BXE_CLOBO
ID BXE_CLOBO Reviewed; 1251 AA.
AC Q00496; Q45862;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Botulinum neurotoxin type E;
DE Short=BoNT/E {ECO:0000303|PubMed:8408542};
DE AltName: Full=Bontoxilysin-E;
DE Contains:
DE RecName: Full=Botulinum neurotoxin E light chain;
DE Short=LC;
DE EC=3.4.24.69 {ECO:0000269|PubMed:8243676};
DE Contains:
DE RecName: Full=Botulinum neurotoxin E heavy chain;
DE Short=HC;
DE Flags: Precursor;
GN Name=botE {ECO:0000303|PubMed:1541280};
OS Clostridium botulinum.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=1491;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Beluga / Type E;
RX PubMed=1543481; DOI=10.1016/0006-291x(92)91615-w;
RA Poulet S., Hauser D., Quanz M., Niemann H., Popoff M.R.;
RT "Sequences of the botulinal neurotoxin E derived from Clostridium botulinum
RT type E (strain Beluga) and Clostridium butyricum (strains ATCC 43181 and
RT ATCC 43755).";
RL Biochem. Biophys. Res. Commun. 183:107-113(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NCTC 11219 / Type E;
RX PubMed=1541280; DOI=10.1111/j.1432-1033.1992.tb16679.x;
RA Whelan S.M., Elmore M.J., Bodsworth N.J., Atkinson T., Minton N.P.;
RT "The complete amino acid sequence of the Clostridium botulinum type-E
RT neurotoxin, derived by nucleotide-sequence analysis of the encoding gene.";
RL Eur. J. Biochem. 204:657-667(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-252.
RC STRAIN=Beluga / Type E;
RX PubMed=2160960; DOI=10.1016/s0021-9258(19)38824-6;
RA Binz T., Kurazono H., Wille M., Frevert J., Wernars K., Niemann H.;
RT "The complete sequence of botulinum neurotoxin type A and comparison with
RT other clostridial neurotoxins.";
RL J. Biol. Chem. 265:9153-9158(1990).
RN [4]
RP PROTEIN SEQUENCE OF 2-14.
RC STRAIN=Alaska E43 / Type E3;
RX PubMed=3888113; DOI=10.1016/0003-9861(85)90198-5;
RA Schmidt J.J., Sathyamoorthy V., Dasgupta B.R.;
RT "Partial amino acid sequences of botulinum neurotoxins types B and E.";
RL Arch. Biochem. Biophys. 238:544-548(1985).
RN [5]
RP PROTEIN SEQUENCE OF 420-427.
RC STRAIN=Alaska E43 / Type E3;
RX PubMed=2116911; DOI=10.1016/0300-9084(90)90075-r;
RA Gimenez J.A., Dasgupta B.R.;
RT "Botulinum neurotoxin type E fragmented with endoproteinase Lys-C reveals
RT the site trypsin nicks and homology with tetanus neurotoxin.";
RL Biochimie 72:213-217(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 616-982.
RC STRAIN=Hazen 36208 / ATCC 9564 / Type E;
RX PubMed=8408542; DOI=10.1128/jcm.31.9.2255-2262.1993;
RA Campbell K.D., Collins M.D., East A.K.;
RT "Gene probes for identification of the botulinal neurotoxin gene and
RT specific identification of neurotoxin types B, E, and F.";
RL J. Clin. Microbiol. 31:2255-2262(1993).
RN [7]
RP RELEASED AS SINGLE CHAIN.
RC STRAIN=Type E;
RX PubMed=6353669; DOI=10.1016/0041-0101(83)90131-9;
RA DasGupta B.R., Rasmussen S.;
RT "Purification and amino acid composition of type E botulinum neurotoxin.";
RL Toxicon 21:535-545(1983).
RN [8]
RP RELEASED AS SINGLE CHAIN.
RC STRAIN=Alaska E43 / Type E3;
RX PubMed=4030755; DOI=10.1016/s0021-9258(19)85105-0;
RA Sathyamoorthy V., DasGupta B.R.;
RT "Separation, purification, partial characterization and comparison of the
RT heavy and light chains of botulinum neurotoxin types A, B, and E.";
RL J. Biol. Chem. 260:10461-10466(1985).
RN [9]
RP IDENTIFICATION AS A ZINC-BINDING PROTEIN, AND COFACTOR.
RC STRAIN=Type E;
RX PubMed=1429690; DOI=10.1016/s0021-9258(18)35863-0;
RA Schiavo G., Rossetto O., Santucci A., Dasgupta B.R., Montecucco C.;
RT "Botulinum neurotoxins are zinc proteins.";
RL J. Biol. Chem. 267:23479-23483(1992).
RN [10]
RP HOST RANGE, AND EPIDEMIOLOGY.
RX PubMed=1431246; DOI=10.1093/infdis/166.6.1281;
RA Woodruff B.A., Griffin P.M., McCroskey L.M., Smart J.F., Wainwright R.B.,
RA Bryant R.G., Hutwagner L.C., Hatheway C.L.;
RT "Clinical and laboratory comparison of botulism from toxin types A, B, and
RT E in the United States, 1975-1988.";
RL J. Infect. Dis. 166:1281-1286(1992).
