BXDN_CBDP
ID BXDN_CBDP Reviewed; 1196 AA.
AC Q9LBR2;
DT 07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Non-toxic nonhemagglutinin type D;
DE Short=NTNHA;
DE AltName: Full=Botulinum neurotoxin type D non-toxic component;
GN Name=ntnha; Synonyms=ntnh;
OS Clostridium botulinum D phage (Clostridium botulinum D bacteriophage).
OC Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes;
OC Caudovirales; Siphoviridae.
OX NCBI_TaxID=29342;
OH NCBI_TaxID=1491; Clostridium botulinum.
RN [1]
RP PROTEIN SEQUENCE OF 1-20 AND 141-157, SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=CB-16 / Type D / phage d-16 phi;
RX PubMed=8569530; DOI=10.1111/j.1348-0421.1995.tb02229.x;
RA Ohyama T., Watanabe T., Fujinaga Y., Inoue K., Sunagawa H., Fujii N.,
RA Oguma K.;
RT "Characterization of nontoxic-nonhemagglutinin component of the two types
RT of progenitor toxin (M and L) produced by Clostridium botulinum type D CB-
RT 16.";
RL Microbiol. Immunol. 39:457-465(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-10 AND 135-151,
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=D-4947 / Type D;
RX PubMed=11713244; DOI=10.1074/jbc.m106762200;
RA Kouguchi H., Watanabe T., Sagane Y., Sunagawa H., Ohyama T.;
RT "In vitro reconstitution of the Clostridium botulinum type D progenitor
RT toxin.";
RL J. Biol. Chem. 277:2650-2656(2002).
RN [3]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=D-4947 / Type D;
RX PubMed=17581814; DOI=10.1074/jbc.m703446200;
RA Hasegawa K., Watanabe T., Suzuki T., Yamano A., Oikawa T., Sato Y.,
RA Kouguchi H., Yoneyama T., Niwa K., Ikeda T., Ohyama T.;
RT "A novel subunit structure of Clostridium botulinum serotype D toxin
RT complex with three extended arms.";
RL J. Biol. Chem. 282:24777-24783(2007).
RN [4] {ECO:0007744|PDB:3VUO}
RP X-RAY CRYSTALLOGRAPHY (3.90 ANGSTROMS), DOMAIN, AND DISULFIDE BONDS.
RC STRAIN=D-4947 / Type D;
RX PubMed=22828508; DOI=10.1016/j.bbrc.2012.07.077;
RA Sagane Y., Miyashita S., Miyata K., Matsumoto T., Inui K., Hayashi S.,
RA Suzuki T., Hasegawa K., Yajima S., Yamano A., Niwa K., Watanabe T.;
RT "Small-angle X-ray scattering reveals structural dynamics of the botulinum
RT neurotoxin associating protein, non-toxic nonhemagglutinin.";
RL Biochem. Biophys. Res. Commun. 425:256-260(2012).
CC -!- FUNCTION: Assembles with botulinum neurotoxin type D (BoNT/D) and
CC protects it against pH-mediated inactivation or protease activity at pH
CC 2.6 (the pH of the animal gastrointestinal tract) but not at pH 6.0.
CC The non-toxic component is necessary to maintain toxicity.
CC {ECO:0000250|UniProtKB:Q45914}.
CC -!- SUBUNIT: Forms a highly interlocked heterodimer with botulinum
CC neurotoxin type C at pH 6.0 but not at pH 7.5 (By similarity).
CC Botulinum toxins are produced as progenitor toxins of large molecular
CC sizes of 12S (M toxin) and 16S (L toxin). M toxin consists of a non-
CC toxic, non-hemagglutinin component (NTNHA) and the neurotoxin
CC (PubMed:8569530, PubMed:11713244, PubMed:17581814). L toxin consists of
CC the M toxin and the 3 subcomponents of hemagglutinin (HA)
CC (PubMed:8569530, PubMed:17581814). HA is composed of subcomponents of
CC 70, 33, and 17 kDa. Erythrocyte agglutination occurs when the entire
CC complex is assembled (PubMed:17581814). The stoichiometry of the whole
CC complex has been modeled as one BoNT/D, one NTNHA, three HA-70, six HA-
CC 33 and three HA-17 (PubMed:17581814). {ECO:0000250|UniProtKB:Q45914,
CC ECO:0000269|PubMed:11713244, ECO:0000269|PubMed:17581814,
CC ECO:0000269|PubMed:8569530}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11713244,
CC ECO:0000269|PubMed:17581814, ECO:0000269|PubMed:8569530}.
