BXD_CBDP
ID BXD_CBDP Reviewed; 1276 AA.
AC P19321;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Botulinum neurotoxin type D;
DE Short=BoNT/D;
DE AltName: Full=Bontoxilysin-D;
DE Contains:
DE RecName: Full=Botulinum neurotoxin D light chain;
DE Short=LC;
DE EC=3.4.24.69 {ECO:0000269|PubMed:8175689};
DE Contains:
DE RecName: Full=Botulinum neurotoxin D heavy chain;
DE Short=HC;
DE Flags: Precursor;
GN Name=botD;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BVD/-3 / Type D;
RX PubMed=2216736; DOI=10.1093/nar/18.18.5556;
RA Binz T., Kurazono H., Popoff M.R., Eklund M.W., Sakaguchi G., Kozaki S.,
RA Krieglstein K., Henschen A., Gill D.M., Niemann H.;
RT "Nucleotide sequence of the gene encoding Clostridium botulinum neurotoxin
RT type D.";
RL Nucleic Acids Res. 18:5556-5556(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CB-16 / Type D / phage d-16 phi;
RX PubMed=1420572; DOI=10.1292/jvms.54.905;
RA Sunagawa H., Ohyama T., Watanabe T., Inoue K.;
RT "The complete amino acid sequence of the Clostridium botulinum type D
RT neurotoxin, deduced by nucleotide sequence analysis of the encoding phage
RT d-16 phi genome.";
RL J. Vet. Med. Sci. 54:905-913(1992).
RN [3]
RP PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN TYPE
RP D), AND RELEASED AS SINGLE CHAIN.
RC STRAIN=D-1873 / Type D, and South African / Type D;
RX PubMed=2668193; DOI=10.1128/iai.57.9.2886-2891.1989;
RA Moriishi K., Syuto B., Kubo S., Oguma K.;
RT "Molecular diversity of neurotoxins from Clostridium botulinum type D
RT strains.";
RL Infect. Immun. 57:2886-2891(1989).
RN [4]
RP PROTEIN SEQUENCE OF 2-21 AND 443-462, RELEASED AS DICHAIN, SUBUNIT, AND
RP 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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-11 AND 443-456,
RP RELEASED AS SINGLE CHAIN, 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 [6]
RP PROTEIN SEQUENCE OF 2-6, RELEASED AS SINGLE CHAIN, SUBUNIT, AND SUBCELLULAR
RP 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 [7]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE D AND BOTULINUM NEUROTOXIN D LIGHT
RP CHAIN), IDENTIFICATION OF SUBSTRATE, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION (BOTULINUM NEUROTOXIN D LIGHT CHAIN), AND SUBCELLULAR LOCATION
RP (BOTULINUM NEUROTOXIN D LIGHT CHAIN).
RC STRAIN=D-1873 / Type D;
RX PubMed=8175689; DOI=10.1016/s0021-9258(18)99941-2;
RA Yamasaki S., Baumeister A., Binz T., Blasi J., Link E., Cornille F.,
RA Roques B., Fykse E.M., Suedhof T.C., Jahn R., Niemann H.;
RT "Cleavage of members of the synaptobrevin/VAMP family by types D and F
RT botulinal neurotoxins and tetanus toxin.";
RL J. Biol. Chem. 269:12764-12772(1994).
RN [8]
RP FUNCTION (BOTULINUM NEUROTOXIN D LIGHT CHAIN), AND CATALYTIC ACTIVITY.
RC STRAIN=Type D;
RX PubMed=8197120; DOI=10.1073/pnas.91.11.4688;
RA Yamasaki S., Hu Y., Binz T., Kalkuhl A., Kurazono H., Tamura T., Jahn R.,
RA Kandel E., Niemann H.;
RT "Synaptobrevin/vesicle-associated membrane protein (VAMP) of Aplysia
RT californica: structure and proteolysis by tetanus toxin and botulinal
RT neurotoxins type D and F.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:4688-4692(1994).
RN [9]
RP SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN D LIGHT CHAIN), RELEASED AS
RP SINGLE CHAIN, AND BIOTECHNOLOGY.
RC STRAIN=Type D;
RX PubMed=15584922; DOI=10.1111/j.1471-4159.2004.02844.x;
RA Bade S., Rummel A., Reisinger C., Karnath T., Ahnert-Hilger G., Bigalke H.,
RA Binz T.;
RT "Botulinum neurotoxin type D enables cytosolic delivery of enzymatically
RT active cargo proteins to neurones via unfolded translocation
RT intermediates.";
RL J. Neurochem. 91:1461-1472(2004).
RN [10]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE D), RELEASED AS DICHAIN, EUKARYOTIC
RP TARGET RANGE, SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=D-1873 / Type D;
RX PubMed=16252491; DOI=10.1637/7347-022305r1.1;
RA Takeda M., Tsukamoto K., Kohda T., Matsui M., Mukamoto M., Kozaki S.;
RT "Characterization of the neurotoxin produced by isolates associated with
RT avian botulism.";
RL Avian Dis. 49:376-381(2005).
RN [11]
RP FUNCTION (BOTULINUM NEUROTOXIN D HEAVY CHAIN), POSSIBLE LACK OF
RP PROTEINACEOUS RECEPTOR, DOMAIN, AND LIPID-BINDING.
