CYAA_BACAN
ID CYAA_BACAN Reviewed; 800 AA.
AC P40136; Q937W4; Q937W5;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Calmodulin-sensitive adenylate cyclase {ECO:0000303|PubMed:2834337, ECO:0000303|PubMed:3149607};
DE EC=4.6.1.1 {ECO:0000269|PubMed:11807546, ECO:0000269|PubMed:2108958, ECO:0000269|PubMed:6285339};
DE AltName: Full=ATP pyrophosphate-lyase;
DE AltName: Full=Adenylyl cyclase;
DE AltName: Full=Anthrax edema toxin adenylate cyclase component;
DE AltName: Full=Edema factor {ECO:0000303|PubMed:3149607};
DE Short=EF {ECO:0000303|PubMed:3149607};
DE Flags: Precursor;
GN Name=cya; OrderedLocusNames=pXO1-122, BXA0141, GBAA_pXO1_0142;
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=2906312; DOI=10.1016/0378-1119(88)90045-5;
RA Escuyer V., Duflot E., Sezer O., Danchin A., Mock M.;
RT "Structural homology between virulence-associated bacterial adenylate
RT cyclases.";
RL Gene 71:293-298(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, AND PROTEIN
RP SEQUENCE OF 34-48.
RX PubMed=3149607; DOI=10.1016/0378-1119(88)90501-x;
RA Robertson D.L., Tippetts M.T., Leppla S.H.;
RT "Nucleotide sequence of the Bacillus anthracis edema factor gene (cya): a
RT calmodulin-dependent adenylate cyclase.";
RL Gene 73:363-371(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Escuyer V., Duflot E., Mock M., Danchin A.;
RT "Nucleotide sequences expressing adenylate cyclase from B.anthracis,
RT proteins having the activity of this adenylate cyclase and biological
RT uses.";
RL Patent number EP0366550, 02-MAY-1990.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2834337; DOI=10.1128/jb.170.5.2263-2266.1988;
RA Tippetts M.T., Robertson D.L.;
RT "Molecular cloning and expression of the Bacillus anthracis edema factor
RT toxin gene: a calmodulin-dependent adenylate cyclase.";
RL J. Bacteriol. 170:2263-2266(1988).
RN [5]
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 [6]
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 [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-783.
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 [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=6285339; DOI=10.1073/pnas.79.10.3162;
RA Leppla S.H.;
RT "Anthrax toxin edema factor: a bacterial adenylate cyclase that increases
RT cyclic AMP concentrations of eukaryotic cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:3162-3166(1982).
RN [10]
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 [11]
RP REVIEW.
RX PubMed=8418825;
RA Danchin A.;
RT "Phylogeny of adenylyl cyclases.";
RL Adv. Second Messenger Phosphoprotein Res. 27:109-162(1993).
RN [12]
RP INTERACTION WITH PA.
RC STRAIN=Sterne;
RX PubMed=9398214; DOI=10.1021/bi971661k;
RA Wang X.-M., Wattiez R., Mock M., Falmagne P., Ruysschaert J.-M.,
RA Cabiaux V.;
RT "Structure and interaction of PA63 and EF (edema toxin) of Bacillus
RT anthracis with lipid membrane.";
RL Biochemistry 36:14906-14913(1997).
RN [13]
RP SUBCELLULAR LOCATION.
RC STRAIN=Sterne;
RX PubMed=11207582; DOI=10.1046/j.1462-5822.2000.00057.x;
RA Guidi-Rontani C., Weber-Levy M., Mock M., Cabiaux V.;
RT "Translocation of Bacillus anthracis lethal and oedema factors across
RT endosome membranes.";
RL Cell. Microbiol. 2:259-264(2000).
RN [14]
RP CHARACTERIZATION OF CALMODULIN-BINDING DOMAIN, AND ACTIVITY REGULATION.
