BXA2_CLOBJ
ID BXA2_CLOBJ Reviewed; 1296 AA.
AC Q45894; C1FUH9; P77780;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Botulinum neurotoxin type A2;
DE Short=BoNT/A;
DE AltName: Full=Bontoxilysin-A {ECO:0000303|Ref.2};
DE Short=BOTOX;
DE Contains:
DE RecName: Full=Botulinum neurotoxin A2 light chain;
DE Short=LC;
DE EC=3.4.24.69 {ECO:0000269|PubMed:16846233};
DE Contains:
DE RecName: Full=Botulinum neurotoxin A2 heavy chain;
DE Short=HC;
DE Flags: Precursor;
GN Name=botA {ECO:0000303|Ref.2};
GN Synonyms=atx, bna, bonT {ECO:0000303|PubMed:8863443};
GN OrderedLocusNames=CLM_0897 {ECO:0000312|EMBL:ACO83782.1};
OS Clostridium botulinum (strain Kyoto / Type A2).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=536232;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Kyoto / Type A2;
RX PubMed=8310180; DOI=10.1016/0923-2508(93)90004-l;
RA Willems A., East A.K., Lawson P.A., Collins M.D.;
RT "Sequence of the gene coding for the neurotoxin of Clostridium botulinum
RT type A associated with infant botulism: comparison with other clostridial
RT neurotoxins.";
RL Res. Microbiol. 144:547-556(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Kyoto / Type A2;
RA Shrivastava S., Brinkac L.M., Brown J.L., Bruce D., Detter C.C.,
RA Johnson E.A., Munk C.A., Smith L.A., Smith T.J., Sutton G., Brettin T.S.;
RT "Genome sequence of Clostridium botulinum A2 Kyoto.";
RL Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-66.
RC STRAIN=Kyoto / Type A2;
RX PubMed=8863443; DOI=10.1099/00207713-46-4-1105;
RA East A.K., Bhandari M., Stacey J.M., Campbell K.D., Collins M.D.;
RT "Organization and phylogenetic interrelationships of genes encoding
RT components of the botulinum toxin complex in proteolytic Clostridium
RT botulinum types A, B, and F: evidence of chimeric sequences in the gene
RT encoding the nontoxic nonhemagglutinin component.";
RL Int. J. Syst. Bacteriol. 46:1105-1112(1996).
RN [4]
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 [5]
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 [6] {ECO:0007744|PDB:1E1H}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 5-250 AND 251-416 IN COMPLEX WITH
RP ZINC, AND COFACTOR.
RX PubMed=15107500; DOI=10.1073/pnas.0400584101;
RA Segelke B., Knapp M., Kadkhodayan S., Balhorn R., Rupp B.;
RT "Crystal structure of Clostridium botulinum neurotoxin protease in a
RT product-bound state: Evidence for noncanonical zinc protease activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6888-6893(2004).
RN [7] {ECO:0007744|PDB:2G7K, ECO:0007744|PDB:2G7P, ECO:0007744|PDB:2G7Q}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 3-426 WITH AND WITHOUT ZINC,
RP FUNCTION (BOTULINUM NEUROTOXIN A2 LIGHT CHAIN), CATALYTIC ACTIVITY,
RP COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION (BOTULINUM NEUROTOXIN A2 LIGHT CHAIN), AND MUTAGENESIS OF ASP-370.
RX PubMed=16846233; DOI=10.1021/bi060786z;
RA Fu Z., Chen S., Baldwin M.R., Boldt G.E., Crawford A., Janda K.D.,
RA Barbieri J.T., Kim J.J.;
RT "Light chain of botulinum neurotoxin serotype A: structural resolution of a
RT catalytic intermediate.";
RL Biochemistry 45:8903-8911(2006).
RN [8] {ECO:0007744|PDB:2G7N}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 3-426.
RA Fu Z., Baldwin M.R., Boldt G.E., Crawford A., Janda K.D., Barbieri J.T.,
RA Kim J.-J.P.;
RT "Structure of the light chain of botulinum neurotoxin serotype A bound to
RT small molecule inhibitors.";
RL Submitted (FEB-2006) to the PDB data bank.
