Reviewed, UniProtKB/Swiss-Prot P18640 (BXC1_CLOBO)

Names and origin

Protein names	Recommended name:     Botulinum neurotoxin type C1       Short name=BoNT/C1     EC=3.4.24.69 Alternative name(s):     Bontoxilysin-C1 Cleaved into the following 2 chains:     1- Recommended name:             Botulinum neurotoxin C1 light chain     2- Recommended name:             Botulinum neurotoxin C1 heavy chain
Organism	Clostridium botulinum
Taxonomic identifier	1491 [NCBI]
Taxonomic lineage	Bacteria › Firmicutes › Clostridia › Clostridiales › Clostridiaceae › Clostridium

Protein attributes

Sequence length	1291 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 cleaves syntaxin.
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 C1 light chain: Secreted. Host cytoplasm › host cytosol. Botulinum neurotoxin C1 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. Botulinum type C1 neurotoxin is synthesized by C strains of C.botulinum which carry the appropriate bacteriophage.
Sequence similarities	Belongs to the peptidase M27 family.

Ontologies

Keywords
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 pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from Experiment. Source: Reactome endocytic vesicle membrane Inferred from Experiment. Source: Reactome host cell cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell host cell synapse Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metalloendopeptidase activity Inferred from Experiment. Source: Reactome 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

Chain

2 – 449

448

Botulinum neurotoxin C1 light chain

PRO_0000029217

Chain

450 – 1291

842

Botulinum neurotoxin C1 heavy chain

PRO_0000029218

Sites

Active site

230

1

By similarity

Metal binding

229

1

Zinc; catalytic By similarity

Metal binding

233

1

Zinc; catalytic By similarity

Amino acid modifications

Disulfide bond

437 ↔ 453

Interchain (between light and heavy chains) Probable

Experimental info

Sequence conflict

85

1

P → T in CAA47060. Ref.2

Sequence conflict

85

1

P → T in CAA51313. Ref.2

Sequence conflict

85

1

P → T in BAA14235. Ref.2

Sequence conflict

85

1

P → T in CAA44263. Ref.2

Secondary structure

1

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1291

Helix Strand Turn

Details...

