575Combined sources3
Beta strandi581 – 583Combined sources3
Helixi588 – 595Combined sources8
Turni600 – 602Combined sources3
Helixi603 – 618Combined sources16
Beta strandi625 – 629Combined sources5
Helixi637 – 641Combined sources5
Turni642 – 644Combined sources3
Helixi649 – 659Combined sources11
Helixi660 – 663Combined sources4
Beta strandi679 – 681Combined sources3
Helixi688 – 720Combined sources33
Helixi722 – 752Combined sources31
Helixi758 – 762Combined sources5
Helixi766 – 799Combined sources34
Helixi801 – 825Combined sources25
Turni826 – 829Combined sources4
Helixi834 – 845Combined sources12
Helixi853 – 855Combined sources3
Helixi860 – 870Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4KS6X-ray1.93A1-425[»]
4KTXX-ray2.59A1-425[»]
4KUFX-ray1.70A1-425[»]
ProteinModelPortaliA5HZZ9.
SMRiA5HZZ9.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiA5HZZ9.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M27 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

HOGENOMiHOG000234384.
KOiK06011.
OMAiDEGYNKA.

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
3.90.1240.10. 1 hit.
InterProiIPR000395. Bot/tetX.
IPR013320. ConA-like_dom.
IPR011065. Kunitz_inhibitor_ST1-like.
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

        10         20         30         40         50
MPFVNKQFNY KDPVNGVDIA YIKIPNAGQM 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):149,426
Last modified:June 26, 2007 - v1
Checksum:iDEA8CF2754AE43E6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1218S → Y AA sequence (PubMed:8397793).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4KS6X-ray1.93A1-425[»]
4KTXX-ray2.59A1-425[»]
4KUFX-ray1.70A1-425[»]
ProteinModelPortaliA5HZZ9.
SMRiA5HZZ9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61682N.

Chemistry databases

BindingDBiA5HZZ9.
ChEMBLiCHEMBL5344.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Phylogenomic databases

HOGENOMiHOG000234384.
KOiK06011.
OMAiDEGYNKA.

Miscellaneous databases

EvolutionaryTraceiA5HZZ9.
PROiA5HZZ9.

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
3.90.1240.10. 1 hit.
InterProiIPR000395. Bot/tetX.
IPR013320. ConA-like_dom.
IPR011065. Kunitz_inhibitor_ST1-like.
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]
ProtoNetiSearch...

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: November 2, 2016
This is version 79 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.