RN [11]
RP FUNCTION (BOTULINUM NEUROTOXIN E LIGHT CHAIN), IDENTIFICATION OF SUBSTRATE,
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN E LIGHT
RP CHAIN).
RC STRAIN=Type E;
RX PubMed=8243676; DOI=10.1016/0014-5793(93)80448-4;
RA Schiavo G., Santtuci A., Dasgupta B.R., Mehta P.P., Jontes J.,
RA Benfenati F., Wilson M.C., Montecucco C.;
RT "Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-
RT terminal peptide bonds.";
RL FEBS Lett. 335:99-103(1993).
RN [12]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE E AND BOTULINUM NEUROTOXIN E LIGHT
RP CHAIN), IDENTIFICATION OF SUBSTRATE, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN E LIGHT CHAIN).
RC STRAIN=Beluga / Type E;
RX PubMed=8294407; DOI=10.1016/s0021-9258(17)42071-0;
RA Binz T., Blasi J., Yamasaki S., Baumeister A., Link E., Suedhof T.C.,
RA Jahn R., Niemann H.;
RT "Proteolysis of SNAP-25 by types E and A botulinal neurotoxins.";
RL J. Biol. Chem. 269:1617-1620(1994).
RN [13]
RP FUNCTION (BOTULINUM NEUROTOXIN E HEAVY CHAIN), AND SUBCELLULAR LOCATION
RP (BOTULINUM NEUROTOXIN E HEAVY CHAIN).
RC STRAIN=NCTC 11219 / Type E;
RX PubMed=10413679; DOI=10.1242/jcs.112.16.2715;
RA Lalli G., Herreros J., Osborne S.L., Montecucco C., Rossetto O.,
RA Schiavo G.;
RT "Functional characterisation of tetanus and botulinum neurotoxins binding
RT domains.";
RL J. Cell Sci. 112:2715-2724(1999).
RN [14]
RP FUNCTION (BOTULINUM NEUROTOXIN E LIGHT CHAIN), SUBSTRATE SPECIFICITY, AND
RP CATALYTIC ACTIVITY.
RC STRAIN=Beluga / Type E;
RX PubMed=9886085; DOI=10.1046/j.1471-4159.1999.0720327.x;
RA Vaidyanathan V.V., Yoshino K., Jahnz M., Doerries C., Bade S.,
RA Nauenburg S., Niemann H., Binz T.;
RT "Proteolysis of SNAP-25 isoforms by botulinum neurotoxin types A, C, and E:
RT domains and amino acid residues controlling the formation of enzyme-
RT substrate complexes and cleavage.";
RL J. Neurochem. 72:327-337(1999).
RN [15]
RP FUNCTION (BOTULINUM NEUROTOXIN E LIGHT AND BOTULINUM NEUROTOXIN E HEAVY
RP CHAIN), AND DISULFIDE BOND.
RC STRAIN=Type E;
RX PubMed=17666397; DOI=10.1074/jbc.m703619200;
RA Fischer A., Montal M.;
RT "Crucial role of the disulfide bridge between botulinum neurotoxin light
RT and heavy chains in protease translocation across membranes.";
RL J. Biol. Chem. 282:29604-29611(2007).
RN [16]
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 [17]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE E), IDENTIFICATION OF HOST RECEPTOR,
RP AND INTERACTION WITH HOST SV2A AND SV2B.
RC STRAIN=Type E;
RX PubMed=18815274; DOI=10.1091/mbc.e08-07-0765;
RA Dong M., Liu H., Tepp W.H., Johnson E.A., Janz R., Chapman E.R.;
RT "Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E
RT into neurons.";
RL Mol. Biol. Cell 19:5226-5237(2008).
RN [18]
RP FUNCTION (BOTULINUM NEUROTOXIN E HEAVY CHAIN), AND INTERACTION WITH HOST
RP SV2 AND SYT1.
RX PubMed=19476346; DOI=10.1021/bi9002138;
RA Fu Z., Chen C., Barbieri J.T., Kim J.J., Baldwin M.R.;
RT "Glycosylated SV2 and gangliosides as dual receptors for botulinum
RT neurotoxin serotype F.";
RL Biochemistry 48:5631-5641(2009).
RN [19]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE E AND BOTULINUM NEUROTOXIN E HEAVY
RP CHAIN), INTERACTION WITH HOST SV2A AND SV2B, GANGLIOSIDE-BINDING, AND
RP MUTAGENESIS OF GLU-1172 AND TRP-1223.
RC STRAIN=NCTC 11219 / Type E;
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 [20]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE E), SUBUNIT, AND SUBCELLULAR LOCATION
RP (BOTULINUM NEUROTOXIN TYPE E).
