LEF_BACAN
ID LEF_BACAN Reviewed; 809 AA.
AC P15917; Q8KYJ6; Q933F6;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Lethal factor {ECO:0000303|PubMed:2509294};
DE Short=LF {ECO:0000303|PubMed:2509294};
DE EC=3.4.24.83 {ECO:0000269|PubMed:14718925, ECO:0000269|PubMed:9563949};
DE AltName: Full=Anthrax lethal toxin endopeptidase component {ECO:0000305};
DE Flags: Precursor;
GN Name=lef {ECO:0000303|PubMed:2509294};
GN OrderedLocusNames=pXO1-107, BXA0172, GBAA_pXO1_0172;
OS Bacillus anthracis.
OG Plasmid pXO1.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus;
OC Bacillus cereus group.
OX NCBI_TaxID=1392;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 34-49, AND
RP SUBCELLULAR LOCATION.
RX PubMed=2509294; DOI=10.1016/0378-1119(89)90335-1;
RA Bragg T.S., Robertson D.L.;
RT "Nucleotide sequence and analysis of the lethal factor gene (lef) from
RT Bacillus anthracis.";
RL Gene 81:45-54(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Lowe J.;
RT "A comparison of Bacillus anthracis sequences.";
RL Submitted (APR-1990) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Sterne;
RX PubMed=10515943; DOI=10.1128/jb.181.20.6509-6515.1999;
RA Okinaka R.T., Cloud K., Hampton O., Hoffmaster A.R., Hill K.K., Keim P.,
RA Koehler T.M., Lamke G., Kumano S., Mahillon J., Manter D., Martinez Y.,
RA Ricke D., Svensson R., Jackson P.J.;
RT "Sequence and organization of pXO1, the large Bacillus anthracis plasmid
RT harboring the anthrax toxin genes.";
RL J. Bacteriol. 181:6509-6515(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Ames / isolate Florida / A2012;
RX PubMed=12004073; DOI=10.1126/science.1071837;
RA Read T.D., Salzberg S.L., Pop M., Shumway M.F., Umayam L., Jiang L.,
RA Holtzapple E., Busch J.D., Smith K.L., Schupp J.M., Solomon D., Keim P.,
RA Fraser C.M.;
RT "Comparative genome sequencing for discovery of novel polymorphisms in
RT Bacillus anthracis.";
RL Science 296:2028-2033(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Ames ancestor;
RX PubMed=18952800; DOI=10.1128/jb.01347-08;
RA Ravel J., Jiang L., Stanley S.T., Wilson M.R., Decker R.S., Read T.D.,
RA Worsham P., Keim P.S., Salzberg S.L., Fraser-Liggett C.M., Rasko D.A.;
RT "The complete genome sequence of Bacillus anthracis Ames 'Ancestor'.";
RL J. Bacteriol. 191:445-446(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-809.
RC STRAIN=Carbosap, and Ferrara;
RX PubMed=12067380; DOI=10.1046/j.1365-2672.2002.01660.x;
RA Adone R., Pasquali P., La Rosa G., Marianelli C., Muscillo M.,
RA Fasanella A., Francia M., Ciuchini F.;
RT "Sequence analysis of the genes encoding for the major virulence factors of
RT Bacillus anthracis vaccine strain 'Carbosap'.";
RL J. Appl. Microbiol. 93:117-121(2002).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=3711080; DOI=10.1016/s0021-9258(17)38364-3;
RA Friedlander A.M.;
RT "Macrophages are sensitive to anthrax lethal toxin through an acid-
RT dependent process.";
RL J. Biol. Chem. 261:7123-7126(1986).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=1512256; DOI=10.1016/s0021-9258(18)41911-4;
RA Novak J.M., Stein M.P., Little S.F., Leppla S.H., Friedlander A.M.;
RT "Functional characterization of protease-treated Bacillus anthracis
RT protective antigen.";
RL J. Biol. Chem. 267:17186-17193(1992).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8380282; DOI=10.1128/iai.61.1.245-252.1993;
RA Friedlander A.M., Bhatnagar R., Leppla S.H., Johnson L., Singh Y.;
RT "Characterization of macrophage sensitivity and resistance to anthrax
RT lethal toxin.";
RL Infect. Immun. 61:245-252(1993).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=9563949; DOI=10.1126/science.280.5364.734;
RA Duesbery N.S., Webb C.P., Leppla S.H., Gordon V.M., Klimpel K.R.,
RA Copeland T.D., Ahn N.G., Oskarsson M.K., Fukasawa K., Paull K.D.,
RA Vande Woude G.F.;
RT "Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor.";
RL Science 280:734-737(1998).
RN [11]
RP FUNCTION.
RX PubMed=9703991; DOI=10.1006/bbrc.1998.9040;
RA Vitale G., Pellizzari R., Recchi C., Napolitani G., Mock M., Montecucco C.;
RT "Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces
RT tyrosine/threonine phosphorylation of MAPKs in cultured macrophages.";
RL Biochem. Biophys. Res. Commun. 248:706-711(1998).
RN [12]
RP FUNCTION.
RX PubMed=10475971; DOI=10.1046/j.1365-2672.1999.00892.x;
RA Duesbery N.S., Vande Woude G.F.;
RT "Anthrax lethal factor causes proteolytic inactivation of mitogen-activated
RT protein kinase kinase.";
RL J. Appl. Microbiol. 87:289-293(1999).
RN [13]
RP INTERACTION WITH PA, AND SUBCELLULAR LOCATION.
RX PubMed=10085027; DOI=10.1128/iai.67.4.1853-1859.1999;
RA Singh Y., Klimpel K.R., Goel S., Swain P.K., Leppla S.H.;
RT "Oligomerization of anthrax toxin protective antigen and binding of lethal
RT factor during endocytic uptake into mammalian cells.";
RL Infect. Immun. 67:1853-1859(1999).
RN [14]
RP FUNCTION.
RX PubMed=11104681; DOI=10.1042/bj3520739;
RA Vitale G., Bernardi L., Napolitani G., Mock M., Montecucco C.;
RT "Susceptibility of mitogen-activated protein kinase kinase family members
RT to proteolysis by anthrax lethal factor.";
RL Biochem. J. 352:739-745(2000).
