ID PAG_BACAN Reviewed; 764 AA. AC P13423; Q937W2; Q937W3; Q9F5R7; Q9KH69; Q9RQU2; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 18-OCT-2001, sequence version 2. DT 03-AUG-2022, entry version 201. DE RecName: Full=Protective antigen {ECO:0000303|PubMed:3148491}; DE Short=PA {ECO:0000303|PubMed:3148491}; DE AltName: Full=Anthrax toxins translocating protein {ECO:0000305}; DE AltName: Full=PA-83 {ECO:0000303|PubMed:8051159}; DE Short=PA83 {ECO:0000303|PubMed:8051159}; DE Contains: DE RecName: Full=Protective antigen PA-20 {ECO:0000305}; DE Short=PA-20 {ECO:0000303|PubMed:11207581, ECO:0000303|PubMed:8051159}; DE Short=PA20 {ECO:0000303|PubMed:11207581, ECO:0000303|PubMed:8051159}; DE Contains: DE RecName: Full=Protective antigen PA-63 {ECO:0000305}; DE Short=PA-63 {ECO:0000303|PubMed:11207581, ECO:0000303|PubMed:8051159}; DE Short=PA63 {ECO:0000303|PubMed:11207581, ECO:0000303|PubMed:8051159}; DE Flags: Precursor; GN Name=pagA; Synonyms=pag; GN OrderedLocusNames=pXO1-110, BXA0164, GBAA_pXO1_0164; 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]. RX PubMed=3148491; DOI=10.1016/0378-1119(88)90439-8; RA Welkos S.L., Lowe J.R., Eden-Mccutchan F., Vodkin M., Leppla S.H., RA Schmidt J.J.; RT "Sequence and analysis of the DNA encoding protective antigen of Bacillus RT anthracis."; RL Gene 69:287-300(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=28, 33, BA1024, and BA1035; RX PubMed=10197996; DOI=10.1128/jb.181.8.2358-2362.1999; RA Price L.B., Hugh-Jones M., Jackson P.J., Keim P.; RT "Genetic diversity in the protective antigen gene of Bacillus anthracis."; RL J. Bacteriol. 181:2358-2362(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=V770-NP1-R / ATCC 14185; RX PubMed=10899854; DOI=10.1128/iai.68.8.4549-4558.2000; RA Cohen S., Mendelson I., Altboum Z., Kobiler D., Elhanany E., Bino T., RA Leitner M., Inbar I., Rosenberg H., Gozes Y., Barak R., Fisher M., RA Kronman C., Velan B., Shafferman A.; RT "Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus RT anthracis spore vaccines protect against anthrax."; RL Infect. Immun. 68:4549-4558(2000). RN [4] 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 [5] 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 [6] 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 [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 9-751. 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 [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 195-434. RC STRAIN=PAI; RX PubMed=14985634; RA Inoue S., Noguchi A., Tanabayashi K., Yamada A.; RT "Preparation of a positive control DNA for molecular diagnosis of Bacillus RT anthracis."; RL Jpn. J. Infect. Dis. 57:29-32(2004). RN [9] RP FUNCTION, AND DOMAINS. RX PubMed=1651334; DOI=10.1016/s0021-9258(18)98643-6; RA Singh Y., Klimpel K.R., Quinn C.P., Chaudhary V.K., Leppla S.H.; RT "The carboxyl-terminal end of protective antigen is required for receptor RT binding and anthrax toxin activity."; RL J. Biol. Chem. 266:15493-15497(1991). RN [10] RP PROTEOLYTIC CLEAVAGE. RX PubMed=1644824; DOI=10.1016/s0021-9258(18)42016-9; RA Molloy S.S., Bresnahan P.A., Leppla S.H., Klimpel K.R., Thomas G.; RT "Human furin is a calcium-dependent serine endoprotease that recognizes the RT sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective RT antigen."; RL J. Biol. Chem. 267:16396-16402(1992). RN [11] RP PROTEOLYTIC CLEAVAGE. 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 [12] RP PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF 193-ARG--ARG-196; ARG-193; RP 194-LYS--ARG-196 AND 194-LYS-LYS-195. RX PubMed=1438214; DOI=10.1073/pnas.89.21.10277; RA Klimpel K.R., Molloy S.S., Thomas G., Leppla S.H.; RT "Anthrax toxin protective antigen is activated by a cell surface protease RT with the sequence specificity and catalytic properties of furin."; RL Proc. Natl. Acad. Sci. U.S.A. 89:10277-10281(1992). RN [13] RP FUNCTION. RC STRAIN=Weybridge; RX PubMed=8300513; DOI=10.1128/jb.176.3.586-595.1994; RA Koehler T.M., Dai Z., Kaufman-Yarbray M.; RT "Regulation of the Bacillus anthracis protective antigen gene: CO2 and a RT trans-acting element activate transcription from one of two promoters."; RL J. Bacteriol. 176:586-595(1994). RN [14] RP PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF PHE-342; 342-PHE-PHE-343; ASP-344 RP AND SER-719. RC STRAIN=Sterne; RX PubMed=7961869; DOI=10.1016/s0021-9258(19)62010-7; RA Singh Y., Klimpel K.R., Arora N., Sharma M., Leppla S.H.; RT "The chymotrypsin-sensitive site, FFD315, in anthrax toxin protective RT antigen is required for translocation of lethal factor."; RL J. Biol. Chem. 269:29039-29046(1994). RN [15] RP PROTEOLYTIC CLEAVAGE, AND SUBUNIT. RC STRAIN=Sterne; RX PubMed=8051159; DOI=10.1016/s0021-9258(17)32036-7; RA Milne J.C., Furlong D., Hanna P.C., Wall J.S., Collier R.J.; RT "Anthrax protective antigen forms oligomers during intoxication of RT mammalian cells."; RL J. Biol. Chem. 269:20607-20612(1994). RN [16] RP FUNCTION (PROTECTIVE ANTIGEN PA-63), INTERACTION WITH LF (PROTECTIVE RP ANTIGEN PA-63), SUBUNIT (PROTECTIVE ANTIGEN PA-63), AND SUBCELLULAR RP LOCATION (PROTECTIVE ANTIGEN PA-63). 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 [17] RP DOMAIN. RC STRAIN=Sterne; RX PubMed=10085028; DOI=10.1128/iai.67.4.1860-1865.1999; RA Varughese M., Teixeira A.V., Liu S., Leppla S.H.; RT "Identification of a receptor-binding region within domain 4 of the RT protective antigen component of anthrax toxin."; RL Infect. Immun. 67:1860-1865(1999). RN [18] RP PROTEOLYTIC CLEAVAGE, AND SUBCELLULAR LOCATION. RX PubMed=11207581; DOI=10.1046/j.1462-5822.2000.00052.x; RA Beauregard K.E., Collier R.J., Swanson J.A.; RT "Proteolytic activation of receptor-bound anthrax protective antigen on RT macrophages promotes its internalization."; RL Cell. Microbiol. 2:251-258(2000). RN [19] RP MUTAGENESIS OF TRP-375; MET-379 AND LEU-381. RC STRAIN=Sterne; RX PubMed=11178978; DOI=10.1006/bbrc.2001.4320; RA Batra S., Gupta P., Chauhan V., Singh A., Bhatnagar R.; RT "Trp 346 and Leu 352 residues in protective antigen are required for the RT expression of anthrax lethal toxin activity."; RL Biochem. Biophys. Res. Commun. 281:186-192(2001). RN [20] RP MUTAGENESIS OF PHE-581; PHE-583; ILE-591; LEU-595 AND ILE-603. RC STRAIN=Sterne; RX PubMed=11554763; DOI=10.1006/bbrc.2001.5613; RA Ahuja N., Kumar P., Bhatnagar R.; RT "Hydrophobic residues Phe552, Phe554, Ile562, Leu566, and Ile574 are RT required for oligomerization of anthrax protective antigen."; RL Biochem. Biophys. Res. Commun. 