RC STRAIN=Type E;
RX PubMed=22720883; DOI=10.1021/bi3004928;
RA Sun S., Tepp W.H., Johnson E.A., Chapman E.R.;
RT "Botulinum neurotoxins B and E translocate at different rates and exhibit
RT divergent responses to GT1b and low pH.";
RL Biochemistry 51:5655-5662(2012).
RN [21]
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 [22] {ECO:0007744|PDB:1T3A, ECO:0007744|PDB:1T3C}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 2-422 IN COMPLEX WITH ZINC,
RP FUNCTION (BOTULINUM NEUROTOXIN E LIGHT CHAIN), REACTION MECHANISM, ACTIVE
RP SITE, COFACTOR, AND MUTAGENESIS OF GLU-213.
RC STRAIN=Type E;
RX PubMed=15157097; DOI=10.1021/bi036278w;
RA Agarwal R., Eswaramoorthy S., Kumaran D., Binz T., Swaminathan S.;
RT "Structural analysis of botulinum neurotoxin type E catalytic domain and
RT its mutant Glu212-->Gln reveals the pivotal role of the Glu212 carboxylate
RT in the catalytic pathway.";
RL Biochemistry 43:6637-6644(2004).
RN [23] {ECO:0007744|PDB:1ZKW, ECO:0007744|PDB:1ZKX, ECO:0007744|PDB:1ZL5, ECO:0007744|PDB:1ZL6, ECO:0007744|PDB:1ZN3}
RP X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS) OF MUTATED 2-421 IN COMPLEX WITH
RP ZINC, FUNCTION (BOTULINUM NEUROTOXIN E LIGHT CHAIN), REACTION MECHANISM,
RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, BIOTECHNOLOGY, AND MUTAGENESIS OF
RP 159-GLU--ASN-161; GLU-250; GLU-336; ARG-348 AND TYR-351.
RC STRAIN=Type E;
RX PubMed=15938619; DOI=10.1021/bi050253a;
RA Agarwal R., Binz T., Swaminathan S.;
RT "Analysis of active site residues of botulinum neurotoxin E by mutational,
RT functional, and structural studies: Glu335Gln is an apoenzyme.";
RL Biochemistry 44:8291-8302(2005).
RN [24]
RP STRUCTURE BY ELECTRON MICROSCOPY (24.0 ANGSTROMS), AND DOMAIN.
RC STRAIN=Type E;
RX PubMed=18032388; DOI=10.1074/jbc.m707917200;
RA Fischer A., Garcia-Rodriguez C., Geren I., Lou J., Marks J.D., Nakagawa T.,
RA Montal M.;
RT "Molecular architecture of botulinum neurotoxin E revealed by single
RT particle electron microscopy.";
RL J. Biol. Chem. 283:3997-4003(2008).
RN [25] {ECO:0007744|PDB:3FFZ}
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) IN COMPLEX WITH ZINC, COFACTOR,
RP DOMAIN, AND DISULFIDE BONDS.
RC STRAIN=Type E;
RX PubMed=19118561; DOI=10.1016/j.jmb.2008.12.027;
RA Kumaran D., Eswaramoorthy S., Furey W., Navaza J., Sax M., Swaminathan S.;
RT "Domain organization in Clostridium botulinum neurotoxin type E is unique:
RT its implication in faster translocation.";
RL J. Mol. Biol. 386:233-245(2009).
CC -!- FUNCTION: [Botulinum neurotoxin type E]: Botulinum toxin causes flaccid
CC paralysis by inhibiting neurotransmitter (acetylcholine) release from
CC the presynaptic membranes of nerve terminals of eukaryotic host
CC skeletal and autonomic nervous system, with frequent heart or
CC respiratory failure. Precursor of botulinum neurotoxin E which has 2
CC coreceptors; complex polysialylated gangliosides found on neural tissue
CC and specific membrane-anchored proteins found in synaptic vesicles.
CC Receptor proteins are exposed on host presynaptic cell membrane during
CC neurotransmitter release, when the toxin heavy chain (HC) binds to them
CC (PubMed:19476346, PubMed:19650874). Upon synaptic vesicle recycling the
CC toxin is taken up via the endocytic pathway. When the pH of the toxin-
CC containing endosome drops a structural rearrangement occurs so that the
CC N-terminus of the HC forms pores that allows the light chain (LC) to
CC translocate into the cytosol (PubMed:22720883). 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 Electrical stimulation increases uptake of toxin, probably by
CC transiently exposing a receptor found in eukaryotic target synaptic
CC vesicles (PubMed:19476346, PubMed:19650874). Uses the large lumenal
CC domain of synaptic vesicle glycoproteins 2A and 2B (SV2A and SV2B) but
CC not SV2C as receptor; an N-linked glycan of SV2 is essential for
CC receptor function (PubMed:18815274, PubMed:19476346). Host cell
CC gangliosides are also required for neurotoxin uptake and full toxicity
CC (PubMed:18815274, PubMed:19650874). BoNT/E is a 'coincidence detector';
CC it requires simultaneous binding to coreceptor GT1b and low pH to
CC transform into a membrane-bound, oligomeric channel (PubMed:22720883).
