Q00496 (BXE_CLOBO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Botulinum neurotoxin type E Short name=BoNT/E EC=3.4.24.69 Alternative name(s): Bontoxilysin-E Cleaved into the following 2 chains: Botulinum neurotoxin E light chain Botulinum neurotoxin E heavy chain
Organism	Clostridium botulinum
Taxonomic identifier	1491 [NCBI]
Taxonomic lineage	Bacteria › Firmicutes › Clostridia › Clostridiales › Clostridiaceae › Clostridium

Protein attributes

Sequence length	1251 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	Botulinum toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that catalyzes the hydrolysis of the 180-Arg-|-Ile-181 bond in SNAP-25.
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 By similarity.
Subunit structure	Disulfide-linked heterodimer of a light chain (L) and a heavy chain (H). The light chain has the pharmacological activity, while the N- and C-terminal of the heavy chain mediate channel formation and toxin binding, respectively.
Subcellular location	Botulinum neurotoxin E light chain: Secreted. Host cytoplasm › host cytosol. Botulinum neurotoxin E heavy chain: Secreted. Host cell junction › host synapse › host presynaptic cell membrane 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
Biological process	Virulence
Cellular component	Host cell junction Host cell membrane Host cytoplasm Host membrane Host synapse Membrane Secreted
Domain	Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Neurotoxin Protease Toxin
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	inhibition of neurotransmitter uptake Inferred from electronic annotation. Source: InterPro neurotransmitter secretion Traceable author statement. Source: Reactome pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Traceable author statement. Source: Reactome endocytic vesicle membrane Traceable author statement. Source: Reactome host cell cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell host cell junction Inferred from electronic annotation. Source: UniProtKB-KW host cell presynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular function	metalloendopeptidase activity Traceable author statement. Source: Reactome toxin receptor binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.4

Chain

2 – 422

421

Botulinum neurotoxin E light chain

PRO_0000029221

Chain

423 – 1251

829

Botulinum neurotoxin E heavy chain

PRO_0000029222

Sites

Active site

213

1

By similarity

Metal binding

212

1

Zinc; catalytic By similarity

Metal binding

216

1

Zinc; catalytic By similarity

Amino acid modifications

Disulfide bond

412 ↔ 426

Interchain (between light and heavy chains) Probable

Experimental info

Sequence conflict

177

1

R → G in CAA44558. Ref.2

Sequence conflict

198

1

C → S Ref.2

Sequence conflict

198

1

C → S Ref.3

Sequence conflict

340

1

R → A in CAA44558. Ref.2

Sequence conflict

773

1

I → L Ref.2

Sequence conflict

773

1

I → L Ref.6

Sequence conflict

963 – 964

2

FE → LQ Ref.2

Sequence conflict

963 – 964

2

FE → LQ Ref.6

Sequence conflict

967

1

R → A Ref.2

Sequence conflict

967

1

R → A Ref.6

Sequence conflict

1195

1

N → NN in CAA44558. Ref.2

Secondary structure

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1251

Helix Strand Turn

Details...