Beta strand

16 – 23

8

Beta strand

34 – 40

7

Beta strand

43 – 46

4

Beta strand

53 – 55

3

Turn

74 – 77

4

Helix

80 – 97

18

Helix

101 – 112

12

Beta strand

126 – 128

3

Beta strand

134 – 141

8

Beta strand

143 – 152

10

Beta strand

155 – 159

5

Beta strand

169 – 171

3

Helix

181 – 183

3

Beta strand

184 – 186

3

Beta strand

190 – 193

4

Beta strand

201 – 207

7

Helix

223 – 238

16

Beta strand

248 – 253

6

Beta strand

256 – 258

3

Beta strand

260 – 266

7

Helix

267 – 273

7

Helix

275 – 280

6

Helix

283 – 304

22

Beta strand

309 – 312

4

Helix

313 – 318

6

Helix

319 – 330

12

Helix

344 – 356

13

Helix

360 – 366

7

Beta strand

372 – 374

3

Turn

390 – 392

3

Turn

395 – 397

3

Helix

402 – 404

3

Helix

411 – 413

3

Turn

415 – 417

3

Sequences

	Sequence		Length	Mass (Da)
	P18640-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 31F1405E2141FB16	FASTA	1,291	148,866
	10 20 30 40 50 60 MPITINNFNY SDPVDNKNIL YLDTHLNTLA NEPEKAFRIT GNIWVIPDRF SRNSNPNLNK 70 80 90 100 110 120 PPRVTSPKSG YYDPNYLSTD SDKDPFLKEI IKLFKRINSR EIGEELIYRL STDIPFPGNN 130 140 150 160 170 180 NTPINTFDFD VDFNSVDVKT RQGNNWVKTG SINPSVIITG PRENIIDPET STFKLTNNTF 190 200 210 220 230 240 AAQEGFGALS IISISPRFML TYSNATNDVG EGRFSKSEFC MDPILILMHE LNHAMHNLYG 250 260 270 280 290 300 IAIPNDQTIS SVTSNIFYSQ YNVKLEYAEI YAFGGPTIDL IPKSARKYFE EKALDYYRSI 310 320 330 340 350 360 AKRLNSITTA NPSSFNKYIG EYKQKLIRKY RFVVESSGEV TVNRNKFVEL YNELTQIFTE 370 380 390 400 410 420 FNYAKIYNVQ NRKIYLSNVY TPVTANILDD NVYDIQNGFN IPKSNLNVLF MGQNLSRNPA 430 440 450 460 470 480 LRKVNPENML YLFTKFCHKA IDGRSLYNKT LDCRELLVKN TDLPFIGDIS DVKTDIFLRK 490 500 510 520 530 540 DINEETEVIY YPDNVSVDQV ILSKNTSEHG QLDLLYPSID SESEILPGEN QVFYDNRTQN 550 560 570 580 590 600 VDYLNSYYYL ESQKLSDNVE DFTFTRSIEE ALDNSAKVYT YFPTLANKVN AGVQGGLFLM 610 620 630 640 650 660 WANDVVEDFT TNILRKDTLD KISDVSAIIP YIGPALNISN SVRRGNFTEA FAVTGVTILL 670 680 690 700 710 720 EAFPEFTIPA LGAFVIYSKV QERNEIIKTI DNCLEQRIKR WKDSYEWMMG TWLSRIITQF 730 740 750 760 770 780 NNISYQMYDS LNYQAGAIKA KIDLEYKKYS GSDKENIKSQ VENLKNSLDV KISEAMNNIN 790 800 810 820 830 840 KFIRECSVTY LFKNMLPKVI DELNEFDRNT KAKLINLIDS HNIILVGEVD KLKAKVNNSF 850 860 870 880 890 900 QNTIPFNIFS YTNNSLLKDI INEYFNNIND SKILSLQNRK NTLVDTSGYN AEVSEEGDVQ 910 920 930 940 950 960 LNPIFPFDFK LGSSGEDRGK VIVTQNENIV YNSMYESFSI SFWIRINKWV SNLPGYTIID 970 980 990 1000 1010 1020 SVKNNSGWSI GIISNFLVFT LKQNEDSEQS INFSYDISNN APGYNKWFFV TVTNNMMGNM 1030 1040 1050 1060 1070 1080 KIYINGKLID TIKVKELTGI NFSKTITFEI NKIPDTGLIT SDSDNINMWI RDFYIFAKEL 1090 1100 1110 1120 1130 1140 DGKDINILFN SLQYTNVVKD YWGNDLRYNK EYYMVNIDYL NRYMYANSRQ IVFNTRRNNN 1150 1160 1170 1180 1190 1200 DFNEGYKIII KRIRGNTNDT RVRGGDILYF DMTINNKAYN LFMKNETMYA DNHSTEDIYA 1210 1220 1230 1240 1250 1260 IGLREQTKDI NDNIIFQIQP MNNTYYYASQ IFKSNFNGEN ISGICSIGTY RFRLGGDWYR 1270 1280 1290 HNYLVPTVKQ GNYASLLEST STHWGFVPVS E

References

[1]	"Nucleotide sequence of Clostridium botulinum C1 neurotoxin." Hauser D., Eklund M.W., Kurazona H., Binz T., Niemann H., Gill D.M., Boquet P., Popoff M.R. Nucleic Acids Res. 18:4924-4924(1990) [PubMed: 2204031] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The complete nucleotide sequence of the gene coding for botulinum type C1 toxin in the C-ST phage genome." Kimura K., Fujii N., Tsuzuki K., Murakami T., Indoh T., Yokosawa N., Takeshi K., Syuto B., Oguma K. Biochem. Biophys. Res. Commun. 171:1304-1311(1990) [PubMed: 2222445] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Type C / Stockholm.
[3]	"Establishment of a monoclonal antibody recognizing an antigenic site common to Clostridium botulinum type B, C1, D, and E toxins and tetanus toxin." Tsuzuki K., Yokosawa N., Syuto B., Ohishi I., Fujii N., Kimura K., Oguma K. Infect. Immun. 56:898-902(1988) [PubMed: 2450068] [Abstract] Cited for: PROTEIN SEQUENCE OF 3-26. Strain: Type C / Stockholm.
[4]	"Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin." Blasi J., Chapman E.R., Yamasaki S., Binz T., Niemann H., Jahn R. EMBO J. 12:4821-4828(1993) [PubMed: 7901002] [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

X66433 Genomic DNA. Translation: CAA47060.1.
X72793 Genomic DNA. Translation: CAA51313.1.
X53751 Genomic DNA. Translation: CAA37780.1.
D90210 Genomic DNA. Translation: BAA14235.1.
X62389 Genomic DNA. Translation: CAA44263.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QN0	X-ray	1.75	A	1-430	[»]
3DEB	X-ray	1.95	A	1-430	[»]

ModBase

Search...

Enzyme and pathway databases

BRENDA

3.4.24.69. 19133.

Pathway_Interaction_DB

botulinumtoxinpathway. Effects of Botulinum toxin.

Reactome

REACT_11184. Botulinum neurotoxicity.

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.

PROSITE

PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

BXC1_CLOBO

Accession

Primary (citable) accession number: P18640

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

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