RN [9] {ECO:0007744|PDB:5MOY}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 871-1296 IN COMPLEX WITH SV2C
RP RECEPTOR FRAGMENT, FUNCTION (BOTULINUM NEUROTOXIN A2 HEAVY CHAIN), SUBUNIT,
RP DOMAIN, AND DISULFIDE BONDS.
RC STRAIN=Kyoto / Type A2;
RX PubMed=28252640; DOI=10.1038/srep43588;
RA Benoit R.M., Scharer M.A., Wieser M.M., Li X., Frey D., Kammerer R.A.;
RT "Crystal structure of the BoNT/A2 receptor-binding domain in complex with
RT the luminal domain of its neuronal receptor SV2C.";
RL Sci. Rep. 7:43588-43588(2017).
RN [10] {ECO:0007744|PDB:6ES1}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 874-1296 IN COMPLEX WITH SV2C
RP RECEPTOR FRAGMENT, FUNCTION (BOTULINUM NEUROTOXIN A2 HEAVY CHAIN), SUBUNIT,
RP DOMAIN, AND MUTAGENESIS OF GLU-1156.
RC STRAIN=Kyoto / Type A2;
RX PubMed=29649119; DOI=10.3390/toxins10040153;
RA Gustafsson R., Zhang S., Masuyer G., Dong M., Stenmark P.;
RT "Crystal structure of botulinum neurotoxin A2 in complex with the human
RT protein receptor SV2C reveals plasticity in receptor binding.";
RL Toxins 10:0-0(2018).
CC -!- FUNCTION: [Botulinum neurotoxin type A2]: Botulinum toxin causes
CC flaccid paralysis by inhibiting neurotransmitter (acetylcholine)
CC release from the presynaptic membranes of nerve terminals of eukaryotic
CC host skeletal and autonomic nervous system, with frequent heart or
CC respiratory failure. Precursor of botulinum neurotoxin A2 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
CC them. Upon synaptic vesicle recycling the toxin is taken up via the
CC endocytic pathway. When the pH of the toxin-containing endosome drops a
CC structural rearrangement occurs so that the N-terminus of the HC forms
CC pores that allows the light chain (LC) to translocate into the cytosol.
CC Once in the cytosol the disulfide bond linking the 2 subunits is
CC reduced and LC cleaves its target protein on synaptic vesicles,
CC preventing their fusion with the cytoplasmic membrane and thus
CC neurotransmitter release (By similarity).
CC {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- FUNCTION: [Botulinum neurotoxin A2 light chain]: Has proteolytic
CC activity. After translocation into the eukaryotic host cytosol, LC
CC hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP25, blocking
CC neurotransmitter release (PubMed:16846233).
CC {ECO:0000305|PubMed:16846233}.
CC -!- FUNCTION: [Botulinum neurotoxin A2 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 RBD is responsible
CC for the adherence of the toxin to the cell surface. It simultaneously
CC recognizes 2 coreceptors; polysialated gangliosides and the receptor
CC protein SV2 in close proximity on host synaptic vesicles
CC (PubMed:28252640, PubMed:29649119). The N-terminus of the TD wraps an
CC extended belt around the perimeter of the LC, protecting Zn(2+) in the
CC active site; it may also prevent premature LC dissociation from the
CC translocation channel and to protect toxin prior to translocation (By
CC similarity). The TD inserts into synaptic vesicle membrane to allow
CC translocation into the host cytosol (By similarity).
CC {ECO:0000250|UniProtKB:P0DPI0, ECO:0000269|PubMed:28252640,
CC ECO:0000269|PubMed:29649119}.
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:16846233};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:15107500, ECO:0000269|PubMed:16846233};
CC Note=Binds 1 zinc ion per subunit (PubMed:15107500, PubMed:16846233).