CC -!- DOMAIN: Has 3 domains that are structurally very similar to those in
CC BoNT/D; light chain (nLC, equivalent to the light chain), N-heavy chain
CC (nHN) and C-heavy chain (nHC). {ECO:0000269|PubMed:22828508}.
CC -!- MISCELLANEOUS: This protein can also be encoded on a prophage.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the botulism non-toxic nonhemagglutinin family.
CC {ECO:0000305}.
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DR EMBL; AB037920; BAA90660.1; -; Genomic_DNA.
DR PDB; 3VUO; X-ray; 3.90 A; A=1-1196.
DR PDBsum; 3VUO; -.
DR SMR; Q9LBR2; -.
DR PATRIC; fig|1491.434.peg.22; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
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:InterPro.
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; IPR013677; Nontoxic_nonhemagglutn_C.
DR InterPro; IPR012928; Toxin_rcpt-bd_N.
DR Pfam; PF08470; NTNH_C; 1.
DR Pfam; PF01742; Peptidase_M27; 1.
DR Pfam; PF07953; Toxin_R_bind_N; 1.
DR PRINTS; PR00760; BONTOXILYSIN.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF58091; SSF58091; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Secreted;
KW Virulence.
FT CHAIN 1..1196
FT /note="Non-toxic nonhemagglutinin type D"
FT /id="PRO_0000445712"
FT REGION 1..408
FT /note="Light chain nLC"
FT /evidence="ECO:0000269|PubMed:22828508"
FT REGION 409..828
FT /note="N-heavy chain nHN"
FT /evidence="ECO:0000269|PubMed:22828508"
FT REGION 829..1195
FT /note="C-heavy chain nHC"
FT /evidence="ECO:0000269|PubMed:22828508"
FT DISULFID 583..754
FT /evidence="ECO:0007744|PDB:3VUO"
SQ SEQUENCE 1196 AA; 138455 MW; 5415088FF959513A CRC64;
MDINDDLNIN SPVDNKNVVI VRARKTNTFF KAFKVAPNIW VAPERYYGEP LDIAEEYKLD
GGIYDSNFLS QDSERENFLQ AIITLLKRIN NTISGKQLLS LISTAIPFPY GYVGGGYSSP
NIFTFGKTPK SNKKLNSLVT STIPFPFGGY RETNYIESQN NKNFYASNIV IFGPGSNIVE
NNVICYKKND AENGMGTMAE ILFQPLLTYK YNKFYIDPAM ELTKCLIKSL YFLYGIKPSD
DLVVPYRLRT ELDNKQFSQL NIIDLLISGG VDLEFINTNP YWFTNSYFSN SIKMFEKYKN
IYETEIEGNN AIGNDIKLRL KQKFQNSVQD IWNLNLNYFS KEFNSIIPDR FSNALKHFYR
KQYYTMDYGD NYNINGFVNG QINTKLPLSD KNTNIISKPE KVVNLVNANN ISLMKSNIYG
DGLKGTTEDF YSTYKIPYNE EYEYRFNDSD NFPLNNISIE EVDSIPEIID INPYKDNSDD
LLFTQITSTT EEVITHTALP VNYLQAQIIT NENFTLSSDF SKVVSSKDKS LVYSFLDNLM
SYLETIKNDG PIDTDKKYYL WLKEVFKNYS FDINLTQEID SSCGINEVVI WFGKALNILN
TSNSFVEEYQ NSGPISLISK KDNLSEPNIE IDDIPDSLLG LSFKDLNNKL YEIYSKNRVY
FRKIYFNFLD QWWTEYYSQY FELICMAKQS ILAQESVVKQ IIQNKFTDLS KASIPPDTLK
LIKETTEKTF IDLSNESQIS MNRVDNFLNK ASICVFVEDI YPKFISYMEK YINNINIKTR
EFIQRCTNIN DNEKSILINS YTFKTIDFKF LNIQAIKNFF NSQVEQVMKE MLSPYQLLLF
ATRGPNSNII EDISGKNTLI QYTESVELVY GVNGESLYLK SPNETVEFSN NFFTNGLTNN
FTICFWLRFT GKDDDKTRLI GNKVNNCGWE IYFEDNGLVF EIIDSNGNQE SVYLSNVINN
NWYYISISVD RLKDQLLIFI NDKNVANVSI EQILNIYSTN VISLVNKNNS IYVEELSVLD
KPVASEEVIR NYFSYLDNSY IRDSSKSLLE YNKNYQLYNY VFPETSLYEV NDNNKSYLSL
KNTDGINIPS VKFKLINIDE SKGYVQKWDE CIICVSDGTE KYLDISPENN RIQLVSSKDN
AKKITVNTDL FRPDCITFSY NDKYFSLSLR DGDYNWMICN DNNKVPKGAH LWILKS