RC STRAIN=D-1873 / Type D;
RX PubMed=16115873; DOI=10.1074/jbc.m507596200;
RA Tsukamoto K., Kohda T., Mukamoto M., Takeuchi K., Ihara H., Saito M.,
RA Kozaki S.;
RT "Binding of Clostridium botulinum type C and D neurotoxins to ganglioside
RT and phospholipid. Novel insights into the receptor for clostridial
RT neurotoxins.";
RL J. Biol. Chem. 280:35164-35171(2005).
RN [12]
RP DISCUSSION OF BELT FUNCTION, AND DOMAIN.
RX PubMed=17907800; DOI=10.1371/journal.ppat.0030113;
RA Brunger A.T., Breidenbach M.A., Jin R., Fischer A., Santos J.S., Montal M.;
RT "Botulinum neurotoxin heavy chain belt as an intramolecular chaperone for
RT the light chain.";
RL PLoS Pathog. 3:1191-1194(2007).
RN [13]
RP EUKARYOTIC TARGET RANGE.
RX PubMed=17913314; DOI=10.1016/j.vaccine.2007.08.051;
RA Steinman A., Galon N., Arazi A., Bar-Giora Y., Shpigel N.Y.;
RT "Cattle immune response to botulinum type D toxoid: results of a
RT vaccination study.";
RL Vaccine 25:7636-7640(2007).
RN [14]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE D AND BOTULINUM NEUROTOXIN D HEAVY
RP CHAIN).
RX PubMed=19650874; DOI=10.1111/j.1471-4159.2009.06298.x;
RA Rummel A., Haefner K., Mahrhold S., Darashchonak N., Holt M., Jahn R.,
RA Beermann S., Karnath T., Bigalke H., Binz T.;
RT "Botulinum neurotoxins C, E and F bind gangliosides via a conserved binding
RT site prior to stimulation-dependent uptake with botulinum neurotoxin F
RT utilising the three isoforms of SV2 as second receptor.";
RL J. Neurochem. 110:1942-1954(2009).
RN [15]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE D AND BOTULINUM NEUROTOXIN D HEAVY
RP CHAIN), POSSIBLE PROTEIN RECEPTOR, INTERACTION WITH EUKARYOTIC SV2B, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=BVD/-3 / Type D;
RX PubMed=21483489; DOI=10.1371/journal.ppat.1002008;
RA Peng L., Tepp W.H., Johnson E.A., Dong M.;
RT "Botulinum neurotoxin D uses synaptic vesicle protein SV2 and gangliosides
RT as receptors.";
RL PLoS Pathog. 7:E1002008-E1002008(2011).
RN [16]
RP FUNCTION (BOTULINUM NEUROTOXIN D LIGHT CHAIN), SUBSTRATE SPECIFICITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22289120; DOI=10.1111/j.1348-0421.2012.00434.x;
RA Yamamoto H., Ida T., Tsutsuki H., Mori M., Matsumoto T., Kohda T.,
RA Mukamoto M., Goshima N., Kozaki S., Ihara H.;
RT "Specificity of botulinum protease for human VAMP family proteins.";
RL Microbiol. Immunol. 56:245-253(2012).
RN [17]
RP BIOTECHNOLOGY.
RX PubMed=24029240; DOI=10.1210/en.2013-1427;
RA Somm E., Bonnet N., Zizzari P., Tolle V., Toulotte A., Jones R.,
RA Epelbaum J., Martinez A., Hueppi P.S., Aubert M.L.;
RT "Comparative inhibition of the GH/IGF-I axis obtained with either the
RT targeted secretion inhibitor SXN101959 or the somatostatin analog
RT octreotide in growing male rats.";
RL Endocrinology 154:4237-4248(2013).
RN [18]
RP REVIEW.
RX PubMed=28356439; DOI=10.1124/pr.116.012658;
RA Pirazzini M., Rossetto O., Eleopra R., Montecucco C.;
RT "Botulinum neurotoxins: Biology, pharmacology, and toxicology.";
RL Pharmacol. Rev. 69:200-235(2017).
RN [19] {ECO:0007744|PDB:2FPQ}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 1-436 IN COMPLEX WITH ZINC, AND
RP COFACTOR.
RC STRAIN=D-1873 / Type D / phage d-16 phi;
RX PubMed=16519520; DOI=10.1021/bi052518r;
RA Arndt J.W., Chai Q., Christian T., Stevens R.C.;
RT "Structure of botulinum neurotoxin type D light chain at 1.65 A resolution:
RT repercussions for VAMP-2 substrate specificity.";
RL Biochemistry 45:3255-3262(2006).
RN [20] {ECO:0007744|PDB:3N7J}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 862-1276, AND DOMAIN.
RC STRAIN=D-1873 / Type D / phage d-16 phi;
RX PubMed=20731382; DOI=10.1021/bi100865f;
RA Karalewitz A.P., Kroken A.R., Fu Z., Baldwin M.R., Kim J.J., Barbieri J.T.;
RT "Identification of a unique ganglioside binding loop within botulinum
RT neurotoxins C and D-SA.";
RL Biochemistry 49:8117-8126(2010).
RN [21] {ECO:0007744|PDB:3OBR, ECO:0007744|PDB:3OBT}
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 863-1276 IN COMPLEX WITH
RP N-ACETYLNEURAMINIC ACID, FUNCTION (BOTULINUM NEUROTOXIN TYPE D AND
RP BOTULINUM NEUROTOXIN D HEAVY CHAIN), DOMAIN, GANGLIOSIDE-BINDING, AND
RP MUTAGENESIS OF LYS-1192; ASP-1233; TYR-1235; TRP-1238; ARG-1239; PHE-1240;
RP PHE-1242; ASN-1244; TYR-1246; VAL-1251; ASN-1253; LYS-1257 AND SER-1262.