RN [15]
RP FUNCTION.
RX PubMed=10338520; DOI=10.1128/iai.67.6.3055-3060.1999;
RA Tang G., Leppla S.H.;
RT "Proteasome activity is required for anthrax lethal toxin to kill
RT macrophages.";
RL Infect. Immun. 67:3055-3060(1999).
RN [16]
RP INTERACTION WITH PA.
RX PubMed=8942659; DOI=10.1021/bi961518b;
RA Wang X.-M., Mock M., Ruysschaert J.-M., Cabiaux V.;
RT "Secondary structure of anthrax lethal toxin proteins and their interaction
RT with large unilamellar vesicles: a Fourier-transform infrared spectroscopy
RT approach.";
RL Biochemistry 35:14939-14946(1996).
RN [17]
RP ZINC-BINDING.
RX PubMed=7851740; DOI=10.1111/j.1574-6968.1994.tb07306.x;
RA Kochi S.K., Schiavo G., Mock M., Montecucco C.;
RT "Zinc content of the Bacillus anthracis lethal factor.";
RL FEMS Microbiol. Lett. 124:343-348(1994).
RN [18]
RP INDUCTION.
RC STRAIN=Sterne;
RX PubMed=8051039; DOI=10.1128/jb.176.16.5188-5192.1994;
RA Sirard J.-C., Mock M., Fouet A.;
RT "The three Bacillus anthracis toxin genes are coordinately regulated by
RT bicarbonate and temperature.";
RL J. Bacteriol. 176:5188-5192(1994).
RN [19]
RP MUTAGENESIS OF HIS-719; GLU-720 AND HIS-723, AND ACTIVE SITE.
RC STRAIN=Sterne;
RX PubMed=9573135; DOI=10.1128/iai.66.5.2374-2378.1998;
RA Hammond S.E., Hanna P.C.;
RT "Lethal factor active-site mutations affect catalytic activity in vitro.";
RL Infect. Immun. 66:2374-2378(1998).
RN [20]
RP MUTAGENESIS OF VAL-180; TYR-181; TYR-182; GLU-183; ILE-184; GLY-185 AND
RP LYS-186.
RC STRAIN=Sterne;
RX PubMed=11162493; DOI=10.1006/bbrc.2000.4099;
RA Gupta P., Singh A., Chauhan V., Bhatnagar R.;
RT "Involvement of residues 147VYYEIGK153 in binding of lethal factor to
RT protective antigen of Bacillus anthracis.";
RL Biochem. Biophys. Res. Commun. 280:158-163(2001).
RN [21]
RP REVIEW.
RX PubMed=11595637; DOI=10.1016/s0041-0101(01)00161-1;
RA Brossier F., Mock M.;
RT "Toxins of Bacillus anthracis.";
RL Toxicon 39:1747-1755(2001).
RN [22]
RP MUTAGENESIS OF ASP-220; LEU-221; LEU-222 AND PHE-223.
RC STRAIN=Sterne;
RX PubMed=12113932; DOI=10.1111/j.1574-6968.2002.tb11264.x;
RA Singh A., Chauhan V., Sodhi A., Bhatnagar R.;
RT "Asp 187 and Phe 190 residues in lethal factor are required for the
RT expression of anthrax lethal toxin activity.";
RL FEMS Microbiol. Lett. 212:183-186(2002).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=12551953; DOI=10.1083/jcb.200211018;
RA Abrami L., Liu S., Cosson P., Leppla S.H., van der Goot F.G.;
RT "Anthrax toxin triggers endocytosis of its receptor via a lipid raft-
RT mediated clathrin-dependent process.";
RL J. Cell Biol. 160:321-328(2003).
RN [24]
RP INTERACTION WITH PA.
RX PubMed=15313199; DOI=10.1016/j.bbrc.2004.07.105;
RA Pimental R.A., Christensen K.A., Krantz B.A., Collier R.J.;
RT "Anthrax toxin complexes: heptameric protective antigen can bind lethal
RT factor and edema factor simultaneously.";
RL Biochem. Biophys. Res. Commun. 322:258-262(2004).
RN [25]
RP FUNCTION.
RX PubMed=16429160; DOI=10.1038/ng1724;
RA Boyden E.D., Dietrich W.F.;
RT "Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin.";
RL Nat. Genet. 38:240-244(2006).
RN [26]
RP FUNCTION, MUTAGENESIS OF GLU-720, AND ACTIVE SITE.
RX PubMed=19651869; DOI=10.1128/iai.00276-09;
RA Liao K.C., Mogridge J.;
RT "Expression of Nlrp1b inflammasome components in human fibroblasts confers
RT susceptibility to anthrax lethal toxin.";
RL Infect. Immun. 77:4455-4462(2009).
RN [27]
RP FUNCTION.
RX PubMed=31268597; DOI=10.15252/embj.2019101996;
RA Xu H., Shi J., Gao H., Liu Y., Yang Z., Shao F., Dong N.;
RT "The N-end rule ubiquitin ligase UBR2 mediates NLRP1B inflammasome
RT activation by anthrax lethal toxin.";
RL EMBO J. 38:e101996-e101996(2019).
RN [28]
RP FUNCTION.
RX PubMed=30872531; DOI=10.1126/science.aau1208;
RA Chui A.J., Okondo M.C., Rao S.D., Gai K., Griswold A.R., Johnson D.C.,
RA Ball D.P., Taabazuing C.Y., Orth E.L., Vittimberga B.A., Bachovchin D.A.;
RT "N-terminal degradation activates the NLRP1B inflammasome.";
RL Science 364:82-85(2019).
RN [29] {ECO:0007744|PDB:1J7N, ECO:0007744|PDB:1JKY}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH ZINC IONS AND MAP2K2,
RP COFACTOR, DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=11700563; DOI=10.1038/n35101998;
RA Pannifer A.D., Wong T.Y., Schwarzenbacher R., Renatus M., Petosa C.,
RA Bienkowska J., Lacy D.B., Collier R.J., Park S., Leppla S.H., Hanna P.C.,
RA Liddington R.C.;
RT "Crystal structure of the anthrax lethal factor.";
RL Nature 414:229-233(2001).