RX PubMed=2114169; DOI=10.1021/bi00472a024;
RA Labruyere E., Mock M., Ladant D., Michelson S., Gilles A.-M., Laoide B.,
RA Barzu O.;
RT "Characterization of ATP and calmodulin-binding properties of a truncated
RT form of Bacillus anthracis adenylate cyclase.";
RL Biochemistry 29:4922-4928(1990).
RN [15]
RP FUNCTION.
RC STRAIN=Sterne;
RX PubMed=11737637; DOI=10.1046/j.1365-2958.2001.02695.x;
RA Guidi-Rontani C., Levy M., Ohayon H., Mock M.;
RT "Fate of germinated Bacillus anthracis spores in primary murine
RT macrophages.";
RL Mol. Microbiol. 42:931-938(2001).
RN [16]
RP ACTIVITY REGULATION.
RX PubMed=12676933; DOI=10.1074/jbc.m301232200;
RA Soelaiman S., Wei B.Q., Bergson P., Lee Y.-S., Shen Y., Mrksich M.,
RA Shoichet B.K., Tang W.-J.;
RT "Structure-based inhibitor discovery against adenylyl cyclase toxins from
RT pathogenic bacteria that cause anthrax and whooping cough.";
RL J. Biol. Chem. 278:25990-25997(2003).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-346; LYS-353 AND
RP GLU-436.
RC STRAIN=SRI-1;
RX PubMed=2108958; DOI=10.1016/s0021-9258(19)39173-2;
RA Xia Z., Storm D.R.;
RT "A-type ATP binding consensus sequences are critical for the catalytic
RT activity of the calmodulin-sensitive adenylyl cyclase from Bacillus
RT anthracis.";
RL J. Biol. Chem. 265:6517-6520(1990).
RN [18]
RP MUTAGENESIS OF LYS-346.
RC STRAIN=Sterne;
RX PubMed=1900429; DOI=10.1021/bi00224a008;
RA Labruyere E., Mock M., Surewicz W.K., Mantsch H.H., Rose T., Munier H.,
RA Sarfati R.S., Barzu O.;
RT "Structural and ligand-binding properties of a truncated form of Bacillus
RT anthracis adenylate cyclase and of a catalytically inactive variant in
RT which glutamine substitutes for lysine-346.";
RL Biochemistry 30:2619-2624(1991).
RN [19]
RP FUNCTION, INTERACTION WITH PA, AND MUTAGENESIS OF VAL-169; TYR-170;
RP TYR-171; GLU-172; ILE-173; GLY-174 AND LYS-175.
RX PubMed=11553601; DOI=10.1128/iai.69.10.6532-6536.2001;
RA Kumar P., Ahuja N., Bhatnagar R.;
RT "Purification of anthrax edema factor from Escherichia coli and
RT identification of residues required for binding to anthrax protective
RT antigen.";
RL Infect. Immun. 69:6532-6536(2001).
RN [20]
RP MUTAGENESIS OF ARG-329; GLU-443; ASP-491 AND ASP-493.
RX PubMed=10926933; DOI=10.1074/jbc.m004778200;
RA Drum C.L., Yan S.-Z., Sarac R., Mabuchi Y., Beckingham K., Bohm A.,
RA Grabarek Z., Tang W.-J.;
RT "An extended conformation of calmodulin induces interactions between the
RT structural domains of adenylyl cyclase from Bacillus anthracis to promote
RT catalysis.";
RL J. Biol. Chem. 275:36334-36340(2000).
RN [21]
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 [22]
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 [23]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, DOMAIN, ACTIVE SITE, AND MUTAGENESIS OF LEU-523;
RP LYS-525; GLN-526; VAL-529; HIS-577; ASN-583; GLU-588; ASP-590; ASN-639 AND
RP ASP-647.