287:542-549(2001). RN [21] RP MUTAGENESIS OF PRO-289. RC STRAIN=Sterne; RX PubMed=11356563; DOI=10.1111/j.1574-6968.2001.tb10646.x; RA Khanna H., Chopra A.P., Arora N., Chaudhry A., Singh Y.; RT "Role of residues constituting the 2beta1 strand of domain II in the RT biological activity of anthrax protective antigen."; RL FEMS Microbiol. Lett. 199:27-31(2001). RN [22] RP MUTAGENESIS OF GLN-512; ASP-541; LEU-543 AND ARG-621. RX PubMed=11222612; DOI=10.1128/jb.183.6.2111-2116.2001; RA Mogridge J., Mourez M., Collier R.J.; RT "Involvement of domain 3 in oligomerization by the protective antigen RT moiety of anthrax toxin."; RL J. Bacteriol. 183:2111-2116(2001). RN [23] RP MUTAGENESIS OF LYS-426; ASP-454 AND PHE-456. RX PubMed=11113126; DOI=10.1074/jbc.m008309200; RA Sellman B.R., Nassi S., Collier R.J.; RT "Point mutations in anthrax protective antigen that block translocation."; RL J. Biol. Chem. 276:8371-8376(2001). RN [24] RP FUNCTION, INTERACTION WITH HOST ANTXR1, AND SUBCELLULAR LOCATION RP (PROTECTIVE ANTIGEN). RX PubMed=11700562; DOI=10.1038/n35101999; RA Bradley K.A., Mogridge J., Mourez M., Collier R.J., Young J.A.T.; RT "Identification of the cellular receptor for anthrax toxin."; RL Nature 414:225-229(2001). RN [25] RP REVIEW. RX PubMed=11544370; DOI=10.1146/annurev.micro.55.1.647; RA Mock M., Fouet A.; RT "Anthrax."; RL Annu. Rev. Microbiol. 55:647-671(2001). RN [26] RP FUNCTION (PROTECTIVE ANTIGEN PA-63), INTERACTION WITH LF (PROTECTIVE RP ANTIGEN PA-63), AND MUTAGENESIS OF PRO-213; LEU-216; PHE-231; LEU-232; RP PRO-234; ILE-236; ILE-239; TRP-255 AND PHE-265. RC STRAIN=Sterne; RX PubMed=12117959; DOI=10.1128/iai.70.8.4477-4484.2002; RA Chauhan V., Bhatnagar R.; RT "Identification of amino acid residues of anthrax protective antigen RT involved in binding with lethal factor."; RL Infect. Immun. 70:4477-4484(2002). RN [27] RP SUBCELLULAR LOCATION. RX PubMed=12606539; DOI=10.1074/jbc.m301244200; RA Williams R.C., Rees M.L., Jacobs M.F., Pragai Z., Thwaite J.E., RA Baillie L.W., Emmerson P.T., Harwood C.R.; RT "Production of Bacillus anthracis protective antigen is dependent on the RT extracellular chaperone, PrsA."; RL J. Biol. Chem. 278:18056-18062(2003). RN [28] RP MUTAGENESIS OF ASN-686; LYS-708; LYS-709; TYR-710; ASN-711; ASP-712; RP LYS-713; LEU-714; PRO-715; LEU-716; TYR-717; ILE-718; ASN-720; PRO-721 AND RP ASN-722. RX PubMed=12771151; DOI=10.1074/jbc.m301154200; RA Rosovitz M.J., Schuck P., Varughese M., Chopra A.P., Mehra V., Singh Y., RA McGinnis L.M., Leppla S.H.; RT "Alanine-scanning mutations in domain 4 of anthrax toxin protective antigen RT reveal residues important for binding to the cellular receptor and to a RT neutralizing monoclonal antibody."; RL J. Biol. Chem. 278:30936-30944(2003). RN [29] RP FUNCTION, INTERACTION WITH HOST ANTXR1, AND SUBCELLULAR LOCATION RP (PROTECTIVE ANTIGEN). RX PubMed=14507921; DOI=10.1074/jbc.m307900200; RA Bradley K.A., Mogridge J., Jonah G., Rainey G.J.A., Batty S., Young J.A.T.; RT "Binding of anthrax toxin to its receptor is similar to alpha integrin- RT ligand interactions."; RL J. Biol. Chem. 278:49342-49347(2003). RN [30] RP FUNCTION (PROTECTIVE ANTIGEN PA-63). 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 [31] RP MUTAGENESIS OF ILE-393; THR-409; SER-411; THR-422; LYS-426; ASN-428; RP TYR-440; ASN-451; ASP-454 AND PHE-456. RX PubMed=14623961; DOI=10.1073/pnas.2436299100; RA Mourez M., Yan M., Lacy D.B., Dillon L., Bentsen L., Marpoe A., Maurin C., RA Hotze E., Wigelsworth D., Pimental R.-A., Ballard J.D., Collier R.J., RA Tweten R.K.; RT "Mapping dominant-negative mutations of anthrax protective antigen by RT scanning mutagenesis."; RL Proc. Natl. Acad. Sci. U.S.A. 100:13803-13808(2003). RN [32] RP FUNCTION (PROTECTIVE ANTIGEN PA-63), INTERACTION WITH LF AND EF (PROTECTIVE RP ANTIGEN PA-63), AND SUBCELLULAR LOCATION. 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 [33] RP FUNCTION (PROTECTIVE ANTIGEN PA-63), SUBUNIT (PROTECTIVE ANTIGEN PA-63), RP DOMAIN (PROTECTIVE ANTIGEN PA-63), SUBCELLULAR LOCATION (PROTECTIVE ANTIGEN RP PA-63), AND MUTAGENESIS OF PHE-456. RX PubMed=16051798; DOI=10.1126/science.1113380; RA Krantz B.A., Melnyk R.A., Zhang S., Juris S.J., Lacy D.B., Wu Z., RA Finkelstein A., Collier R.J.; RT "A phenylalanine clamp catalyzes protein translocation through the anthrax RT toxin pore."; RL Science 309:777-781(2005). RN [34] RP SUBUNIT (PROTECTIVE ANTIGEN PA-63). RX PubMed=19627991; DOI=10.1016/j.jmb.2009.07.037; RA Kintzer A.F., Thoren K.L., Sterling H.J., Dong K.C., Feld G.K., Tang I.I., RA Zhang T.T., Williams E.R., Berger J.M., Krantz B.A.; RT "The protective antigen component of anthrax toxin forms functional RT octameric complexes."; RL J. Mol. Biol. 392:614-629(2009). RN [35] RP SUBUNIT (PROTECTIVE ANTIGEN PA-63). RX PubMed=20433851; DOI=10.1016/j.jmb.2010.04.041; RA Kintzer A.F., Sterling H.J., Tang I.I., Abdul-Gader A., Miles A.J., RA Wallace B.A., Williams E.R., Krantz B.A.; RT "Role of the protective antigen octamer in the molecular mechanism of RT anthrax lethal toxin stabilization in plasma."; RL J. Mol. Biol. 399:741-758(2010). RN [36] RP SUBCELLULAR LOCATION (PROTECTIVE ANTIGEN PA-63). RX PubMed=20221438; DOI=10.1371/journal.ppat.1000792; RA Abrami L., Bischofberger M., Kunz B., Groux R., van der Goot F.G.; RT "Endocytosis of the anthrax toxin is mediated by clathrin, actin and RT unconventional adaptors."; RL PLoS Pathog. 6:e1000792-e1000792(2010). RN [37] {ECO:0007744|PDB:1ACC} RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH CALCIUM, AND DOMAIN. RX PubMed=9039918; DOI=10.1038/385833a0; RA Petosa C., Collier R.J., Klimpel K.R., Leppla S.H., Liddington R.C.; RT "Crystal structure of the anthrax toxin protective antigen."; RL Nature 385:833-838(1997). RN [38] {ECO:0007744|PDB:1T6B} RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 30-764 IN COMPLEX WITH HOST ANTXR2 RP AND CALCIUM, AND FUNCTION. RX PubMed=15243628; DOI=10.1038/nature02763; RA Santelli E., Bankston L.A., Leppla S.H., Liddington R.C.; RT "Crystal structure of a complex between anthrax toxin and its host cell RT receptor."; RL Nature 430:905-908(2004). RN [39] {ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO} RP X-RAY CRYSTALLOGRAPHY (4.3 ANGSTROMS) OF 203-764 IN COMPLEX WITH HOST RP ANTXR2 AND CALCIUM, AND FUNCTION. RX PubMed=15326297; DOI=10.1073/pnas.0405405101; RA Lacy D.B., Wigelsworth D.J., Melnyk R.A., Harrison S.C., Collier R.J.; RT "Structure of heptameric protective antigen bound to an anthrax toxin RT receptor: a role for receptor in pH-dependent pore formation."; RL Proc. Natl. Acad. Sci. U.S.A. 101:13147-13151(2004). RN [40] {ECO:0007744|PDB:3KWV} RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 197-764 IN COMPLEX WITH EF AND RP CALCIUM, FUNCTION (PROTECTIVE ANTIGEN PA-63), DOMAIN (PROTECTIVE ANTIGEN RP PA-63), INTERACTION WITH LF (PROTECTIVE ANTIGEN PA-63), AND MUTAGENESIS OF RP ARG-207; ARG-229; PHE-231; PRO-234; ILE-236; HIS-240 AND PHE-265. 