BXB_CLOBO
ID BXB_CLOBO Reviewed; 1291 AA.
AC P10844; P10843;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Botulinum neurotoxin type B;
DE Short=BoNT/B;
DE AltName: Full=Bontoxilysin-B;
DE Contains:
DE RecName: Full=Botulinum neurotoxin B light chain;
DE Short=LC;
DE EC=3.4.24.69 {ECO:0000269|PubMed:1331807};
DE Contains:
DE RecName: Full=Botulinum neurotoxin B heavy chain;
DE Short=HC;
DE Flags: Precursor;
GN Name=botB {ECO:0000303|PubMed:1514783};
OS Clostridium botulinum.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=1491;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Danish / Type B;
RX PubMed=1514783; DOI=10.1128/aem.58.8.2345-2354.1992;
RA Whelan S.M., Elmore M.J., Bodsworth N.J., Brehm J.K., Atkinson T.,
RA Minton N.P.;
RT "Molecular cloning of the Clostridium botulinum structural gene encoding
RT the type B neurotoxin and determination of its entire nucleotide
RT sequence.";
RL Appl. Environ. Microbiol. 58:2345-2354(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 36-246.
RC STRAIN=NCTC 7273 / Type B;
RA Szabo E.A., Pemberton J.M., Desmarchelier P.M.;
RL Submitted (APR-1992) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 634-994.
RC STRAIN=NCTC 7273 / Type B;
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 [4]
RP PROTEIN SEQUENCE OF 2-45 AND 442-467, SUBUNIT, SUBCELLULAR LOCATION, AND
RP DISULFIDE BOND.
RC STRAIN=B-657 / Type B;
RX PubMed=3139097; DOI=10.1016/0300-9084(88)90111-3;
RA Dasgupta B.R., Datta A.;
RT "Botulinum neurotoxin type B (strain 657): partial sequence and similarity
RT with tetanus toxin.";
RL Biochimie 70:811-817(1988).
RN [5]
RP RELEASED AS SINGLE CHAIN.
RC STRAIN=Okra / Type B1;
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 [6]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE B AND BOTULINUM NEUROTOXIN B HEAVY
RP CHAIN), AND DOMAIN.
RC STRAIN=Type B;
RX PubMed=3856850; DOI=10.1073/pnas.82.6.1692;
RA Hoch D.H., Romero-Mira M., Ehrlich B.E., Finkelstein A., DasGupta B.R.,
RA Simpson L.L.;
RT "Channels formed by botulinum, tetanus, and diphtheria toxins in planar
RT lipid bilayers: relevance to translocation of proteins across membranes.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:1692-1696(1985).
RN [7]
RP IDENTIFICATION AS A ZINC-BINDING PROTEIN, AND COFACTOR.
RC STRAIN=Type B;
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 [8]
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 [9]
RP FUNCTION (BOTULINUM NEUROTOXIN B LIGHT CHAIN), IDENTIFICATION OF SUBSTRATE,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND SUBCELLULAR LOCATION
RP (BOTULINUM NEUROTOXIN B LIGHT CHAIN).
RC STRAIN=Type B;
RX PubMed=1331807; DOI=10.1038/359832a0;
RA Schiavo G., Benfenati F., Poulain B., Rossetto O., de Laureto P.P.,
RA Dasgupta B.R., Montecucco C.;
RT "Tetanus and botulinum-B neurotoxins block neurotransmitter release by
RT proteolytic cleavage of synaptobrevin.";
RL Nature 359:832-835(1992).
RN [10]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE B), AND SUBSTRATE SPECIFICITY.
RX PubMed=7803399; DOI=10.1021/bi00255a017;
RA Foran P., Shone C.C., Dolly J.O.;
RT "Differences in the protease activities of tetanus and botulinum B toxins
RT revealed by the cleavage of vesicle-associated membrane protein and various
RT sized fragments.";
RL Biochemistry 33:15365-15374(1994).
RN [11]
RP IDENTIFICATION OF HOST RECEPTOR (BOTULINUM NEUROTOXIN TYPE B), INTERACTION
RP WITH HOST SYT1, AND SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN B LIGHT
RP CHAIN).
RC STRAIN=Type B;
RX PubMed=8144634; DOI=10.1016/s0021-9258(17)34087-5;
RA Nishiki T., Kamata Y., Nemoto Y., Omori A., Ito T., Takahashi M.,
RA Kozaki S.;
RT "Identification of protein receptor for Clostridium botulinum type B
RT neurotoxin in rat brain synaptosomes.";
RL J. Biol. Chem. 269:10498-10503(1994).
RN [12]
RP FUNCTION (BOTULINUM NEUROTOXIN B HEAVY CHAIN), AND LIPID-BINDING.
RC STRAIN=B600 / Type B;
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 [13]
RP RETRACTED PAPER.
RX PubMed=10932255; DOI=10.1038/77997;
RA Hanson M.A., Stevens R.C.;
RT "Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type
RT B at 2.0 A resolution.";
RL Nat. Struct. Biol. 7:687-692(2000).
RN [14]
RP RETRACTION NOTICE OF PUBMED:10932255.
RX PubMed=19578378; DOI=10.1038/nsmb0709-795;
RA Hanson M.A., Stevens R.C.;
RT "Retraction: Cocrystal structure of synaptobrevin-II bound to botulinum
RT neurotoxin type B at 2.0 A resolution.";
RL Nat. Struct. Mol. Biol. 16:795-795(2009).