RX PubMed=11807546; DOI=10.1038/415396a;
RA Drum C.L., Yan S.-Z., Bard J., Shen Y.-Q., Lu D., Soelaiman S.,
RA Grabarek Z., Bohm A., Tang W.-J.;
RT "Structural basis for the activation of anthrax adenylyl cyclase exotoxin
RT by calmodulin.";
RL Nature 415:396-402(2002).
RN [24] {ECO:0007744|PDB:1XFU, ECO:0007744|PDB:1XFV, ECO:0007744|PDB:1XFW, ECO:0007744|PDB:1XFX, ECO:0007744|PDB:1XFY, ECO:0007744|PDB:1XFZ, ECO:0007744|PDB:1Y0V}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 31-800 IN COMPLEX WITH
RP CALMODULIN; MAGNESIUM AND CAMP.
RX PubMed=15719022; DOI=10.1038/sj.emboj.7600574;
RA Shen Y., Zhukovskaya N.L., Guo Q., Florian J., Tang W.-J.;
RT "Calcium-independent calmodulin binding and two-metal-ion catalytic
RT mechanism of anthrax edema factor.";
RL EMBO J. 24:929-941(2005).
RN [25] {ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) OF 34-800 IN COMPLEX WITH
RP PA, 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 [26] {ECO:0007744|PDB:6VRA}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) OF 34-800 IN COMPLEX WITH
RP PA.
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: Edema factor (EF), which constitutes one of the three
CC proteins composing the anthrax toxin, causes edema in the host
CC (PubMed:6285339, PubMed:2108958, PubMed:11807546). Acts as a
CC calmodulin-dependent adenylyl cyclase by converting ATP to cAMP,
CC leading to dramatic elevation of intracellular cAMP levels in the host,
CC thereby causing edema (PubMed:6285339, PubMed:2108958,
CC PubMed:11807546). EF is not toxic by itself and only acts as a edema
CC factor when associated with protective antigen (PA) to form the edema
CC toxin (EdTx) (PubMed:11553601, PubMed:2108958). Required for the
CC survival of germinated spores within macrophages at the early stages of
CC infection (PubMed:11737637). {ECO:0000269|PubMed:11553601,
CC ECO:0000269|PubMed:11737637, ECO:0000269|PubMed:11807546,
CC ECO:0000269|PubMed:2108958, ECO:0000269|PubMed:6285339}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1;
CC Evidence={ECO:0000269|PubMed:11807546, ECO:0000269|PubMed:2108958,
CC ECO:0000269|PubMed:6285339};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC -!- ACTIVITY REGULATION: Host calmodulin is an absolute requirement for its
CC activation (PubMed:2114169, PubMed:11807546). Inhibited by ethyl 5-
CC aminopyrazolo[1,5-a]quinazoline-3-carboxylate (PubMed:12676933).
CC {ECO:0000269|PubMed:11807546, ECO:0000269|PubMed:12676933,
CC ECO:0000269|PubMed:2114169}.
CC -!- SUBUNIT: Interacts (via ATLF domain) with the cleaved form of
CC protective antigen (PA-63) anthrax toxin; interaction is required for
CC EF translocation into the host cytoplasm. {ECO:0000269|PubMed:11553601,
CC ECO:0000269|PubMed:15313199, ECO:0000269|PubMed:32047164,
CC ECO:0000269|PubMed:9398214}.
CC -!- INTERACTION:
CC P40136; P62155: calm2; Xeno; NbExp=2; IntAct=EBI-457011, EBI-397568;
CC P40136; P62158: CALM3; Xeno; NbExp=10; IntAct=EBI-457011, EBI-397435;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3149607}. 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, EF
CC binds via its N-terminal region to the upper rim of the ring-shaped
CC homooligomer (homoheptamer or homooctamer) formed by PA-63 on the host
CC cell membrane (PubMed:32047164). In this PA-63 pre-pore state, the N-
CC terminal segment of EF refolds into an alpha helix engaged in the
CC alpha-clamp of the PA-63 pre-pore (PubMed:32047164, PubMed:32521227).