CC Requires trypsinization and reduction before it can be used in assays
CC in vitro (PubMed:8294407). {ECO:0000250|UniProtKB:P0DPI0,
CC ECO:0000269|PubMed:18815274, ECO:0000269|PubMed:19476346,
CC ECO:0000269|PubMed:19650874, ECO:0000269|PubMed:22720883,
CC ECO:0000305|PubMed:8294407}.
CC -!- FUNCTION: [Botulinum neurotoxin E light chain]: Has proteolytic
CC activity (PubMed:8243676, PubMed:8294407, PubMed:9886085). After
CC translocation into the eukaryotic host cytosol, inhibits
CC neurotransmitter release by acting as a zinc endopeptidase that
CC catalyzes the hydrolysis of the '180-Arg-|-Ile-181' bond in SNAP25
CC (PubMed:8243676, PubMed:8294407, PubMed:9886085). Hydrolyzes the '185-
CC Arg-|-Ile-186' bond of mouse SNAP23, but not in human which has a
CC different sequence (PubMed:9886085). Recognizes the '146-Met--Asp-186'
CC region of SNAP25 (PubMed:9886085). The reaction mechanism probably has
CC a nucleophilic water held in place by Glu-213 (PubMed:15157097,
CC PubMed:15938619). Reduction of the interchain disulfide bond occurs in
CC the host cytosol and probably prevents retrotranslocation into the
CC synaptic vesicle (PubMed:17666397). {ECO:0000269|PubMed:15157097,
CC ECO:0000269|PubMed:15938619, ECO:0000269|PubMed:17666397,
CC ECO:0000269|PubMed:8243676, ECO:0000269|PubMed:8294407,
CC ECO:0000269|PubMed:9886085}.
CC -!- FUNCTION: [Botulinum neurotoxin E heavy chain]: Responsible for host
CC epithelial cell transcytosis, host nerve cell targeting and
CC translocation of light chain (LC) into host cytosol (PubMed:17666397).
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 cell surface
CC (PubMed:10413679). It probably simultaneously recognizes 2 coreceptors;
CC polysialated gangliosides and either of the receptor proteins SV2A and
CC SV2B in close proximity on host synaptic vesicles (PubMed:18815274,
CC PubMed:19650874, PubMed:19476346). The N-terminus of the TD wraps an
CC extended belt around the perimeter of the light chain (LC), protecting
CC Zn(2+) in the active site (PubMed:19118561). The belt may also prevent
CC premature LC dissociation from the translocation channel and protect
CC toxin prior to translocation (PubMed:17907800). The TD inserts into
CC synaptic vesicle membrane to allow translocation into the host cytosol
CC (By similarity). Responsible for adherence of the toxin to the cell
CC surface; HC alone prevents uptake of whole toxin by neural cells, and
CC delays paralysis onset by 154% (PubMed:10413679). Significantly
CC decreases uptake and toxicity of whole BoNT/E, but also interferes with
CC uptake of BoNT/C; binds GT1b in vitro (PubMed:19650874). Binds to
CC synaptic vesicle glycoproteins SV2A and SV2B which serve as coreceptors
CC with gangliosides (PubMed:18815274, PubMed:19650874). Interaction with
CC SV2 proteins requires SV2 glycosylation (PubMed:19476346). HC alone
CC significantly decreases uptake and toxicity of whole BoNT/E
CC (PubMed:19650874). HC is responsible for translocation of LC into the
CC host cytosol; an intact disulfide bond between the 2 subunits is
CC required for translocation, which is reduced upon contact with the host
CC cytosol (PubMed:17666397). {ECO:0000250|UniProtKB:P0DPI0,
CC ECO:0000269|PubMed:10413679, ECO:0000269|PubMed:17666397,
CC ECO:0000269|PubMed:18815274, ECO:0000269|PubMed:19476346,
CC ECO:0000269|PubMed:19650874, 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:8243676, ECO:0000269|PubMed:8294407,
CC ECO:0000269|PubMed:9886085};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:1429690, ECO:0000269|PubMed:15157097,
CC ECO:0000269|PubMed:15938619, ECO:0000269|PubMed:19118561};
CC Note=Binds 1 zinc ion per subunit (PubMed:1429690, PubMed:15157097,
CC PubMed:15938619, PubMed:19118561). {ECO:0000269|PubMed:1429690,
CC ECO:0000269|PubMed:15157097, ECO:0000269|PubMed:15938619,
CC ECO:0000269|PubMed:19118561};
CC -!- ACTIVITY REGULATION: Proteolysis of SNAP25 by whole toxin inhibited by
CC dipicolinic acid, 1,10-phenanthroline and EDTA (PubMed:8294407).
CC {ECO:0000269|PubMed:8294407}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.9 uM for purified SNAP25 with botulinum neurotoxin E light chain
CC {ECO:0000269|PubMed:15938619};
CC Note=kcat is 257 min (-1) with botulinum neurotoxin E light chain.