RN [15]
RP FUNCTION, IDENTIFICATION OF HOST RECEPTOR (BOTULINUM NEUROTOXIN TYPE B AND
RP BOTULINUM NEUROTOXIN B HEAVY CHAIN), INTERACTION WITH HOST SYT1 AND SYT2,
RP AND SUBCELLULAR LOCATION (BOTULINUM NEUROTOXIN TYPE B).
RC STRAIN=Type B;
RX PubMed=14504267; DOI=10.1083/jcb.200305098;
RA Dong M., Richards D.A., Goodnough M.C., Tepp W.H., Johnson E.A.,
RA Chapman E.R.;
RT "Synaptotagmins I and II mediate entry of botulinum neurotoxin B into
RT cells.";
RL J. Cell Biol. 162:1293-1303(2003).
RN [16]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE B AND BOTULINUM NEUROTOXIN B HEAVY
RP CHAIN), AND INTERACTION WITH HOST SYT1 AND SYT2.
RC STRAIN=Type B;
RX PubMed=15123599; DOI=10.1074/jbc.m403945200;
RA Rummel A., Karnath T., Henke T., Bigalke H., Binz T.;
RT "Synaptotagmins I and II act as nerve cell receptors for botulinum
RT neurotoxin G.";
RL J. Biol. Chem. 279:30865-30870(2004).
RN [17]
RP FUNCTION, GANGLIOSIDE-BINDING (BOTULINUM NEUROTOXIN A HEAVY CHAIN), AND
RP MUTAGENESIS OF GLU-1189; GLU-1190; HIS-1241; SER-1260; TRP-1262 AND
RP TYR-1263.
RC STRAIN=Okra / Type B1;
RX PubMed=14731268; DOI=10.1046/j.1365-2958.2003.03872.x;
RA Rummel A., Mahrhold S., Bigalke H., Binz T.;
RT "The HCC-domain of botulinum neurotoxins A and B exhibits a singular
RT ganglioside binding site displaying serotype specific carbohydrate
RT interaction.";
RL Mol. Microbiol. 51:631-643(2004).
RN [18]
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 [19]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE B AND BOTULINUM NEUROTOXIN B HEAVY
RP CHAIN), INTERACTION WITH HOST SYT1 AND SYT2, AND MUTAGENESIS OF VAL-1118;
RP TYR-1183; GLU-1191; LYS-1192 AND TRP-1262.
RC STRAIN=Type B;
RX PubMed=17185412; DOI=10.1073/pnas.0609713104;
RA Rummel A., Eichner T., Weil T., Karnath T., Gutcaits A., Mahrhold S.,
RA Sandhoff K., Proia R.L., Acharya K.R., Bigalke H., Binz T.;
RT "Identification of the protein receptor binding site of botulinum
RT neurotoxins B and G proves the double-receptor concept.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:359-364(2007).
RN [20]
RP FUNCTION (BOTULINUM NEUROTOXIN B 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 [21]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE B AND BOTULINUM NEUROTOXIN B HEAVY
RP CHAIN), AND MUTAGENESIS OF LYS-1192 AND TRP-1262.
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 [22]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE B AND BOTULINUM NEUROTOXIN B HEAVY
RP CHAIN), ACTIVITY REGULATION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=Type B;
RX PubMed=21925111; DOI=10.1016/j.chom.2011.06.012;
RA Sun S., Suresh S., Liu H., Tepp W.H., Johnson E.A., Edwardson J.M.,
RA Chapman E.R.;
RT "Receptor binding enables botulinum neurotoxin B to sense low pH for
RT translocation channel assembly.";
RL Cell Host Microbe 10:237-247(2011).
RN [23]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE B), AND SUBUNIT.
RC STRAIN=Type B;
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 [24]
RP FUNCTION (BOTULINUM NEUROTOXIN B 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 [25]
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 [26] {ECO:0007744|PDB:1EPW, ECO:0007744|PDB:1F31}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 2-1291 IN COMPLEX WITH ZINC AND
RP GANGLIOSIDE ANALOG, FUNCTION (BOTULINUM NEUROTOXIN B HEAVY CHAIN),
RP COFACTOR, DOMAIN, AND GLYCAN-BINDING.
RX PubMed=10932256; DOI=10.1038/78005;
RA Swaminathan S., Eswaramoorthy S.;
RT "Structural analysis of the catalytic and binding sites of Clostridium
RT botulinum neurotoxin B.";
RL Nat. Struct. Biol. 7:693-699(2000).
RN [27] {ECO:0007744|PDB:2NM1}
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 858-1291 IN COMPLEX WITH SYT2
RP RECEPTOR FRAGMENT, FUNCTION (BOTULINUM NEUROTOXIN TYPE B AND BOTULINUM
RP NEUROTOXIN B HEAVY CHAIN), SUBUNIT, AND MUTAGENESIS OF VAL-1118; LYS-1192;
RP PHE-1194; ALA-1196; SER-1199 AND PHE-1204.
RC STRAIN=Type B;
RX PubMed=17167421; DOI=10.1038/nature05387;
RA Jin R., Rummel A., Binz T., Brunger A.T.;
RT "Botulinum neurotoxin B recognizes its protein receptor with high affinity
RT and specificity.";
RL Nature 444:1092-1095(2006).
RN [28] {ECO:0007744|PDB:2NP0}
RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 2-1291 IN COMPLEX WITH ZINC AND
RP SYT2 RECEPTOR FRAGMENT, FUNCTION (BOTULINUM NEUROTOXIN TYPE B AND BOTULINUM
RP NEUROTOXIN B HEAVY CHAIN), COFACTOR, SUBUNIT, AND DISULFIDE BOND.
