BXB_CLOBK
ID BXB_CLOBK Reviewed; 1291 AA.
AC B1INP5;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Botulinum neurotoxin type B;
DE Short=BoNT/B;
DE AltName: Full=Bontoxilysin-B;
DE Contains:
DE RecName: Full=Botulinum neurotoxin B light chain;
DE Short=LC;
DE EC=3.4.24.69;
DE Contains:
DE RecName: Full=Botulinum neurotoxin B heavy chain;
DE Short=HC;
DE Flags: Precursor;
GN Name=botB; OrderedLocusNames=CLD_A0068;
OS Clostridium botulinum (strain Okra / Type B1).
OG Plasmid pCLD.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=498213;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Okra / Type B1;
RX PubMed=18060065; DOI=10.1371/journal.pone.0001271;
RA Smith T.J., Hill K.K., Foley B.T., Detter J.C., Munk A.C., Bruce D.C.,
RA Doggett N.A., Smith L.A., Marks J.D., Xie G., Brettin T.S.;
RT "Analysis of the neurotoxin complex genes in Clostridium botulinum A1-A4
RT and B1 strains: BoNT/A3, /Ba4 and /B1 clusters are located within
RT plasmids.";
RL PLoS ONE 2:E1271-E1271(2007).
RN [2]
RP PROTEIN SEQUENCE OF 2-17 AND 442-459.
RC STRAIN=Okra / Type B1;
RX PubMed=3888113; DOI=10.1016/0003-9861(85)90198-5;
RA Schmidt J.J., Sathyamoorthy V., Dasgupta B.R.;
RT "Partial amino acid sequences of botulinum neurotoxins types B and E.";
RL Arch. Biochem. Biophys. 238:544-548(1985).
RN [3]
RP RELEASED AS SINGLE CHAIN.
RC STRAIN=Okra / Type B1;
RX PubMed=4030755; DOI=10.1016/s0021-9258(19)85105-0;
RA Sathyamoorthy V., DasGupta B.R.;
RT "Separation, purification, partial characterization and comparison of the
RT heavy and light chains of botulinum neurotoxin types A, B, and E.";
RL J. Biol. Chem. 260:10461-10466(1985).
RN [4]
RP HOST RANGE, AND EPIDEMIOLOGY.
RX PubMed=1431246; DOI=10.1093/infdis/166.6.1281;
RA Woodruff B.A., Griffin P.M., McCroskey L.M., Smart J.F., Wainwright R.B.,
RA Bryant R.G., Hutwagner L.C., Hatheway C.L.;
RT "Clinical and laboratory comparison of botulism from toxin types A, B, and
RT E in the United States, 1975-1988.";
RL J. Infect. Dis. 166:1281-1286(1992).
CC -!- FUNCTION: [Botulinum neurotoxin type B]: Botulinum toxin causes flaccid
CC paralysis by inhibiting neurotransmitter (acetylcholine) release from
CC the presynaptic membranes of nerve terminals of eukaryotic host
CC skeletal and autonomic nervous system, with frequent heart or
CC respiratory failure. Precursor of botulinum neurotoxin B which has 2
CC coreceptors; complex polysialylated gangliosides found on neural tissue
CC and specific membrane-anchored proteins found in synaptic vesicles.
CC Receptor proteins are exposed on host presynaptic cell membrane during
CC neurotransmitter release, when the toxin heavy chain (HC) binds to
CC them. Upon synaptic vesicle recycling the toxin is taken up via the
CC endocytic pathway. When the pH of the toxin-containing endosome drops a
CC structural rearrangement occurs so that the N-terminus of the HC forms
CC pores that allows the light chain (LC) to translocate into the cytosol.
CC Once in the cytosol the disulfide bond linking the 2 subunits is
CC reduced and LC cleaves its target protein on synaptic vesicles,
CC preventing their fusion with the cytoplasmic membrane and thus
CC neurotransmitter release (By similarity).