CC {ECO:0000269|PubMed:15938619};
CC -!- SUBUNIT: Heterodimer; disulfide-linked heterodimer of a light chain
CC (LC) and a heavy chain (HC); cleavage occurs after bacterial export by
CC host proteases (PubMed:6353669, PubMed:4030755, PubMed:19118561). The
CC LC has the proteolytic/pharmacological activity, while the N- and C-
CC terminal of the HC mediate channel formation and toxin binding,
CC respectively. Oligomerizes in the presence of coreceptor ganglioside
CC GT1b between pH 4.4 and 8.0; it might oligomerize on host cell surface
CC (PubMed:22720883). Interacts with host synaptic vesicle glycoproteins
CC SV2A and SV2B (PubMed:18815274, PubMed:19650874). HC interacts with a
CC complex including at least host SV2 and synaptotagmin-1 (SYT1);
CC copurification depends on glycosylation of SV2 (PubMed:19476346).
CC {ECO:0000269|PubMed:18815274, ECO:0000269|PubMed:19118561,
CC ECO:0000269|PubMed:19476346, ECO:0000269|PubMed:19650874,
CC ECO:0000269|PubMed:22720883, ECO:0000269|PubMed:4030755,
CC ECO:0000269|PubMed:6353669}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin type E]: Secreted
CC {ECO:0000305|PubMed:8294407}. Note=At pH 4.4 in the presence of
CC ganglioside GT1b, becomes a membrane-associated hydrophobic protein
CC (PubMed:22720883). {ECO:0000269|PubMed:22720883}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin E light chain]: Secreted.
CC Host cytoplasm, host cytosol {ECO:0000305|PubMed:8243676,
CC ECO:0000305|PubMed:8294407}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin E heavy chain]: Secreted.
CC Host synapse, host presynaptic cell membrane
CC {ECO:0000305|PubMed:10413679}. Host cytoplasmic vesicle, host secretory
CC vesicle, host synaptic vesicle membrane {ECO:0000250|UniProtKB:P0DPI0};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- DOMAIN: [Botulinum neurotoxin E light chain]: Has protease activity
CC (PubMed:8243676, PubMed:8294407, PubMed:9886085).
CC {ECO:0000269|PubMed:8243676, ECO:0000269|PubMed:8294407,
CC ECO:0000269|PubMed:9886085}.
CC -!- DOMAIN: [Botulinum neurotoxin E heavy chain]: Has 3 functional domains;
CC the translocation domain (TD) and the receptor-binding domain (RBD)
CC which is further subdivided into N- and C-terminal domains (N-RBD and
CC C-RBD) (PubMed:19118561). In BoNT/E the domains are arranged
CC differently than BoNT/A and BoNT/B; in BoNT/E the LC and RBD are on the
CC same side of the TD and are in contact, whereas in BoNT/A and BoNT/B
CC the LC is separated from the RBD by the TD (PubMed:19118561). The
CC putative transmembrane region is closer to the receptor-binding regions
CC in this toxin, which may explain why it acts faster than BoNT/A and
CC BoNT/B (PubMed:19118561). The N-terminus of the TD wraps an extended
CC belt around the perimeter of the LC, partially protecting Zn(2+) in the
CC active site (PubMed:19118561). The belt may be a pseudosubstrate
CC inhibitor which serves as an intramolecular chaperone for the LC prior
CC to its translocation into the host cytosol (PubMed:17907800). The RBD
CC binds transiently exposed coreceptors on the host presynaptic cell
CC membrane (PubMed:18815274, PubMed:19650874, PubMed:19476346).
CC {ECO:0000269|PubMed:18815274, ECO:0000269|PubMed:19118561,
CC ECO:0000269|PubMed:19476346, ECO:0000269|PubMed:19650874,
CC ECO:0000305|PubMed:17907800}.
CC -!- BIOTECHNOLOGY: Double mutants Gln-213/Gln-336 or Gln-213/Ala-351 might
CC be suitable as vaccine candiates (PubMed:15938619).
CC {ECO:0000305|PubMed:15938619}.
CC -!- MISCELLANEOUS: There are seven antigenically distinct forms of
CC botulinum neurotoxin: Types A, B, C, D, E, F, and G; new subtypes are
CC quite frequent.
CC -!- MISCELLANEOUS: Botulism poisoning is usually food-borne, either by
CC ingesting toxin or bacterial-contaminated food, or less frequently by
CC inhalation poisoning. In both cases the neurotoxin binds to the apical
CC surface of epithelial cells in the gut or airway. Toxin undergoes
CC receptor-mediated endocytosis (using a different receptor than on
CC target nerve cells), transcytosis across the epithelial cells and
CC release into the general circulation. Once in the general circulation
CC it binds to its target cells. {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- MISCELLANEOUS: Types A, B and E are the most frequent cause of adult
CC human foodborne botulism; type A is the most severe, while type E has
CC the shortest incubation period (PubMed:1431246).
CC {ECO:0000269|PubMed:1431246}.
