Botulinum neurotoxin type D precursor

Preferred order of sections

Names and origin

Protein names

Recommended name:
Botulinum neurotoxin type D
Short name=BoNT/D
EC=3.4.24.69

Alternative name(s):
Bontoxilysin-D

Cleaved into the following 2 chains:

Botulinum neurotoxin D light chain
Botulinum neurotoxin D heavy chain

Gene names

Name:

botD

Organism

Clostridium botulinum

Taxonomic identifier

1491 [NCBI]

Taxonomic lineage

Bacteria › Firmicutes › Clostridia › Clostridiales › Clostridiaceae › Clostridium

Protein attributes

Sequence length	1276 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 the '60-Lys-\|-Leu-61' bond of synaptobrevins-1 and -2.
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 D light chain: Secreted. Host cytoplasm › host cytosol. Botulinum neurotoxin D 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 D neurotoxin is synthesized by D strains of C.botulinum which carry the appropriate bacteriophage.
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 extracellular region 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 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

Chain

1 – 442

442

Botulinum neurotoxin D light chain

PRO_0000029219

Chain

443 – 1276

834

Botulinum neurotoxin D heavy chain

PRO_0000029220

Sites

Active site

230

1

By similarity

Metal binding

229

1

Zinc; catalytic

Metal binding

233

1

Zinc; catalytic

Metal binding

269

1

Zinc; catalytic

Amino acid modifications

Disulfide bond

437 ↔ 450

Interchain (between light and heavy chains) Probable

Natural variations

Natural variant

15 – 16

2

ND → PV in strain: D-SA.

Natural variant

17 – 18

2

ND → LQ in strain: D-1873.

Natural variant

452

1

K → Q in strain: D-SA.

Natural variant

457

1

R → F in strain: D-1873.

Natural variant

457

1

R → T in strain: D-SA.

Natural variant

462

1

A → D in strain: D-1873.

Natural variant

489

1

K → N in strain: CB16.

Natural variant

644

1

N → K in strain: CB16.

Natural variant

1122

1

Q → R in strain: CB16.

Secondary structure

1

.

1276

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P19321 [UniParc].

Last modified November 1, 1990. Version 1.
Checksum: C1EC50F46C8233E2
Show »

FASTA

1,276

146,872

        10         20         30         40         50         60 
MTWPVKDFNY SDPVNDNDIL YLRIPQNKLI TTPVKAFMIT QNIWVIPERF SSDTNPSLSK 

        70         80         90        100        110        120 
PPRPTSKYQS YYDPSYLSTD EQKDTFLKGI IKLFKRINER DIGKKLINYL VVGSPFMGDS 

       130        140        150        160        170        180 
STPEDTFDFT RHTTNIAVEK FENGSWKVTN IITPSVLIFG PLPNILDYTA SLTLQGQQSN 

       190        200        210        220        230        240 
PSFEGFGTLS ILKVAPEFLL TFSDVTSNQS SAVLGKSIFC MDPVIALMHE LTHSLHQLYG 

       250        260        270        280        290        300 
INIPSDKRIR PQVSEGFFSQ DGPNVQFEEL YTFGGLDVEI IPQIERSQLR EKALGHYKDI 

       310        320        330        340        350        360 
AKRLNNINKT IPSSWISNID KYKKIFSEKY NFDKDNTGNF VVNIDKFNSL YSDLTNVMSE 

       370        380        390        400        410        420 
VVYSSQYNVK NRTHYFSRHY LPVFANILDD NIYTIRDGFN LTNKGFNIEN SGQNIERNPA 

       430        440        450        460        470        480 
LQKLSSESVV DLFTKVCLRL TKNSRDDSTC IKVKNNRLPY VADKDSISQE IFENKIITDE 

       490        500        510        520        530        540 
TNVQNYSDKF SLDESILDGQ VPINPEIVDP LLPNVNMEPL NLPGEEIVFY DDITKYVDYL 

       550        560        570        580        590        600 
NSYYYLESQK LSNNVENITL TTSVEEALGY SNKIYTFLPS LAEKVNKGVQ AGLFLNWANE 

       610        620        630        640        650        660 
VVEDFTTNIM KKDTLDKISD VSVIIPYIGP ALNIGNSALR GNFNQAFATA GVAFLLEGFP 

       670        680        690        700        710        720 
EFTIPALGVF TFYSSIQERE KIIKTIENCL EQRVKRWKDS YQWMVSNWLS RITTQFNHIN 

       730        740        750        760        770        780 
YQMYDSLSYQ ADAIKAKIDL EYKKYSGSDK ENIKSQVENL KNSLDVKISE AMNNINKFIR 