CC {ECO:0000250|UniProtKB:P10844}.
CC -!- FUNCTION: [Botulinum neurotoxin B light chain]: Has proteolytic
CC activity. After translocation into the eukaryotic host cytosol, LC
CC hydrolyzes the '76-Gln-|-Phe-77' bond in synaptobrevin-2/VAMP2,
CC blocking neurotransmitter release (By similarity).
CC {ECO:0000250|UniProtKB:P10844}.
CC -!- FUNCTION: [Botulinum neurotoxin B heavy chain]: Responsible for host
CC epithelial cell transcytosis, host nerve cell targeting and
CC translocation of light chain (LC) into host cytosol. Composed of 3
CC subdomains; the translocation domain (TD), and N-terminus and C-
CC terminus of the receptor-binding domain (RBD). The RBD is responsible
CC for the adherence of the toxin to the cell surface. It simultaneously
CC recognizes 2 coreceptors; polysialated gangliosides and host
CC synaptotagmin-1 and -2 (SYT1 and SYT2) which bind simultaneously to
CC adjacent but separate sites at the tip of the HC. The N-terminus of the
CC TD wraps an extended belt around the perimeter of the LC, protecting
CC Zn(2+) in the active site; it may also prevent premature LC
CC dissociation from the translocation channel and protect toxin prior to
CC translocation (By similarity). The TD inserts into synaptic vesicle
CC membrane to allow translocation into the host cytosol (By similarity).
CC {ECO:0000250|UniProtKB:P10844}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Limited hydrolysis of proteins of the neuroexocytosis
CC apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on
CC small molecule substrates.; EC=3.4.24.69;
CC Evidence={ECO:0000250|UniProtKB:P10844};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P10844};
CC Note=Binds 1 zinc ion per subunit (By similarity).
CC {ECO:0000250|UniProtKB:P10844};
CC -!- SUBUNIT: Heterodimer; disulfide-linked heterodimer of a light chain
CC (LC) and a heavy chain (HC). Interacts with host synaptic vesicle
CC proteins synaptotagmin-1 and -2 which serve as coreceptors with complex
CC gangliosides (By similarity). {ECO:0000250|UniProtKB:P10844}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin type B]: Secreted
CC {ECO:0000250|UniProtKB:P10844}. Host synapse, host presynaptic cell
CC membrane {ECO:0000250|UniProtKB:P10844}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin B light chain]: Secreted
CC {ECO:0000250|UniProtKB:P10844}. Host cytoplasm, host cytosol
CC {ECO:0000250|UniProtKB:P10844}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin B heavy chain]: Secreted
CC {ECO:0000250|UniProtKB:P10844}. Host synapse, host presynaptic cell
CC membrane {ECO:0000250|UniProtKB:P10844}. Host cytoplasmic vesicle, host
CC secretory vesicle, host synaptic vesicle membrane
CC {ECO:0000250|UniProtKB:P0DPI0}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- DOMAIN: Botulinum neurotoxin A light chain: Has protease activity.
CC {ECO:0000250|UniProtKB:P10844}.
CC -!- DOMAIN: Botulinum neurotoxin A heavy chain: Has 3 functional domains;
CC the translocation domain (TD) and the receptor-binding domain (RBD)
CC which is further subdivided into N- and C-terminal domains (N-RBD and
CC C-RBD). The N-terminus of the TD wraps an extended belt around the
CC perimeter of the LC, protecting Zn(2+) in the active site and may be a
CC pseudosubstrate inhibitor which serves as an intramolecular chaperone
CC for the LC prior to its translocation into the host cytosol. The RBD
CC binds transiently exposed coreceptors on the host presynaptic cell
CC membrane. {ECO:0000250|UniProtKB:P0DPI0, ECO:0000250|UniProtKB:P10844}.