RC STRAIN=BVD/-3 / Type D;
RX PubMed=20704566; DOI=10.1042/bj20101042;
RA Strotmeier J., Lee K., Volker A.K., Mahrhold S., Zong Y., Zeiser J.,
RA Zhou J., Pich A., Bigalke H., Binz T., Rummel A., Jin R.;
RT "Botulinum neurotoxin serotype D attacks neurons via two carbohydrate-
RT binding sites in a ganglioside-dependent manner.";
RL Biochem. J. 431:207-216(2010).
RN [22] {ECO:0007744|PDB:3RMX, ECO:0007744|PDB:3RMY}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF MUTATED 862-1276, FUNCTION
RP (BOTULINUM NEUROTOXIN TYPE D AND BOTULINUM NEUROTOXIN D HEAVY CHAIN),
RP SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN D HEAVY CHAIN),
RP GANGLIOSIDE-BINDING, AND MUTAGENESIS OF TRP-1238; ARG-1239 AND PHE-1240.
RC STRAIN=D-1873 / Type D;
RX PubMed=21632541; DOI=10.1074/jbc.m111.254086;
RA Kroken A.R., Karalewitz A.P., Fu Z., Kim J.J., Barbieri J.T.;
RT "Novel ganglioside-mediated entry of botulinum neurotoxin serotype D into
RT neurons.";
RL J. Biol. Chem. 286:26828-26837(2011).
RN [23] {ECO:0007744|PDB:5BQM, ECO:0007744|PDB:5BQN}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-896 IN COMPLEX WITH ZINC,
RP COFACTOR, DOMAIN, BIOTECHNOLOGY, AND DISULFIDE BOND.
RX PubMed=26324071; DOI=10.1038/srep13397;
RA Masuyer G., Davies J.R., Moore K., Chaddock J.A., Ravi Acharya K.;
RT "Structural analysis of Clostridium botulinum neurotoxin type D as a
RT platform for the development of targeted secretion inhibitors.";
RL Sci. Rep. 5:13397-13397(2015).
CC -!- FUNCTION: [Botulinum neurotoxin type D]: Botulinum toxin causes flaccid
CC paralysis by inhibiting neurotransmitter (acetylcholine) release from
CC the presynaptic membranes of nerve terminals of the eukaryotic host
CC skeletal and autonomic nervous system, with frequent heart or
CC respiratory failure (PubMed:8175689, PubMed:16252491). Precursor of
CC botulinum neurotoxin D for which a proteinaceous coreceptor is
CC controversial. In double SV2A/SV2B knockout mice this toxin does not
CC degrade its synaptobrevin target; introducing SV2A, SV2B or SV2C
CC restores target cleavage (PubMed:21483489). Recognition of SV2 by this
CC toxin does not occur via SV2 glycosylation or its large extracellular
CC loop 4 (PubMed:21483489). Another group does not find a convincing
CC interaction with SV2 (PubMed:21632541). Thus a protein receptor for
CC this BoNT serotype has yet to be definitively proven. Recognizes at
CC least 1 complex polysialylated ganglioside found on neural tissue.
CC Electrical stimulation increases uptake of toxin in an ex vivo assay,
CC presumably by transiently exposing a receptor usually found in
CC eukaryotic target synaptic vesicles (PubMed:19650874, PubMed:21483489,
CC PubMed:21632541). Upon synaptic vesicle recycling the toxin is taken up
CC via the endocytic pathway; when the pH of the toxin-containing endosome
CC drops a structural rearrangement occurs so that the N-terminus of the
CC heavy chain (HC) forms pores that allows the light chain (LC) to
CC translocate into the cytosol (By similarity). Once in the cytosol the
CC disulfide bond linking the 2 subunits is reduced and LC cleaves its
CC target protein on synaptic vesicles, preventing their fusion with the
CC cytoplasmic membrane and thus neurotransmitter release (By similarity).
CC Requires complex eukaryotic host polysialogangliosides for full
CC neurotoxicity and for binding to neurons (PubMed:20704566,
CC PubMed:21483489). {ECO:0000250|UniProtKB:P0DPI0,
CC ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:19650874,
CC ECO:0000269|PubMed:20704566, ECO:0000269|PubMed:21483489,
CC ECO:0000269|PubMed:21632541, ECO:0000269|PubMed:8175689, ECO:0000305}.
CC -!- FUNCTION: [Botulinum neurotoxin D light chain]: Has proteolytic
CC activity (PubMed:8175689, PubMed:8197120). After translocation into the
CC eukaryotic host cytosol, inhibits neurotransmitter release by acting as
CC a zinc endopeptidase that cleaves the '61-Lys-|-Leu-62' bond of
CC synaptobrevin-1 (VAMP1), and the equivalent 'Lys-|-Leu' sites in VAMP2
CC and VAMP3 (PubMed:8175689). Cleaves the '49-Lys-|-Ile-50' bond of
CC A.californica synaptobrevin (AC P35589) (PubMed:8197120). This chain
CC probably has to be partially unfolded to translocate into the
CC eukaryotic host cell cytosol (PubMed:15584922).
CC {ECO:0000269|PubMed:8175689, ECO:0000269|PubMed:8197120,
CC ECO:0000305|PubMed:15584922}.