RN [30] {ECO:0007744|PDB:1PWQ, ECO:0007744|PDB:1PWU, ECO:0007744|PDB:1PWV, ECO:0007744|PDB:1PWW}
RP X-RAY CRYSTALLOGRAPHY (3.52 ANGSTROMS) OF 34-809 IN COMPLEX WITH ZINC IONS
RP AND PEPTIDE SUBSTRATE ANALOG, AND COFACTOR.
RX PubMed=14718924; DOI=10.1038/nsmb708;
RA Turk B.E., Wong T.Y., Schwarzenbacher R., Jarrell E.T., Leppla S.H.,
RA Collier R.J., Liddington R.C., Cantley L.C.;
RT "The structural basis for substrate and inhibitor selectivity of the
RT anthrax lethal factor.";
RL Nat. Struct. Mol. Biol. 11:60-66(2004).
RN [31] {ECO:0007744|PDB:1PWP}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 34-809 IN COMPLEX WITH ZINC AND
RP NSC-12155 INHIBITOR, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP COFACTOR.
RX PubMed=14718925; DOI=10.1038/nsmb711;
RA Panchal R.G., Hermone A.R., Nguyen T.L., Wong T.Y., Schwarzenbacher R.,
RA Schmidt J., Lane D., McGrath C., Turk B.E., Burnett J., Aman M.J.,
RA Little S., Sausville E.A., Zaharevitz D.W., Cantley L.C., Liddington R.C.,
RA Gussio R., Bavari S.;
RT "Identification of small molecule inhibitors of anthrax lethal factor.";
RL Nat. Struct. Mol. Biol. 11:67-72(2004).
RN [32] {ECO:0007744|PDB:1YQY}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 297-809 IN COMPLEX WITH ZINC IONS
RP AND PROTEASE INHIBITOR, AND COFACTOR.
RX PubMed=15911756; DOI=10.1073/pnas.0502159102;
RA Shoop W.L., Xiong Y., Wiltsie J., Woods A., Guo J., Pivnichny J.V.,
RA Felcetto T., Michael B.F., Bansal A., Cummings R.T., Cunningham B.R.,
RA Friedlander A.M., Douglas C.M., Patel S.B., Wisniewski D., Scapin G.,
RA Salowe S.P., Zaller D.M., Chapman K.T., Scolnick E.M., Schmatz D.M.,
RA Bartizal K., MacCoss M., Hermes J.D.;
RT "Anthrax lethal factor inhibition.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:7958-7963(2005).
RN [33] {ECO:0007744|PDB:2L0R}
RP STRUCTURE BY NMR OF 705-809.
RX PubMed=21121613; DOI=10.1021/bi1017792;
RA Dalkas G.A., Chasapis C.T., Gkazonis P.V., Bentrop D., Spyroulias G.A.;
RT "Conformational dynamics of the anthrax lethal factor catalytic center.";
RL Biochemistry 49:10767-10769(2010).
RN [34] {ECO:0007744|PDB:3KWV}
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 34-296 IN COMPLEX WITH PA-63,
RP INTERACTION WITH PA, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-68;
RP LEU-69; ILE-72; MET-73; HIS-75; ILE-76 AND TYR-269.
RX PubMed=21037566; DOI=10.1038/nsmb.1923;
RA Feld G.K., Thoren K.L., Kintzer A.F., Sterling H.J., Tang I.I.,
RA Greenberg S.G., Williams E.R., Krantz B.A.;
RT "Structural basis for the unfolding of anthrax lethal factor by protective
RT antigen oligomers.";
RL Nat. Struct. Mol. Biol. 17:1383-1390(2010).
RN [35] {ECO:0007744|PDB:4DV8}
RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 296-809 IN COMPLEX WITH ZINC,
RP COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=22342144; DOI=10.1016/j.bmcl.2012.01.095;
RA Jiao G.S., Kim S., Moayeri M., Crown D., Thai A., Cregar-Hernandez L.,
RA McKasson L., Sankaran B., Lehrer A., Wong T., Johns L., Margosiak S.A.,
RA Leppla S.H., Johnson A.T.;
RT "Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of
RT core structures and further modifications to the C2-side chain.";
RL Bioorg. Med. Chem. Lett. 22:2242-2246(2012).
RN [36] {ECO:0007744|PDB:4PKQ, ECO:0007744|PDB:4PKR, ECO:0007744|PDB:4PKS, ECO:0007744|PDB:4PKT, ECO:0007744|PDB:4PKU, ECO:0007744|PDB:4PKV, ECO:0007744|PDB:4PKW}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 298-809 IN COMPLEX WITH ZINC,
RP COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=25372673; DOI=10.1107/s1399004714018161;
RA Maize K.M., Kurbanov E.K., De La Mora-Rey T., Geders T.W., Hwang D.J.,
RA Walters M.A., Johnson R.L., Amin E.A., Finzel B.C.;
RT "Anthrax toxin lethal factor domain 3 is highly mobile and responsive to
RT ligand binding.";
RL Acta Crystallogr. D 70:2813-2822(2014).
RN [37] {ECO:0007744|PDB:4XM6, ECO:0007744|PDB:4XM7, ECO:0007744|PDB:4XM8}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 298-809 IN COMPLEX WITH ZINC,
RP COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=26578066; DOI=10.1016/j.febslet.2015.11.005;
RA Maize K.M., Kurbanov E.K., Johnson R.L., Amin E.A., Finzel B.C.;
RT "Ligand-induced expansion of the S1' site in the anthrax toxin lethal
RT factor.";
RL FEBS Lett. 589:3836-3841(2015).
RN [38] {ECO:0007744|PDB:4WF6, ECO:0007744|PDB:5D1S, ECO:0007744|PDB:5D1T, ECO:0007744|PDB:5D1U}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 298-809 IN COMPLEX WITH ZINC,
RP COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=26492514; DOI=10.1021/acs.jmedchem.5b01446;
RA Kurbanov E.K., Chiu T.L., Solberg J., Francis S., Maize K.M., Fernandez J.,
RA Johnson R.L., Hawkinson J.E., Walters M.A., Finzel B.C., Amin E.A.;
RT "Probing the S2' subsite of the anthrax toxin lethal factor using novel N-
RT alkylated hydroxamates.";
RL J. Med. Chem. 58:8723-8733(2015).