CC -!- MISCELLANEOUS: Unlike botulinum neurotoxin type A, type E is released
CC from bacteria as a single chain and cleaved by host proteases into the
CC active dichain (PubMed:6353669, PubMed:4030755, PubMed:19118561,
CC PubMed:8294407). {ECO:0000269|PubMed:19118561,
CC ECO:0000269|PubMed:4030755, ECO:0000269|PubMed:6353669,
CC ECO:0000305|PubMed:8294407}.
CC -!- SIMILARITY: Belongs to the peptidase M27 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=BotDB - A Database Resource for Clostridial
CC Neurotoxins;
CC URL="https://botdb.abcc.ncifcrf.gov/";
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; X62089; CAA43999.1; -; Genomic_DNA.
DR EMBL; X62683; CAA44558.1; -; Genomic_DNA.
DR EMBL; X70815; CAA50146.1; -; Genomic_DNA.
DR PIR; S08575; S08575.
DR PIR; S21178; S21178.
DR RefSeq; WP_003372387.1; NZ_LHUM01000023.1.
DR PDB; 1T3A; X-ray; 2.16 A; A/B=2-422.
DR PDB; 1T3C; X-ray; 1.90 A; A/B=2-422.
DR PDB; 1ZKW; X-ray; 2.17 A; A/B=2-421.
DR PDB; 1ZKX; X-ray; 2.52 A; A/B=2-421.
DR PDB; 1ZL5; X-ray; 2.60 A; A/B=2-421.
DR PDB; 1ZL6; X-ray; 2.40 A; A/B=2-421.
DR PDB; 1ZN3; X-ray; 2.60 A; A/B=2-421.
DR PDB; 3FFZ; X-ray; 2.65 A; A/B=1-1251.
DR PDB; 7K7Y; X-ray; 3.60 A; A/B/E/G=1-845.
DR PDB; 7K84; X-ray; 2.50 A; A=1-845.
DR PDBsum; 1T3A; -.
DR PDBsum; 1T3C; -.
DR PDBsum; 1ZKW; -.
DR PDBsum; 1ZKX; -.
DR PDBsum; 1ZL5; -.
DR PDBsum; 1ZL6; -.
DR PDBsum; 1ZN3; -.
DR PDBsum; 3FFZ; -.
DR PDBsum; 7K7Y; -.
DR PDBsum; 7K84; -.
DR AlphaFoldDB; Q00496; -.
DR SMR; Q00496; -.
DR DIP; DIP-46083N; -.
DR IntAct; Q00496; 4.
DR MINT; Q00496; -.
DR BindingDB; Q00496; -.
DR ChEMBL; CHEMBL1697662; -.
DR DrugBank; DB13897; Equine Botulinum Neurotoxin E Immune FAB2.
DR TCDB; 1.C.8.1.3; the botulinum and tetanus toxin (btt) family.
DR ABCD; Q00496; 8 sequenced antibodies.
DR KEGG; ag:CAA43999; -.
DR BRENDA; 3.4.24.69; 1462.
DR Reactome; R-HSA-5250992; Toxicity of botulinum toxin type E (botE).
DR EvolutionaryTrace; Q00496; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044161; C:host cell cytoplasmic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0044156; C:host cell junction; IEA:UniProtKB-KW.
DR GO; GO:0044231; C:host cell presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0008320; F:protein transmembrane transporter activity; EXP: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 DisProt; DP00732; -.
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;
KW Host cell membrane; Host cytoplasm; Host cytoplasmic vesicle;
KW Host membrane; Host synapse; Hydrolase; Lipid-binding; Membrane;
KW Metal-binding; Metalloprotease; Neurotoxin; Protease; Secreted; Toxin;
KW Transmembrane; Virulence; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:3888113"
FT CHAIN 2..1251
FT /note="Botulinum neurotoxin type E"
FT /id="PRO_0000444907"
FT CHAIN 2..422
FT /note="Botulinum neurotoxin E light chain"
FT /id="PRO_0000029221"
FT CHAIN 423..1251
FT /note="Botulinum neurotoxin E heavy chain"
FT /id="PRO_0000029222"
FT REGION 423..819
FT /note="Translocation domain (TD)"
FT /evidence="ECO:0000305|PubMed:19118561"
FT REGION 466..515
FT /note="Belt"
FT /evidence="ECO:0000305|PubMed:19118561"
FT REGION 845..1067
FT /note="N-terminus of receptor binding domain (N-RBD)"
FT /evidence="ECO:0000305|PubMed:19118561"
FT REGION 850..1251
FT /note="Receptor-binding domain (TD)"
FT /evidence="ECO:0000305|PubMed:19118561"
FT REGION 1068..1251
FT /note="C-terminus of receptor binding domain (C-RBD)"
FT /evidence="ECO:0000305|PubMed:19118561"
FT MOTIF 1221..1224
FT /note="Host ganglioside-binding motif"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000305|PubMed:19650874"
FT ACT_SITE 213
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000305|PubMed:15157097"
FT BINDING 212
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0007744|PDB:1T3A, ECO:0007744|PDB:1T3C,
FT ECO:0007744|PDB:1ZKW, ECO:0007744|PDB:1ZKX,
FT ECO:0007744|PDB:1ZL6, ECO:0007744|PDB:1ZN3,
FT ECO:0007744|PDB:3FFZ"
FT BINDING 216
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0007744|PDB:1T3A, ECO:0007744|PDB:1T3C,
FT ECO:0007744|PDB:1ZKW, ECO:0007744|PDB:1ZKX,
FT ECO:0007744|PDB:1ZL6, ECO:0007744|PDB:1ZN3,
FT ECO:0007744|PDB:3FFZ"
FT BINDING 251
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0007744|PDB:1T3A, ECO:0007744|PDB:1T3C,
FT ECO:0007744|PDB:1ZKW, ECO:0007744|PDB:1ZKX,
FT ECO:0007744|PDB:1ZL6, ECO:0007744|PDB:1ZN3,
FT ECO:0007744|PDB:3FFZ"
FT DISULFID 412..426
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000269|PubMed:19118561,
FT ECO:0000305|PubMed:17666397, ECO:0007744|PDB:3FFZ"
FT MUTAGEN 159..161
FT /note="ETN->AAA: KM for SNAP25 unchanged, kcat 10-fold
FT reduced."