CC -!- FUNCTION: [Botulinum neurotoxin D heavy chain]: Responsible for host
CC epithelial cell transcytosis, host nerve cell targeting and
CC translocation of light chain (LC) into eukaryotic host cell cytosol.
CC Composed of 3 subdomains; the translocation domain (TD), and N-terminus
CC and C-terminus of the receptor-binding domain (RBD). The RBD is
CC responsible for the adherence of the toxin to the eukaryotic target
CC cell surface. The N-terminus of the TD wraps an extended belt around
CC the perimeter of the LC, protecting Zn(2+) in the active site; it may
CC also prevent premature LC dissociation from the translocation channel
CC and protect toxin prior to translocation (PubMed:17907800). The TD
CC inserts into synaptic vesicle membrane to allow translocation into the
CC host cytosol (By similarity). The RBD binds eukaryotic host
CC phosphatidylethanolamine, which may serve as toxin receptor
CC (PubMed:16115873). Treatment of synaptosomes with proteinase K does not
CC reduce HC binding, suggesting there is no protein receptor or it is
CC protected from extracellular proteases (PubMed:16115873). HC
CC significantly decreases uptake and toxicity of whole BoNT/D
CC (PubMed:19650874, PubMed:21483489). HC also interferes with uptake of
CC tetanus toxin (PubMed:19650874). Has 2 closely located carbohydrate-
CC binding receptor sites and binds at least 1 GT1b ganglioside
CC (PubMed:20704566). Bind gangliosides in the order GD2 > GT1b > GD1b
CC (PubMed:21632541). Interacts with eukaryotic target protein SV2B
CC (synaptic vesicle glycoprotein 2B) (PubMed:21483489). Expression of
CC SV2A, SV2B or SV2C in mice knocked-out for the SV2 proteins restores
CC entry of BoNT/D and cleavage of VAMP2, suggesting SV2 acts as its
CC receptor (PubMed:21483489). Unlike BoNT/A and BoNT/E, toxin uptake is
CC not mediated by large extracellular loop 4 of SV2 (PubMed:21483489).
CC Another group finds very poor interaction with SV2 proteins, suggesting
CC the possible protein receptor may not have been identified
CC (PubMed:21632541). {ECO:0000250|UniProtKB:P0DPI0,
CC ECO:0000269|PubMed:16115873, ECO:0000269|PubMed:19650874,
CC ECO:0000269|PubMed:20704566, ECO:0000269|PubMed:21483489,
CC ECO:0000269|PubMed:21632541, ECO:0000305|PubMed:17907800}.
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:0000269|PubMed:8175689, ECO:0000269|PubMed:8197120};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:16519520, ECO:0000269|PubMed:26324071};
CC Note=Binds 1 zinc ion per subunit (PubMed:16519520, PubMed:26324071).
CC {ECO:0000269|PubMed:16519520, ECO:0000269|PubMed:26324071};
CC -!- ACTIVITY REGULATION: [Botulinum neurotoxin D light chain]: Inhibited by
CC dipicolinic acid, captopril, 1,10-phenanthroline and EDTA.
CC {ECO:0000269|PubMed:8175689}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=28.9 uM for over-expressed human VAMP1
CC {ECO:0000269|PubMed:22289120};
CC KM=28.0 uM for over-expressed human VAMP2
CC {ECO:0000269|PubMed:22289120};
CC KM=11.1 uM for over-expressed human VAMP3
CC {ECO:0000269|PubMed:22289120};
CC Note=kcat is 0.59, 146.60 and 113.41 sec(-1) for over-expressed human
CC VAMP1, VAMP2 and VAMP3 respectively. {ECO:0000269|PubMed:22289120};
CC -!- SUBUNIT: Heterodimer; disulfide-linked heterodimer of a light chain
CC (LC) and a heavy chain (HC) (PubMed:26324071). The LC has the
CC proteolytic/pharmacological activity (PubMed:8175689, PubMed:8197120).
CC The N- and C-termini of the HC mediate channel formation and eukaryotic
CC host cell binding, respectively. Can also be purified in complex with a
CC non-toxic component that is larger than the HC (PubMed:16252491).
CC Single chain toxin from strain D-4947 copurifies with NTHNA, and in
CC complexes that include NTNHA, HA-70, HA-33 and HA-17 (PubMed:11713244,
CC PubMed:17581814). Dichain toxin from strain CB-16 phage d-16 phi
CC copurifies with NTHNA, and in complexes that include NTNHA, HA-55, HA-
CC 33, HA-22 and HA-17 (PubMed:8569530). 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). HC interacts with eukaryotic
CC protein synaptic vesicle glycoprotein 2B (SV2B), which may serve as its
CC receptor (PubMed:21483489). Another group does not find a convincing
CC interaction with SV2 (PubMed:21632541). {ECO:0000269|PubMed:11713244,
CC ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:16519520,
CC ECO:0000269|PubMed:17581814, ECO:0000269|PubMed:21483489,
CC ECO:0000269|PubMed:21632541, ECO:0000269|PubMed:8175689,
CC ECO:0000269|PubMed:8197120, ECO:0000269|PubMed:8569530,
CC ECO:0000305|PubMed:26324071}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin type D]: Secreted
CC {ECO:0000269|PubMed:11713244, ECO:0000269|PubMed:17581814,
CC ECO:0000269|PubMed:2668193}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin D light chain]: Secreted
CC {ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:8569530}. Note=In
CC animals that have ingested BoNT/D LC acts in the eukaryotic host
CC cytosol (Probable). {ECO:0000305|PubMed:15584922,
CC ECO:0000305|PubMed:8175689}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin D heavy chain]: Secreted
CC {ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:8569530}. Note=Upon
CC incubation with hippocampal cell colocalizes with SV2C, probably in
CC host synaptic vesicles (PubMed:21483489). Upon incubation with primary
CC neurons HC colocalizes with synaptophysin probably in synaptic vesicles
CC of presynaptic cells; a small portion also colocalizes with RAB5 and
CC may be in synaptic vesicle protein sorting endosomes (PubMed:21632541).