RX PubMed=17167418; DOI=10.1038/nature05411;
RA Chai Q., Arndt J.W., Dong M., Tepp W.H., Johnson E.A., Chapman E.R.,
RA Stevens R.C.;
RT "Structural basis of cell surface receptor recognition by botulinum
RT neurotoxin B.";
RL Nature 444:1096-1100(2006).
RN [29] {ECO:0007744|PDB:4KBB}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 857-1291 IN COMPLEX WITH
RP CORECEPTORS SYT2 AND GANGLIOSIDE GD1A, FUNCTION (BOTULINUM NEUROTOXIN B
RP HEAVY CHAIN), AND SUBUNIT.
RC STRAIN=Okra / Type B1;
RX PubMed=23807078; DOI=10.1038/ncomms3058;
RA Berntsson R.P., Peng L., Dong M., Stenmark P.;
RT "Structure of dual receptor binding to botulinum neurotoxin B.";
RL Nat. Commun. 4:2058-2058(2013).
CC -!- FUNCTION: [Botulinum neurotoxin type B]: 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. Precursor of botulinum neurotoxin B which has 2
CC coreceptors; complex polysialylated gangliosides found on neural tissue
CC and specific membrane-anchored proteins found in synaptic vesicles
CC (PubMed:17185412, PubMed:17167421, PubMed:17167418, PubMed:23807078).
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:14504267). Upon synaptic vesicle recycling the toxin is taken
CC up via the endocytic pathway (PubMed:14504267). When the pH of the
CC toxin-containing endosome drops a structural rearrangement occurs so
CC that the N-terminus of the HC forms pores that allows the light chain
CC (LC) to translocate into the cytosol (PubMed:3856850). Once in the
CC cytosol the disulfide bond linking the 2 subunits is reduced and LC
CC cleaves its target protein on synaptic vesicles, preventing their
CC fusion with the cytoplasmic membrane and thus neurotransmitter release.
CC Binds to host peripheral neuronal presynaptic membranes via
CC synaptotagmins 1 and 2 (SYT1 and SYT2) (PubMed:8144634,
CC PubMed:14504267). Toxin binds to the membrane proximal extra-
CC cytoplasmic region of host SYT1 and SYT2 that is transiently exposed
CC outside of cells during exocytosis; exogenous gangliosides enhance
CC binding and subsequent uptake of toxin into host cells
CC (PubMed:14504267, PubMed:15123599). Toxin uptake into neural cells
CC requires stimulation (incubation with K(+) to stimulate SYT protein
CC receptor exposure); subsequently the toxin colocalizes with its
CC receptor in host cells with a concomitant decrease in target protein
CC (synaptobrevin-2/VAMP2) immunoreactivity (PubMed:14504267). Toxin
CC uptake can be blocked by the appropriate synaptotagmin protein
CC fragments and gangliosides in cell culture and in mice
CC (PubMed:14504267, PubMed:15123599). BoNT/B 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:21925111,
CC PubMed:22720883). Whole toxin only has protease activity after
CC reduction which releases LC (PubMed:1331807, PubMed:7803399).
CC {ECO:0000269|PubMed:1331807, ECO:0000269|PubMed:14504267,
CC ECO:0000269|PubMed:15123599, ECO:0000269|PubMed:17167418,
CC ECO:0000269|PubMed:17167421, ECO:0000269|PubMed:17185412,
CC ECO:0000269|PubMed:21925111, ECO:0000269|PubMed:22720883,
CC ECO:0000269|PubMed:23807078, ECO:0000269|PubMed:3856850,
CC ECO:0000269|PubMed:7803399, ECO:0000269|PubMed:8144634}.
CC -!- FUNCTION: [Botulinum neurotoxin B light chain]: Has proteolytic
CC activity (PubMed:1331807). After translocation into the eukaryotic host
CC cytosol, inhibits neurotransmitter release by acting as a zinc
CC endopeptidase that cleaves the '76-Gln-|-Phe-77' bond of synaptobrevin-
CC 2/VAMP2, blocking neurotransmitter release (PubMed:1331807,
CC PubMed:7803399). In vitro the LC only has protease activity after
CC reduction (PubMed:1331807, PubMed:7803399).
CC {ECO:0000269|PubMed:1331807, ECO:0000305|PubMed:7803399}.
CC -!- FUNCTION: [Botulinum neurotoxin B heavy chain]: Responsible for host
CC epithelial cell transcytosis, host nerve cell targeting and
CC translocation of light chain (LC) into host cytosol. Composed of 3
CC subdomains; the translocation domain (TD), and N-terminus and C-
CC terminus of the receptor-binding domain (RBD). The N-terminus of the TD
CC wraps an extended belt around the perimeter of the LC; it does not seem
CC to protect the active site, but might prevent premature LC dissociation
CC from the translocation channel and protect toxin prior to translocation
CC (PubMed:10932256, PubMed:17167418). Has 2 coreceptors; complex
CC gangliosides found primarily on neural tissue and host synaptotagmin-1
CC and -2 (SYT1 and SYT2) which bind simultaneously to adjacent but
CC separate sites at the tip of the HC (PubMed:8144634, PubMed:17185412,
CC PubMed:17167421, PubMed:17167418, PubMed:23807078). HC alone partially
CC prevents uptake of whole toxin by neural cells, and delays paralysis
CC onset by 160% (PubMed:10413679). Binding probably positions the TD for
CC integration into the synaptic vesicle membrane (PubMed:17167418,
CC PubMed:23807078). The HC forms channels at low pH that mediate
CC transport of the light chain (LC) from the endocytic vesicle to the
CC cytosol (PubMed:3856850). Binds gangliosides GD1b and GT1b
CC (PubMed:10413679, PubMed:14731268). Gangliosides are not only a
CC coreceptor, but also required for uptake into nerve cells
CC (PubMed:21925111, PubMed:17167418). HC alone binds to host receptor
CC proteins SYT1 and SYT2 (PubMed:14504267, PubMed:15123599,
CC PubMed:17185412, PubMed:19650874). Interaction with SYT1 protein does
CC not require SYT1 glycosylation (PubMed:19476346). The HC C-terminus
CC (approximately residues 1079-1291) interacts with host SYT2
CC (PubMed:15123599, PubMed:17167421, PubMed:17167418, PubMed:23807078).