Beta strand

15 – 22

8

Beta strand

30 – 36

7

Beta strand

39 – 45

7

Helix

52 – 55

4

Turn

61 – 64

4

Turn

71 – 74

4

Helix

77 – 94

18

Helix

98 – 108

11

Turn

128 – 130

3

Beta strand

132 – 135

4

Beta strand

141 – 144

4

Beta strand

147 – 152

6

Beta strand

161 – 164

4

Helix

168 – 170

3

Helix

173 – 175

3

Beta strand

176 – 178

3

Beta strand

182 – 185

4

Beta strand

190 – 195

6

Beta strand

201 – 203

3

Helix

206 – 221

16

Turn

226 – 230

5

Beta strand

231 – 233

3

Helix

249 – 255

7

Helix

257 – 262

6

Helix

265 – 287

23

Helix

294 – 296

3

Helix

297 – 306

10

Beta strand

309 – 311

3

Beta strand

317 – 319

3

Helix

321 – 332

12

Helix

336 – 343

8

Beta strand

357 – 361

5

Turn

366 – 368

3

Turn

371 – 373

3

Helix

378 – 387

10

Turn

389 – 391

3

Helix

393 – 395

3

Turn

400 – 403

4

Helix

404 – 407

4

Beta strand

408 – 410

3

Sequences

	Sequence		Length	Mass (Da)
	Q00496 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: B05AA65FF1B30362	FASTA	1,251	143,844
	10 20 30 40 50 60 MPKINSFNYN DPVNDRTILY IKPGGCQEFY KSFNIMKNIW IIPERNVIGT TPQDFHPPTS 70 80 90 100 110 120 LKNGDSSYYD PNYLQSDEEK DRFLKIVTKI FNRINNNLSG GILLEELSKA NPYLGNDNTP 130 140 150 160 170 180 DNQFHIGDAS AVEIKFSNGS QDILLPNVII MGAEPDLFET NSSNISLRNN YMPSNHRFGS 190 200 210 220 230 240 IAIVTFSPEY SFRFNDNCMN EFIQDPALTL MHELIHSLHG LYGAKGITTK YTITQKQNPL 250 260 270 280 290 300 ITNIRGTNIE EFLTFGGTDL NIITSAQSND IYTNLLADYK KIASKLSKVQ VSNPLLNPYK 310 320 330 340 350 360 DVFEAKYGLD KDASGIYSVN INKFNDIFKK LYSFTEFDLR TKFQVKCRQT YIGQYKYFKL 370 380 390 400 410 420 SNLLNDSIYN ISEGYNINNL KVNFRGQNAN LNPRIITPIT GRGLVKKIIR FCKNIVSVKG 430 440 450 460 470 480 IRKSICIEIN NGELFFVASE NSYNDDNINT PKEIDDTVTS NNNYENDLDQ VILNFNSESA 490 500 510 520 530 540 PGLSDEKLNL TIQNDAYIPK YDSNGTSDIE QHDVNELNVF FYLDAQKVPE GENNVNLTSS 550 560 570 580 590 600 IDTALLEQPK IYTFFSSEFI NNVNKPVQAA LFVSWIQQVL VDFTTEANQK STVDKIADIS 610 620 630 640 650 660 IVVPYIGLAL NIGNEAQKGN FKDALELLGA GILLEFEPEL LIPTILVFTI KSFLGSSDNK 670 680 690 700 710 720 NKVIKAINNA LKERDEKWKE VYSFIVSNWM TKINTQFNKR KEQMYQALQN QVNAIKTIIE 730 740 750 760 770 780 SKYNSYTLEE KNELTNKYDI KQIENELNQK VSIAMNNIDR FLTESSISYL MKIINEVKIN 790 800 810 820 830 840 KLREYDENVK TYLLNYIIQH GSILGESQQE LNSMVTDTLN NSIPFKLSSY TDDKILISYF 850 860 870 880 890 900 NKFFKRIKSS SVLNMRYKND KYVDTSGYDS NININGDVYK YPTNKNQFGI YNDKLSEVNI 910 920 930 940 950 960 SQNDYIIYDN KYKNFSISFW VRIPNYDNKI VNVNNEYTII NCMRDNNSGW KVSLNHNEII 970 980 990 1000 1010 1020 WTFEDNRGIN QKLAFNYGNA NGISDYINKW IFVTITNDRL GDSKLYINGN LIDQKSILNL 1030 1040 1050 1060 1070 1080 GNIHVSDNIL FKIVNCSYTR YIGIRYFNIF DKELDETEIQ TLYSNEPNTN ILKDFWGNYL 1090 1100 1110 1120 1130 1140 LYDKEYYLLN VLKPNNFIDR RKDSTLSINN IRSTILLANR LYSGIKVKIQ RVNNSSTNDN 1150 1160 1170 1180 1190 1200 LVRKNDQVYI NFVASKTHLF PLYADTATTN KEKTIKISSS GNRFNQVVVM NSVGNCTMNF 1210 1220 1230 1240 1250 KNNNGNNIGL LGFKADTVVA STWYYTHMRD HTNSNGCFWN FISEEHGWQE K