RN [39] {ECO:0007744|PDB:6PSN}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.60 ANGSTROMS) IN COMPLEX WITH PA,
RP INTERACTION WITH PA, AND SUBCELLULAR LOCATION.
RX PubMed=32047164; DOI=10.1038/s41467-020-14658-6;
RA Hardenbrook N.J., Liu S., Zhou K., Ghosal K., Hong Zhou Z., Krantz B.A.;
RT "Atomic structures of anthrax toxin protective antigen channels bound to
RT partially unfolded lethal and edema factors.";
RL Nat. Commun. 11:840-840(2020).
RN [40] {ECO:0007744|PDB:6ZXJ, ECO:0007744|PDB:6ZXK, ECO:0007744|PDB:6ZXL}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS) IN COMPLEX WITH PA,
RP INTERACTION WITH PA, AND SUBCELLULAR LOCATION.
RX PubMed=32810181; DOI=10.1371/journal.ppat.1008530;
RA Antoni C., Quentin D., Lang A.E., Aktories K., Gatsogiannis C., Raunser S.;
RT "Cryo-EM structure of the fully-loaded asymmetric anthrax lethal toxin in
RT its heptameric pre-pore state.";
RL PLoS Pathog. 16:e1008530-e1008530(2020).
RN [41] {ECO:0007744|PDB:6WJJ}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) OF 62-801 IN COMPLEX WITH
RP PA, INTERACTION WITH PA, AND SUBCELLULAR LOCATION.
RX PubMed=32521227; DOI=10.1016/j.str.2020.05.009;
RA Zhou K., Liu S., Hardenbrook N.J., Cui Y., Krantz B.A., Zhou Z.H.;
RT "Atomic structures of anthrax prechannel bound with full-length Lethal and
RT Edema factors.";
RL Structure 28:879-887(2020).
CC -!- FUNCTION: Lethal factor (LF), which constitutes one of the three
CC proteins composing the anthrax toxin, is able to trigger rapid cell
CC death in macrophages (PubMed:3711080, PubMed:8380282, PubMed:9563949,
CC PubMed:10475971, PubMed:11104681, PubMed:9703991). Acts as a protease
CC that cleaves the N-terminal of most dual specificity mitogen-activated
CC protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5): cleavage
CC invariably occurs within the N-terminal proline-rich region preceding
CC the kinase domain, thus disrupting a sequence involved in directing
CC specific protein-protein interactions necessary for the assembly of
CC signaling complexes (PubMed:9563949, PubMed:10475971, PubMed:11104681,
CC PubMed:9703991, PubMed:14718925). Also cleaves mouse Nlrp1b: host
CC Nlrp1b cleavage promotes ubiquitination and degradation of the N-
CC terminal part of Nlrp1b by the proteasome, thereby releasing the
CC cleaved C-terminal part of Nlrp1b, which polymerizes and forms the
CC Nlrp1b inflammasome followed by host cell pyroptosis (PubMed:10338520,
CC PubMed:19651869, PubMed:31268597, PubMed:30872531). Able to cleave
CC mouse Nlrp1b alleles 1 and 5, while it is not able to cleave Nlrp1b
CC alleles 2, 3 and 4 (PubMed:16429160, PubMed:19651869). In contrast,
CC does not cleave NLRP1 human ortholog (PubMed:19651869). LF is not toxic
CC by itself and only acts as a lethal factor when associated with
CC protective antigen (PA) to form the lethal toxin (LeTx): PA is required
CC for LF translocation into the host cytosol (PubMed:9563949,
CC PubMed:10475971, PubMed:11104681, PubMed:9703991).
CC {ECO:0000269|PubMed:10338520, ECO:0000269|PubMed:10475971,
CC ECO:0000269|PubMed:11104681, ECO:0000269|PubMed:14718925,
CC ECO:0000269|PubMed:16429160, ECO:0000269|PubMed:19651869,
CC ECO:0000269|PubMed:30872531, ECO:0000269|PubMed:31268597,
CC ECO:0000269|PubMed:3711080, ECO:0000269|PubMed:8380282,
CC ECO:0000269|PubMed:9563949, ECO:0000269|PubMed:9703991}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferred amino acids around the cleavage site can be denoted
CC BBBBxHx-|-H, in which B denotes Arg or Lys, H denotes a hydrophobic
CC amino acid, and x is any amino acid. The only known protein
CC substrates are mitogen-activated protein (MAP) kinase kinases.;
CC EC=3.4.24.83; Evidence={ECO:0000269|PubMed:14718925,
CC ECO:0000269|PubMed:9563949};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01339,
CC ECO:0000269|PubMed:11700563, ECO:0000269|PubMed:14718924,
CC ECO:0000269|PubMed:14718925, ECO:0000269|PubMed:15911756,
CC ECO:0000269|PubMed:22342144, ECO:0000269|PubMed:25372673,
CC ECO:0000269|PubMed:26492514, ECO:0000269|PubMed:26578066,
CC ECO:0000269|PubMed:7851740};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU01339, ECO:0000269|PubMed:14718924,
CC ECO:0000269|PubMed:14718925, ECO:0000269|PubMed:15911756,
CC ECO:0000269|PubMed:22342144, ECO:0000269|PubMed:25372673,
CC ECO:0000269|PubMed:26492514, ECO:0000269|PubMed:26578066};
CC -!- ACTIVITY REGULATION: Inhibited by NSC-12155 (1,3-Bis(2-methyl-4-
CC aminoquinoline-6-yl)ure) (PubMed:14718925). Inhibited by phenoxyacetic
CC acid bearing alpha-benzyl substituents on the C2-side chain
CC (PubMed:22342144). Inhibited by sulfonamide hydroxamate with benzylic
CC additions at the sulfonamide nitrogen (PubMed:25372673). Also inhibited
CC by sulfonamide hydroxamates with alkylation at the sulfonamide nitrogen
CC (PubMed:26492514). Inhibited by hydroxamic acid inhibitors
CC (PubMed:26578066). {ECO:0000269|PubMed:14718925,
CC ECO:0000269|PubMed:22342144, ECO:0000269|PubMed:25372673,
CC ECO:0000269|PubMed:26492514, ECO:0000269|PubMed:26578066}.