CC -!- MISCELLANEOUS: There are seven antigenically distinct forms of
CC botulinum neurotoxin: Types A, B, C, D, E, F, and G; new subtypes are
CC quite frequent.
CC -!- MISCELLANEOUS: Botulism poisoning is usually food-borne, either by
CC ingesting toxin or bacterial-contaminated food, or less frequently by
CC inhalation poisoning. In both cases the neurotoxin binds to the apical
CC surface of epithelial cells in the gut or airway. Toxin undergoes
CC receptor-mediated endocytosis (using a different receptor than on
CC target nerve cells), transcytosis across the epithelial cells and
CC release into the general circulation. Once in the general circulation
CC it binds to its target cells. {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- MISCELLANEOUS: Types A, B and E are the most frequent cause of adult
CC human foodborne botulism; type A is the most severe, while type E has
CC the shortest incubation period (PubMed:1431246).
CC {ECO:0000269|PubMed:1431246}.
CC -!- MISCELLANEOUS: Neurotoxin type B is released from bacteria mostly as a
CC single chain and cleaved by host proteases into the active dichain
CC (PubMed:4030755). {ECO:0000269|PubMed:4030755}.
CC -!- SIMILARITY: Belongs to the peptidase M27 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=BotDB - A Database Resource for Clostridial
CC Neurotoxins;
CC URL="https://botdb.abcc.ncifcrf.gov/";
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DR EMBL; CP000940; ACA46990.1; -; Genomic_DNA.
DR PIR; A48940; A48940.
DR RefSeq; WP_012291519.1; NC_010379.1.
DR AlphaFoldDB; B1INP5; -.
DR SMR; B1INP5; -.
DR DIP; DIP-61160N; -.
DR IntAct; B1INP5; 1.
DR MEROPS; M27.002; -.
DR ABCD; B1INP5; 21 sequenced antibodies.
DR EnsemblBacteria; ACA46990; ACA46990; CLD_A0068.
DR KEGG; cbb:CLD_A0068; -.
DR HOGENOM; CLU_262205_0_0_9; -.
DR OMA; VSFWIRI; -.
DR BRENDA; 3.4.24.69; 1462.
DR Proteomes; UP000008541; Plasmid pCLD.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044161; C:host cell cytoplasmic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0044156; C:host cell junction; IEA:UniProtKB-KW.
DR GO; GO:0044231; C:host cell presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0008320; F:protein transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0046929; P:negative regulation of neurotransmitter secretion; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1120.10; -; 1.
DR InterPro; IPR000395; Bot/tetX_LC.
DR InterPro; IPR036248; Clostridium_toxin_transloc.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR011065; Kunitz_inhibitor_STI-like_sf.
DR InterPro; IPR013104; Toxin_rcpt-bd_C.
DR InterPro; IPR012928; Toxin_rcpt-bd_N.
DR InterPro; IPR012500; Toxin_trans.
DR Pfam; PF01742; Peptidase_M27; 1.
DR Pfam; PF07951; Toxin_R_bind_C; 1.
DR Pfam; PF07953; Toxin_R_bind_N; 1.
DR Pfam; PF07952; Toxin_trans; 1.
DR PRINTS; PR00760; BONTOXILYSIN.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF50386; SSF50386; 1.