CC Recruitment to the PA-63 pre-pore enables domain reorganization of EF
CC (PubMed:32521227). Loaded complexes are then endocytosed, followed by a
CC conformational change of oligomerized PA-63 from the pre-pore to pore
CC state, which is triggered by the low pH in the endosome
CC (PubMed:11207582). EF is then unfolded to pass through the PA-63 pore
CC and translocate into the host cytosol (PubMed:32047164).
CC {ECO:0000269|PubMed:11207582, ECO:0000269|PubMed:32047164,
CC ECO:0000269|PubMed:32521227}.
CC -!- DOMAIN: The N-terminal region contains the ATLF domain responsible for
CC binding to the cleaved form of protective antigen (PA-63)
CC (PubMed:11807546). The C-terminal region contains the calmodulin-
CC dependent activation domain and the catalytic site (PubMed:11807546).
CC This region is composed of three globular domains: CA, CB and a helical
CC domain connected to CA by a linker (PubMed:11807546). The active site
CC lies at the interface of CA and CB (PubMed:11807546). The metal ion is
CC coordinated by residues from CA; calmodulin probably binds in a
CC multistep fashion first to residues in CA and then to residues present
CC in the linker and the helical domain (PubMed:11807546).
CC {ECO:0000269|PubMed:11807546}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-2 family.
CC {ECO:0000305}.
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DR EMBL; M23179; AAA22374.1; -; Genomic_DNA.
DR EMBL; M24074; AAA79215.1; -; Genomic_DNA.
DR EMBL; A07289; CAA00652.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AF065404; AAD32426.1; -; Genomic_DNA.
DR EMBL; AE011190; AAM26089.1; -; Genomic_DNA.
DR EMBL; AE017336; AAT28883.2; -; Genomic_DNA.
DR EMBL; AJ413930; CAC93924.1; -; Genomic_DNA.
DR EMBL; AJ413931; CAC93925.1; -; Genomic_DNA.
DR PIR; B59106; B59106.
DR PIR; JS0029; JS0029.
DR RefSeq; NP_052818.1; NC_001496.1.
DR RefSeq; WP_000197748.1; NZ_VTZH01000015.1.
DR PDB; 1K8T; X-ray; 2.60 A; A=291-800.
DR PDB; 1K90; X-ray; 2.75 A; A/B/C=291-800.
DR PDB; 1K93; X-ray; 2.95 A; A/B/C=291-800.
DR PDB; 1LVC; X-ray; 3.60 A; A/B/C=291-800.
DR PDB; 1PK0; X-ray; 3.30 A; A/B/C=292-798.
DR PDB; 1S26; X-ray; 3.00 A; A/B/C=291-800.
DR PDB; 1SK6; X-ray; 3.20 A; A/B/C=291-800.
DR PDB; 1XFU; X-ray; 3.35 A; A/B/C/D/E/F=64-800.
DR PDB; 1XFV; X-ray; 3.35 A; A/B/C/D/E/F=33-800.
DR PDB; 1XFW; X-ray; 3.40 A; A/B/C/D/E/F=33-800.
DR PDB; 1XFX; X-ray; 3.20 A; A/B/C/D/E/F=33-800.
DR PDB; 1XFY; X-ray; 3.30 A; A/B/C/D/E/F=33-800.
DR PDB; 1XFZ; X-ray; 3.25 A; A/B/C/D/E/F=33-800.
DR PDB; 1Y0V; X-ray; 3.60 A; A/B/C/D/E/F=33-800.
DR PDB; 6UZB; EM; 3.20 A; H=34-800.
DR PDB; 6UZD; EM; 3.40 A; H/I=34-800.
DR PDB; 6UZE; EM; 3.40 A; H/I=34-800.
DR PDB; 6VRA; EM; 3.30 A; I/J/K/L=34-800.
DR PDBsum; 1K8T; -.
DR PDBsum; 1K90; -.
DR PDBsum; 1K93; -.