       790        800        810        820        830        840 
ECSVTYLFKN MLPKVIDELN KFDLRTKTEL INLIDSHNII LVGEVDRLKA KVNESFENTM 

       850        860        870        880        890        900 
PFNIFSYTNN SLLKDIINEY FNSINDSKIL SLQNKKNALV DTSGYNAEVR VGDNVQLNTI 

       910        920        930        940        950        960 
YTNDFKLSSS GDKIIVNLNN NILYSAIYEN SSVSFWIKIS KDLTNSHNEY TIINSIEQNS 

       970        980        990       1000       1010       1020 
GWKLCIRNGN IEWILQDVNR KYKSLIFDYS ESLSHTGYTN KWFFVTITNN IMGYMKLYIN 

      1030       1040       1050       1060       1070       1080 
GELKQSQKIE DLDEVKLDKT IVFGIDENID ENQMLWIRDF NIFSKELSNE DINIVYEGQI 

      1090       1100       1110       1120       1130       1140 
LRNVIKDYWG NPLKFDTEYY IINDNYIDRY IAPESNVLVL VQYPDRSKLY TGNPITIKSV 

      1150       1160       1170       1180       1190       1200 
SDKNPYSRIL NGDNIILHML YNSRKYMIIR DTDTIYATQG GECSQNCVYA LKLQSNLGNY 

      1210       1220       1230       1240       1250       1260 
GIGIFSIKNI VSKNKYCSQI FSSFRENTML LADIYKPWRF SFKNAYTPVA VTNYETKLLS 

      1270 
TSSFWKFISR DPGWVE

« Hide

References

[1]	"Nucleotide sequence of the gene encoding Clostridium botulinum neurotoxin type D." Binz T., Kurazono H., Popoff M.R., Eklund M.W., Sakaguchi G., Kozaki S., Krieglstein K., Henschen A., Gill D.M., Niemann H. Nucleic Acids Res. 18:5556-5556(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Type D / BVD/-3.
[2]	"The complete amino acid sequence of the Clostridium botulinum type D neurotoxin, deduced by nucleotide sequence analysis of the encoding phage d-16 phi genome." Sunagawa H., Ohyama T., Watanabe T., Inoue K. J. Vet. Med. Sci. 54:905-913(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Type D / CB-16.
[3]	"Molecular diversity of neurotoxins from Clostridium botulinum type D strains." Moriishi K., Syuto B., Kubo S., Oguma K. Infect. Immun. 57:2886-2891(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE. Strain: Type D / D-1873 and Type D / South African.
[4]	"Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin." Yamasaki S., Baumeister A., Binz T., Blasi J., Link E., Cornille F., Roques B., Fykse E.M., Suedhof T.C., Jahn R., Niemann H. J. Biol. Chem. 269:12764-12772(1994) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF SUBSTRATE.
[5]	"Structure of botulinum neurotoxin type D light chain at 1.65 A resolution: repercussions for VAMP-2 substrate specificity." Arndt J.W., Chai Q., Christian T., Stevens R.C. Biochemistry 45:3255-3262(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 1-436 IN COMPLEX WITH ZINC IONS.
+	Additional computationally mapped references.

Web resources

BotDB - A Database Resource for Clostridial Neurotoxins

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X54254 Genomic DNA. Translation: CAA38175.1.
S49407 Genomic DNA. Translation: AAB24244.1.

PIR

S11455.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FPQ	X-ray	1.65	A	1-436	[»]
3N7J	X-ray	2.00	A	862-1276	[»]
3OBR	X-ray	1.72	A	863-1276	[»]
3OBT	X-ray	2.00	A	863-1276	[»]
3OGG	X-ray	1.65	A	863-1276	[»]
3RMX	X-ray	2.75	A/B/C/D	862-1276	[»]
3RMY	X-ray	2.30	A/B/C/D	862-1276	[»]

ProteinModelPortal

P19321.

ModBase

Search...

Protein family/group databases

MEROPS

M27.002.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Enzyme and pathway databases

Pathway_Interaction_DB

botulinumtoxinpathway. Effects of Botulinum toxin.

Reactome

REACT_116125. Disease.
REACT_13685. Neuronal System.

Family and domain databases

Gene3D

2.60.120.200. 1 hit.
3.90.1240.10. 1 hit.

InterPro

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]

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...

Other

EvolutionaryTrace

P19321.

Entry information

Entry name

BXD_CLOBO

Accession

Primary (citable) accession number: P19321

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	April 3, 2013
This is version 121 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families