CC Has higher affinity for SYT2 than SYT1 (PubMed:17185412,
CC PubMed:17167421). Significantly decreases uptake and toxicity of whole
CC BoNT/B and BoNT/G (PubMed:19650874). {ECO:0000269|PubMed:10413679,
CC ECO:0000269|PubMed:10932256, ECO:0000269|PubMed:14504267,
CC ECO:0000269|PubMed:14731268, ECO:0000269|PubMed:15123599,
CC ECO:0000269|PubMed:17167418, ECO:0000269|PubMed:17167421,
CC ECO:0000269|PubMed:17185412, ECO:0000269|PubMed:19650874,
CC ECO:0000269|PubMed:23807078, ECO:0000269|PubMed:8144634,
CC ECO:0000305|PubMed:21925111, ECO:0000305|PubMed:3856850}.
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:1331807};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:10932256, ECO:0000269|PubMed:1429690,
CC ECO:0000269|PubMed:17167418};
CC Note=Binds 1 zinc ion per subunit, to the LC (PubMed:1429690,
CC PubMed:10932256, PubMed:17167418). {ECO:0000269|PubMed:10932256,
CC ECO:0000269|PubMed:1429690, ECO:0000269|PubMed:17167418};
CC -!- ACTIVITY REGULATION: Proteolysis inhibited by EDTA and captopril, and
CC by peptides that encompass the VAMP2 cleavage site (Ala-Ser-Gln-Phe-
CC Glu-Thr-Ser and Gln-Phe-Glu-Thr) (PubMed:1331807). Translocation of
CC whole toxin into neurons is inhibited by toosendanin (PubMed:21925111).
CC {ECO:0000269|PubMed:1331807, ECO:0000269|PubMed:21925111}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=19.2 uM for over-expressed human VAMP1
CC {ECO:0000269|PubMed:22289120};
CC KM=29.9 uM for over-expressed human VAMP2
CC {ECO:0000269|PubMed:22289120};
CC KM=11.6 uM for over-expressed human VAMP3
CC {ECO:0000269|PubMed:22289120};
CC Note=kcat is 3.96, 4.68 and 3.50 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:3139097, PubMed:1331807). At pH 4.4
CC in the presence of ganglioside GT1b may form trimers (PubMed:21925111,
CC PubMed:22720883). Interacts with host receptor synaptotagmin-1 (SYT1);
CC interaction is improved in the presence of gangliosides
CC (PubMed:8144634, PubMed:14504267, PubMed:19650874). Interacts with host
CC receptor synaptotagmin-2 (SYT2) (PubMed:14504267, PubMed:15123599,
CC PubMed:19650874, PubMed:17167421, PubMed:17167418, PubMed:23807078).
CC SYT2 interaction and toxin uptake do not require gangliosides but are
CC improved in their presence (PubMed:14504267, PubMed:15123599). HC
CC interacts with a complex including at least host synaptic vesicle
CC glycoprotein 2 (SV2) and synaptotagmin-1 (SYT1); copurification does
CC not depend on glycosylation of either protein (PubMed:19476346).
CC {ECO:0000269|PubMed:1331807, ECO:0000269|PubMed:14504267,
CC ECO:0000269|PubMed:15123599, ECO:0000269|PubMed:17167418,
CC ECO:0000269|PubMed:17167421, ECO:0000269|PubMed:19476346,
CC ECO:0000269|PubMed:19650874, ECO:0000269|PubMed:21925111,
CC ECO:0000269|PubMed:22720883, ECO:0000269|PubMed:23807078,
CC ECO:0000269|PubMed:3139097, ECO:0000269|PubMed:8144634}.
CC -!- INTERACTION:
CC P10844; P29101: Syt2; Xeno; NbExp=6; IntAct=EBI-7661991, EBI-458017;
CC P10844; P46097: Syt2; Xeno; NbExp=3; IntAct=EBI-7661991, EBI-457969;
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin type B]: Secreted
CC {ECO:0000269|PubMed:3139097}. Host synapse, host presynaptic cell
CC membrane {ECO:0000269|PubMed:14504267}. Note=Colocalizes with its SYT1
CC receptor, probably in synaptic vesicles (PubMed:14504267). At pH 4.4 in
CC the presence of ganglioside GT1b becomes a membrane-associated
CC hydrophobic protein (PubMed:21925111). {ECO:0000269|PubMed:14504267,
CC ECO:0000269|PubMed:21925111}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin B light chain]: Secreted
CC {ECO:0000269|PubMed:3139097}. Host cytoplasm, host cytosol
CC {ECO:0000305|PubMed:1331807, ECO:0000305|PubMed:8144634}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin B heavy chain]: Secreted
CC {ECO:0000269|PubMed:3139097}. Host synapse, host presynaptic cell
CC membrane {ECO:0000269|PubMed:14504267}. Host cytoplasmic vesicle, host
CC secretory vesicle, host synaptic vesicle membrane
CC {ECO:0000305|PubMed:21925111}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- DOMAIN: [Botulinum neurotoxin B light chain]: Has protease activity
CC (PubMed:1331807). {ECO:0000269|PubMed:1331807}.