FT /evidence="ECO:0000269|PubMed:15938619"
FT MUTAGEN 213
FT /note="E->Q: No cleavage of SNAP25."
FT /evidence="ECO:0000269|PubMed:15157097"
FT MUTAGEN 250
FT /note="E->A: KM unchanged, kcat 10-fold reduced."
FT /evidence="ECO:0000269|PubMed:15938619"
FT MUTAGEN 336
FT /note="E->A: KM unchanged, kcat 30-fold reduced, binds zinc
FT in crystal."
FT /evidence="ECO:0000269|PubMed:15938619"
FT MUTAGEN 336
FT /note="E->Q: No cleavage of SNAP25. KM unchanged, kcat
FT 5700-fold reduced, zinc replaced by H(2)O in crystal."
FT /evidence="ECO:0000269|PubMed:15157097,
FT ECO:0000269|PubMed:15938619"
FT MUTAGEN 348
FT /note="R->A: KM unchanged, kcat 700-fold reduced."
FT /evidence="ECO:0000269|PubMed:15938619"
FT MUTAGEN 351
FT /note="Y->A: No cleavage of SNAP25."
FT /evidence="ECO:0000269|PubMed:15938619"
FT MUTAGEN 1172
FT /note="E->A: Significantly decreased toxicity, dramatically
FT decreased binding of heavy chain to synaptosomes,
FT significantly decreased binding to ganglioside GT1b."
FT /evidence="ECO:0000269|PubMed:19650874"
FT MUTAGEN 1223
FT /note="W->L: Dramatically decreased toxicity, dramatically
FT decreased binding of heavy chain to synaptosomes,
FT dramatically decreased binding to ganglioside GT1b."
FT /evidence="ECO:0000269|PubMed:19650874"
FT CONFLICT 177
FT /note="R -> G (in Ref. 2; CAA44558)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="C -> S (in Ref. 2; CAA44558 and 3; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="R -> A (in Ref. 2; CAA44558)"
FT /evidence="ECO:0000305"
FT CONFLICT 773
FT /note="I -> L (in Ref. 2; CAA44558 and 6; CAA50146)"
FT /evidence="ECO:0000305"
FT CONFLICT 963..964
FT /note="FE -> LQ (in Ref. 2; CAA44558 and 6; CAA50146)"
FT /evidence="ECO:0000305"
FT CONFLICT 967
FT /note="R -> A (in Ref. 2; CAA44558 and 6; CAA50146)"
FT /evidence="ECO:0000305"
FT CONFLICT 1195
FT /note="N -> NN (in Ref. 2; CAA44558)"
FT /evidence="ECO:0000305"
FT STRAND 15..22
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 30..36
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 39..45
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:1T3C"
FT TURN 61..64
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:1ZL5"
FT TURN 71..74
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 77..94
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 98..108
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:7K84"
FT TURN 128..130
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 206..221
FT /evidence="ECO:0007829|PDB:1T3C"
FT TURN 226..230
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:1T3A"
FT TURN 235..239
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:1ZKW"
FT HELIX 249..255
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 257..262
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 265..287
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 297..306
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 321..333
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 336..343
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 349..351
FT /evidence="ECO:0007829|PDB:7K84"
FT STRAND 357..361
FT /evidence="ECO:0007829|PDB:1T3C"
FT TURN 366..368
FT /evidence="ECO:0007829|PDB:1T3C"
FT TURN 371..373
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 378..387
FT /evidence="ECO:0007829|PDB:1T3C"
FT TURN 389..391
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:1T3C"
FT TURN 400..403
FT /evidence="ECO:0007829|PDB:1T3C"
FT HELIX 404..408
FT /evidence="ECO:0007829|PDB:1T3C"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 422..430
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 431..433
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 440..442
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 446..449
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 468..472
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 505..508
FT /evidence="ECO:0007829|PDB:7K84"
FT STRAND 510..513
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 519..524
FT /evidence="ECO:0007829|PDB:7K84"
FT STRAND 536..539
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 541..546
FT /evidence="ECO:0007829|PDB:7K84"
FT STRAND 550..552
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 557..564
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 569..571
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 572..587
FT /evidence="ECO:0007829|PDB:7K84"
FT STRAND 594..596
FT /evidence="ECO:0007829|PDB:3FFZ"
FT HELIX 606..610
FT /evidence="ECO:0007829|PDB:7K84"
FT TURN 615..620