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 [41] {ECO:0007744|PDB:3J9C} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 203-764 IN COMPLEX RP WITH CALCIUM, DOMAIN (PROTECTIVE ANTIGEN PA-63), SUBCELLULAR LOCATION RP (PROTECTIVE ANTIGEN PA-63), AND SUBUNIT (PROTECTIVE ANTIGEN PA-63). RX PubMed=25778700; DOI=10.1038/nature14247; RA Jiang J., Pentelute B.L., Collier R.J., Zhou Z.H.; RT "Atomic structure of anthrax protective antigen pore elucidates toxin RT translocation."; RL Nature 521:545-549(2015). RN [42] {ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) OF 203-764 IN COMPLEX RP WITH CALCIUM; LF AND EF, INTERACTION WITH LF AND EF (PROTECTIVE ANTIGEN RP PA-63), FUNCTION (PROTECTIVE ANTIGEN PA-63), AND DOMAIN (PROTECTIVE ANTIGEN RP PA-63). 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 [43] {ECO:0007744|PDB:6ZXJ, ECO:0007744|PDB:6ZXK, ECO:0007744|PDB:6ZXL} RP STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS) OF 202-764 IN COMPLEX RP WITH LF, INTERACTION WITH LF (PROTECTIVE ANTIGEN PA-63), SUBUNIT RP (PROTECTIVE ANTIGEN PA-63), AND FUNCTION (PROTECTIVE ANTIGEN PA-63). 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 [44] {ECO:0007744|PDB:6VRA, ECO:0007744|PDB:6WJJ} RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) OF 203-764 IN COMPLEX RP WITH CALCIUM; LF AND EF, INTERACTION WITH LF AND EF (PROTECTIVE ANTIGEN RP PA-63), FUNCTION (PROTECTIVE ANTIGEN PA-63), AND DOMAIN (PROTECTIVE ANTIGEN RP PA-63). 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: Protective antigen constitutes one of the three proteins CC composing the anthrax toxin; it mediates attachment to host cells and CC translocation of edema factor (EF) and lethal factor (LF) into the host CC cytoplasm (PubMed:11700562, PubMed:14507921, PubMed:15243628, CC PubMed:15326297). PA associated with LF forms the lethal toxin (LeTx) CC and causes death when injected; PA associated with EF forms the edema CC toxin (EdTx) and produces edema (PubMed:1651334). PA induces immunity CC to infection with anthrax (PubMed:11544370). CC {ECO:0000269|PubMed:11700562, ECO:0000269|PubMed:14507921, CC ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, CC ECO:0000269|PubMed:1651334, ECO:0000303|PubMed:11544370}. CC -!- FUNCTION: [Protective antigen]: Mediates the attachment to host cells CC by binding host cell receptors ANTXR1 and ANTXR2 (PubMed:11700562, CC PubMed:14507921, PubMed:15243628, PubMed:15326297). Following host cell CC surface attachment, PA is cleaved by FURIN to generate the PA-63 CC (Protective antigen PA-63) form, which constitutes the mature form of CC the protein that oligomerizes and forms a pore to translocate the CC enzymatic toxin components edema factor (EF) and lethal factor (LF) CC into the host cytosol (PubMed:11700562, PubMed:15243628, CC PubMed:15326297). {ECO:0000269|PubMed:11700562, CC ECO:0000269|PubMed:14507921, ECO:0000269|PubMed:15243628, CC ECO:0000269|PubMed:15326297}. CC -!- FUNCTION: [Protective antigen PA-63]: Mature form that oligomerizes and CC forms a pore to translocate the enzymatic toxin components edema factor CC (EF) and lethal factor (LF) into the host cytosol (PubMed:15243628, CC PubMed:15326297). Following attachment to host cell receptors and CC cleavage by FURIN, homooligomerizes to form ring-shaped oligomers that CC are in a pre-pore conformation, and associates with EF and LF CC (PubMed:10085027, PubMed:12117959, PubMed:15313199). Toxin-leaded CC complexes are then endocytosed in a clathrin-dependent process, CC followed by a conformational change of oligomerized PA-63 from the pre- CC pore to pore state, which is triggered by the low pH in the endosome CC (PubMed:10085027, PubMed:12551953, PubMed:20221438, PubMed:15326297). CC Once active, the pore mediates unfolding of EF and LF, which pass CC through the pore and translocate into the host cytosol CC (PubMed:16051798, PubMed:21037566, PubMed:32047164, PubMed:32810181, CC PubMed:32521227). {ECO:0000269|PubMed:10085027, CC ECO:0000269|PubMed:12117959, ECO:0000269|PubMed:12551953, CC ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15313199, CC ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:16051798, CC ECO:0000269|PubMed:20221438, ECO:0000269|PubMed:21037566, CC ECO:0000269|PubMed:32047164, ECO:0000269|PubMed:32521227, CC ECO:0000269|PubMed:32810181}. CC -!- SUBUNIT: [Protective antigen]: Interacts with host ANTXR1 and ANTXR2. CC {ECO:0000269|PubMed:11700562, ECO:0000269|PubMed:14507921, CC ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297}. CC -!- SUBUNIT: [Protective antigen PA-63]: Homooligomer; homooligomerizes to CC form homoheptamers (PA-63(7)) or homooctamers (PA-63(8)) CC (PubMed:10085027, PubMed:16051798, PubMed:19627991, PubMed:20433851, CC PubMed:25778700, PubMed:32810181). PA-63(7) or PA-63(8) form ring- CC shaped oligomers that are in a pre-pore conformation, which do not CC penetrate the host membrane (PubMed:19627991, PubMed:20433851, CC PubMed:32810181). PA-63(8) displays an enhanced stability, suggesting CC that this form circulates in the blood to reach and exert toxicity even CC in distant tissues (PubMed:20433851). Interacts with lethal factor (LF) CC and edema factor (EF); can bind LF and EF simultaneously and CC interaction takes place following homooligomerization on the host cell CC membrane (PubMed:10085027, PubMed:12117959, PubMed:15313199, CC PubMed:21037566, PubMed:32047164, PubMed:32810181, PubMed:32521227). CC PA-63(7) homoheptamer interacts with three molecules of LF to form the CC PA(7)LF(3) complex, in which the relative position of the N-terminal CC alpha-helices in the three LFs determines which factor is translocated CC first (PubMed:32810181). {ECO:0000269|PubMed:10085027, CC ECO:0000269|PubMed:12117959, ECO:0000269|PubMed:15313199, CC ECO:0000269|PubMed:16051798, ECO:0000269|PubMed:19627991, CC ECO:0000269|PubMed:20433851, ECO:0000269|PubMed:21037566, CC ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, CC ECO:0000269|PubMed:32521227, ECO:0000269|PubMed:32810181}. CC -!- INTERACTION: CC P13423; P15917: lef; NbExp=28; IntAct=EBI-456868, EBI-456923; CC P13423; P13423: pagA; NbExp=16; IntAct=EBI-456868, EBI-456868; CC P13423; Q9H6X2-2: ANTXR1; Xeno; NbExp=3; IntAct=EBI-456868, EBI-905659; CC P13423; P58335: ANTXR2; Xeno; NbExp=7; IntAct=EBI-456868, EBI-456840; CC P13423; P0A6F5: groEL; Xeno; NbExp=2; IntAct=EBI-456868, EBI-543750; CC -!- SUBCELLULAR LOCATION: [Protective antigen]: Secreted CC {ECO:0000269|PubMed:11207581, ECO:0000269|PubMed:12606539}. Host cell CC membrane {ECO:0000269|PubMed:11700562, ECO:0000269|PubMed:14507921}. CC Note=Secreted through the Sec-dependent secretion pathway CC (PubMed:12606539). Therefore, PA is translocated across the membrane in CC an unfolded state and then it is folded into its native configuration CC on the trans side of the membrane, prior to its release to the CC environment (PubMed:12606539). PA requires the extracellular chaperone CC PrsA for efficient folding (PubMed:12606539). It circulates in the host CC blood and binds host cell receptors at the cell surface CC (PubMed:11700562, PubMed:14507921). {ECO:0000269|PubMed:11700562, CC ECO:0000269|PubMed:12606539, ECO:0000269|PubMed:14507921}. CC -!