BXJ_ENTS3
ID BXJ_ENTS3 Reviewed; 1279 AA.
AC A0A242DI27;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2017, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Botulinum-like toxin eBoNT/J {ECO:0000303|PubMed:29323697};
DE Short=eBoNT/J {ECO:0000303|PubMed:29323697};
DE Contains:
DE RecName: Full=Botulinum-like toxin eBoNT/J light chain;
DE Short=LC;
DE EC=3.4.24.69 {ECO:0000305};
DE Contains:
DE RecName: Full=Botulinum-like toxin eBoNT/J heavy chain;
DE Short=HC;
GN ORFNames=A5816_002916;
OS Enterococcus sp. (strain 3G1_DIV0629).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=1834176;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3G1_DIV0629;
RG The Broad Institute Genomics Platform;
RG The Broad Institute Genomic Center for Infectious Diseases;
RA Earl A., Manson A., Schwartman J., Gilmore M., Abouelleil A., Cao P.,
RA Chapman S., Cusick C., Shea T., Young S., Neafsey D., Nusbaum C.,
RA Birren B.;
RT "The Genome Sequence of Enterococcus sp. 3G1_DIV0629.";
RL Submitted (MAY-2017) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP DISCUSSION OF SEQUENCE.
RC STRAIN=3G1_DIV0629;
RX PubMed=29323697; DOI=10.1002/1873-3468.12969;
RA Brunt J., Carter A.T., Stringer S.C., Peck M.W.;
RT "Identification of a novel botulinum neurotoxin gene cluster in
RT Enterococcus.";
RL FEBS Lett. 592:310-317(2018).
CC -!- FUNCTION: Strongly resembles a botulinum-type toxin, with the
CC appropriate domains and residues to have proteolytic function, although
CC its C-terminus (which binds to a eukaryotic host cell) is different
CC enough from clostrial botulinum toxins that it might bind another cell
CC target (PubMed:29323697). Might be a precursor of a toxin that binds to
CC an unknown eukaryotic cell receptor(s), and be taken up into the host
CC cell via the endocytic pathway. When the pH of the putative toxin-
CC containing endosome drops a structural rearrangement occurs so that the
CC N-terminus of the heavy chain forms pores that allows the light chain
CC to translocate into the cytosol. Once in the cytosol the disulfide bond
CC linking the 2 subunits is reduced and light chain cleaves its target
CC protein (By similarity). {ECO:0000250|UniProtKB:P0DPI0,
CC ECO:0000305|PubMed:29323697}.
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:P0DPI0};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P0DPI0};
CC Note=Binds 1 zinc ion per subunit (By similarity).
CC {ECO:0000250|UniProtKB:P0DPI0};
CC -!- SUBUNIT: Might be a disulfide-linked heterodimer of a light chain (LC)
CC and heavy chain (HC). {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- SUBCELLULAR LOCATION: [Botulinum-like toxin eBoNT/J]: Secreted
CC {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- SUBCELLULAR LOCATION: [Botulinum-like toxin eBoNT/J light chain]:
CC Secreted {ECO:0000250|UniProtKB:P0DPI0}. Host cytoplasm, host cytosol
CC {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- SUBCELLULAR LOCATION: [Botulinum-like toxin eBoNT/J heavy chain]:
CC Secreted {ECO:0000250|UniProtKB:P0DPI0}. Host cell membrane
CC {ECO:0000250|UniProtKB:P0DPI0}. Host cytoplasmic vesicle membrane
CC {ECO:0000305}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- DOMAIN: The light chain (LC) has protease activity. HC has 3 functional
CC domains; the translocation domain (TD) and the receptor-binding domain
CC (RBD) which is further subdivided into N- and C-terminal domains (N-RBD
CC and C-RBD). The N-terminus of the TD wraps an extended belt around the
CC perimeter of the light chain, protecting Zn(2+) in the active site and
CC may be a pseudosubstrate inhibitor which serves as an intramolecular
CC chaperone for the LC prior to its translocation into the host cytosol.
CC The RBD binds transiently exposed coreceptors on the host presynaptic
CC cell membrane.
CC -!- MISCELLANEOUS: There are seven antigenically distinct forms of
CC botulinum neurotoxin: Types A, B, C, D, E, F, and G; this protein has
CC not been tested seriologically. New subtypes are quite frequent.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: This strain was isolated from cow feces in South
CC Carolina, USA, but whether the cattle were infected with botulism is
CC not known. This locus includes a number of other genes usually
CC associated with the botulinum neurotoxin cluster in Clostridia (botR,
CC hemagglutinin genes and p47 proteins), which might permit the toxin to
CC survive in a host. {ECO:0000303|PubMed:29323697}.
CC -!- SIMILARITY: Belongs to the peptidase M27 family. {ECO:0000305}.
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DR EMBL; NGLI01000004; OTO22244.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A242DI27; -.