CC -!- DOMAIN: [Botulinum neurotoxin B 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:10932256). HC forms channels in bilayers at low pH
CC (PubMed:3856850). The N-terminal belt of the TD wraps an extended belt
CC around the perimeter of the LC; it is shorter than in BoNT/A and does
CC not block the active site (PubMed:10932256). The belt may be a
CC pseudosubstrate inhibitor which serves as an intramolecular chaperone
CC for the LC prior to its translocation into the host cytosol
CC (PubMed:17907800). {ECO:0000269|PubMed:10932256,
CC ECO:0000269|PubMed:3856850, ECO:0000305|PubMed:17907800}.
CC -!- PHARMACEUTICAL: Available under the name MYOBLOC (rimabotulinumtoxinB,
CC US WorldMeds, LLC) for the treatment of adults with cervical dystonia.
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: Neurotoxin type B is released from bacteria mostly as a
CC single chain and cleaved by host proteases into the active dichain
CC (PubMed:4030755). {ECO:0000269|PubMed:4030755}.
CC -!- SIMILARITY: Belongs to the peptidase M27 family. {ECO:0000305}.
CC -!- CAUTION: A structure of a fragment of this protein in complex with the
CC catalytic domain of C.botulinum neurotoxin type B (BoNT/B, botB) was
CC reported; because of the lack of clear and continuous electron density
CC for the VAMP2 peptide in the complex structure, the paper was
CC retracted. One of its associated structures remains valid (PDB:1F82,
CC light chain alone) (PubMed:10932255, PubMed:19578378).
CC {ECO:0000269|PubMed:10932255, ECO:0000269|PubMed:19578378}.
CC -!- WEB RESOURCE: Name=BotDB - A Database Resource for Clostridial
CC Neurotoxins;
CC URL="https://botdb.abcc.ncifcrf.gov/";
CC ---------------------------------------------------------------------------
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DR EMBL; M81186; AAA23211.1; -; Genomic_DNA.
DR EMBL; Z11934; CAA77991.1; -; Genomic_DNA.
DR EMBL; X70817; CAA50148.1; -; Genomic_DNA.
DR PIR; A48940; A48940.
DR RefSeq; WP_012291519.1; NZ_JACBEH010000008.1.
DR PDB; 1EPW; X-ray; 1.90 A; A=2-1291.
DR PDB; 1F31; X-ray; 2.60 A; A=2-1291.
DR PDB; 1F82; X-ray; 2.20 A; A=2-425.
DR PDB; 1G9A; X-ray; 2.10 A; A=2-1291.
DR PDB; 1G9B; X-ray; 2.00 A; A=2-1291.
DR PDB; 1G9C; X-ray; 2.35 A; A=2-1291.
DR PDB; 1G9D; X-ray; 2.20 A; A=2-1291.
DR PDB; 1I1E; X-ray; 2.50 A; A=2-1291.
DR PDB; 1S0B; X-ray; 2.00 A; A=2-1291.
DR PDB; 1S0C; X-ray; 2.20 A; A=2-1291.
DR PDB; 1S0D; X-ray; 2.20 A; A=2-1291.
DR PDB; 1S0E; X-ray; 1.90 A; A=2-1291.
DR PDB; 1S0F; X-ray; 2.30 A; A=2-1291.
DR PDB; 1S0G; X-ray; 2.60 A; A=2-1291.
DR PDB; 1Z0H; X-ray; 2.00 A; A/B=854-1291.
DR PDB; 2ETF; X-ray; 2.29 A; A/B=1-441.
DR PDB; 2NM1; X-ray; 2.15 A; A=858-1291.
DR PDB; 2NP0; X-ray; 2.62 A; A=2-1291.
DR PDB; 2XHL; X-ray; 2.80 A; A=1-437, B=446-858.
DR PDB; 3ZUQ; X-ray; 2.70 A; A=1-437, A=446-858.
DR PDB; 4KBB; X-ray; 2.30 A; A/B=857-1291.
DR PDB; 5VID; X-ray; 2.75 A; A/B/C/D/E=859-1291.
DR PDB; 5VMR; X-ray; 1.95 A; A/B=859-1291.
DR PDB; 6G5F; X-ray; 2.50 A; A/B=1-1291.
DR PDB; 6G5G; X-ray; 2.00 A; A/B=1-1291.
DR PDB; 6G5K; X-ray; 2.00 A; A/B=857-1291.
DR PDB; 6QNS; X-ray; 2.40 A; A=857-1291.
DR PDB; 6UC6; X-ray; 2.32 A; A/B=859-1291.
DR PDB; 6UFT; X-ray; 2.90 A; A=859-1291.
DR PDB; 6UHT; X-ray; 2.20 A; A/B=859-1291.
DR PDB; 6UL4; X-ray; 3.18 A; A=859-1291.
DR PDB; 7NA9; X-ray; 1.76 A; A=1-441.
DR PDB; 7QFQ; EM; 3.60 A; A=1-1291.
DR PDB; 7T5F; X-ray; 2.60 A; A/D=1-425.
DR PDBsum; 1EPW; -.
DR PDBsum; 1F31; -.
DR PDBsum; 1F82; -.
DR PDBsum; 1G9A; -.
DR PDBsum; 1G9B; -.
DR PDBsum; 1G9C; -.
DR PDBsum; 1G9D; -.
DR PDBsum; 1I1E; -.
DR PDBsum; 1S0B; -.
DR PDBsum; 1S0C; -.
DR PDBsum; 1S0D; -.
DR PDBsum; 1S0E; -.