CC {ECO:0000269|PubMed:15107500, ECO:0000269|PubMed:16846233};
CC -!- ACTIVITY REGULATION: Protease activity of LC inhibited by arginine
CC hydroxamate. {ECO:0000269|PubMed:16846233}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14.1 uM for SNAP25 fragment (146-206) with isolated botulinum
CC neurotoxin A2 light chain {ECO:0000269|PubMed:16846233};
CC Note=kcat is 0.13 sec(-1), for botulinum neurotoxin A2 light chain.
CC {ECO:0000269|PubMed:16846233};
CC -!- SUBUNIT: Heterodimer; disulfide-linked heterodimer of a light chain
CC (LC) and a heavy chain (HC). Interacts with host synaptic vesicle
CC glycoprotein 2C (SV2C) which serves as a coreceptor (PubMed:28252640).
CC Also binds host receptor proteins SV2A and SV2B; glycosylation of host
CC protein greatly improves the interaction (PubMed:29649119).
CC {ECO:0000269|PubMed:28252640, ECO:0000269|PubMed:29649119}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin A2 light chain]: Secreted.
CC Host cytoplasm, host cytosol {ECO:0000305|PubMed:16846233}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin A2 heavy chain]: Secreted.
CC Host synapse, host presynaptic cell membrane
CC {ECO:0000305|PubMed:28252640}. 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 A2 light chain]: Has protease activity.
CC {ECO:0000305|PubMed:16846233}.
CC -!- DOMAIN: [Botulinum neurotoxin A2 heavy chain]: Has 3 functional
CC domains; the translocation domain (TD) and the receptor-binding domain
CC (RBD) which is further subdivided into N- and C-terminal domains (N-RBD
CC and C-RBD) (PubMed:28252640, PubMed:29649119). The N-terminus of the TD
CC wraps an extended belt around the perimeter of the LC, protecting
CC Zn(2+) in the active site and may be a pseudosubstrate inhibitor which
CC serves as an intramolecular chaperone for the LC prior to its
CC translocation into the host cytosol. The RBD binds transiently exposed
CC coreceptors on the host presynaptic cell membrane (PubMed:28252640).
CC {ECO:0000250|UniProtKB:P0DPI0, ECO:0000269|PubMed:28252640,
CC ECO:0000269|PubMed:29649119}.
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 -!- 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; X73423; CAA51824.1; -; Genomic_DNA.
DR EMBL; CP001581; ACO83782.1; -; Genomic_DNA.
DR EMBL; X87974; CAA61234.1; -; Genomic_DNA.
DR PIR; I40645; I40645.
DR RefSeq; WP_012703873.1; NC_012563.1.
DR PDB; 1E1H; X-ray; 1.80 A; A/C=10-250, B/D=251-416.
DR PDB; 2G7K; X-ray; 2.80 A; A/B=3-426.
DR PDB; 2G7N; X-ray; 1.90 A; A=3-426.
DR PDB; 2G7P; X-ray; 2.30 A; A/B=3-426.
DR PDB; 2G7Q; X-ray; 2.41 A; A/B=3-426.
DR PDB; 5MOY; X-ray; 2.30 A; A=871-1296.
DR PDB; 6ES1; X-ray; 2.00 A; A=874-1296.
DR PDBsum; 1E1H; -.
DR PDBsum; 2G7K; -.
DR PDBsum; 2G7N; -.
DR PDBsum; 2G7P; -.
DR PDBsum; 2G7Q; -.
DR PDBsum; 5MOY; -.
DR PDBsum; 6ES1; -.
DR AlphaFoldDB; Q45894; -.
DR SMR; Q45894; -.
DR DIP; DIP-437N; -.
DR STRING; 536232.CLM_0897; -.
DR Allergome; 12104; Clo bo Toxin.
DR EnsemblBacteria; ACO83782; ACO83782; CLM_0897.
DR KEGG; cby:CLM_0897; -.
DR eggNOG; ENOG5032QRH; Bacteria.
DR HOGENOM; CLU_262205_0_0_9; -.
DR OMA; DEGYNKA; -.
DR EvolutionaryTrace; Q45894; -.
DR Proteomes; UP000001374; Chromosome.
