Reviewed, UniProtKB/Swiss-Prot Q45894 (BXA2_CLOBO)

Names and origin

Protein names

Recommended name:
    Botulinum neurotoxin type A
      Short name=BoNT/A
    EC=3.4.24.69
Alternative name(s):
    Bontoxilysin-A
      Short name=BOTOX
Cleaved into the following 2 chains:
    1- Recommended name:
            Botulinum neurotoxin A light chain
    2- Recommended name:
            Botulinum neurotoxin A heavy chain

Gene names

Name:	botA
Synonyms:	atx, bna

Organism

Clostridium botulinum

Taxonomic identifier

1491 [NCBI]

Taxonomic lineage

Bacteria › Firmicutes › Clostridia › Clostridiales › Clostridiaceae › Clostridium

Protein attributes

Sequence length	1296 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 the three isoforms 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 By similarity.
Catalytic activity	Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on small molecule substrates.
Subunit structure	Disulfide-linked heterodimer of a light chain (L) and a heavy chain (H) By similarity.
Subcellular location	Botulinum neurotoxin A light chain: Secreted. Host cytoplasm › host cytosol. Botulinum neurotoxin A heavy chain: Secreted. Host cell junction › host synapse › host presynaptic cell membrane; Multi-pass membrane protein Potential.
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.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Membrane Secreted Synapse
Domain	Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Neurotoxin Protease Toxin
PTM	Disulfide bond
Technical term	3D-structure
Gene Ontology (GO)
Biological process	inhibition of neurotransmitter uptake Inferred from electronic annotation. Source: InterPro pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW synapse Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro toxin receptor binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 448

447

Botulinum neurotoxin A light chain

PRO_0000029213

Chain

449 – 1296

848

Botulinum neurotoxin A heavy chain

PRO_0000029214

Regions

Transmembrane

627 – 647

21

Potential

Transmembrane

656 – 676

21

Potential

Sites

Active site

224

1

By similarity

Metal binding

223

1

Zinc; catalytic By similarity

Metal binding

227

1

Zinc; catalytic By similarity

Amino acid modifications

Disulfide bond

430 ↔ 454

Interchain (between light and heavy chains) By similarity

Disulfide bond

1235 ↔ 1280

By similarity

Secondary structure

1

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1296

Helix Strand Turn

Details...