DR PDBsum; 1S0F; -.
DR PDBsum; 1S0G; -.
DR PDBsum; 1Z0H; -.
DR PDBsum; 2ETF; -.
DR PDBsum; 2NM1; -.
DR PDBsum; 2NP0; -.
DR PDBsum; 2XHL; -.
DR PDBsum; 3ZUQ; -.
DR PDBsum; 4KBB; -.
DR PDBsum; 5VID; -.
DR PDBsum; 5VMR; -.
DR PDBsum; 6G5F; -.
DR PDBsum; 6G5G; -.
DR PDBsum; 6G5K; -.
DR PDBsum; 6QNS; -.
DR PDBsum; 6UC6; -.
DR PDBsum; 6UFT; -.
DR PDBsum; 6UHT; -.
DR PDBsum; 6UL4; -.
DR PDBsum; 7NA9; -.
DR PDBsum; 7QFQ; -.
DR PDBsum; 7T5F; -.
DR AlphaFoldDB; P10844; -.
DR SMR; P10844; -.
DR DIP; DIP-42782N; -.
DR IntAct; P10844; 4.
DR MINT; P10844; -.
DR BindingDB; P10844; -.
DR ChEMBL; CHEMBL1075064; -.
DR DrugBank; DB02379; Beta-D-Glucose.
DR DrugBank; DB01705; Bis(5-Amidino-Benzimidazolyl)Methane.
DR DrugBank; DB13903; Equine Botulinum Neurotoxin B Immune FAB2.
DR DrugBank; DB03721; N-acetyl-alpha-neuraminic acid.
DR MEROPS; M27.002; -.
DR UniLectin; P10844; -.
DR ABCD; P10844; 27 sequenced antibodies.
DR BRENDA; 3.4.24.69; 1462.
DR Reactome; R-HSA-5250958; Toxicity of botulinum toxin type B (botB).
DR EvolutionaryTrace; P10844; -.
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 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; Pharmaceutical; Protease;
KW Secreted; Toxin; Transmembrane; Virulence; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:3139097"
FT CHAIN 2..1291
FT /note="Botulinum neurotoxin type B"
FT /id="PRO_0000444904"
FT CHAIN 2..441
FT /note="Botulinum neurotoxin B light chain"
FT /id="PRO_0000029215"
FT CHAIN 442..1291
FT /note="Botulinum neurotoxin B heavy chain"
FT /id="PRO_0000029216"
FT REGION 442..857
FT /note="Translocation domain (TD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 481..532
FT /note="Belt; not required for channel formation"
FT /evidence="ECO:0000305|PubMed:10932256"
FT REGION 858..1079
FT /note="N-terminus of receptor binding domain (N-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 1080..1291
FT /note="C-terminus of receptor binding domain (C-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT MOTIF 1260..1263
FT /note="Host ganglioside-binding motif"
FT /evidence="ECO:0000269|PubMed:10932256,
FT ECO:0000305|PubMed:14731268, ECO:0000305|PubMed:17185412"
FT ACT_SITE 231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 230
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:10932256, ECO:0000305|PubMed:1429690,
FT ECO:0007744|PDB:1EPW, ECO:0007744|PDB:1F31,
FT ECO:0007744|PDB:2NP0"
FT BINDING 234
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:10932256, ECO:0000305|PubMed:1429690,
FT ECO:0007744|PDB:1EPW, ECO:0007744|PDB:1F31,
FT ECO:0007744|PDB:2NP0"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:10932256,
FT ECO:0007744|PDB:1EPW, ECO:0007744|PDB:1F31,
FT ECO:0007744|PDB:2NP0"
FT BINDING 1025
FT /ligand="ganglioside GT1b (d18:1(4E))"
FT /ligand_id="ChEBI:CHEBI:78452"
FT /ligand_note="host ganglioside"
FT /evidence="ECO:0007744|PDB:4KBB"
FT BINDING 1189..1190
FT /ligand="ganglioside GT1b (d18:1(4E))"
FT /ligand_id="ChEBI:CHEBI:78452"
FT /ligand_note="host ganglioside"
FT /evidence="ECO:0000269|PubMed:10932256,
FT ECO:0000305|PubMed:14731268, ECO:0007744|PDB:4KBB"
FT BINDING 1240..1241
FT /ligand="D-galactose"
FT /ligand_id="ChEBI:CHEBI:4139"
FT /evidence="ECO:0000269|PubMed:10932256,
FT ECO:0000305|PubMed:14731268, ECO:0007744|PDB:4KBB"
FT DISULFID 437..446
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000269|PubMed:10932256,
FT ECO:0000269|PubMed:17167418, ECO:0000305|PubMed:3139097,
FT ECO:0007744|PDB:1EPW, ECO:0007744|PDB:1F31,
FT ECO:0007744|PDB:2NP0"
FT MUTAGEN 1118
FT /note="V->D: Greatly decreased binding of heavy chain (HC)
FT to host SYT2, whole toxin about 200-fold less toxic.
FT Significantly decreased binding of HC to host SYT1 and SYT2
FT independent of gangliosides; whole toxin about 100-fold
FT less toxic."
FT /evidence="ECO:0000269|PubMed:17167421,
FT ECO:0000269|PubMed:17185412"
FT MUTAGEN 1183
FT /note="Y->R: Significantly decreased binding of heavy chain
FT to host SYT1 and SYT2 independent of gangliosides."
FT /evidence="ECO:0000269|PubMed:17185412"
FT MUTAGEN 1189
FT /note="E->L: Decreased toxicity, heavy chain has decreased
FT binding to synaptosomes and to GT1b."