CC -!- SUBUNIT: Interacts (via ATLF domain 1) with the cleaved form of
CC protective antigen (PA-63) anthrax toxin; interaction is required for
CC LF translocation into the host cytoplasm (PubMed:10085027,
CC PubMed:8942659, PubMed:15313199, PubMed:21037566, PubMed:32047164,
CC PubMed:32810181, PubMed:32521227). Interacts with PA-63 homooligomers
CC (either homoheptamers or homooctamers): three molecules of LF bind the
CC PA-63 homoheptamer to form the PA(7)LF(3) complex, in which the
CC relative position of the N-terminal alpha-helices in the three LFs
CC determines which factor is translocated first (PubMed:32810181).
CC {ECO:0000269|PubMed:10085027, ECO:0000269|PubMed:15313199,
CC ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:32047164,
CC ECO:0000269|PubMed:32521227, ECO:0000269|PubMed:32810181,
CC ECO:0000269|PubMed:8942659}.
CC -!- INTERACTION:
CC P15917; P13423: pagA; NbExp=28; IntAct=EBI-456923, EBI-456868;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2509294}. Host
CC cytoplasm, host cytosol {ECO:0000269|PubMed:1512256}.
CC Note=Translocation into host cytosol is mediated via interaction with
CC the cleaved form of protective antigen (PA-63): following secretion, LF
CC binds via its N-terminal region to the upper rim of the ring-shaped
CC homooligomer formed by PA-63 on the host cell membrane
CC (PubMed:21037566, PubMed:32810181). In this PA-63 pre-pore state, the
CC N-terminal segment of LF refolds into an alpha helix engaged in the
CC alpha-clamp of the PA-63 pre-pore (PubMed:32047164, PubMed:32521227).
CC Loaded complexes are then endocytosed, followed by a conformational
CC change of oligomerized PA-63 from the pre-pore to pore state, which is
CC triggered by the low pH in the endosome (PubMed:3711080,
CC PubMed:8380282, PubMed:10085027, PubMed:12551953). LF is then unfolded
CC to pass through the PA-63 pore and translocate into the host cytosol
CC (PubMed:21037566, PubMed:32047164, PubMed:32521227).
CC {ECO:0000269|PubMed:10085027, ECO:0000269|PubMed:12551953,
CC ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:32047164,
CC ECO:0000269|PubMed:32521227, ECO:0000269|PubMed:32810181,
CC ECO:0000269|PubMed:3711080, ECO:0000269|PubMed:8380282}.
CC -!- INDUCTION: Positively transcriptionally regulated by AtxA, which, in
CC turn, is induced by bicarbonate and high temperatures (37 degrees
CC Celsius). {ECO:0000269|PubMed:8051039}.
CC -!- DOMAIN: Lethal factor (LF) is composed of four domains: domain I
CC contains the first ATLF domain that binds the membrane-translocating
CC component protective antigen (PA); domains II, III and IV together
CC create a long deep groove that holds the 16-residue N-terminal tail of
CC MAPKK before cleavage (PubMed:11700563). Domain IV contains the
CC catalytic center (PubMed:11700563). {ECO:0000269|PubMed:11700563}.
CC -!- SIMILARITY: Belongs to the peptidase M34 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; M29081; AAA79216.1; -; Genomic_DNA.
DR EMBL; M30210; AAA22569.1; -; Genomic_DNA.
DR EMBL; AF065404; AAD32411.1; -; Genomic_DNA.
DR EMBL; AE011190; AAM26117.1; -; Genomic_DNA.
DR EMBL; AE017336; AAT28913.2; -; Genomic_DNA.
DR EMBL; AJ413934; CAC93932.1; -; Genomic_DNA.
DR EMBL; AJ413935; CAC93933.1; -; Genomic_DNA.
DR PIR; JQ0032; JQ0032.
DR RefSeq; NP_052803.1; NC_001496.1.
DR RefSeq; WP_001022097.1; NZ_VTZH01000015.1.
DR RefSeq; WP_010890024.1; NZ_QPEZ01000014.1.
DR PDB; 1J7N; X-ray; 2.30 A; A/B=34-809.
DR PDB; 1JKY; X-ray; 3.90 A; A=34-809.
DR PDB; 1PWP; X-ray; 2.90 A; A/B=34-809.
DR PDB; 1PWQ; X-ray; 3.52 A; A/B=34-809.
DR PDB; 1PWU; X-ray; 2.70 A; A/B=34-809.
DR PDB; 1PWV; X-ray; 2.85 A; A/B=34-809.
DR PDB; 1PWW; X-ray; 2.80 A; A/B=34-809.
DR PDB; 1YQY; X-ray; 2.30 A; A=297-809.
DR PDB; 1ZXV; X-ray; 2.67 A; A/B=34-809.
DR PDB; 2L0R; NMR; -; A=705-809.
DR PDB; 3KWV; X-ray; 3.10 A; C/F=34-296.
DR PDB; 4DV8; X-ray; 1.63 A; A=296-809.
DR PDB; 4PKQ; X-ray; 2.20 A; A=298-809.
DR PDB; 4PKR; X-ray; 2.20 A; A=298-809.
DR PDB; 4PKS; X-ray; 2.30 A; A=298-809.
DR PDB; 4PKT; X-ray; 2.40 A; A=298-809.
DR PDB; 4PKU; X-ray; 2.40 A; A=298-809.
DR PDB; 4PKV; X-ray; 2.50 A; A=298-809.
DR PDB; 4PKW; X-ray; 1.75 A; A=298-809.
DR PDB; 4WF6; X-ray; 2.65 A; A=298-809.
DR PDB; 4XM6; X-ray; 2.35 A; A=298-809.
DR PDB; 4XM7; X-ray; 2.70 A; A=298-809.
DR PDB; 4XM8; X-ray; 2.70 A; A=298-809.