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 621..628
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 630..633
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 660..692
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 694..724
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 728..734
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 740..779
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 781..799
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 801..804
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 805..807
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 808..820
FT /evidence="ECO:0007829|PDB:7K84"
FT HELIX 827..829
FT /evidence="ECO:0007829|PDB:7K84"
FT STRAND 830..832
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 842..844
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 851..858
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 861..864
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 866..868
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 871..876
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 888..894
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 896..901
FT /evidence="ECO:0007829|PDB:3FFZ"
FT TURN 904..906
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 916..922
FT /evidence="ECO:0007829|PDB:3FFZ"
FT TURN 929..931
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 937..944
FT /evidence="ECO:0007829|PDB:3FFZ"
FT TURN 945..947
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 948..955
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 958..964
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 966..968
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 970..976
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 991..997
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1001..1007
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1010..1016
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1027..1035
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1041..1052
FT /evidence="ECO:0007829|PDB:3FFZ"
FT HELIX 1056..1063
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1073..1079
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1081..1083
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1085..1092
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1096..1100
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1104..1111
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1126..1133
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1147..1155
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1158..1165
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1168..1177
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1185..1194
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1196..1202
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1207..1214
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1217..1222
FT /evidence="ECO:0007829|PDB:3FFZ"
FT HELIX 1223..1226
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1228..1230
FT /evidence="ECO:0007829|PDB:3FFZ"
FT STRAND 1239..1242
FT /evidence="ECO:0007829|PDB:3FFZ"
SQ SEQUENCE 1251 AA; 143844 MW; B05AA65FF1B30362 CRC64;
MPKINSFNYN DPVNDRTILY IKPGGCQEFY KSFNIMKNIW IIPERNVIGT TPQDFHPPTS
LKNGDSSYYD PNYLQSDEEK DRFLKIVTKI FNRINNNLSG GILLEELSKA NPYLGNDNTP
DNQFHIGDAS AVEIKFSNGS QDILLPNVII MGAEPDLFET NSSNISLRNN YMPSNHRFGS
IAIVTFSPEY SFRFNDNCMN EFIQDPALTL MHELIHSLHG LYGAKGITTK YTITQKQNPL
ITNIRGTNIE EFLTFGGTDL NIITSAQSND IYTNLLADYK KIASKLSKVQ VSNPLLNPYK
DVFEAKYGLD KDASGIYSVN INKFNDIFKK LYSFTEFDLR TKFQVKCRQT YIGQYKYFKL
SNLLNDSIYN ISEGYNINNL KVNFRGQNAN LNPRIITPIT GRGLVKKIIR FCKNIVSVKG
IRKSICIEIN NGELFFVASE NSYNDDNINT PKEIDDTVTS NNNYENDLDQ VILNFNSESA
PGLSDEKLNL TIQNDAYIPK YDSNGTSDIE QHDVNELNVF FYLDAQKVPE GENNVNLTSS
IDTALLEQPK IYTFFSSEFI NNVNKPVQAA LFVSWIQQVL VDFTTEANQK STVDKIADIS
IVVPYIGLAL NIGNEAQKGN FKDALELLGA GILLEFEPEL LIPTILVFTI KSFLGSSDNK
NKVIKAINNA LKERDEKWKE VYSFIVSNWM TKINTQFNKR KEQMYQALQN QVNAIKTIIE
SKYNSYTLEE KNELTNKYDI KQIENELNQK VSIAMNNIDR FLTESSISYL MKIINEVKIN
KLREYDENVK TYLLNYIIQH GSILGESQQE LNSMVTDTLN NSIPFKLSSY TDDKILISYF
NKFFKRIKSS SVLNMRYKND KYVDTSGYDS NININGDVYK YPTNKNQFGI YNDKLSEVNI
SQNDYIIYDN KYKNFSISFW VRIPNYDNKI VNVNNEYTII NCMRDNNSGW KVSLNHNEII
WTFEDNRGIN QKLAFNYGNA NGISDYINKW IFVTITNDRL GDSKLYINGN LIDQKSILNL
GNIHVSDNIL FKIVNCSYTR YIGIRYFNIF DKELDETEIQ TLYSNEPNTN ILKDFWGNYL
LYDKEYYLLN VLKPNNFIDR RKDSTLSINN IRSTILLANR LYSGIKVKIQ RVNNSSTNDN
LVRKNDQVYI NFVASKTHLF PLYADTATTN KEKTIKISSS GNRFNQVVVM NSVGNCTMNF
KNNNGNNIGL LGFKADTVVA STWYYTHMRD HTNSNGCFWN FISEEHGWQE K