- SUBCELLULAR LOCATION: [Protective antigen PA-63]: Host cell membrane CC {ECO:0000305|PubMed:16051798, ECO:0000305|PubMed:25778700}; Multi-pass CC membrane protein {ECO:0000269|PubMed:25778700, CC ECO:0000269|PubMed:32047164}. Host endosome membrane CC {ECO:0000305|PubMed:10085027}; Multi-pass membrane protein CC {ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164}. CC Note=Following attachment to host cell receptors at the cell surface CC and cleavage by FURIN, homooligomerizes to form ring-shaped oligomers CC that are in a pre-pore conformation, and associates with EF and LF CC (PubMed:15313199). Loaded complexes are then endocytosed in a clathrin- CC dependent process, followed by a conformational change of oligomerized CC PA-63 from the pre-pore to pore state, which is triggered by the low pH CC in the endosome (PubMed:10085027, PubMed:15326297). CC {ECO:0000269|PubMed:10085027, ECO:0000269|PubMed:15313199, CC ECO:0000269|PubMed:15326297}. CC -!- DOMAIN: The molecule is folded into four functional domains CC (PubMed:1651334, PubMed:9039918). Each domain is required for a CC particular step in the toxicity process (PubMed:1651334). Domain 1 CC contains two calcium ions and the proteolytic activation site CC (PubMed:1651334). Cleavage of the PA monomer releases the subdomain 1a, CC which is the N-terminal fragment of 20-kDa (PA-20) (PubMed:8051159, CC PubMed:11207581, PubMed:9039918). The subdomain 1b is part of the CC remaining 63-kDa fragment (PA-63) and contains the binding sites for LP CC and EF (PubMed:8051159, PubMed:11207581, PubMed:9039918). Domain 2 is a CC beta-barrel core containing a large flexible loop that has been CC implicated in membrane insertion and pore formation (PubMed:1651334, CC PubMed:11356563, PubMed:9039918). There is a chymotrypsin cleavage site CC in this loop that is required for toxicity (PubMed:1512256, CC PubMed:7961869, PubMed:9039918). Domain 3 has a hydrophobic patch CC thought to be involved in protein-protein interactions (PubMed:1651334, CC PubMed:11222612, PubMed:9039918). Domain 4 appears to be a separate CC domain and shows limited contact with the other three domains: it would CC swing out of the way during membrane insertion (PubMed:1651334, CC PubMed:10085028, PubMed:12771151, PubMed:9039918). It is required for CC binding to the receptor; the small loop is involved in receptor CC recognition (PubMed:1651334, PubMed:10085028, PubMed:12771151, CC PubMed:9039918). {ECO:0000269|PubMed:10085028, CC ECO:0000269|PubMed:11207581, ECO:0000269|PubMed:11222612, CC ECO:0000269|PubMed:11356563, ECO:0000269|PubMed:12771151, CC ECO:0000269|PubMed:1512256, ECO:0000269|PubMed:1651334, CC ECO:0000269|PubMed:7961869, ECO:0000269|PubMed:8051159, CC ECO:0000269|PubMed:9039918}. CC -!- DOMAIN: [Protective antigen PA-63]: Phe-456 residue forms the phi-clamp CC in the pore and catalyzes protein translocation via a charge-state- CC dependent Brownian ratchet (PubMed:16051798, PubMed:25778700). During CC conversion of the heptameric pre-pore precursor to the pore, the seven CC Phe-427 residues converge within the lumen to generate the narrowest CC point in the channel lumen (6 Angstroms in width) (PubMed:16051798, CC PubMed:25778700). To pass through this hydrophobic restriction, CC substrate proteins LF and EF need to be unfolded prior to translocation CC (PubMed:25778700). {ECO:0000269|PubMed:16051798, CC ECO:0000269|PubMed:25778700}. CC -!- DOMAIN: [Protective antigen PA-63]: The alpha-clamp consists in an CC amphipathic cleft between two adjacent PA protomers, which assists the CC unfolding of substrate proteins LF and EF (PubMed:21037566, CC PubMed:32047164, PubMed:32521227). The alpha-clamp binds non- CC specifically to alpha-helices of substrate proteins LF and EF CC (PubMed:21037566, PubMed:32047164, PubMed:32521227). CC {ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:32047164, CC ECO:0000269|PubMed:32521227}. CC -!- PTM: Proteolytic activation by FURIN cleaves the protein in two parts, CC PA-20 and PA-63; the latter is the mature protein (PubMed:1644824, CC PubMed:1438214, PubMed:8051159, PubMed:11207581). The cleavage occurs CC at the cell surface and probably in the serum of infected animals as CC well; both native and cleaved PA are able to bind to the cell receptor CC (PubMed:8051159, PubMed:11207581). The release of PA-20 from the CC remaining receptor-bound PA-63 exposes the binding site for EF and LF, CC and promotes oligomerization and internalization of the protein CC (PubMed:8051159, PubMed:11207581). {ECO:0000269|PubMed:11207581, CC ECO:0000269|PubMed:1438214, ECO:0000269|PubMed:1644824, CC ECO:0000269|PubMed:8051159}. CC -!- SIMILARITY: Belongs to the bacterial binary toxin family. CC {ECO:0000305}. 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; M22589; AAA22637.1; -; Genomic_DNA. DR EMBL; AF306778; AAG24446.1; -; Genomic_DNA. DR EMBL; AF306779; AAG24447.1; -; Genomic_DNA. DR EMBL; AF306780; AAG24448.1; -; Genomic_DNA. DR EMBL; AF306781; AAG24449.1; -; Genomic_DNA. DR EMBL; AF306782; AAG24450.1; -; Genomic_DNA. DR EMBL; AF306783; AAG24451.1; -; Genomic_DNA. DR EMBL; AF268967; AAF86457.1; -; Genomic_DNA. DR EMBL; AF065404; AAD32414.1; -; Genomic_DNA. DR EMBL; AE011190; AAM26109.1; -; Genomic_DNA. DR EMBL; AE017336; AAT28905.2; -; Genomic_DNA. DR EMBL; AJ413936; CAC93934.1; -; Genomic_DNA. DR EMBL; AJ413937; CAC93935.1; -; Genomic_DNA. DR EMBL; AB125961; BAD14937.1; -; Genomic_DNA. DR PIR; I39934; I39934. DR RefSeq; NP_052806.1; NC_001496.1. DR RefSeq; WP_000746486.1; NZ_SDEF01000130.1. DR RefSeq; WP_000746487.1; NZ_QAEM01000007.1. DR RefSeq; WP_000746488.1; NZ_VTZH01000015.1. DR PDB; 1ACC; X-ray; 2.10 A; A=30-764. DR PDB; 1T6B; X-ray; 2.50 A; X=30-764. DR PDB; 1TZN; X-ray; 4.30 A; A/B/C/D/E/F/G/H/I/J/K/L/M/O=203-764. DR PDB; 1TZO; X-ray; 3.60 A; A/B/C/D/E/F/G/H/I/J/K/L/M/O=203-764. DR PDB; 3ETB; X-ray; 3.80 A; J/K/L/M=621-764. DR PDB; 3INO; X-ray; 1.95 A; A/B=624-764. DR PDB; 3J9C; EM; 2.90 A; A=203-764. DR PDB; 3KWV; X-ray; 3.10 A; A/B/D/E=197-764. DR PDB; 3MHZ; X-ray; 1.70 A; A=30-764. DR PDB; 3Q8A; X-ray; 3.13 A; A=30-764. DR PDB; 3Q8B; X-ray; 2.00 A; A=30-764. DR PDB; 3Q8C; X-ray; 2.85 A; A=30-764. DR PDB; 3Q8E; X-ray; 2.10 A; A=30-764. DR PDB; 3Q8F; X-ray; 2.10 A; A=30-764. DR PDB; 3TEW; X-ray; 1.45 A; A=30-764. DR PDB; 3TEX; X-ray; 1.70 A; A=30-764. DR PDB; 3TEY; X-ray; 2.12 A; A=30-764. DR PDB; 3TEZ; X-ray; 1.83 A; A=30-764. DR PDB; 4EE2; X-ray; 1.91 A; A=30-764. DR PDB; 4H2A; X-ray; 1.62 A; A=30-764. DR PDB; 4NAM; X-ray; 1.70 A; A=30-764. DR PDB; 5FR3; X-ray; 1.94 A; A=43-764. DR