DR PDB; 5D1S; X-ray; 2.10 A; A=298-809.
DR PDB; 5D1T; X-ray; 2.20 A; A=298-809.
DR PDB; 5D1U; X-ray; 2.85 A; A=298-809.
DR PDB; 6PSN; EM; 4.60 A; L=1-809.
DR PDB; 6WJJ; EM; 3.80 A; I/J/K/L=29-809.
DR PDB; 6ZXJ; EM; 3.50 A; H/I=1-809.
DR PDB; 6ZXK; EM; 3.80 A; H/I/J=1-809.
DR PDB; 6ZXL; EM; 4.20 A; H/I/J=1-809.
DR PDB; 7KXR; EM; 3.30 A; L=34-296.
DR PDBsum; 1J7N; -.
DR PDBsum; 1JKY; -.
DR PDBsum; 1PWP; -.
DR PDBsum; 1PWQ; -.
DR PDBsum; 1PWU; -.
DR PDBsum; 1PWV; -.
DR PDBsum; 1PWW; -.
DR PDBsum; 1YQY; -.
DR PDBsum; 1ZXV; -.
DR PDBsum; 2L0R; -.
DR PDBsum; 3KWV; -.
DR PDBsum; 4DV8; -.
DR PDBsum; 4PKQ; -.
DR PDBsum; 4PKR; -.
DR PDBsum; 4PKS; -.
DR PDBsum; 4PKT; -.
DR PDBsum; 4PKU; -.
DR PDBsum; 4PKV; -.
DR PDBsum; 4PKW; -.
DR PDBsum; 4WF6; -.
DR PDBsum; 4XM6; -.
DR PDBsum; 4XM7; -.
DR PDBsum; 4XM8; -.
DR PDBsum; 5D1S; -.
DR PDBsum; 5D1T; -.
DR PDBsum; 5D1U; -.
DR PDBsum; 6PSN; -.
DR PDBsum; 6WJJ; -.
DR PDBsum; 6ZXJ; -.
DR PDBsum; 6ZXK; -.
DR PDBsum; 6ZXL; -.
DR PDBsum; 7KXR; -.
DR AlphaFoldDB; P15917; -.
DR BMRB; P15917; -.
DR SMR; P15917; -.
DR DIP; DIP-29871N; -.
DR IntAct; P15917; 6.
DR MINT; P15917; -.
DR BindingDB; P15917; -.
DR ChEMBL; CHEMBL4372; -.
DR DrugBank; DB07290; (2R)-2-{[(4-FLUORO-3-METHYLPHENYL)SULFONYL]AMINO}-N-HYDROXY-2-TETRAHYDRO-2H-PYRAN-4-YLACETAMIDE.
DR DrugBank; DB08177; (E)-3-(5((5-(4-CHLOROPHENYL)FURAN-2-YL)METHYLENE)-4-OXO-2-THIOXOTHIAZOLIDIN-3-YL)PROPANOIC ACID.
DR DrugBank; DB04452; Aminoquinuride.
DR DrugBank; DB02255; Ilomastat.
DR DrugBank; DB01883; N-(Sulfanylacetyl)Tyrosylprolylmethioninamide.
DR DrugCentral; P15917; -.
DR MEROPS; M34.001; -.
DR ABCD; P15917; 3 sequenced antibodies.
DR EnsemblBacteria; AAT28913; AAT28913; GBAA_pXO1_0172.
DR GeneID; 45025515; -.
DR KEGG; bar:GBAA_pXO1_0172; -.
DR HOGENOM; CLU_348409_0_0_9; -.
DR OMA; RMMARYE; -.
DR BRENDA; 3.4.24.83; 634.
DR Reactome; R-HSA-5210891; Uptake and function of anthrax toxins.
DR EvolutionaryTrace; P15917; -.
DR PHI-base; PHI:4092; -.
DR PRO; PR:P15917; -.
DR Proteomes; UP000000594; Plasmid pXO1.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008237; F:metallopeptidase activity; ISA:CACAO.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:CACAO.
DR Gene3D; 3.40.390.10; -; 2.
DR InterPro; IPR015239; Anthrax_LF_cen.
DR InterPro; IPR003541; Anthrax_toxin_lethal/edema.
DR InterPro; IPR014781; Anthrax_toxin_lethal/edema_N/C.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR Pfam; PF09156; Anthrax-tox_M; 1.
DR Pfam; PF07737; ATLF; 2.
DR PRINTS; PR01392; ANTHRAXTOXNA.
DR PROSITE; PS51995; ATLF; 2.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Host cytoplasm; Hydrolase;
KW Metal-binding; Metalloprotease; Plasmid; Protease; Reference proteome;
KW Repeat; Secreted; Signal; Toxin; Virulence; Zinc.