CC Probably integrates into the eukaryotic host synaptic vesicle membrane.
CC {ECO:0000269|PubMed:21483489, ECO:0000269|PubMed:21632541,
CC ECO:0000305}.
CC -!- DOMAIN: [Botulinum neurotoxin D light chain]: Has protease activity
CC (PubMed:8175689, PubMed:8197120). {ECO:0000269|PubMed:8175689,
CC ECO:0000269|PubMed:8197120}.
CC -!- DOMAIN: [Botulinum neurotoxin D 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, also called Hcn and Hcc) (PubMed:20731382, PubMed:20704566). The
CC N-terminus of the TD wraps an extended belt around the perimeter of the
CC LC which occludes the catalytic pocket (PubMed:26324071). The belt
CC region may be a pseudosubstrate inhibitor which serves as an
CC intramolecular chaperone for the LC prior to its translocation into the
CC host cytosol (PubMed:17907800). {ECO:0000269|PubMed:20704566,
CC ECO:0000269|PubMed:20731382, ECO:0000269|PubMed:26324071,
CC ECO:0000305|PubMed:17907800}.
CC -!- BIOTECHNOLOGY: Cargo proteins fused to the N-terminus of whole toxin
CC are imported into neurons; stabilized cargo proteins are poorer
CC substrates, suggesting partial unfolding of the cargo protein is
CC necessary for import (PubMed:15584922). {ECO:0000269|PubMed:15584922}.
CC -!- BIOTECHNOLOGY: Can be used for targeted secretion inhibition in
CC eukaryotic cells. A construct with a mammalian growth hormone-releasing
CC factor ligand domain (GHRH) inserted between the LC and TD, when
CC injected into rats, leads to decreased growth hormone production. The
CC GHRH ligand domain binds to the GHRH receptor on somatotrophs where it
CC is taken up into endosomes. There the TD inserts into the membrane,
CC releasing LC which cleaves synaptobrevin and inhibits growth hormone
CC exocytosis (PubMed:24029240, PubMed:26324071).
CC {ECO:0000269|PubMed:24029240, ECO:0000305|PubMed:26324071}.
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. Types C and D can undergo domain swapping to create
CC hybrid types.
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: Botulinum type D neurotoxin is synthesized by D strains
CC of C.botulinum which carry the appropriate bacteriophage.
CC {ECO:0000305|PubMed:1420572, ECO:0000305|PubMed:20731382,
CC ECO:0000305|PubMed:2216736}.
CC -!- MISCELLANEOUS: Botulinum type D South African (D-SA) neurotoxin is
CC released from bacteria as a single chain and presumably cleaved by host
CC proteases into the active dichain (PubMed:2668193). Botulinum type D-
CC 1873 neurotoxin is released from bacteria as an already-cleaved dichain
CC (PubMed:16252491). Toxin from strain CB-16 phage d-16 phi is released
CC as an alread-cleaved dichain (PubMed:8569530). Another toxin (possibly
CC from phage CE-beta) is released from over-producing E.coli as a single
CC chain (PubMed:15584922). Type D-4947 is released as a single chain
CC (PubMed:17581814). {ECO:0000269|PubMed:15584922,
CC ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:17581814,
CC ECO:0000269|PubMed:2668193, ECO:0000269|PubMed:8569530}.
CC -!- MISCELLANEOUS: This protein can also be encoded on a prophage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: BoNT/D causes animal botulism; it is 1,000-fold less
CC toxic in chickens than BoNT/C1 (PubMed:16252491, PubMed:16115873).
CC Cattle botulism is often caused by type D (PubMed:17913314).
CC {ECO:0000269|PubMed:16252491, ECO:0000269|PubMed:17913314,
CC ECO:0000305|PubMed:16115873}.
CC -!- SIMILARITY: Belongs to the peptidase M27 family. {ECO:0000305}.
CC -!- CAUTION: The existence of a proteinaceous coreceptor is unclear. In
CC double SV2A/SV2B knockout mice this toxin does not degrade its VAMP
CC target; introducing SV2A, SV2B or SV2C restores target cleavage
CC (PubMed:21483489). However another group does not find a convincing
CC interaction with SV2 (PubMed:21632541). {ECO:0000269|PubMed:21483489,
CC ECO:0000269|PubMed:21632541}.
CC -!- WEB RESOURCE: Name=BotDB - A Database Resource for Clostridial
CC Neurotoxins;
CC URL="https://botdb.abcc.ncifcrf.gov/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X54254; CAA38175.1; -; Genomic_DNA.
DR EMBL; S49407; AAB24244.1; -; Genomic_DNA.
DR PIR; S11455; S11455.
DR PDB; 2FPQ; X-ray; 1.65 A; A=1-436.
DR PDB; 3N7J; X-ray; 2.00 A; A=862-1276.
DR PDB; 3OBR; X-ray; 1.72 A; A=863-1276.
