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A5HZZ9

- BXA1_CLOBH

UniProt

A5HZZ9 - BXA1_CLOBH

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Protein

Botulinum neurotoxin type A

Gene
botA, CBO0806, CLC_0862
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

Binds 1 zinc ion per subunit.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi223 – 2231Zinc; catalytic By similarity
Active sitei224 – 2241 By similarity
Metal bindingi227 – 2271Zinc; catalytic By similarity
Metal bindingi262 – 2621Zinc; catalytic By similarity

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 – 64721Helical; Reviewed predictionAdd
BLAST
Transmembranei656 – 67621Helical; Reviewed predictionAdd
BLAST

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
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 – 11Removed By 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 ↔ 1280 By 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.

Miscellaneous databases

EvolutionaryTraceiA5HZZ9.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M27 family.

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1218 – 12181S → Y AA sequence 1 Publication

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

« 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: September 3, 2014
This is version 59 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

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