Beta strand

16 – 23

8

Beta strand

33 – 39

7

Beta strand

42 – 48

7

Turn

75 – 78

4

Helix

81 – 99

19

Helix

102 – 113

12

Beta strand

126 – 128

3

Beta strand

133 – 138

6

Beta strand

144 – 148

5

Beta strand

150 – 155

6

Beta strand

164 – 166

3

Turn

175 – 177

3

Beta strand

184 – 187

4

Beta strand

192 – 198

7

Beta strand

211 – 214

4

Helix

217 – 232

16

Beta strand

242 – 246

5

Beta strand

254 – 259

6

Helix

260 – 266

7

Helix

268 – 273

6

Helix

276 – 299

24

Beta strand

305 – 308

4

Helix

310 – 321

12

Helix

335 – 347

13

Helix

351 – 358

8

Beta strand

364 – 366

3

Beta strand

373 – 375

3

Turn

381 – 383

3

Turn

386 – 388

3

Helix

402 – 404

3

Turn

406 – 409

4

Helix

410 – 412

3

Sequences

	Sequence		Length	Mass (Da)
	Q45894-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 6F12E7BF28ED69D1	FASTA	1,296	149,411
	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 DVLNLTRNGY 190 200 210 220 230 240 GSTQYIRFSP DFTFGFEESL EVDTNPLLGA GKFATDPAVT LAHELIHAEH RLYGIAINPN 250 260 270 280 290 300 RVFKVNTNAY YEMSGLEVSF EELRTFGGHD AKFIDSLQEN EFRLYYYNKF KDVASTLNKA 310 320 330 340 350 360 KSIIGTTASL QYMKNVFKEK YLLSEDTSGK FSVDKLKFDK LYKMLTEIYT EDNFVNFFKV 370 380 390 400 410 420 INRKTYLNFD KAVFRINIVP DENYTIKDGF NLKGANLSTN FNGQNTEINS RNFTRLKNFT 430 440 450 460 470 480 GLFEFYKLLC VRGIIPFKTK SLDEGYNKAL NDLCIKVNNW DLFFSPSEDN FTNDLDKVEE 490 500 510 520 530 540 ITADTNIEAA EENISLDLIQ QYYLTFDFDN EPENISIENL SSDIIGQLEP MPNIERFPNG 550 560 570 580 590 600 KKYELDKYTM FHYLRAQEFE HGDSRIILTN SAEEALLKPN VAYTFFSSKY VKKINKAVEA 610 620 630 640 650 660 FMFLNWAEEL VYDFTDETNE VTTMDKIADI TIIVPYIGPA LNIGNMLSKG EFVEAIIFTG 670 680 690 700 710 720 VVAMLEFIPE YALPVFGTFA IVSYIANKVL TVQTINNALS KRNEKWDEVY KYTVTNWLAK 730 740 750 760 770 780 VNTQIDLIRE KMKKALENQA EATKAIINYQ YNQYTEEEKN NINFNIDDLS SKLNESINSA 790 800 810 820 830 840 MININKFLDQ CSVSYLMNSM IPYAVKRLKD FDASVRDVLL KYIYDNRGTL VLQVDRLKDE 850 860 870 880 890 900 VNNTLSADIP FQLSKYVDNK KLLSTFTEYI KNIVNTSILS IVYKKDDLID LSRYGAKINI 910 920 930 940 950 960 GDRVYYDSID KNQIKLINLE SSTIEVILKN AIVYNSMYEN FSTSFWIKIP KYFSKINLNN 970 980 990 1000 1010 1020 EYTIINCIEN NSGWKVSLNY GEIIWTLQDN KQNIQRVVFK YSQMVNISDY INRWIFVTIT 1030 1040 1050 1060 1070 1080 NNRLTKSKIY INGRLIDQKP ISNLGNIHAS NKIMFKLDGC RDPRRYIMIK YFNLFDKELN 1090 1100 1110 1120 1130 1140 EKEIKDLYDS QSNSGILKDF WGNYLQYDKP YYMLNLFDPN KYVDVNNIGI RGYMYLKGPR 1150 1160 1170 1180 1190 1200 GSVVTTNIYL NSTLYEGTKF IIKKYASGNE DNIVRNNDRV YINVVVKNKE YRLATNASQA 1210 1220 1230 1240 1250 1260 GVEKILSALE IPDVGNLSQV VVMKSKDDQG IRNKCKMNLQ DNNGNDIGFI GFHLYDNIAK 1270 1280 1290 LVASNWYNRQ VGKASRTFGC SWEFIPVDDG WGESSL

References

[1]	"Sequence of the gene coding for the neurotoxin of Clostridium botulinum type A associated with infant botulism: comparison with other clostridial neurotoxins." Willems A., East A.K., Lawson P.A., Collins M.D. Res. Microbiol. 144:547-556(1993) [PubMed: 8310180] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Type A / Kyoto-F.
[2]	"Organization and phylogenetic interrelationships of genes encoding components of the botulinum toxin complex in proteolytic Clostridium botulinum types A, B, and F: evidence of chimeric sequences in the gene encoding the nontoxic nonhemagglutinin component." East A.K., Bhandari M., Stacey J.M., Campbell K.D., Collins M.D. Int. J. Syst. Bacteriol. 46:1105-1112(1996) [PubMed: 8863443] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-66. Strain: Type A / Kyoto-F.
+	Additional computationally mapped references.

Web resources

BotDB - A Database Resource for Clostridial Neurotoxins

Cross-references

Sequence databases

EMBLGenBankDDBJ

X73423 Genomic DNA. Translation: CAA51824.1.
X87974 Genomic DNA. Translation: CAA61234.1.

PIR

I40645.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E1H	X-ray	1.80	A/C	10-250	[»]
			B/D	251-416	[»]
2G7K	X-ray	2.80	A/B	3-425	[»]
2G7N	X-ray	1.90	A	3-425	[»]
2G7P	X-ray	2.30	A/B	3-425	[»]
2G7Q	X-ray	2.41	A/B	3-425	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:437N.

Enzyme and pathway databases

BRENDA

3.4.24.69. 19133.

Family and domain databases

InterPro

IPR013320. ConA-like_subgrp.
IPR006025. Pept_M_Zn_BS.
IPR000395. Peptidase_M27.
IPR013104. Toxin_rcpt_bd_C.
IPR012928. Toxin_rcpt_bd_N.
IPR012500. Toxin_trans.
[Graphical view]

Gene3D

G3DSA:2.60.120.200. ConA_like_subgrp. 1 hit.
G3DSA:3.90.1240.10. Peptidase_M27. 1 hit.

Pfam

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]

PRINTS

PR00760. BONTOXILYSIN.

ProDom

PD001963. Botulinum. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS00142. ZINC_PROTEASE. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

Q45894.

Entry information

Entry name

BXA2_CLOBO

Accession

Primary (citable) accession number: Q45894
Secondary accession number(s): P77780

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2002
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 84 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)