PDB; 6PSN; EM; 4.60 A; A/B/C/D/E/F/G=197-764. DR PDB; 6UJI; X-ray; 5.50 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N=197-764. DR PDB; 6UZB; EM; 3.20 A; A/B/C/D/E/F/G=30-764. DR PDB; 6UZD; EM; 3.40 A; A/B/C/D/E/F/G=30-764. DR PDB; 6UZE; EM; 3.40 A; A/B/C/D/E/F/G=30-764. DR PDB; 6VRA; EM; 3.30 A; A/B/C/D/E/F/G/H=33-764. DR PDB; 6WJJ; EM; 3.80 A; A/B/C/D/E/F/G/H=33-764. DR PDB; 6ZXJ; EM; 3.50 A; A/B/C/D/E/F/G=29-764. DR PDB; 6ZXK; EM; 3.80 A; A/B/C/D/E/F/G=29-764. DR PDB; 6ZXL; EM; 4.20 A; A/B/C/D/E/F/G=29-764. DR PDB; 7KXR; EM; 3.30 A; A/B/C/D/E/F/G=203-764. DR PDB; 7O85; EM; 3.30 A; A/D/G/J/M/P/S=203-643. DR PDBsum; 1ACC; -. DR PDBsum; 1T6B; -. DR PDBsum; 1TZN; -. DR PDBsum; 1TZO; -. DR PDBsum; 3ETB; -. DR PDBsum; 3INO; -. DR PDBsum; 3J9C; -. DR PDBsum; 3KWV; -. DR PDBsum; 3MHZ; -. DR PDBsum; 3Q8A; -. DR PDBsum; 3Q8B; -. DR PDBsum; 3Q8C; -. DR PDBsum; 3Q8E; -. DR PDBsum; 3Q8F; -. DR PDBsum; 3TEW; -. DR PDBsum; 3TEX; -. DR PDBsum; 3TEY; -. DR PDBsum; 3TEZ; -. DR PDBsum; 4EE2; -. DR PDBsum; 4H2A; -. DR PDBsum; 4NAM; -. DR PDBsum; 5FR3; -. DR PDBsum; 6PSN; -. DR PDBsum; 6UJI; -. DR PDBsum; 6UZB; -. DR PDBsum; 6UZD; -. DR PDBsum; 6UZE; -. DR PDBsum; 6VRA; -. DR PDBsum; 6WJJ; -. DR PDBsum; 6ZXJ; -. DR PDBsum; 6ZXK; -. DR PDBsum; 6ZXL; -. DR PDBsum; 7KXR; -. DR PDBsum; 7O85; -. DR AlphaFoldDB; P13423; -. DR SMR; P13423; -. DR DIP; DIP-29841N; -. DR IntAct; P13423; 16. DR MINT; P13423; -. DR BindingDB; P13423; -. DR ChEMBL; CHEMBL5352; -. DR DrugBank; DB09057; Anthrax immune globulin human. DR DrugBank; DB08902; Raxibacumab. DR DrugCentral; P13423; -. DR TCDB; 1.C.42.1.1; the channel-forming bacillus anthracis protective antigen (bapa) family. DR ABCD; P13423; 43 sequenced antibodies. DR EnsemblBacteria; AAT28905; AAT28905; GBAA_pXO1_0164. DR GeneID; 45025512; -. DR KEGG; bar:GBAA_pXO1_0164; -. DR HOGENOM; CLU_015269_0_0_9; -. DR OMA; YINANVR; -. DR Reactome; R-HSA-5210891; Uptake and function of anthrax toxins. DR EvolutionaryTrace; P13423; -. DR PHI-base; PHI:4090; -. DR PRO; PR:P13423; -. DR Proteomes; UP000000594; Plasmid pXO1. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0044164; C:host cell cytosol; IDA:UniProtKB. DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0015267; F:channel activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB. DR GO; GO:0043409; P:negative regulation of MAPK cascade; IGI:UniProtKB. DR GO; GO:0044533; P:positive regulation of apoptotic process in another organism; IGI:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0071806; P:protein transmembrane transport; IDA:UniProtKB. DR GO; GO:0051844; P:translocation of peptides or proteins into symbiont; IDA:UniProtKB. DR Gene3D; 2.60.120.240; -; 1. DR Gene3D; 2.60.40.810; -; 1. DR InterPro; IPR003896; Bacterial_exotoxin_B. DR InterPro; IPR035331; Binary_toxB_3. DR InterPro; IPR037524; PA14/GLEYA. DR InterPro; IPR011658; PA14_dom. DR InterPro; IPR035088; PA_Ca-bd. DR InterPro; IPR027441; PA_dom4. DR InterPro; IPR027439; PA_heptamer_dom. DR InterPro; IPR037149; PA_heptamer_dom_sf. DR Pfam; PF03495; Binary_toxB; 1. DR Pfam; PF17475; Binary_toxB_2; 1. DR Pfam; PF17476; Binary_toxB_3; 1. DR Pfam; PF07691; PA14; 1. DR PRINTS; PR01391; BINARYTOXINB. DR SMART; SM00758; PA14; 1. DR PROSITE; PS51820; PA14; 1. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Cleavage on pair of basic residues; KW Host cell membrane; Host endosome; Host membrane; Membrane; Metal-binding; KW Plasmid; Reference proteome; Secreted; Signal; Toxin; Transmembrane; KW Transmembrane beta strand; Virulence. FT SIGNAL 1..29 FT /evidence="ECO:0000305|PubMed:9039918" FT CHAIN 30..764 FT /note="Protective antigen" FT /id="PRO_0000021996" FT CHAIN 30..196 FT /note="Protective antigen PA-20" FT /evidence="ECO:0000305|PubMed:11207581, FT ECO:0000305|PubMed:8051159" FT /id="PRO_0000021997" FT CHAIN 197..764 FT /note="Protective antigen PA-63" FT /evidence="ECO:0000305|PubMed:11207581, FT ECO:0000305|PubMed:8051159" FT /id="PRO_0000021998" FT TRANSMEM 331..342 FT /note="Beta stranded" FT /evidence="ECO:0000269|PubMed:25778700, FT ECO:0000269|PubMed:32047164, ECO:0007744|PDB:3J9C, FT ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, FT ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE" FT TRANSMEM 345..354 FT /note="Beta stranded" FT /evidence="ECO:0000269|PubMed:25778700, FT ECO:0000269|PubMed:32047164, ECO:0007744|PDB:3J9C, FT ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, FT ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE" FT DOMAIN 43..179 FT /note="PA14" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01164" FT REGION 30..287 FT /note="Domain 1, calcium-binding; LF and EF binding sites" FT /evidence="ECO:0000303|PubMed:9039918" FT REGION 176..214 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 231..239 FT /note="Alpha-clamp" FT /evidence="ECO:0000269|PubMed:21037566" FT REGION 288..516 FT /note="Domain 2, membrane insertion and heptamerization" FT /evidence="ECO:0000303|PubMed:9039918" FT REGION 302..333 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 517..624 FT /note="Domain 3, heptamerization" FT /evidence="ECO:0000303|PubMed:9039918" FT REGION 625..764 FT /note="Domain 4, binding to the receptor" FT /evidence="ECO:0000303|PubMed:9039918" FT COMPBIAS 302..331 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 206 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15243628, FT ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, FT ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, FT ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, FT ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, FT ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, FT ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, FT ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, FT ECO:0007744|PDB:6UZE" FT BINDING 208 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15243628, FT ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, FT ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, FT ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, FT ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, FT ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, FT ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, FT ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, FT ECO:0007744|PDB:6UZE" FT BINDING 208 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15243628, FT ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, FT ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, FT ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, FT ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZO, FT ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, FT ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, FT ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE" FT BINDING 210 