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:0004222; F:metalloendopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0008320; F:protein transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0046929; P:negative regulation of neurotransmitter secretion; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA: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.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Host cell membrane; Host cytoplasm;
KW Host cytoplasmic vesicle; Host membrane; Host synapse; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Neurotoxin; Protease; Secreted; Toxin;
KW Transmembrane; Transmembrane helix; Virulence; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT CHAIN 2..1296
FT /note="Botulinum neurotoxin type A2"
FT /id="PRO_0000444918"
FT CHAIN 2..448
FT /note="Botulinum neurotoxin A2 light chain"
FT /id="PRO_0000029213"
FT CHAIN 449..1296
FT /note="Botulinum neurotoxin A2 heavy chain"
FT /id="PRO_0000029214"
FT TRANSMEM 627..647
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 656..676
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 449..870
FT /note="Translocation domain (TD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 492..545
FT /note="Belt; not required for channel formation"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 871..1092
FT /note="N-terminus of receptor binding domain (N-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000305|PubMed:28252640"
FT REGION 1093..1296
FT /note="C-terminus of receptor binding domain (C-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000305|PubMed:28252640"
FT MOTIF 1264..1267
FT /note="Host ganglioside-binding motif"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT ACT_SITE 224
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 223
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:15107500,
FT ECO:0000269|PubMed:16846233, ECO:0007744|PDB:2G7P,
FT ECO:0007744|PDB:2G7Q"
FT BINDING 227
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:15107500,
FT ECO:0000269|PubMed:16846233, ECO:0007744|PDB:2G7P,
FT ECO:0007744|PDB:2G7Q"
FT BINDING 262
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:15107500,
FT ECO:0000269|PubMed:16846233, ECO:0007744|PDB:2G7P,
FT ECO:0007744|PDB:2G7Q"
FT SITE 366
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000305|PubMed:16846233"
FT DISULFID 430..454
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000250|UniProtKB:P10844"
FT DISULFID 1235..1280
FT /evidence="ECO:0000269|PubMed:28252640,
FT ECO:0007744|PDB:5MOY"
FT MUTAGEN 370
FT /note="D->A: 600-fold decrease in cleavage rate of SNAP25
FT by light chain."
FT /evidence="ECO:0000269|PubMed:16846233"
FT MUTAGEN 1156
FT /note="E->R: Decreased binding to human SV2C extracellular
FT loop 4 fragment."
FT /evidence="ECO:0000269|PubMed:29649119"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 42..48
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:2G7N"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:2G7P"
FT TURN 75..78
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 81..99
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 102..113
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:1E1H"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 192..198
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:2G7N"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 217..232
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 242..246
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 254..259
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 260..266
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 268..273
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 276..299
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 305..308
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 310..321
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 335..347
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 351..358
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:1E1H"
FT TURN 381..383
FT /evidence="ECO:0007829|PDB:1E1H"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 393..395
FT /evidence="ECO:0007829|PDB:2G7N"
FT HELIX 396..398
FT /evidence="ECO:0007829|PDB:2G7P"
FT HELIX 402..404
FT /evidence="ECO:0007829|PDB:1E1H"
FT TURN 406..409