DR PDBsum; 1LVC; -.
DR PDBsum; 1PK0; -.
DR PDBsum; 1S26; -.
DR PDBsum; 1SK6; -.
DR PDBsum; 1XFU; -.
DR PDBsum; 1XFV; -.
DR PDBsum; 1XFW; -.
DR PDBsum; 1XFX; -.
DR PDBsum; 1XFY; -.
DR PDBsum; 1XFZ; -.
DR PDBsum; 1Y0V; -.
DR PDBsum; 6UZB; -.
DR PDBsum; 6UZD; -.
DR PDBsum; 6UZE; -.
DR PDBsum; 6VRA; -.
DR AlphaFoldDB; P40136; -.
DR SMR; P40136; -.
DR DIP; DIP-31055N; -.
DR IntAct; P40136; 3.
DR BindingDB; P40136; -.
DR ChEMBL; CHEMBL5396; -.
DR PRIDE; P40136; -.
DR ABCD; P40136; 7 sequenced antibodies.
DR EnsemblBacteria; AAT28883; AAT28883; GBAA_pXO1_0142.
DR GeneID; 45025501; -.
DR KEGG; bar:GBAA_pXO1_0142; -.
DR HOGENOM; CLU_346710_0_0_9; -.
DR OMA; DKFEVFQ; -.
DR Reactome; R-HSA-5210891; Uptake and function of anthrax toxins.
DR EvolutionaryTrace; P40136; -.
DR PHI-base; PHI:4091; -.
DR PRO; PR:P40136; -.
DR Proteomes; UP000000594; Plasmid pXO1.
DR GO; GO:1902494; C:catalytic complex; IMP:CAFA.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IDA:UniProtKB.
DR GO; GO:0004016; F:adenylate cyclase activity; EXP:Reactome.
DR GO; GO:0005524; F:ATP binding; IMP:CAFA.
DR GO; GO:0008294; F:calcium- and calmodulin-responsive adenylate cyclase activity; IDA:CACAO.
DR GO; GO:0005516; F:calmodulin binding; IPI:CAFA.
DR GO; GO:0046872; F:metal ion binding; IMP:CAFA.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0099004; P:calmodulin dependent kinase signaling pathway; IMP:CAFA.
DR GO; GO:0006171; P:cAMP biosynthetic process; IEA:UniProtKB-KW.
DR DisProt; DP00395; -.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 3.90.1760.10; -; 1.
DR InterPro; IPR035099; Anthrax_toxin_C-terminal.
DR InterPro; IPR005165; Anthrax_toxin_edema_cen.
DR InterPro; IPR037017; Anthrax_toxin_edema_cen_sf.
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; PF03497; Anthrax_toxA; 1.
DR Pfam; PF07737; ATLF; 1.
DR PRINTS; PR01392; ANTHRAXTOXNA.
DR SUPFAM; SSF81298; SSF81298; 1.
DR PROSITE; PS51995; ATLF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Calcium; Calmodulin-binding; cAMP biosynthesis;
KW Direct protein sequencing; Host cytoplasm; Lyase; Magnesium; Metal-binding;
KW Nucleotide-binding; Plasmid; Reference proteome; Secreted; Signal; Toxin;
KW Virulence.