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15243628, FT ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, FT ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, FT ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, FT ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, FT ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, FT ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, FT ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, FT ECO:0007744|PDB:6UZE" FT BINDING 210 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15243628, FT ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, FT ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, FT ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, FT ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, FT ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, FT ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, FT ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, FT ECO:0007744|PDB:6UZE" FT BINDING 212 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15243628, FT ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, FT ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, FT ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, FT ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, FT ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, FT ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, FT ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, FT ECO:0007744|PDB:6UZE" FT BINDING 217 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15243628, FT ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, FT ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, FT ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, FT ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, FT ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, FT ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, FT ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, FT ECO:0007744|PDB:6UZE" FT BINDING 217 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15326297, FT ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, FT ECO:0000269|PubMed:32047164, ECO:0007744|PDB:1ACC, FT ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, FT ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, FT ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, FT ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE" FT BINDING 251 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15243628, FT ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, FT ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, FT ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, FT ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, FT ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, FT ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, FT ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE" FT BINDING 254 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15243628, FT ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, FT ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, FT ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, FT ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, FT ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, FT ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, FT ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE" FT BINDING 264 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15243628, FT ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, FT ECO:0000269|PubMed:32047164, ECO:0007744|PDB:1ACC, FT ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, FT ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3KWV, FT ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, FT ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE" FT SITE 196..197 FT /note="Cleavage; by FURIN" FT /evidence="ECO:0000269|PubMed:11207581, FT ECO:0000269|PubMed:1438214, ECO:0000269|PubMed:1644824" FT SITE 207 FT /note="Alpha-clamp" FT /evidence="ECO:0000269|PubMed:21037566" FT SITE 216 FT /note="Alpha-clamp" FT /evidence="ECO:0000269|PubMed:21037566" FT SITE 265 FT /note="Alpha-clamp" FT /evidence="ECO:0000269|PubMed:21037566" FT SITE 343..344 FT /note="Cleavage; by chymotrypsin; required for FT translocation of LF and EF" FT /evidence="ECO:0000269|PubMed:7961869" FT SITE 456 FT /note="Phi-clamp" FT /evidence="ECO:0000269|PubMed:16051798, FT ECO:0000269|PubMed:25778700" FT SITE 493 FT /note="Alpha-clamp" FT /evidence="ECO:0000269|PubMed:21037566" FT SITE 712 FT /note="Essential for binding to cell receptor" FT /evidence="ECO:0000269|PubMed:12771151" FT VARIANT 295 FT /note="M -> I (in strain: PAI)" FT /evidence="ECO:0000269|PubMed:14985634" FT VARIANT 392 FT /note="N -> D (in strain: PAI)" FT /evidence="ECO:0000269|PubMed:14985634" FT VARIANT 560 FT /note="F -> L (in Sverdlovsk sample)" FT VARIANT 565 FT /note="P -> S (in strain: BA1024)" FT /evidence="ECO:0000269|PubMed:10197996" FT VARIANT 600 FT /note="A -> V (in strain: BA1024, V770-NP1-R, Carbosap and FT Ferrara)" FT /evidence="ECO:0000269|PubMed:10197996" FT MUTAGEN 193..196 FT /note="RKKR->SNSS,SNKE: Abolished cleavage by FURIN and FT abolished toxin activity." FT /evidence="ECO:0000269|PubMed:1438214" FT MUTAGEN 193 FT /note="R->A: Reduced cleavage by FURIN and reduced toxin FT activity." FT /evidence="ECO:0000269|PubMed:1438214" FT MUTAGEN 194..196 FT /note="KKR->EGG: Abolished cleavage by FURIN and abolished FT toxin activity." FT /evidence="ECO:0000269|PubMed:1438214" FT MUTAGEN 194..195 FT /note="KK->AA: Does not affect cleavage by FURIN and does FT not affect toxin activity." FT /evidence="ECO:0000269|PubMed:1438214" FT MUTAGEN 207 FT /note="R->A: Abolished interaction with LF." FT /evidence="ECO:0000269|PubMed:21037566" FT MUTAGEN 213 FT /note="P->A: Decrease in the ability to bind to LF and FT partially toxic at high concentrations." FT /evidence="ECO:0000269|PubMed:12117959" FT MUTAGEN 216 FT /note="L->A: Decrease in the ability to bind to LF and FT partially toxic at high concentrations." FT /evidence="ECO:0000269|PubMed:12117959" FT MUTAGEN 229 FT /note="R->S: Abolished interaction with LF." FT /evidence="ECO:0000269|PubMed:21037566" FT MUTAGEN 231 FT /note="F->A: Loss of ability to bind to LF and completely FT non-toxic." FT /evidence="ECO:0000269|PubMed:12117959" FT MUTAGEN 231 FT /note="F->S: Does not affect significantly interaction with FT LF, while it impairs tranlocation of LF." FT /evidence="ECO:0000269|PubMed:21037566" FT MUTAGEN 232 FT /note="L->A: Loss of ability to bind to LF and completely FT non-toxic." FT /evidence="ECO:0000269|PubMed:12117959" FT MUTAGEN 234 FT /note="P->A: Loss of ability to bind to LF and completely FT non-toxic." FT /evidence="ECO:0000269|PubMed:12117959" FT MUTAGEN 234 FT /note="P->S: Does not affect significantly interaction with FT LF." FT /evidence="ECO:0000269|PubMed:21037566" FT MUTAGEN 236 FT /note="I->A: Loss of ability to bind to LF and completely FT non-toxic." FT /evidence="ECO:0000269|PubMed:12117959" FT MUTAGEN 236 FT /note="I->S: Abolished interaction with LF." FT /evidence="ECO:0000269|PubMed:21037566" FT MUTAGEN 239 FT /note="I->A: Decrease in the ability to bind to LF and FT partially toxic at high concentrations." FT /evidence="ECO:0000269|PubMed:12117959" FT MUTAGEN 240 FT /note="H->A: Abolished interaction with LF." FT /evidence="ECO:0000269|PubMed:21037566" FT MUTAGEN 255 FT /note="W->A: No effect on LF-binding ability and as toxic FT as the wild-type." FT /evidence="ECO:0000269|PubMed:12117959" FT MUTAGEN 265 FT /note="F->A: No effect on LF-binding ability and as toxic FT as the wild-type." FT /evidence="ECO:0000269|PubMed:12117959" FT MUTAGEN 265 FT /note="F->S: Impaired translocation of LF." FT /evidence="ECO:0000269|PubMed:21037566" FT MUTAGEN 289 FT /note="P->A: Reduced toxicity in combination with lethal FT factor. Decreased membrane insertion and translocation of FT LF." FT /evidence="ECO:0000269|PubMed:11356563" FT MUTAGEN 342..344 FT /note="FFD->AAA: Decrease in toxicity probably due to slow FT translocation of LF." FT /evidence="ECO:0000269|PubMed:10085028" FT MUTAGEN 342..343 FT /note="Missing: Loss of toxicity probably due to loss of FT capability to translocate LF." FT /evidence="ECO:0000269|PubMed:7961869" FT MUTAGEN 342 FT /note="F->C: Loss of toxicity probably due to loss of FT capability to translocate LF." FT /evidence="ECO:0000269|PubMed:10085028" FT MUTAGEN 344 FT /note="D->A: Decrease in toxicity probably due to slow FT translocation of LF." FT /evidence="ECO:0000269|PubMed:7961869" FT MUTAGEN 375 FT /note="W->A: Loss of toxicity probably due to faulty FT membrane insertion or translocation of LF/EF into the FT cytosol." FT /evidence="ECO:0000269|PubMed:11178978" FT MUTAGEN 379 FT /note="M->A: No effect." FT /evidence="ECO:0000269|PubMed:11178978" FT MUTAGEN 381 FT /note="L->A: Loss of toxicity probably due to faulty FT membrane insertion or translocation of LF/EF into the FT cytosol." FT /evidence="ECO:0000269|PubMed:11178978" FT MUTAGEN 393 FT /note="I->C: Loss of capability to undergo conformational FT changes that lead to pore formation and translocation." FT /evidence="ECO:0000269|PubMed:14623961" FT MUTAGEN 409 FT /note="T->C: Loss of capability to undergo conformational FT changes that lead to pore formation and translocation." FT /evidence="ECO:0000269|PubMed:14623961" FT MUTAGEN 411 FT /note="S->C: Loss of capability to undergo conformational FT changes that lead to pore formation and translocation." FT /evidence="ECO:0000269|PubMed:14623961" FT MUTAGEN 422 FT /note="T->C: Loss of capability to undergo conformational FT changes that lead to pore formation and translocation." FT /evidence="ECO:0000269|PubMed:14623961" FT MUTAGEN 426 FT /note="K->A,D: Loss of capability to undergo conformational FT changes that lead to pore formation and translocation." FT /evidence="ECO:0000269|PubMed:11113126, FT ECO:0000269|PubMed:14623961" FT MUTAGEN 428 FT /note="N->C: Loss of capability to undergo conformational FT changes that lead to pore formation and translocation." FT /evidence="ECO:0000269|PubMed:14623961" FT MUTAGEN 440 FT /note="Y->C: Loss of capability to undergo conformational FT changes that lead to pore formation and translocation." FT /evidence="ECO:0000269|PubMed:14623961" FT MUTAGEN 451 FT /note="N->C: Loss of capability to undergo conformational FT changes that lead to pore formation and translocation." FT /evidence="ECO:0000269|PubMed:14623961" FT MUTAGEN 454 FT /note="D->A,K: Loss of capability to undergo conformational FT changes that lead to pore formation and translocation." FT /evidence="ECO:0000269|PubMed:11113126, FT ECO:0000269|PubMed:14623961" FT MUTAGEN 456 FT /note="F->A: Loss of capability to undergo conformational FT changes that lead to pore formation and translocation." FT /evidence="ECO:0000269|PubMed:11113126, FT ECO:0000269|PubMed:14623961" FT MUTAGEN 456 FT /note="F->C: Abolished ability for mediate LF and EF FT protein translocation." FT /evidence="ECO:0000269|PubMed:16051798" FT MUTAGEN 512 FT /note="Q->A: Loss of heptamerization capability." FT /evidence="ECO:0000269|PubMed:11222612" FT MUTAGEN 541 FT /note="D->A: Loss of heptamerization capability." FT /evidence="ECO:0000269|PubMed:11222612" FT MUTAGEN 543 FT /note="L->A: Decrease in heptamerization capability." FT /evidence="ECO:0000269|PubMed:11222612" FT MUTAGEN 581 FT /note="F->A: Loss of toxicity due to defective FT oligomerization." FT /evidence="ECO:0000269|PubMed:11554763" FT MUTAGEN 583 FT /note="F->A: Decrease in toxicity due to defective FT oligomerization." FT /evidence="ECO:0000269|PubMed:11554763" FT MUTAGEN 591 FT /note="I->A: Loss of toxicity due to defective FT oligomerization." FT /evidence="ECO:0000269|PubMed:11554763" FT MUTAGEN 595 FT /note="L->A: Loss of toxicity due to defective FT oligomerization." FT /evidence="ECO:0000269|PubMed:11554763" FT MUTAGEN 603 FT /note="I->A: Loss of toxicity due to defective FT oligomerization." FT /evidence="ECO:0000269|PubMed:11554763" FT MUTAGEN 621 FT /note="R->A: No effect." FT /evidence="ECO:0000269|PubMed:11222612" FT MUTAGEN 686 FT /note="N->A: Decrease in toxicity due to decrease in cell FT binding." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 708 FT /note="K->A: No effect on toxicity." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 709 FT /note="K->A: Slight decrease in toxicity." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 710 FT /note="Y->A: Great decrease in toxicity due to decrease in FT cell binding." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 711 FT /note="N->A: Loss of toxicity due to decrease in cell FT binding." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 712 FT /note="D->A: Loss of toxicity due to decrease in cell FT binding." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 713 FT /note="K->A: No effect on toxicity." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 714 FT /note="L->A: No effect on toxicity." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 715 FT /note="P->A: Great decrease in toxicity due to decrease in FT cell binding." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 716 FT /note="L->A: Decrease in toxicity due to decrease in cell FT binding." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 717 FT /note="Y->A: No effect on toxicity." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 718 FT /note="I->A: Decrease in toxicity due to decrease in cell FT binding." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 719 FT /note="S->A: No effect on toxicity." FT /evidence="ECO:0000269|PubMed:10085028" FT MUTAGEN 720 FT /note="N->A: No effect on toxicity." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 721 FT /note="P->A: No effect on toxicity." FT /evidence="ECO:0000269|PubMed:12771151" FT MUTAGEN 722 FT /note="N->A: No effect on toxicity." FT /evidence="ECO:0000269|PubMed:12771151" FT CONFLICT 314 FT /note="Q -> E (in Ref. 1; AAA22637)" FT /evidence="ECO:0000305" FT HELIX 41..44 FT /evidence="ECO:0007829|PDB:4H2A" FT STRAND 47..55 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 60..71 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 76..78 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 84..86 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 91..99 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 104..110 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 113..115 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 116..120 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 123..129 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 135..137 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 142..150 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 155..159 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 162..166 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:1ACC" FT STRAND 172..174 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 177..179 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 186..188 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 191..193 FT /evidence="ECO:0007829|PDB:4H2A" FT STRAND 199..201 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 210..212 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 214..219 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 221..225 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 230..234 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 237..240 FT /evidence="ECO:0007829|PDB:3TEW" FT TURN 241..244 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 255..258 FT /evidence="ECO:0007829|PDB:3Q8A" FT STRAND 259..262 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 264..269 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 278..281 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 291..302 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 314..316 FT /evidence="ECO:0007829|PDB:6VRA" FT STRAND 318..326 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 331..340 FT /evidence="ECO:0007829|PDB:3J9C" FT STRAND 341..343 FT /evidence="ECO:0007829|PDB:6UZB" FT STRAND 345..354 FT /evidence="ECO:0007829|PDB:3J9C" FT STRAND 357..363 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 369..371 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 375..379 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 383..385 FT /evidence="ECO:0007829|PDB:3J9C" FT STRAND 386..397 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 399..401 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 403..405 FT /evidence="ECO:0007829|PDB:4EE2" FT STRAND 410..414 FT /evidence="ECO:0007829|PDB:3TEW" FT TURN 415..417 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 418..423 FT /evidence="ECO:0007829|PDB:3TEW" FT TURN 427..429 FT /evidence="ECO:0007829|PDB:3J9C" FT STRAND 431..434 FT /evidence="ECO:0007829|PDB:6UZB" FT STRAND 438..441 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 448..451 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 456..458 FT /evidence="ECO:0007829|PDB:3KWV" FT STRAND 461..464 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 465..474 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 476..481 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 487..492 FT /evidence="ECO:0007829|PDB:3TEW" FT TURN 493..496 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 497..505 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 506..508 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 510..516 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 517..522 FT /evidence="ECO:0007829|PDB:3TEW" FT TURN 524..527 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 530..535 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 539..541 FT /evidence="ECO:0007829|PDB:7O85" FT HELIX 542..546 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 552..560 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 565..568 FT /evidence="ECO:0007829|PDB:3MHZ" FT STRAND 570..575 FT /evidence="ECO:0007829|PDB:6UZD" FT HELIX 576..578 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 579..583 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 585..597 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 603..605 FT /evidence="ECO:0007829|PDB:3TEW" FT TURN 607..609 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 611..613 FT /evidence="ECO:0007829|PDB:3MHZ" FT STRAND 617..622 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 625..627 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 633..636 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 638..644 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 648..652 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 655..658 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 662..666 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 668..676 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 678..680 FT /evidence="ECO:0007829|PDB:3KWV" FT STRAND 682..684 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 689..691 FT /evidence="ECO:0007829|PDB:4EE2" FT STRAND 695..697 FT /evidence="ECO:0007829|PDB:3TEW" FT TURN 699..701 FT /evidence="ECO:0007829|PDB:3KWV" FT STRAND 703..708 FT /evidence="ECO:0007829|PDB:3TEW" FT TURN 709..713 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 723..731 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 732..734 FT /evidence="ECO:0007829|PDB:3TEW" FT STRAND 741..743 FT /evidence="ECO:0007829|PDB:1ACC" FT STRAND 753..759 FT /evidence="ECO:0007829|PDB:3TEW" FT HELIX 760..763 FT /evidence="ECO:0007829|PDB:3TEW" SQ SEQUENCE 764 AA; 85811 MW; 3AE1EFBF48FAA03F CRC64; MKKRKVLIPL MALSTILVSS TGNLEVIQAE VKQENRLLNE SESSSQGLLG YYFSDLNFQA PMVVTSSTTG DLSIPSSELE NIPSENQYFQ SAIWSGFIKV KKSDEYTFAT SADNHVTMWV DDQEVINKAS NSNKIRLEKG RLYQIKIQYQ RENPTEKGLD FKLYWTDSQN KKEVISSDNL QLPELKQKSS NSRKKRSTSA GPTVPDRDND GIPDSLEVEG YTVDVKNKRT FLSPWISNIH EKKGLTKYKS SPEKWSTASD PYSDFEKVTG RIDKNVSPEA RHPLVAAYPI VHVDMENIIL SKNEDQSTQN TDSQTRTISK NTSTSRTHTS EVHGNAEVHA SFFDIGGSVS AGFSNSNSST VAIDHSLSLA GERTWAETMG LNTADTARLN ANIRYVNTGT APIYNVLPTT SLVLGKNQTL ATIKAKENQL SQILAPNNYY PSKNLAPIAL NAQDDFSSTP ITMNYNQFLE LEKTKQLRLD TDQVYGNIAT YNFENGRVRV DTGSNWSEVL PQIQETTARI IFNGKDLNLV ERRIAAVNPS DPLETTKPDM TLKEALKIAF GFNEPNGNLQ YQGKDITEFD FNFDQQTSQN IKNQLAELNA TNIYTVLDKI KLNAKMNILI RDKRFHYDRN NIAVGADESV VKEAHREVIN SSTEGLLLNI DKDIRKILSG YIVEIEDTEG LKEVINDRYD MLNISSLRQD GKTFIDFKKY NDKLPLYISN PNYKVNVYAV TKENTIINPS ENGDTSTNGI KKILIFSKKG YEIG //