BXE_CLOBU
ID BXE_CLOBU Reviewed; 1251 AA.
AC P30995;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Botulinum neurotoxin type E;
DE Short=BoNT/E;
DE AltName: Full=Bontoxilysin-E;
DE Contains:
DE RecName: Full=Botulinum neurotoxin E light chain;
DE Short=LC;
DE EC=3.4.24.69;
DE Contains:
DE RecName: Full=Botulinum neurotoxin E heavy chain;
DE Short=HC;
DE Flags: Precursor;
OS Clostridium butyricum.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=1492;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 43181, and ATCC 43755;
RX PubMed=1543481; DOI=10.1016/0006-291x(92)91615-w;
RA Poulet S., Hauser D., Quanz M., Niemann H., Popoff M.R.;
RT "Sequences of the botulinal neurotoxin E derived from Clostridium botulinum
RT type E (strain Beluga) and Clostridium butyricum (strains ATCC 43181 and
RT ATCC 43755).";
RL Biochem. Biophys. Res. Commun. 183:107-113(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-252.
RC STRAIN=BL6340;
RX PubMed=2033376; DOI=10.1099/00221287-137-3-519;
RA Fujii N., Kimura K., Murakami T., Indoh T., Tsuzuki K., Yokosawa N.,
RA Yashiki T., Oguma K.;
RT "Cloning of a DNA fragment encoding the 5'-terminus of the botulinum type E
RT toxin gene from Clostridium butyricum strain BL6340.";
RL J. Gen. Microbiol. 137:519-525(1991).
RN [3]
RP PROTEIN SEQUENCE OF 2-49.
RC STRAIN=5262;
RA Gimenez J., Foley J., Dasgupta B.R.;
RT "Neurotoxin type E from Clostridium botulinum and C. butyricum; partial
RT sequence and comparison.";
RL FASEB J. 2:A1750-A1750(1988).
RN [4]
RP FUNCTION (BOTULINUM NEUROTOXIN E HEAVY CHAIN), GANGLIOSIDE-BINDING, AND
RP MUTAGENESIS OF LYS-1093; LYS-1214 AND ARG-1229.
RC STRAIN=ATCC 43181, and ATCC 43755;
RX PubMed=21849494; DOI=10.1074/jbc.m111.272054;
RA Benson M.A., Fu Z., Kim J.J., Baldwin M.R.;
RT "Unique ganglioside recognition strategies for clostridial neurotoxins.";
RL J. Biol. Chem. 286:34015-34022(2011).
CC -!- FUNCTION: [Botulinum neurotoxin type E]: 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 E 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:Q00496}.
CC -!- FUNCTION: [Botulinum neurotoxin E light chain]: Has proteolytic
CC activity. After translocation into the eukaryotic host cytosol, LC
CC hydrolyzes the '180-Arg-|-Ile-181' bond in SNAP25, blocking
CC neurotransmitter release (By similarity).
CC {ECO:0000250|UniProtKB:Q00496}.
CC -!- FUNCTION: [Botulinum neurotoxin E 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; host polysialated gangliosides and the
CC receptor proteins SV2A and SV2B in close proximity on host synaptic
CC vesicles. Interaction with SV2 proteins requires SV2 glycosylation. The
CC N-terminus of the TD wraps an extended belt around the perimeter of the
CC LC, protecting Zn(2+) in the active site; it may also prevent premature
CC LC dissociation from the translocation channel and protect toxin prior
CC to translocation (By similarity). The TD inserts into synaptic vesicle
CC membrane to allow translocation into the host cytosol (By similarity).
CC Binds ganglioside GD1a in vitro (PubMed:21849494).
CC {ECO:0000250|UniProtKB:Q00496, ECO:0000269|PubMed:21849494}.
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:Q00496};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q00496};
CC Note=Binds 1 zinc ion per subunit (By similarity).
CC {ECO:0000250|UniProtKB:Q00496};
CC -!- SUBUNIT: Heterodimer; disulfide-linked heterodimer of a light chain
CC (LC) and a heavy chain (HC). The LC has the proteolytic/pharmacological
CC activity, while the N- and C-terminal of the HC mediate channel
CC formation and toxin binding, respectively. Interacts with host synaptic
CC vesicle glycoproteins SV2A and SV2B which probably serve as
CC coreceptors. {ECO:0000250|UniProtKB:Q00496}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin type E]: Secreted
CC {ECO:0000250|UniProtKB:Q00496}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin E light chain]: Secreted.
CC Host cytoplasm, host cytosol {ECO:0000250|UniProtKB:Q00496}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin E heavy chain]: Secreted.
CC Host synapse, host presynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q00496}. 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 E light chain]: Has protease activity (By
CC similarity). {ECO:0000250|UniProtKB:Q00496}.
CC -!- DOMAIN: [Botulinum neurotoxin E 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) (By similarity). In BoNT/E the domains are arranged differently
CC than BoNT/A and BoNT/B; in BoNT/E the LC and RBD are on the same side
CC of the TD and are in contact, whereas in BoNT/A and BoNT/B the LC is
CC separated from the RBD by the TD (By similarity). The putative
CC transmembrane region is closer to the receptor-binding regions in this
CC toxin, which may explain why it acts faster than BoNT/A and BoNT/B (By
CC similarity). 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 (By
CC similarity). The RBD binds transiently exposed coreceptors on the host
CC presynaptic cell membrane (By similarity).
CC {ECO:0000250|UniProtKB:Q00496}.
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: Unlike botulinum neurotoxin type A, type E is released
CC from bacteria as a single chain and cleaved by host proteases into the
CC active dichain (Probable). {ECO:0000250|UniProtKB:Q00496, ECO:0000305}.