FT /evidence="ECO:0007829|PDB:1E1H"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:1E1H"
FT STRAND 414..418
FT /evidence="ECO:0007829|PDB:2G7N"
FT STRAND 877..883
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 885..890
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 897..900
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 904..906
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 908..910
FT /evidence="ECO:0007829|PDB:5MOY"
FT STRAND 914..919
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 924..927
FT /evidence="ECO:0007829|PDB:6ES1"
FT HELIX 930..932
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 935..938
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 941..948
FT /evidence="ECO:0007829|PDB:6ES1"
FT HELIX 955..957
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 962..969
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 972..979
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 982..988
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 994..1000
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1005..1007
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1015..1021
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1025..1031
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1034..1040
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1051..1059
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1066..1077
FT /evidence="ECO:0007829|PDB:6ES1"
FT HELIX 1081..1091
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1102..1104
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1111..1117
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1122..1129
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1134..1137
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1142..1145
FT /evidence="ECO:0007829|PDB:6ES1"
FT TURN 1146..1148
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1149..1152
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1160..1164
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1171..1173
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1179..1186
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1189..1195
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1199..1205
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1207..1209
FT /evidence="ECO:0007829|PDB:6ES1"
FT HELIX 1211..1213
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1220..1226
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1232..1240
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1246..1255
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1258..1264
FT /evidence="ECO:0007829|PDB:6ES1"
FT HELIX 1265..1272
FT /evidence="ECO:0007829|PDB:6ES1"
FT STRAND 1282..1285
FT /evidence="ECO:0007829|PDB:6ES1"
FT TURN 1289..1291
FT /evidence="ECO:0007829|PDB:6ES1"
SQ SEQUENCE 1296 AA; 149411 MW; 6F12E7BF28ED69D1 CRC64;
MPFVNKQFNY KDPVNGVDIA YIKIPNAGQM QPVKAFKIHN KIWVIPERDT FTNPEEGDLN
PPPEAKQVPV SYYDSTYLST DNEKDNYLKG VTKLFERIYS TDLGRMLLTS IVRGIPFWGG
STIDTELKVI DTNCINVIQP DGSYRSEELN LVIIGPSADI IQFECKSFGH DVLNLTRNGY
GSTQYIRFSP DFTFGFEESL EVDTNPLLGA GKFATDPAVT LAHELIHAEH RLYGIAINPN
RVFKVNTNAY YEMSGLEVSF EELRTFGGHD AKFIDSLQEN EFRLYYYNKF KDVASTLNKA
KSIIGTTASL QYMKNVFKEK YLLSEDTSGK FSVDKLKFDK LYKMLTEIYT EDNFVNFFKV
INRKTYLNFD KAVFRINIVP DENYTIKDGF NLKGANLSTN FNGQNTEINS RNFTRLKNFT
GLFEFYKLLC VRGIIPFKTK SLDEGYNKAL NDLCIKVNNW DLFFSPSEDN FTNDLDKVEE
ITADTNIEAA EENISLDLIQ QYYLTFDFDN EPENISIENL SSDIIGQLEP MPNIERFPNG
KKYELDKYTM FHYLRAQEFE HGDSRIILTN SAEEALLKPN VAYTFFSSKY VKKINKAVEA
FMFLNWAEEL VYDFTDETNE VTTMDKIADI TIIVPYIGPA LNIGNMLSKG EFVEAIIFTG
VVAMLEFIPE YALPVFGTFA IVSYIANKVL TVQTINNALS KRNEKWDEVY KYTVTNWLAK
VNTQIDLIRE KMKKALENQA EATKAIINYQ YNQYTEEEKN NINFNIDDLS SKLNESINSA
MININKFLDQ CSVSYLMNSM IPYAVKRLKD FDASVRDVLL KYIYDNRGTL VLQVDRLKDE
VNNTLSADIP FQLSKYVDNK KLLSTFTEYI KNIVNTSILS IVYKKDDLID LSRYGAKINI
GDRVYYDSID KNQIKLINLE SSTIEVILKN AIVYNSMYEN FSTSFWIKIP KYFSKINLNN
EYTIINCIEN NSGWKVSLNY GEIIWTLQDN KQNIQRVVFK YSQMVNISDY INRWIFVTIT
NNRLTKSKIY INGRLIDQKP ISNLGNIHAS NKIMFKLDGC RDPRRYIMIK YFNLFDKELN
EKEIKDLYDS QSNSGILKDF WGNYLQYDKP YYMLNLFDPN KYVDVNNIGI RGYMYLKGPR
GSVVTTNIYL NSTLYEGTKF IIKKYASGNE DNIVRNNDRV YINVVVKNKE YRLATNASQA
GVEKILSALE IPDVGNLSQV VVMKSKDDQG IRNKCKMNLQ DNNGNDIGFI GFHLYDNIAK
LVASNWYNRQ VGKASRTFGC SWEFIPVDDG WGESSL