FT SIGNAL 1..33
FT /evidence="ECO:0000269|PubMed:2509294"
FT CHAIN 34..809
FT /note="Lethal factor"
FT /id="PRO_0000029233"
FT DOMAIN 70..282
FT /note="ATLF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339"
FT REPEAT 315..333
FT /note="1"
FT /evidence="ECO:0000303|PubMed:11700563"
FT REPEAT 342..357
FT /note="2"
FT /evidence="ECO:0000303|PubMed:11700563"
FT REPEAT 360..378
FT /note="3"
FT /evidence="ECO:0000303|PubMed:11700563"
FT REPEAT 380..397
FT /note="4"
FT /evidence="ECO:0000303|PubMed:11700563"
FT REPEAT 399..416
FT /note="5"
FT /evidence="ECO:0000303|PubMed:11700563"
FT DOMAIN 609..804
FT /note="ATLF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339"
FT REGION 39..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 60..295
FT /note="I; PA-binding region"
FT /evidence="ECO:0000303|PubMed:11700563"
FT REGION 296..330
FT /note="IIA"
FT /evidence="ECO:0000303|PubMed:11700563"
FT REGION 315..416
FT /note="5 X approximate repeats"
FT /evidence="ECO:0000303|PubMed:11700563"
FT REGION 336..416
FT /note="III"
FT /evidence="ECO:0000303|PubMed:11700563"
FT REGION 420..583
FT /note="IIB"
FT /evidence="ECO:0000303|PubMed:11700563"
FT REGION 585..809
FT /note="IV"
FT /evidence="ECO:0000303|PubMed:11700563"
FT COMPBIAS 40..66
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 720
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339,
FT ECO:0000269|PubMed:19651869, ECO:0000269|PubMed:9573135"
FT BINDING 719
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339,
FT ECO:0000269|PubMed:11700563, ECO:0000269|PubMed:14718924,
FT ECO:0000269|PubMed:14718925, ECO:0000269|PubMed:15911756,
FT ECO:0000269|PubMed:22342144, ECO:0000269|PubMed:25372673,
FT ECO:0000269|PubMed:26492514, ECO:0000269|PubMed:26578066,
FT ECO:0007744|PDB:1J7N, ECO:0007744|PDB:1PWP,
FT ECO:0007744|PDB:1PWQ, ECO:0007744|PDB:1PWU,
FT ECO:0007744|PDB:1PWW, ECO:0007744|PDB:1YQY,
FT ECO:0007744|PDB:4DV8, ECO:0007744|PDB:4PKQ,
FT ECO:0007744|PDB:4PKR, ECO:0007744|PDB:4PKS,
FT ECO:0007744|PDB:4PKT, ECO:0007744|PDB:4PKV,
FT ECO:0007744|PDB:4PKW, ECO:0007744|PDB:4WF6,
FT ECO:0007744|PDB:4XM6, ECO:0007744|PDB:4XM7,
FT ECO:0007744|PDB:5D1S, ECO:0007744|PDB:5D1T"
FT BINDING 723
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339,
FT ECO:0000269|PubMed:11700563, ECO:0000269|PubMed:14718924,
FT ECO:0000269|PubMed:14718925, ECO:0000269|PubMed:15911756,
FT ECO:0000269|PubMed:22342144, ECO:0000269|PubMed:25372673,
FT ECO:0000269|PubMed:26492514, ECO:0000269|PubMed:26578066,
FT ECO:0007744|PDB:1J7N, ECO:0007744|PDB:1PWP,
FT ECO:0007744|PDB:1PWQ, ECO:0007744|PDB:1PWU,
FT ECO:0007744|PDB:1PWW, ECO:0007744|PDB:1YQY,
FT ECO:0007744|PDB:4DV8, ECO:0007744|PDB:4PKQ,
FT ECO:0007744|PDB:4PKR, ECO:0007744|PDB:4PKS,
FT ECO:0007744|PDB:4PKT, ECO:0007744|PDB:4PKV,
FT ECO:0007744|PDB:4PKW, ECO:0007744|PDB:4WF6,
FT ECO:0007744|PDB:4XM6, ECO:0007744|PDB:4XM7,
FT ECO:0007744|PDB:5D1S, ECO:0007744|PDB:5D1T"
FT BINDING 761
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339"
FT BINDING 768
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339,
FT ECO:0000269|PubMed:11700563, ECO:0000269|PubMed:14718924,
FT ECO:0000269|PubMed:14718925, ECO:0000269|PubMed:15911756,
FT ECO:0000269|PubMed:22342144, ECO:0000269|PubMed:25372673,
FT ECO:0000269|PubMed:26492514, ECO:0000269|PubMed:26578066,
FT ECO:0007744|PDB:1J7N, ECO:0007744|PDB:1PWP,
FT ECO:0007744|PDB:1PWQ, ECO:0007744|PDB:1PWU,
FT ECO:0007744|PDB:1PWW, ECO:0007744|PDB:1YQY,
FT ECO:0007744|PDB:4DV8, ECO:0007744|PDB:4PKQ,
FT ECO:0007744|PDB:4PKR, ECO:0007744|PDB:4PKS,
FT ECO:0007744|PDB:4PKT, ECO:0007744|PDB:4PKV,
FT ECO:0007744|PDB:4PKW, ECO:0007744|PDB:4WF6,
FT ECO:0007744|PDB:4XM6, ECO:0007744|PDB:4XM7,
FT ECO:0007744|PDB:5D1S, ECO:0007744|PDB:5D1T"
FT VARIANT 299
FT /note="A -> S (in strain: Sterne)"
FT MUTAGEN 68
FT /note="H->A,Y: Impaired translocation into host cytoplasm."
FT /evidence="ECO:0000269|PubMed:21037566"
FT MUTAGEN 69
FT /note="L->A: Does not affect translocation into host
FT cytoplasm."
FT /evidence="ECO:0000269|PubMed:21037566"
FT MUTAGEN 72
FT /note="I->A: Does not affect translocation into host
FT cytoplasm."
FT /evidence="ECO:0000269|PubMed:21037566"
FT MUTAGEN 73
FT /note="M->A: Impaired translocation into host cytoplasm."
FT /evidence="ECO:0000269|PubMed:21037566"
FT MUTAGEN 75
FT /note="H->A: Impaired translocation into host cytoplasm."
FT /evidence="ECO:0000269|PubMed:21037566"
FT MUTAGEN 76
FT /note="I->A: Does not affect translocation into host
FT cytoplasm."
FT /evidence="ECO:0000269|PubMed:21037566"
FT MUTAGEN 180
FT /note="V->A: No effect on PA-binding ability."
FT /evidence="ECO:0000269|PubMed:11162493"
FT MUTAGEN 181
FT /note="Y->A: Loss of ability to bind to PA."
FT /evidence="ECO:0000269|PubMed:11162493"
FT MUTAGEN 182
FT /note="Y->A: Loss of ability to bind to PA."
FT /evidence="ECO:0000269|PubMed:11162493"
FT MUTAGEN 183
FT /note="E->A: No effect on PA-binding ability."
FT /evidence="ECO:0000269|PubMed:11162493"
FT MUTAGEN 184
FT /note="I->A: Loss of ability to bind to PA."
FT /evidence="ECO:0000269|PubMed:11162493"
FT MUTAGEN 185
FT /note="G->A: No effect on PA-binding ability."
FT /evidence="ECO:0000269|PubMed:11162493"
FT MUTAGEN 186
FT /note="K->A: Loss of ability to bind to PA."