FT SIGNAL 1..33
FT /evidence="ECO:0000269|PubMed:3149607"
FT CHAIN 34..800
FT /note="Calmodulin-sensitive adenylate cyclase"
FT /id="PRO_0000001317"
FT DOMAIN 60..273
FT /note="ATLF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339"
FT REGION 294..349
FT /note="Catalytic CA1"
FT /evidence="ECO:0000269|PubMed:11807546"
FT REGION 350..489
FT /note="Catalytic CB"
FT /evidence="ECO:0000269|PubMed:11807546"
FT REGION 490..622
FT /note="Catalytic CA2"
FT /evidence="ECO:0000269|PubMed:11807546"
FT REGION 623..800
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000269|PubMed:2114169"
FT ACT_SITE 351
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:11807546"
FT BINDING 491
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15719022,
FT ECO:0007744|PDB:1XFU, ECO:0007744|PDB:1XFV,
FT ECO:0007744|PDB:1XFW, ECO:0007744|PDB:1XFX,
FT ECO:0007744|PDB:1XFY, ECO:0007744|PDB:1XFZ,
FT ECO:0007744|PDB:1Y0V"
FT BINDING 493
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15719022,
FT ECO:0007744|PDB:1XFU, ECO:0007744|PDB:1XFV,
FT ECO:0007744|PDB:1XFW, ECO:0007744|PDB:1XFX,
FT ECO:0007744|PDB:1XFY, ECO:0007744|PDB:1XFZ,
FT ECO:0007744|PDB:1Y0V"
FT BINDING 548
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:15719022,
FT ECO:0007744|PDB:1XFW"
FT BINDING 577..579
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:15719022,
FT ECO:0007744|PDB:1XFW"
FT BINDING 577
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15719022,
FT ECO:0007744|PDB:1XFU, ECO:0007744|PDB:1XFV,
FT ECO:0007744|PDB:1XFW, ECO:0007744|PDB:1XFX,
FT ECO:0007744|PDB:1XFY, ECO:0007744|PDB:1XFZ,
FT ECO:0007744|PDB:1Y0V"
FT MUTAGEN 169
FT /note="V->A: No effect."
FT /evidence="ECO:0000269|PubMed:11553601"
FT MUTAGEN 170
FT /note="Y->A: Loss of cytotoxicity due to inability to bind
FT PA."
FT /evidence="ECO:0000269|PubMed:11553601"
FT MUTAGEN 171
FT /note="Y->A: Loss of cytotoxicity due to inability to bind
FT PA."
FT /evidence="ECO:0000269|PubMed:11553601"
FT MUTAGEN 172
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:11553601"
FT MUTAGEN 173
FT /note="I->A: Loss of cytotoxicity due to inability to bind
FT PA."
FT /evidence="ECO:0000269|PubMed:11553601"
FT MUTAGEN 174
FT /note="G->A: No effect."
FT /evidence="ECO:0000269|PubMed:11553601"
FT MUTAGEN 175
FT /note="K->A: Loss of cytotoxicity due to inability to bind
FT PA."
FT /evidence="ECO:0000269|PubMed:11553601"
FT MUTAGEN 329
FT /note="R->M: Great decrease in activity."
FT /evidence="ECO:0000269|PubMed:10926933"
FT MUTAGEN 346
FT /note="K->M,R: Loss of activity."
FT /evidence="ECO:0000269|PubMed:1900429,
FT ECO:0000269|PubMed:2108958"
FT MUTAGEN 346
FT /note="K->Q: Loss of activity due to inability to bind the
FT substrate."
FT /evidence="ECO:0000269|PubMed:1900429,
FT ECO:0000269|PubMed:2108958"
FT MUTAGEN 353
FT /note="K->M,R,A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:2108958"
FT MUTAGEN 436
FT /note="E->Q: Decreases activity."
FT /evidence="ECO:0000269|PubMed:2108958"
FT MUTAGEN 443
FT /note="E->Q: Decreases activity."
FT /evidence="ECO:0000269|PubMed:10926933"
FT MUTAGEN 491
FT /note="D->N: Great decrease in activity."
FT /evidence="ECO:0000269|PubMed:10926933"
FT MUTAGEN 493
FT /note="D->N: Great decrease in activity."
FT /evidence="ECO:0000269|PubMed:10926933"
FT MUTAGEN 523
FT /note="L->A: Little effect on activation by calmodulin."
FT /evidence="ECO:0000269|PubMed:11807546"
FT MUTAGEN 525
FT /note="K->A: Great decrease in calmodulin binding."