DR SMR; A0A242DI27; -.
DR Proteomes; UP000194867; Unassembled WGS sequence.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; 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; IPR012928; Toxin_rcpt-bd_N.
DR InterPro; IPR012500; Toxin_trans.
DR Pfam; PF01742; Peptidase_M27; 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 3: Inferred from homology;
KW Disulfide bond; Host cell membrane; Host cytoplasm;
KW Host cytoplasmic vesicle; Host membrane; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Neurotoxin; Protease; Secreted; Toxin;
KW Zinc.
FT CHAIN 1..1279
FT /note="Botulinum-like toxin eBoNT/J"
FT /id="PRO_0000444915"
FT CHAIN 1..434
FT /note="Botulinum-like toxin eBoNT/J light chain"
FT /id="PRO_0000444916"
FT CHAIN 435..1279
FT /note="Botulinum-like toxin eBoNT/J heavy chain"
FT /id="PRO_0000444917"
FT REGION 435..843
FT /note="Translocation domain (TD)"
FT /evidence="ECO:0000305|PubMed:29323697"
FT REGION 476..525
FT /note="Belt; not required for channel formation"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 860..1080
FT /note="N-terminus of receptor binding domain (N-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 1081..1279
FT /note="C-terminus of receptor binding domain (C-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT MOTIF 1250..1253
FT /note="Host ganglioside-binding motif"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000305|PubMed:29323697"
FT ACT_SITE 226
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 225
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000305|PubMed:29323697"
FT BINDING 229
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000305|PubMed:29323697"
FT BINDING 269
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000305|PubMed:29323697"
FT DISULFID 424..438
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000305|PubMed:29323697"
SQ SEQUENCE 1279 AA; 147267 MW; 9619E3D0C227D82C CRC64;
MVTINDLHYS DPIDEDNIIN MRIPLYDLEV DDQFINHNVP DLKAFQVFPN VWVVPERYTF
YSTMKNLDAP ANPSRSSYYD PTYLQSDAEK EVFLQQMILL FKRINSTQEG QQFLNLLSRS
IPVPYESNGD VAMGTTQVIK QMDDKGNVLK HRRAHIIIYG PGPDLMAKGS KALTKSRETG
RGCMAEIYFS PMYHKTYSTK LTNKNSLVDK SVQEFVPDPA VTLIHELCHG LHALYGIDLG
NVGSWEFNSN PNSLFSSWFS SKEAVNFEEV MTFGGEDVKV IKSEIDKKIP GILNLIKTTV
EPIINKITDP HDEMLQCLQS KYPSLKGTLG QFFFDDTQLE KDIRDLWMVM NETMFAENLK
ALTRARYLVP KVENIVQVDI LSPNVYTIDK GFNHLSKGFK GQSVSQSYFR KISALARGAV
VRACPNPHFS SQRGLSSCIE ILEDDLFIMS SKDSFTDTDF SEPSVGPVSY KAKKGADTIL
DSTLSNYDFS KEINFTSTVP IITVEDPLET DEDVPVISED RTVYVDDYTT FHFLEAQKIG
KEVVPTQTKV VFTTNMEEAL FDSKKVYTVF ENTASRINEA GTGIANGMMF YQWLKGIVQD
FTEEATQKDT FDKISDVTMI VPYLGNILNI GNDIRKGDFM GAVELGGVTI LLEAIPELTL
PVLIGLTIIE DELEKEQVSQ TVYNVLDKRD EKWEEVYGFV KQQWWWMVHT QFETRILHAY
QALNHQVEAI KANMTYQLAN YRGNQEDKEL LEKAIDDTLQ SLYYAVDQAM HNIKRFLIQS
SKSYLLNQML PKTKEQLLAF DQQTLRNVND FINKNQGVLG ESLAKDLKKK VEKRLTSLPV
FNLEDLPISE FEDLIHSHEI DIQDSEVLNI GVNNGKIQDL SGENTPLTLG ENLHIVNGRD
NQAVRLNNQL DSKLEIQSRP NIHFTAFEDF SISIWIRCSM LRNNRNRGQK YTIIQQFNKY
GWQLAIQDSV FVWTLHDTFN NQIQLTSGSA LTNKNYLLQN FWLHITVTNK RSEKSRLYIN
GVLQDQKDIS VLGNCHPKEP ILFSIQDNSD PNYFVRFEQF NVYRKALTDS EVNRLYWKYF
EGSYLRDVWG ERLTYNRDYY MQLSTLPGRG IKREYRTWSG FDYIILSELG TQKIPTHEVT
YPKLYQGQKI TIHSDGKNLE PHVKSNKNIR LKIDDFYIGV VNPFKLPEWR PESGAYVVTT
YNHAEDLCLY FRTRSSSQSL YYGQLIMNDG RNKSLLNYTL KGSTYWIWSS AWYYENYNTS
SKTAGNWYFI PVDEGWKED