DR SUPFAM; SSF58091; SSF58091; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Host cell membrane;
KW Host cytoplasm; Host cytoplasmic vesicle; Host membrane; Host synapse;
KW Hydrolase; Lipid-binding; Membrane; Metal-binding; Metalloprotease;
KW Neurotoxin; Plasmid; Protease; Secreted; Toxin; Transmembrane; Virulence;
KW Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:3888113"
FT CHAIN 2..1291
FT /note="Botulinum neurotoxin type B"
FT /id="PRO_0000444919"
FT CHAIN 2..441
FT /note="Botulinum neurotoxin B light chain"
FT /id="PRO_0000337075"
FT CHAIN 442..1291
FT /note="Botulinum neurotoxin B heavy chain"
FT /id="PRO_0000337076"
FT REGION 442..857
FT /note="Translocation domain (TD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 481..532
FT /note="Belt"
FT /evidence="ECO:0000250|UniProtKB:P10844"
FT REGION 858..1079
FT /note="N-terminus of receptor binding domain (N-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 1080..1291
FT /note="C-terminus of receptor binding domain (C-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT MOTIF 1260..1263
FT /note="Host ganglioside-binding motif"
FT /evidence="ECO:0000250|UniProtKB:P10844"
FT ACT_SITE 231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 230
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P10844,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 234
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P10844,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P10844"
FT DISULFID 437..446
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000250|UniProtKB:P10844"
SQ SEQUENCE 1291 AA; 150803 MW; 921DE5C518140DBD CRC64;
MPVTINNFNY NDPIDNNNII MMEPPFARGT GRYYKAFKIT DRIWIIPERY TFGYKPEDFN
KSSGIFNRDV CEYYDPDYLN TNDKKNIFLQ TMIKLFNRIK SKPLGEKLLE MIINGIPYLG
DRRVPLEEFN TNIASVTVNK LISNPGEVER KKGIFANLII FGPGPVLNEN ETIDIGIQNH
FASREGFGGI MQMKFCPEYV SVFNNVQENK GASIFNRRGY FSDPALILMH ELIHVLHGLY
GIKVDDLPIV PNEKKFFMQS TDAIQAEELY TFGGQDPSII TPSTDKSIYD KVLQNFRGIV
DRLNKVLVCI SDPNININIY KNKFKDKYKF VEDSEGKYSI DVESFDKLYK SLMFGFTETN
IAENYKIKTR ASYFSDSLPP VKIKNLLDNE IYTIEEGFNI SDKDMEKEYR GQNKAINKQA
YEEISKEHLA VYKIQMCKSV KAPGICIDVD NEDLFFIADK NSFSDDLSKN ERIEYNTQSN
YIENDFPINE LILDTDLISK IELPSENTES LTDFNVDVPV YEKQPAIKKI FTDENTIFQY
LYSQTFPLDI RDISLTSSFD DALLFSNKVY SFFSMDYIKT ANKVVEAGLF AGWVKQIVND
FVIEANKSNT MDKIADISLI VPYIGLALNV GNETAKGNFE NAFEIAGASI LLEFIPELLI
PVVGAFLLES YIDNKNKIIK TIDNALTKRN EKWSDMYGLI VAQWLSTVNT QFYTIKEGMY
KALNYQAQAL EEIIKYRYNI YSEKEKSNIN IDFNDINSKL NEGINQAIDN INNFINGCSV
SYLMKKMIPL AVEKLLDFDN TLKKNLLNYI DENKLYLIGS AEYEKSKVNK YLKTIMPFDL
SIYTNDTILI EMFNKYNSEI LNNIILNLRY KDNNLIDLSG YGAKVEVYDG VELNDKNQFK
LTSSANSKIR VTQNQNIIFN SVFLDFSVSF WIRIPKYKND GIQNYIHNEY TIINCMKNNS
GWKISIRGNR IIWTLIDING KTKSVFFEYN IREDISEYIN RWFFVTITNN LNNAKIYING
KLESNTDIKD IREVIANGEI IFKLDGDIDR TQFIWMKYFS IFNTELSQSN IEERYKIQSY
SEYLKDFWGN PLMYNKEYYM FNAGNKNSYI KLKKDSPVGE ILTRSKYNQN SKYINYRDLY
IGEKFIIRRK SNSQSINDDI VRKEDYIYLD FFNLNQEWRV YTYKYFKKEE EKLFLAPISD
SDEFYNTIQI KEYDEQPTYS CQLLFKKDEE STDEIGLIGI HRFYESGIVF EEYKDYFCIS
KWYLKEVKRK PYNLKLGCNW QFIPKDEGWT E