DR PDB; 3OBT; X-ray; 2.00 A; A=863-1276.
DR PDB; 3OGG; X-ray; 1.65 A; A=863-1276.
DR PDB; 3RMX; X-ray; 2.75 A; A/B/C/D=862-1276.
DR PDB; 3RMY; X-ray; 2.30 A; A/B/C/D=862-1276.
DR PDB; 5BQM; X-ray; 3.10 A; A/C=1-437, B/D=450-861.
DR PDB; 5BQN; X-ray; 2.30 A; A=1-437, A=450-862.
DR PDBsum; 2FPQ; -.
DR PDBsum; 3N7J; -.
DR PDBsum; 3OBR; -.
DR PDBsum; 3OBT; -.
DR PDBsum; 3OGG; -.
DR PDBsum; 3RMX; -.
DR PDBsum; 3RMY; -.
DR PDBsum; 5BQM; -.
DR PDBsum; 5BQN; -.
DR SMR; P19321; -.
DR DrugBank; DB13902; Equine Botulinum Neurotoxin D Immune FAB2.
DR UniLectin; P19321; -.
DR ABCD; P19321; 36 sequenced antibodies.
DR BRENDA; 3.4.24.69; 1462.
DR Reactome; R-HSA-5250955; Toxicity of botulinum toxin type D (botD).
DR EvolutionaryTrace; P19321; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:1905576; F:ganglioside GT1b binding; IDA:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0008320; F:protein transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
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 3D-structure; Direct protein sequencing; Disulfide bond; Hydrolase;
KW Lipid-binding; Metal-binding; Metalloprotease; Neurotoxin; Protease;
KW Secreted; Toxin; Virulence; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:11713244,
FT ECO:0000269|PubMed:17581814, ECO:0000269|PubMed:8569530"
FT CHAIN 2..1276
FT /note="Botulinum neurotoxin type D"
FT /id="PRO_0000444906"
FT CHAIN 2..442
FT /note="Botulinum neurotoxin D light chain"
FT /id="PRO_0000029219"
FT CHAIN 443..1276
FT /note="Botulinum neurotoxin D heavy chain"
FT /evidence="ECO:0000269|PubMed:8569530,
FT ECO:0000305|PubMed:11713244"
FT /id="PRO_0000029220"
FT REGION 443..862
FT /note="Translocation domain (TD)"
FT /evidence="ECO:0000269|PubMed:20704566,
FT ECO:0000269|PubMed:20731382"
FT REGION 458..547
FT /note="Belt"
FT /evidence="ECO:0000269|PubMed:26324071"
FT REGION 863..1082
FT /note="N-terminus of receptor binding domain (N-RBD), Hcn"
FT /evidence="ECO:0000269|PubMed:20704566,
FT ECO:0000269|PubMed:20731382"
FT REGION 1083..1276
FT /note="C-terminus of receptor binding domain (C-RBD), Hcc"
FT /evidence="ECO:0000269|PubMed:20704566,
FT ECO:0000269|PubMed:20731382"
FT REGION 1172..1173
FT /note="N-acetyl-beta-neuraminic acid"
FT /evidence="ECO:0000269|PubMed:20704566,
FT ECO:0007744|PDB:3OBT"
FT REGION 1235..1245
FT /note="Ganglioside-binding loop"
FT /evidence="ECO:0000269|PubMed:21632541"
FT MOTIF 1252..1255
FT /note="Host ganglioside-binding motif"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000305|PubMed:20704566"
FT ACT_SITE 230
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 229
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16519520,
FT ECO:0000269|PubMed:26324071, ECO:0007744|PDB:2FPQ,
FT ECO:0007744|PDB:5BQM"
FT BINDING 233
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16519520,
FT ECO:0000269|PubMed:26324071, ECO:0007744|PDB:2FPQ,
FT ECO:0007744|PDB:5BQM"
FT BINDING 269
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16519520,
FT ECO:0000269|PubMed:26324071, ECO:0007744|PDB:2FPQ,
FT ECO:0007744|PDB:5BQM"
FT BINDING 1192
FT /ligand="N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:58705"
FT /evidence="ECO:0000269|PubMed:20704566,
FT ECO:0007744|PDB:3OBT"
FT BINDING 1239
FT /ligand="N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:58705"
FT /evidence="ECO:0000269|PubMed:20704566,
FT ECO:0007744|PDB:3OBT"
FT DISULFID 437..450
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000305|PubMed:26324071,
FT ECO:0007744|PDB:5BQM, ECO:0007744|PDB:5BQN"
FT VARIANT 15..16
FT /note="ND -> PV (in strain: D-SA)"
FT VARIANT 17..18
FT /note="ND -> LQ (in strain: D-1873)"
FT VARIANT 452
FT /note="K -> Q (in strain: D-SA and D-4947)"
FT VARIANT 457
FT /note="R -> F (in strain: D-1873)"
FT VARIANT 457
FT /note="R -> T (in strain: D-SA)"
FT VARIANT 462
FT /note="A -> D (in strain: D-1873)"
FT VARIANT 489
FT /note="K -> N (in strain: CB16)"
FT VARIANT 644
FT /note="N -> K (in strain: CB16)"
FT VARIANT 1122
FT /note="Q -> R (in strain: CB16)"
FT MUTAGEN 1192
FT /note="K->A: Decreased binding of heavy chain (HC) to
FT synaptosomes. Significantly decreased HC binding, whole
FT toxin is dramatically less neurotoxic; when associated with
FT A-1239."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1233
FT /note="D->A: Significantly decreased binding of heavy chain
FT (HC) to synaptosomes, whole toxin is significantly less
FT neurotoxic. Dramatically decreased HC binding, whole toxin
FT is dramatically less neurotoxic; when associated with A-
FT 1239."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1235
FT /note="Y->A: Significantly decreased binding of heavy chain
FT to synaptosomes, whole toxin is significantly less
FT neurotoxic."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1235
FT /note="Y->W: Increased binding of heavy chain to
FT synaptosomes, whole toxin has half neurotoxicity."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1238
FT /note="W->A: Dramatically decreased binding of heavy chain
FT (HC) to synaptosomes, whole toxin is dramatically less
FT neurotoxic. Loss of HC binding to GD1b, GT1b, GD2 and
FT synaptic vesicles, ganglioside-binding loop is disordered
FT in crystal."
