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A5HZZ9

- BXA1_CLOBH

UniProt

A5HZZ9 - BXA1_CLOBH

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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: 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)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
Complete GO annotation...

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

Topology

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

GO - Cellular componenti

  1. host cell cytoplasm Source: UniProtKB-KW
  2. host cell junction Source: UniProtKB-KW
  3. host cell synapse Source: UniProtKB-KW
  4. integral component of membrane Source: UniProtKB-KW
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.

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 – 63Combined sources
Beta strandi16 – 238Combined sources
Beta strandi26 – 283Combined sources
Beta strandi33 – 397Combined sources
Beta strandi42 – 487Combined sources
Beta strandi50 – 523Combined sources
Helixi54 – 563Combined sources
Beta strandi63 – 653Combined sources
Turni68 – 703Combined sources
Turni75 – 784Combined sources
Helixi81 – 9919Combined sources
Helixi102 – 11312Combined sources
Beta strandi126 – 1283Combined sources
Helixi131 – 1333Combined sources
Beta strandi134 – 1385Combined sources
Beta strandi144 – 1485Combined sources
Beta strandi150 – 1556Combined sources
Beta strandi164 – 1663Combined sources
Beta strandi171 – 1733Combined sources
Turni175 – 1773Combined sources
Beta strandi184 – 1874Combined sources
Beta strandi192 – 1965Combined sources
Helixi200 – 2034Combined sources
Beta strandi211 – 2144Combined sources
Helixi217 – 23216Combined sources
Beta strandi242 – 2443Combined sources
Helixi249 – 2524Combined sources
Turni253 – 2553Combined sources
Beta strandi257 – 2593Combined sources
Helixi260 – 2667Combined sources
Helixi268 – 2736Combined sources
Helixi276 – 29924Combined sources
Beta strandi302 – 3087Combined sources
Helixi310 – 32112Combined sources
Beta strandi323 – 3253Combined sources
Beta strandi327 – 3293Combined sources
Beta strandi331 – 3333Combined sources
Helixi335 – 34713Combined sources
Helixi351 – 3588Combined sources
Beta strandi366 – 3683Combined sources
Beta strandi372 – 3754Combined sources
Turni381 – 3833Combined sources
Turni386 – 3883Combined sources
Beta strandi393 – 3953Combined sources
Helixi396 – 3983Combined sources
Turni400 – 4045Combined sources
Turni406 – 4094Combined sources
Helixi410 – 4123Combined sources
Beta strandi414 – 4185Combined sources
Turni420 – 4223Combined sources
Beta strandi425 – 4317Combined sources
Beta strandi453 – 4586Combined sources
Helixi459 – 4613Combined sources
Helixi468 – 4703Combined sources
Beta strandi479 – 4813Combined sources
Helixi496 – 5049Combined sources
Beta strandi542 – 5476Combined sources
Helixi550 – 5567Combined sources
Beta strandi568 – 5725Combined sources
Helixi573 – 5753Combined sources
Beta strandi581 – 5833Combined sources
Helixi588 – 5958Combined sources
Turni600 – 6023Combined sources
Helixi603 – 61816Combined sources
Beta strandi625 – 6295Combined sources
Helixi637 – 6415Combined sources
Turni642 – 6443Combined sources
Helixi649 – 65911Combined sources
Helixi660 – 6634Combined sources
Beta strandi679 – 6813Combined sources
Helixi688 – 72033Combined sources
Helixi722 – 75231Combined sources
Helixi758 – 7625Combined sources
Helixi766 – 79934Combined sources
Helixi801 – 82525Combined sources
Turni826 – 8294Combined sources
Helixi834 – 84512Combined sources
Helixi853 – 8553Combined sources
Helixi860 – 87011Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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[»]
4KS6X-ray1.93A1-425[»]
4KUFX-ray1.70A1-425[»]
ProteinModelPortaliA5HZZ9.
SMRiA5HZZ9. Positions 1-423.
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.
OMAiHASNKIM.
OrthoDBiEOG67T5DS.

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
3.90.1240.10. 1 hit.
InterProiIPR013320. ConA-like_dom.
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

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

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 .
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:
PDBei
RCSB PDBi
PDBji
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 [» ]
4KS6 X-ray 1.93 A 1-425 [» ]
4KUF X-ray 1.70 A 1-425 [» ]
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 IPR013320. ConA-like_dom.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 62 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