FT /evidence="ECO:0000269|PubMed:11807546"
FT MUTAGEN 526
FT /note="Q->A: Little effect on activation by calmodulin."
FT /evidence="ECO:0000269|PubMed:11807546"
FT MUTAGEN 529
FT /note="V->A: Little effect on activation by calmodulin."
FT /evidence="ECO:0000269|PubMed:11807546"
FT MUTAGEN 577
FT /note="H->N,D: Loss of function."
FT /evidence="ECO:0000269|PubMed:11807546"
FT MUTAGEN 583
FT /note="N->A: Decreases activity."
FT /evidence="ECO:0000269|PubMed:11807546"
FT MUTAGEN 583
FT /note="N->Q,H: Loss of function."
FT /evidence="ECO:0000269|PubMed:11807546"
FT MUTAGEN 588
FT /note="E->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:11807546"
FT MUTAGEN 590
FT /note="D->A: Decreases activity."
FT /evidence="ECO:0000269|PubMed:11807546"
FT MUTAGEN 639
FT /note="N->A: Decreases catalysis rate."
FT /evidence="ECO:0000269|PubMed:11807546"
FT MUTAGEN 647
FT /note="D->A: Decreases activity due to reduced activation
FT by calmodulin."
FT /evidence="ECO:0000269|PubMed:11807546"
FT CONFLICT 350
FT /note="V -> E (in Ref. 2; AAA79215)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="Q -> T (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 512..513
FT /note="EW -> RM (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 760
FT /note="V -> L (in Ref. 3; CAA00652)"
FT /evidence="ECO:0000305"
FT HELIX 54..62
FT /evidence="ECO:0007829|PDB:6UZB"
FT TURN 63..66
FT /evidence="ECO:0007829|PDB:6UZB"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:1XFX"
FT HELIX 76..86
FT /evidence="ECO:0007829|PDB:1XFX"
FT HELIX 91..99
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 103..109
FT /evidence="ECO:0007829|PDB:1XFX"
FT TURN 111..114
FT /evidence="ECO:0007829|PDB:1XFY"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:6UZB"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:1XFX"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:6UZE"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:1XFX"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:1XFX"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:6VRA"
FT TURN 163..168
FT /evidence="ECO:0007829|PDB:1XFX"
FT HELIX 169..176
FT /evidence="ECO:0007829|PDB:1XFX"
FT TURN 177..182
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 183..188
FT /evidence="ECO:0007829|PDB:1XFX"
FT HELIX 192..197
FT /evidence="ECO:0007829|PDB:1XFX"
FT TURN 198..202
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:6VRA"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:6UZD"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:1XFX"
FT TURN 230..235
FT /evidence="ECO:0007829|PDB:1XFX"
FT HELIX 236..249
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:1XFX"
FT HELIX 255..259
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:1XFX"
FT HELIX 263..273
FT /evidence="ECO:0007829|PDB:1XFX"
FT HELIX 275..290
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:1SK6"
FT HELIX 299..305
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 309..322
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 324..328
FT /evidence="ECO:0007829|PDB:1K8T"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 336..340
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:6UZB"
FT STRAND 356..360
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:6UZE"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 368..370
FT /evidence="ECO:0007829|PDB:1K8T"
FT TURN 372..375
FT /evidence="ECO:0007829|PDB:1K90"
FT HELIX 377..393
FT /evidence="ECO:0007829|PDB:1K8T"
FT TURN 394..396