References

[1]	"Sequences of the botulinal neurotoxin E derived from Clostridium botulinum type E (strain Beluga) and Clostridium butyricum (strains ATCC 43181 and ATCC 43755)." Poulet S., Hauser D., Quanz M., Niemann H., Popoff M.R. Biochem. Biophys. Res. Commun. 183:107-113(1992) [PubMed: 1543481] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Type E / Beluga.
[2]	"The complete amino acid sequence of the Clostridium botulinum type-E neurotoxin, derived by nucleotide-sequence analysis of the encoding gene." Whelan S.M., Elmore M.J., Bodsworth N.J., Atkinson T., Minton N.P. Eur. J. Biochem. 204:657-667(1992) [PubMed: 1541280] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The complete sequence of botulinum neurotoxin type A and comparison with other clostridial neurotoxins." Binz T., Kurazono H., Wille M., Frevert J., Wernars K., Niemann H. J. Biol. Chem. 265:9153-9158(1990) [PubMed: 2160960] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-252.
[4]	"Partial amino acid sequences of botulinum neurotoxins types B and E." Schmidt J.J., Sathyamoorthy V., Dasgupta B.R. Arch. Biochem. Biophys. 238:544-548(1985) [PubMed: 3888113] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-14.
[5]	"Botulinum neurotoxin type E fragmented with endoproteinase Lys-C reveals the site trypsin nicks and homology with tetanus neurotoxin." Gimenez J.A., Dasgupta B.R. Biochimie 72:213-217(1990) [PubMed: 2116911] [Abstract] Cited for: PROTEIN SEQUENCE OF 420-427.
[6]	"Gene probes for identification of the botulinal neurotoxin gene and specific identification of neurotoxin types B, E, and F." Campbell K.D., Collins M.D., East A.K. J. Clin. Microbiol. 31:2255-2262(1993) [PubMed: 8408542] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 616-982. Strain: Type E / Hazen 36208.
[7]	"Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds." Schiavo G., Santtuci A., Dasgupta B.R., Mehta P.P., Jontes J., Benfenati F., Wilson M.C., Montecucco C. FEBS Lett. 335:99-103(1993) [PubMed: 8243676] [Abstract] Cited for: IDENTIFICATION OF SUBSTRATE.
[8]	"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: 8294407] [Abstract] Cited for: IDENTIFICATION OF SUBSTRATE.
+	Additional computationally mapped references.

Web resources

BotDB - A Database Resource for Clostridial Neurotoxins

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X62089 Genomic DNA. Translation: CAA43999.1.
X62683 Genomic DNA. Translation: CAA44558.1.
X70815 Genomic DNA. Translation: CAA50146.1.

PIR

S08575.
S21178.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T3A	X-ray	2.16	A/B	2-422	[»]
1T3C	X-ray	1.90	A/B	2-422	[»]
1ZKW	X-ray	2.17	A/B	2-421	[»]
1ZKX	X-ray	2.52	A/B	2-421	[»]
1ZL5	X-ray	2.60	A/B	2-421	[»]
1ZL6	X-ray	2.40	A/B	2-421	[»]
1ZN3	X-ray	2.60	A/B	2-421	[»]
3FFZ	X-ray	2.65	A/B	1-1251	[»]

ProteinModelPortal

Q00496.

SMR

Q00496. Positions 2-412.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46083N.

Protein family/group databases

MEROPS

M27.002.

TCDB

1.C.8.1.3. botulinum and tetanus toxin (BTT) family.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Enzyme and pathway databases

Pathway_Interaction_DB

botulinumtoxinpathway. Effects of Botulinum toxin.

Reactome

REACT_13685. Neuronal System.

Family and domain databases

InterPro

IPR008985. ConA-like_lec_gl.
IPR013320. ConA-like_subgrp.
IPR011065. Kunitz_inhibitor_ST1-like.
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.

SUPFAM

SSF49899. ConA_like_lec_gl. 1 hit.
SSF50386. Kunitz_like. 1 hit.

PROSITE

PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

BXE_CLOBO

Accession

Primary (citable) accession number: Q00496
Secondary accession number(s): Q45862

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	January 23, 2007
Last modified:	November 16, 2011
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program