FT /evidence="ECO:0000269|PubMed:20704566,
FT ECO:0000269|PubMed:21632541"
FT MUTAGEN 1238
FT /note="W->F,Y: Decreased binding of heavy chain to
FT synaptosomes, whole toxin is significantly less
FT neurotoxic."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1238
FT /note="W->L: Significantly decreased binding of heavy chain
FT to synaptosomes, whole toxin is dramatically less
FT neurotoxic."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1239
FT /note="R->A: Significantly decreased binding of heavy chain
FT (HC) to synaptosomes, whole toxin is dramatically less
FT neurotoxic. Dramatically decreased HC binding, whole toxin
FT is dramatically less neurotoxic; when associated with A-
FT 1192. Significantly decreased HC binding, whole toxin is
FT dramatically less neurotoxic; when associated with A-1233.
FT Decrease in HC binding to GD1b, GT1b, GD2 and synaptic
FT vesicles."
FT /evidence="ECO:0000269|PubMed:20704566,
FT ECO:0000269|PubMed:21632541"
FT MUTAGEN 1239
FT /note="R->Y: Significantly decreased binding of heavy chain
FT to synaptosomes, whole toxin is dramatically less
FT neurotoxic."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1240
FT /note="F->A: Significantly decreased binding of heavy chain
FT to synaptosomes, whole toxin is dramatically less
FT neurotoxic. Significant decrease in HC binding to GD1b,
FT GT1b, GD2 and synaptic vesicles, GBL is well ordered in
FT crystal."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1240
FT /note="F->W: Increased binding of heavy chain (HC) to
FT synaptosomes, whole toxin is slightly less neurotoxic.
FT Slightly greater than wild-type HC binding to GT1b."
FT /evidence="ECO:0000269|PubMed:20704566,
FT ECO:0000269|PubMed:21632541"
FT MUTAGEN 1242
FT /note="F->S: Significantly decreased binding of heavy chain
FT to synaptosomes, whole toxin is dramatically less
FT neurotoxic."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1242
FT /note="F->W: No effect on heavy chain binding to
FT synaptosomes, whole toxin is slightly less neurotoxic."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1244
FT /note="N->A: Significantly decreased binding of heavy chain
FT to synaptosomes, whole toxin is significantly less
FT neurotoxic."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1246
FT /note="Y->A,S,W: Significantly decreased binding of heavy
FT chain to synaptosomes, whole toxin is significantly less
FT neurotoxic."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1251
FT /note="V->F: Significantly decreased binding of heavy chain
FT to synaptosomes, whole toxin is significantly less
FT neurotoxic."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1253
FT /note="N->A: Significantly decreased binding of heavy chain
FT to synaptosomes."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1257
FT /note="K->A: Decreased binding of heavy chain to
FT synaptosomes."
FT /evidence="ECO:0000269|PubMed:20704566"
FT MUTAGEN 1262
FT /note="S->F: Decreased binding of heavy chain to
FT synaptosomes."