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 397..402
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 407..415
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 424..427
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 430..436
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 440..450
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 452..457
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 464..466
FT /evidence="ECO:0007829|PDB:6UZB"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:1K90"
FT STRAND 475..489
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 494..500
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 501..507
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 510..516
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 517..521
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 522..525
FT /evidence="ECO:0007829|PDB:6UZD"
FT HELIX 527..535
FT /evidence="ECO:0007829|PDB:1K8T"
FT TURN 536..538
FT /evidence="ECO:0007829|PDB:1XFX"
FT STRAND 541..543
FT /evidence="ECO:0007829|PDB:1K93"
FT STRAND 544..546
FT /evidence="ECO:0007829|PDB:1K90"
FT STRAND 547..549
FT /evidence="ECO:0007829|PDB:1K93"
FT HELIX 551..565
FT /evidence="ECO:0007829|PDB:1K8T"
FT TURN 566..568
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 570..572
FT /evidence="ECO:0007829|PDB:6UZB"
FT HELIX 580..582
FT /evidence="ECO:0007829|PDB:1K90"
FT STRAND 593..596
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 598..600
FT /evidence="ECO:0007829|PDB:1XFU"
FT STRAND 602..607
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 608..618
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 620..622
FT /evidence="ECO:0007829|PDB:1K8T"
FT TURN 630..633
FT /evidence="ECO:0007829|PDB:1K90"
FT STRAND 634..636
FT /evidence="ECO:0007829|PDB:1XFV"
FT TURN 637..639
FT /evidence="ECO:0007829|PDB:1K90"
FT TURN 648..650
FT /evidence="ECO:0007829|PDB:1K8T"
FT TURN 652..655
FT /evidence="ECO:0007829|PDB:1K90"
FT HELIX 660..674
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 679..681
FT /evidence="ECO:0007829|PDB:1K90"
FT STRAND 683..685
FT /evidence="ECO:0007829|PDB:1PK0"
FT HELIX 687..706
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 707..710
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 714..737
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 743..767
FT /evidence="ECO:0007829|PDB:1K8T"
FT HELIX 771..777
FT /evidence="ECO:0007829|PDB:1K8T"
FT STRAND 778..780
FT /evidence="ECO:0007829|PDB:1SK6"
FT HELIX 786..798
FT /evidence="ECO:0007829|PDB:1K8T"
SQ SEQUENCE 800 AA; 92478 MW; F4F7EB485DF4C5A6 CRC64;
MTRNKFIPNK FSIISFSVLL FAISSSQAIE VNAMNEHYTE SDIKRNHKTE KNKTEKEKFK
DSINNLVKTE FTNETLDKIQ QTQDLLKKIP KDVLEIYSEL GGEIYFTDID LVEHKELQDL
SEEEKNSMNS RGEKVPFASR FVFEKKRETP KLIINIKDYA INSEQSKEVY YEIGKGISLD
IISKDKSLDP EFLNLIKSLS DDSDSSDLLF SQKFKEKLEL NNKSIDINFI KENLTEFQHA
FSLAFSYYFA PDHRTVLELY APDMFEYMNK LEKGGFEKIS ESLKKEGVEK DRIDVLKGEK
ALKASGLVPE HADAFKKIAR ELNTYILFRP VNKLATNLIK SGVATKGLNV HGKSSDWGPV
AGYIPFDQDL SKKHGQQLAV EKGNLENKKS ITEHEGEIGK IPLKLDHLRI EELKENGIIL
KGKKEIDNGK KYYLLESNNQ VYEFRISDEN NEVQYKTKEG KITVLGEKFN WRNIEVMAKN
VEGVLKPLTA DYDLFALAPS LTEIKKQIPQ KEWDKVVNTP NSLEKQKGVT NLLIKYGIER
KPDSTKGTLS NWQKQMLDRL NEAVKYTGYT GGDVVNHGTE QDNEEFPEKD NEIFIINPEG
EFILTKNWEM TGRFIEKNIT GKDYLYYFNR SYNKIAPGNK AYIEWTDPIT KAKINTIPTS
AEFIKNLSSI RRSSNVGVYK DSGDKDEFAK KESVKKIAGY LSDYYNSANH IFSQEKKRKI
SIFRGIQAYN EIENVLKSKQ IAPEYKNYFQ YLKERITNQV QLLLTHQKSN IEFKLLYKQL
NFTENETDNF EVFQKIIDEK