FT /evidence="ECO:0000269|PubMed:11162493"
FT MUTAGEN 220
FT /note="D->A: Loss of ability to bind to PA and loss of
FT toxicity."
FT /evidence="ECO:0000269|PubMed:12113932"
FT MUTAGEN 221
FT /note="L->A: No effect on PA-binding ability and fully
FT toxic."
FT /evidence="ECO:0000269|PubMed:12113932"
FT MUTAGEN 222
FT /note="L->A: No effect on PA-binding ability and fully
FT toxic."
FT /evidence="ECO:0000269|PubMed:12113932"
FT MUTAGEN 223
FT /note="F->A: Loss of ability to bind to PA and non-toxic."
FT /evidence="ECO:0000269|PubMed:12113932"
FT MUTAGEN 269
FT /note="Y->A: Impaired interaction with interaction with the
FT cleaved form of protective antigen (PA-63)."
FT /evidence="ECO:0000269|PubMed:21037566"
FT MUTAGEN 719
FT /note="H->A: Loss of activity and zinc binding."
FT /evidence="ECO:0000269|PubMed:9573135"
FT MUTAGEN 720
FT /note="E->C,D: Loss of activity. No effect on zinc
FT binding."
FT /evidence="ECO:0000269|PubMed:19651869,
FT ECO:0000269|PubMed:9573135"
FT MUTAGEN 723
FT /note="H->A: Loss of activity and zinc binding."
FT /evidence="ECO:0000269|PubMed:9573135"
FT TURN 62..65
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 66..76
FT /evidence="ECO:0007829|PDB:1J7N"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 87..97
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 101..109
FT /evidence="ECO:0007829|PDB:1J7N"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 132..135
FT /evidence="ECO:0007829|PDB:1J7N"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:1J7N"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:1J7N"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:1J7N"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:1J7N"
FT STRAND 161..165
FT /evidence="ECO:0007829|PDB:1J7N"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 174..190
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 201..211
FT /evidence="ECO:0007829|PDB:1J7N"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 217..222
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 225..228
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 236..240
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 243..258
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 260..269
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 271..282
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 284..293
FT /evidence="ECO:0007829|PDB:1J7N"
FT HELIX 300..310
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 312..317
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 320..330
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 337..342
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 346..354
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 357..359
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:4PKW"
FT HELIX 365..379
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:4PKR"
FT HELIX 384..389
FT /evidence="ECO:0007829|PDB:4DV8"
FT TURN 390..392
FT /evidence="ECO:0007829|PDB:5D1S"
FT TURN 393..396
FT /evidence="ECO:0007829|PDB:4PKV"
FT HELIX 403..412
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 413..415
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 421..428
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 435..437
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 439..455
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 458..460
FT /evidence="ECO:0007829|PDB:1PWV"
FT HELIX 461..464
FT /evidence="ECO:0007829|PDB:4DV8"
FT TURN 465..467
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 470..474
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 476..478
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 481..484
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 486..488
FT /evidence="ECO:0007829|PDB:5D1T"
FT HELIX 498..505
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 510..515
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 518..522
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 532..537
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 543..547
FT /evidence="ECO:0007829|PDB:4DV8"
FT TURN 548..550
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 551..554
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 556..570
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 573..583
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 585..607
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 616..619
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 625..642
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 645..657
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 662..667
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 669..671
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 673..676
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 682..684
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 688..693
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 694..696
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 698..705
FT /evidence="ECO:0007829|PDB:4DV8"
FT TURN 709..711
FT /evidence="ECO:0007829|PDB:2L0R"
FT HELIX 713..733
FT /evidence="ECO:0007829|PDB:4DV8"
FT STRAND 735..737
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 741..743
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 745..754
FT /evidence="ECO:0007829|PDB:4DV8"
FT TURN 755..757
FT /evidence="ECO:0007829|PDB:4PKV"
FT HELIX 761..763
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 766..777
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 782..791
FT /evidence="ECO:0007829|PDB:4DV8"
FT HELIX 793..807
FT /evidence="ECO:0007829|PDB:4DV8"
SQ SEQUENCE 809 AA; 93770 MW; 2076B4D7277317EE CRC64;
MNIKKEFIKV ISMSCLVTAI TLSGPVFIPL VQGAGGHGDV GMHVKEKEKN KDENKRKDEE
RNKTQEEHLK EIMKHIVKIE VKGEEAVKKE AAEKLLEKVP SDVLEMYKAI GGKIYIVDGD
ITKHISLEAL SEDKKKIKDI YGKDALLHEH YVYAKEGYEP VLVIQSSEDY VENTEKALNV
YYEIGKILSR DILSKINQPY QKFLDVLNTI KNASDSDGQD LLFTNQLKEH PTDFSVEFLE
QNSNEVQEVF AKAFAYYIEP QHRDVLQLYA PEAFNYMDKF NEQEINLSLE ELKDQRMLAR
YEKWEKIKQH YQHWSDSLSE EGRGLLKKLQ IPIEPKKDDI IHSLSQEEKE LLKRIQIDSS
DFLSTEEKEF LKKLQIDIRD SLSEEEKELL NRIQVDSSNP LSEKEKEFLK KLKLDIQPYD
INQRLQDTGG LIDSPSINLD VRKQYKRDIQ NIDALLHQSI GSTLYNKIYL YENMNINNLT
ATLGADLVDS TDNTKINRGI FNEFKKNFKY SISSNYMIVD INERPALDNE RLKWRIQLSP
DTRAGYLENG KLILQRNIGL EIKDVQIIKQ SEKEYIRIDA KVVPKSKIDT KIQEAQLNIN
QEWNKALGLP KYTKLITFNV HNRYASNIVE SAYLILNEWK NNIQSDLIKK VTNYLVDGNG
RFVFTDITLP NIAEQYTHQD EIYEQVHSKG LYVPESRSIL LHGPSKGVEL RNDSEGFIHE
FGHAVDDYAG YLLDKNQSDL VTNSKKFIDI FKEEGSNLTS YGRTNEAEFF AEAFRLMHST
DHAERLKVQK NAPKTFQFIN DQIKFIINS