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 (By similarity). Type E neurotoxin from
CC C.butyricum strains ATCC 43181, ATCC 43775 and BL6340 were all isolated
CC from cases of human infant botulism (PubMed:1543481, PubMed:2033376).
CC {ECO:0000250|UniProtKB:Q00496, ECO:0000269|PubMed:1543481,
CC ECO:0000269|PubMed:2033376}.
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; X62088; CAA43998.1; -; Genomic_DNA.
DR EMBL; X53180; CAA37321.1; -; Genomic_DNA.
DR PIR; JH0256; JH0256.
DR AlphaFoldDB; P30995; -.
DR SMR; P30995; -.
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; Protease; Secreted; Toxin; Transmembrane; Virulence; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.3"
FT CHAIN 2..1251
FT /note="Botulinum neurotoxin type E"
FT /id="PRO_0000444920"
FT CHAIN 2..422
FT /note="Botulinum neurotoxin E light chain"
FT /id="PRO_0000029223"
FT CHAIN 423..1251
FT /note="Botulinum neurotoxin E heavy chain"
FT /id="PRO_0000029224"
FT REGION 423..819
FT /note="Translocation domain (TD)"
FT /evidence="ECO:0000250|UniProtKB:Q00496"
FT REGION 466..515
FT /note="Belt"
FT /evidence="ECO:0000250|UniProtKB:Q00496"
FT REGION 845..1067
FT /note="N-terminus of receptor binding domain (N-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 1068..1251
FT /note="C-terminus of receptor binding domain (C-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT MOTIF 1221..1224
FT /note="Host ganglioside-binding motif"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT ACT_SITE 213
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 212
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 216
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 251
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q00496"
FT DISULFID 412..426
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0, ECO:0000305"
FT MUTAGEN 1093
FT /note="K->A,R: Wild-type binding of heavy chain to
FT ganglioside GD1a."
FT /evidence="ECO:0000269|PubMed:21849494"
FT MUTAGEN 1214
FT /note="K->A: Loss of heavy chain binding to ganglioside
FT GD1a."
FT /evidence="ECO:0000269|PubMed:21849494"
FT MUTAGEN 1214
FT /note="K->H: Significant decrease in heavy chain binding to
FT ganglioside GD1a."
FT /evidence="ECO:0000269|PubMed:21849494"
FT MUTAGEN 1229
FT /note="R->A: Wild-type binding of heavy chain to
FT ganglioside GD1a."
FT /evidence="ECO:0000269|PubMed:21849494"
FT CONFLICT 230
FT /note="K -> M (in Ref. 2; CAA37321)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1251 AA; 143397 MW; E8D7F180E9863581 CRC64;
MPTINSFNYN DPVNNRTILY IKPGGCQQFY KSFNIMKNIW IIPERNVIGT IPQDFLPPTS
LKNGDSSYYD PNYLQSDQEK DKFLKIVTKI FNRINDNLSG RILLEELSKA NPYLGNDNTP
DGDFIINDAS AVPIQFSNGS QSILLPNVII MGAEPDLFET NSSNISLRNN YMPSNHGFGS
IAIVTFSPEY SFRFKDNSMN EFIQDPALTL MHELIHSLHG LYGAKGITTK YTITQKQNPL
ITNIRGTNIE EFLTFGGTDL NIITSAQSND IYTNLLADYK KIASKLSKVQ VSNPLLNPYK
DVFEAKYGLD KDASGIYSVN INKFNDIFKK LYSFTEFDLA TKFQVKCRQT YIGQYKYFKL
SNLLNDSIYN ISEGYNINNL KVNFRGQNAN LNPRIITPIT GRGLVKKIIR FCKNIVSVKG
IRKSICIEIN NGELFFVASE NSYNDDNINT PKEIDDTVTS NNNYENDLDQ VILNFNSESA
PGLSDEKLNL TIQNDAYIPK YDSNGTSDIE QHDVNELNVF FYLDAQKVPE GENNVNLTSS
IDTALLEQPK IYTFFSSEFI NNVNKPVQAA LFVGWIQQVL VDFTTEANQK STVDKIADIS
IVVPYIGLAL NIGNEAQKGN FKDALELLGA GILLEFEPEL LIPTILVFTI KSFLGSSDNK
NKVIKAINNA LKERDEKWKE VYSFIVSNWM TKINTQFNKR KEQMYQALQN QVNALKAIIE
SKYNSYTLEE KNELTNKYDI EQIENELNQK VSIAMNNIDR FLTESSISYL MKLINEVKIN
KLREYDENVK TYLLDYIIKH GSILGESQQE LNSMVIDTLN NSIPFKLSSY TDDKILISYF
NKFFKRIKSS SVLNMRYKND KYVDTSGYDS NININGDVYK YPTNKNQFGI YNDKLSEVNI
SQNDYIIYDN KYKNFSISFW VRIPNYDNKI VNVNNEYTII NCMRDNNSGW KVSLNHNEII
WTLQDNSGIN QKLAFNYGNA NGISDYINKW IFVTITNDRL GDSKLYINGN LIDKKSILNL
GNIHVSDNIL FKIVNCSYTR YIGIRYFNIF DKELDETEIQ TLYNNEPNAN ILKDFWGNYL
LYDKEYYLLN VLKPNNFINR RTDSTLSINN IRSTILLANR LYSGIKVKIQ RVNNSSTNDN
LVRKNDQVYI NFVASKTHLL PLYADTATTN KEKTIKISSS GNRFNQVVVM NSVGNCTMNF
KNNNGNNIGL LGFKADTVVA STWYYTHMRD NTNSNGFFWN FISEEHGWQE K