FT /evidence="ECO:0000269|PubMed:20704566"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 34..40
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:5BQN"
FT TURN 67..69
FT /evidence="ECO:0007829|PDB:2FPQ"
FT TURN 74..77
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 80..97
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 101..112
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:5BQM"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:2FPQ"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 136..142
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 145..152
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 155..159
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:2FPQ"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:5BQN"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 223..238
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 267..273
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 275..280
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 283..306
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 309..312
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 313..318
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 319..329
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 344..355
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 360..366
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 380..384
FT /evidence="ECO:0007829|PDB:5BQN"
FT TURN 390..392
FT /evidence="ECO:0007829|PDB:2FPQ"
FT TURN 395..397
FT /evidence="ECO:0007829|PDB:2FPQ"
FT HELIX 403..405
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:5BQM"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:2FPQ"
FT TURN 415..417
FT /evidence="ECO:0007829|PDB:2FPQ"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:2FPQ"
FT TURN 426..428
FT /evidence="ECO:0007829|PDB:5BQN"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:5BQN"
FT STRAND 451..454
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 455..457
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:5BQN"
FT STRAND 533..539
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 542..548
FT /evidence="ECO:0007829|PDB:5BQN"
FT STRAND 559..562
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 564..569
FT /evidence="ECO:0007829|PDB:5BQN"
FT STRAND 573..575
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 579..586
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 594..609
FT /evidence="ECO:0007829|PDB:5BQN"
FT STRAND 620..624
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 628..632
FT /evidence="ECO:0007829|PDB:5BQN"
FT TURN 638..641
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 643..650
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 652..655
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 680..682
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 684..711
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 713..744
FT /evidence="ECO:0007829|PDB:5BQN"
FT TURN 748..753
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 754..762
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 764..789
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 792..816
FT /evidence="ECO:0007829|PDB:5BQN"
FT TURN 817..821
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 828..832
FT /evidence="ECO:0007829|PDB:5BQN"
FT TURN 833..836
FT /evidence="ECO:0007829|PDB:5BQN"
FT STRAND 844..846
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 847..849
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 850..860
FT /evidence="ECO:0007829|PDB:5BQN"
FT HELIX 864..867
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 868..875
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 878..881
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 883..885
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 888..891
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 896..901
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 904..907
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 909..911
FT /evidence="ECO:0007829|PDB:3OBT"
FT STRAND 914..917
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 931..939
FT /evidence="ECO:0007829|PDB:3OGG"
FT HELIX 941..944
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 948..954
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 957..959
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 961..967
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 970..976
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 982..988
FT /evidence="ECO:0007829|PDB:3OGG"
FT TURN 991..993
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1003..1009
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1013..1019
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1022..1028
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1040..1044
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1055..1065
FT /evidence="ECO:0007829|PDB:3OGG"
FT HELIX 1069..1079
FT /evidence="ECO:0007829|PDB:3OGG"
FT TURN 1080..1083
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1090..1092
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1098..1103
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1109..1114
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1117..1122
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1135..1139
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1150..1152
FT /evidence="ECO:0007829|PDB:3RMX"
FT STRAND 1154..1161
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1164..1170
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1188..1196
FT /evidence="ECO:0007829|PDB:3OGG"
FT HELIX 1201..1203
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1204..1209
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1218..1222
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1224..1226
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1228..1235
FT /evidence="ECO:0007829|PDB:3OGG"
FT TURN 1239..1242
FT /evidence="ECO:0007829|PDB:3RMY"
FT STRAND 1245..1253
FT /evidence="ECO:0007829|PDB:3OGG"
FT HELIX 1255..1257
FT /evidence="ECO:0007829|PDB:3OGG"
FT HELIX 1261..1263
FT /evidence="ECO:0007829|PDB:3OGG"
FT STRAND 1265..1268
FT /evidence="ECO:0007829|PDB:3OGG"
SQ SEQUENCE 1276 AA; 146872 MW; C1EC50F46C8233E2 CRC64;
MTWPVKDFNY SDPVNDNDIL YLRIPQNKLI TTPVKAFMIT QNIWVIPERF SSDTNPSLSK
PPRPTSKYQS YYDPSYLSTD EQKDTFLKGI IKLFKRINER DIGKKLINYL VVGSPFMGDS
STPEDTFDFT RHTTNIAVEK FENGSWKVTN IITPSVLIFG PLPNILDYTA SLTLQGQQSN
PSFEGFGTLS ILKVAPEFLL TFSDVTSNQS SAVLGKSIFC MDPVIALMHE LTHSLHQLYG
INIPSDKRIR PQVSEGFFSQ DGPNVQFEEL YTFGGLDVEI IPQIERSQLR EKALGHYKDI
AKRLNNINKT IPSSWISNID KYKKIFSEKY NFDKDNTGNF VVNIDKFNSL YSDLTNVMSE
VVYSSQYNVK NRTHYFSRHY LPVFANILDD NIYTIRDGFN LTNKGFNIEN SGQNIERNPA
LQKLSSESVV DLFTKVCLRL TKNSRDDSTC IKVKNNRLPY VADKDSISQE IFENKIITDE
TNVQNYSDKF SLDESILDGQ VPINPEIVDP LLPNVNMEPL NLPGEEIVFY DDITKYVDYL
NSYYYLESQK LSNNVENITL TTSVEEALGY SNKIYTFLPS LAEKVNKGVQ AGLFLNWANE
VVEDFTTNIM KKDTLDKISD VSVIIPYIGP ALNIGNSALR GNFNQAFATA GVAFLLEGFP
EFTIPALGVF TFYSSIQERE KIIKTIENCL EQRVKRWKDS YQWMVSNWLS RITTQFNHIN
YQMYDSLSYQ ADAIKAKIDL EYKKYSGSDK ENIKSQVENL KNSLDVKISE AMNNINKFIR
ECSVTYLFKN MLPKVIDELN KFDLRTKTEL INLIDSHNII LVGEVDRLKA KVNESFENTM
PFNIFSYTNN SLLKDIINEY FNSINDSKIL SLQNKKNALV DTSGYNAEVR VGDNVQLNTI
YTNDFKLSSS GDKIIVNLNN NILYSAIYEN SSVSFWIKIS KDLTNSHNEY TIINSIEQNS
GWKLCIRNGN IEWILQDVNR KYKSLIFDYS ESLSHTGYTN KWFFVTITNN IMGYMKLYIN
GELKQSQKIE DLDEVKLDKT IVFGIDENID ENQMLWIRDF NIFSKELSNE DINIVYEGQI
LRNVIKDYWG NPLKFDTEYY IINDNYIDRY IAPESNVLVL VQYPDRSKLY TGNPITIKSV
SDKNPYSRIL NGDNIILHML YNSRKYMIIR DTDTIYATQG GECSQNCVYA LKLQSNLGNY
GIGIFSIKNI VSKNKYCSQI FSSFRENTML LADIYKPWRF SFKNAYTPVA VTNYETKLLS
TSSFWKFISR DPGWVE
