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 02-SEP-2026, entry version 189. 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. 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:16252491, PubMed:8175689). 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 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:20704566, PubMed:20731382). 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 already-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:16115873, PubMed:16252491). 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 --------------------------------------------------------------------------- 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 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; EXP:UniProtKB. DR GO; GO:1905576; F:ganglioside GT1b binding; IDA:UniProtKB. DR GO; GO:0004222; F:metalloendopeptidase activity; EXP:UniProtKB. DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW. DR GO; GO:0008320; F:transmembrane protein transporter activity; TAS:Reactome. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd23391; Toxin_R_bind_C_BoNTD_like; 1. DR FunFam; 1.20.1120.10:FF:000002; Botulinum neurotoxin type D; 1. DR FunFam; 2.80.10.50:FF:000149; Botulinum neurotoxin type D; 1. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 2.80.10.50; -; 1. DR Gene3D; 1.20.1120.10; Clostridium botulinum neurotoxin b, 'coiled-coil' domain; 1. DR Gene3D; 3.90.1240.10; Metalloproteases ('zincins'), catalytic domain like; 2. 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; SSF58091; Clostridium neurotoxins, 'coiled-coil' domain; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR SUPFAM; SSF50386; STI-like; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. 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; -. 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 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 1172 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 1173 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 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 FT A-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 FT A-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 HELIX 114..116 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 HELIX 242..244 FT /evidence="ECO:0007829|PDB:2FPQ" FT STRAND 247..249 FT /evidence="ECO:0007829|PDB:5BQN" FT HELIX 262..264 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..352 FT /evidence="ECO:0007829|PDB:2FPQ" FT HELIX 353..357 FT /evidence="ECO:0007829|PDB:2FPQ" FT HELIX 360..366 FT /evidence="ECO:0007829|PDB:2FPQ" FT HELIX 377..379 FT /evidence="ECO:0007829|PDB:5BQN" 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 HELIX 517..519 FT /evidence="ECO:0007829|PDB:5BQN" FT HELIX 529..532 FT /evidence="ECO:0007829|PDB:5BQM" FT STRAND 533..539 FT /evidence="ECO:0007829|PDB:5BQN" FT HELIX 542..548 FT /evidence="ECO:0007829|PDB:5BQN" FT HELIX 550..552 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 659..662 FT /evidence="ECO:0007829|PDB:5BQM" FT HELIX 666..669 FT /evidence="ECO:0007829|PDB:5BQN" FT HELIX 680..682 FT /evidence="ECO:0007829|PDB:5BQN" FT HELIX 684..707 FT /evidence="ECO:0007829|PDB:5BQN" FT HELIX 708..712 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..785 FT /evidence="ECO:0007829|PDB:5BQN" FT HELIX 786..791 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 HELIX 1036..1038 FT /evidence="ECO:0007829|PDB:3N7J" 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 HELIX 1174..1176 FT /evidence="ECO:0007829|PDB:3N7J" 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 //