FT /evidence="ECO:0000269|PubMed:14731268"
FT MUTAGEN 1190
FT /note="E->L: Greatly decreased toxicity, heavy chain has
FT decreased binding to synaptosomes, binds less GT1b."
FT /evidence="ECO:0000269|PubMed:14731268"
FT MUTAGEN 1191
FT /note="E->L: Increased binding of heavy chain to host SYT1,
FT no effect on binding to SYT2 independent of gangliosides."
FT /evidence="ECO:0000269|PubMed:17185412"
FT MUTAGEN 1192
FT /note="K->E: Greatly decreased binding of heavy chain to
FT host SYT2, whole toxin about dramatically less toxic.
FT Significantly decreased binding of heavy chain to host SYT1
FT and SYT2 independent of gangliosides; whole toxin
FT significantly less toxic. Essentially non-toxic; when
FT associated with L-1262. Heavy chain no longer inhibits
FT whole-toxin uptake and toxicity."
FT /evidence="ECO:0000269|PubMed:17167421,
FT ECO:0000269|PubMed:17185412, ECO:0000269|PubMed:19650874"
FT MUTAGEN 1192
FT /note="K->M,Y: Decreased binding of heavy chain to host
FT SYT1 and SYT2 independent of gangliosides."
FT /evidence="ECO:0000269|PubMed:17185412"
FT MUTAGEN 1194
FT /note="F->A: Greatly decreased binding of heavy chain to
FT host SYT2, whole toxin about 40-fold less toxic."
FT /evidence="ECO:0000269|PubMed:17167421"
FT MUTAGEN 1196
FT /note="A->K: Greatly decreased binding of heavy chain to
FT host SYT2, whole toxin about 1000-fold less toxic."
FT /evidence="ECO:0000269|PubMed:17167421"
FT MUTAGEN 1199
FT /note="S->Y: Increased binding of heavy chain to host SYT2,
FT no effect on toxicity."
FT /evidence="ECO:0000269|PubMed:17167421"
FT MUTAGEN 1204
FT /note="F->A: Greatly decreased binding of heavy chain to
FT host SYT2, whole toxin about 30-fold less toxic."
FT /evidence="ECO:0000269|PubMed:17167421"
FT MUTAGEN 1241
FT /note="H->A: Decreased toxicity, heavy chain has decreased
FT binding to synaptosomes and to GT1b."
FT /evidence="ECO:0000269|PubMed:14731268"
FT MUTAGEN 1241
FT /note="H->W: Greatly decreased toxicity, heavy chain has
FT decreased binding to synaptosomes and dramatic decrease in
FT GT1b binding."
FT /evidence="ECO:0000269|PubMed:14731268"
FT MUTAGEN 1260
FT /note="S->A: Greatly decreased toxicity, heavy chain has
FT decreased binding to synaptosome and binds less GT1b."
FT /evidence="ECO:0000269|PubMed:14731268"
FT MUTAGEN 1262
FT /note="W->L: Greatly decreased toxicity, heavy chain has
FT decreased binding to synaptosomes, heavy chain has dramatic
FT decrease in GT1b binding. Gangliosides no longer increase
FT heavy chain affinity for SYT1 or SYT2; whole toxin
FT significantly less toxic. Essentially non-toxic; when
FT associated with E-1192. Heavy chain no longer inhibits
FT whole-toxin uptake and toxicity. In mice without complex
FT gangliosides no change compared to wild-type protein."
FT /evidence="ECO:0000269|PubMed:14731268,
FT ECO:0000269|PubMed:17185412, ECO:0000269|PubMed:19650874"
FT MUTAGEN 1263
FT /note="Y->F: Greatly decreased toxicity, heavy chain has
FT intermediate binding to synaptosomes, binds less GT1b."
FT /evidence="ECO:0000269|PubMed:14731268"
FT MUTAGEN 1263
FT /note="Y->S: Greatly decreased toxicity, heavy chain has
FT decreased binding to synaptosomes and dramatic decrease in
FT GT1b binding."
FT /evidence="ECO:0000269|PubMed:14731268"
FT CONFLICT 30
FT /note="T -> M (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="R -> G (in Ref. 2; CAA77991)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="A -> S (in Ref. 2; CAA77991)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="S -> R (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 25..27
FT /evidence="ECO:0007829|PDB:7NA9"
FT TURN 28..31
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 34..40
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 56..59
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 63..66
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:1EPW"
FT TURN 76..79
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 82..100
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 103..114
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:1G9D"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:6G5G"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:1G9D"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 191..194
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 197..200
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:6G5G"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:1S0E"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 224..239
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 266..272
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 276..279
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 282..305
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 308..311
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 317..327
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:1F82"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:1F82"
FT HELIX 342..354
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 358..365
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 381..384
FT /evidence="ECO:0007829|PDB:7NA9"
FT TURN 389..391
FT /evidence="ECO:0007829|PDB:7NA9"
FT TURN 394..396
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 401..403
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 407..412
FT /evidence="ECO:0007829|PDB:7NA9"
FT TURN 414..416
FT /evidence="ECO:0007829|PDB:7NA9"
FT HELIX 418..420
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:1S0E"
FT HELIX 426..437
FT /evidence="ECO:0007829|PDB:7NA9"
FT STRAND 446..450
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 451..453
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 460..462
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 488..493
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 495..498
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 506..508
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 524..531
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 537..542
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 554..557
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 559..564
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 568..570
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 575..581
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 587..606
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 607..609
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 610..612
FT /evidence="ECO:0007829|PDB:1G9B"
FT HELIX 613..615
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 617..620
FT /evidence="ECO:0007829|PDB:1G9B"
FT HELIX 624..628
FT /evidence="ECO:0007829|PDB:1EPW"
FT TURN 631..635
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 639..646
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 647..651
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 666..668
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 675..707
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 709..738
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 743..747
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 753..786
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 788..812
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 814..817
FT /evidence="ECO:0007829|PDB:1EPW"
FT TURN 819..824
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 825..831
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 840..842
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 847..857
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 860..863
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 864..870
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 872..877
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 879..881
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 884..887
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 891..893
FT /evidence="ECO:0007829|PDB:5VMR"
FT STRAND 897..901
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 909..912
FT /evidence="ECO:0007829|PDB:1EPW"
FT TURN 915..917
FT /evidence="ECO:0007829|PDB:6G5K"
FT STRAND 918..923
FT /evidence="ECO:0007829|PDB:5VMR"
FT STRAND 926..933
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 939..941
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 942..947
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 949..957
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 960..967
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 970..976
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 978..980
FT /evidence="ECO:0007829|PDB:1S0F"
FT STRAND 982..988
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 991..995
FT /evidence="ECO:0007829|PDB:2NM1"
FT STRAND 1003..1009
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1011..1018
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1021..1027
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1038..1047
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1054..1064
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 1068..1079
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1089..1091
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1093..1095
FT /evidence="ECO:0007829|PDB:1Z0H"
FT STRAND 1097..1102
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 1103..1105
FT /evidence="ECO:0007829|PDB:1Z0H"
FT STRAND 1108..1112
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1116..1123
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1145..1149
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1152..1154
FT /evidence="ECO:0007829|PDB:6QNS"
FT STRAND 1158..1160
FT /evidence="ECO:0007829|PDB:6UL4"
FT STRAND 1166..1173
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1176..1183
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1188..1192
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1194..1198
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1202..1205
FT /evidence="ECO:0007829|PDB:5VMR"
FT STRAND 1208..1211
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1215..1217
FT /evidence="ECO:0007829|PDB:5VID"
FT STRAND 1221..1231
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1234..1246
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1248..1250
FT /evidence="ECO:0007829|PDB:6G5G"
FT STRAND 1251..1260
FT /evidence="ECO:0007829|PDB:1EPW"
FT HELIX 1263..1266
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1269..1271
FT /evidence="ECO:0007829|PDB:1EPW"
FT STRAND 1280..1283
FT /evidence="ECO:0007829|PDB:1EPW"
SQ SEQUENCE 1291 AA; 150803 MW; 921DE5C518140DBD CRC64;
MPVTINNFNY NDPIDNNNII MMEPPFARGT GRYYKAFKIT DRIWIIPERY TFGYKPEDFN
KSSGIFNRDV CEYYDPDYLN TNDKKNIFLQ TMIKLFNRIK SKPLGEKLLE MIINGIPYLG
DRRVPLEEFN TNIASVTVNK LISNPGEVER KKGIFANLII FGPGPVLNEN ETIDIGIQNH
FASREGFGGI MQMKFCPEYV SVFNNVQENK GASIFNRRGY FSDPALILMH ELIHVLHGLY
GIKVDDLPIV PNEKKFFMQS TDAIQAEELY TFGGQDPSII TPSTDKSIYD KVLQNFRGIV
DRLNKVLVCI SDPNININIY KNKFKDKYKF VEDSEGKYSI DVESFDKLYK SLMFGFTETN
IAENYKIKTR ASYFSDSLPP VKIKNLLDNE IYTIEEGFNI SDKDMEKEYR GQNKAINKQA
YEEISKEHLA VYKIQMCKSV KAPGICIDVD NEDLFFIADK NSFSDDLSKN ERIEYNTQSN
YIENDFPINE LILDTDLISK IELPSENTES LTDFNVDVPV YEKQPAIKKI FTDENTIFQY
LYSQTFPLDI RDISLTSSFD DALLFSNKVY SFFSMDYIKT ANKVVEAGLF AGWVKQIVND
FVIEANKSNT MDKIADISLI VPYIGLALNV GNETAKGNFE NAFEIAGASI LLEFIPELLI
PVVGAFLLES YIDNKNKIIK TIDNALTKRN EKWSDMYGLI VAQWLSTVNT QFYTIKEGMY
KALNYQAQAL EEIIKYRYNI YSEKEKSNIN IDFNDINSKL NEGINQAIDN INNFINGCSV
SYLMKKMIPL AVEKLLDFDN TLKKNLLNYI DENKLYLIGS AEYEKSKVNK YLKTIMPFDL
SIYTNDTILI EMFNKYNSEI LNNIILNLRY KDNNLIDLSG YGAKVEVYDG VELNDKNQFK
LTSSANSKIR VTQNQNIIFN SVFLDFSVSF WIRIPKYKND GIQNYIHNEY TIINCMKNNS
GWKISIRGNR IIWTLIDING KTKSVFFEYN IREDISEYIN RWFFVTITNN LNNAKIYING
KLESNTDIKD IREVIANGEI IFKLDGDIDR TQFIWMKYFS IFNTELSQSN IEERYKIQSY
SEYLKDFWGN PLMYNKEYYM FNAGNKNSYI KLKKDSPVGE ILTRSKYNQN SKYINYRDLY
IGEKFIIRRK SNSQSINDDI VRKEDYIYLD FFNLNQEWRV YTYKYFKKEE EKLFLAPISD
SDEFYNTIQI KEYDEQPTYS CQLLFKKDEE STDEIGLIGI HRFYESGIVF EEYKDYFCIS
KWYLKEVKRK PYNLKLGCNW QFIPKDEGWT E
