| IED ID | IndEnz0002001452 |
| Enzyme Type ID | protease001452 |
| Protein Name |
Protective antigen PA Anthrax toxins translocating protein PA-83 PA83 Cleaved into: Protective antigen PA-20 PA-20 PA20 ; Protective antigen PA-63 PA-63 PA63 |
| Gene Name | pagA pag pXO1-110 BXA0164 GBAA_pXO1_0164 |
| Organism | Bacillus anthracis |
| Taxonomic Lineage | cellular organisms Bacteria Terrabacteria group Firmicutes Bacilli Bacillales Bacillaceae Bacillus Bacillus cereus group Bacillus anthracis |
| Enzyme Sequence | MKKRKVLIPLMALSTILVSSTGNLEVIQAEVKQENRLLNESESSSQGLLGYYFSDLNFQAPMVVTSSTTGDLSIPSSELENIPSENQYFQSAIWSGFIKVKKSDEYTFATSADNHVTMWVDDQEVINKASNSNKIRLEKGRLYQIKIQYQRENPTEKGLDFKLYWTDSQNKKEVISSDNLQLPELKQKSSNSRKKRSTSAGPTVPDRDNDGIPDSLEVEGYTVDVKNKRTFLSPWISNIHEKKGLTKYKSSPEKWSTASDPYSDFEKVTGRIDKNVSPEARHPLVAAYPIVHVDMENIILSKNEDQSTQNTDSQTRTISKNTSTSRTHTSEVHGNAEVHASFFDIGGSVSAGFSNSNSSTVAIDHSLSLAGERTWAETMGLNTADTARLNANIRYVNTGTAPIYNVLPTTSLVLGKNQTLATIKAKENQLSQILAPNNYYPSKNLAPIALNAQDDFSSTPITMNYNQFLELEKTKQLRLDTDQVYGNIATYNFENGRVRVDTGSNWSEVLPQIQETTARIIFNGKDLNLVERRIAAVNPSDPLETTKPDMTLKEALKIAFGFNEPNGNLQYQGKDITEFDFNFDQQTSQNIKNQLAELNATNIYTVLDKIKLNAKMNILIRDKRFHYDRNNIAVGADESVVKEAHREVINSSTEGLLLNIDKDIRKILSGYIVEIEDTEGLKEVINDRYDMLNISSLRQDGKTFIDFKKYNDKLPLYISNPNYKVNVYAVTKENTIINPSENGDTSTNGIKKILIFSKKGYEIG |
| Enzyme Length | 764 |
| Uniprot Accession Number | P13423 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Protective antigen constitutes one of the three proteins composing the anthrax toxin; it mediates attachment to host cells and translocation of edema factor (EF) and lethal factor (LF) into the host cytoplasm (PubMed:11700562, PubMed:14507921, PubMed:15243628, PubMed:15326297). PA associated with LF forms the lethal toxin (LeTx) and causes death when injected; PA associated with EF forms the edema toxin (EdTx) and produces edema (PubMed:1651334). PA induces immunity to infection with anthrax (PubMed:11544370). {ECO:0000269|PubMed:11700562, ECO:0000269|PubMed:14507921, ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:1651334, ECO:0000303|PubMed:11544370}.; FUNCTION: [Protective antigen]: Mediates the attachment to host cells by binding host cell receptors ANTXR1 and ANTXR2 (PubMed:11700562, PubMed:14507921, PubMed:15243628, PubMed:15326297). Following host cell surface attachment, PA is cleaved by FURIN to generate the PA-63 (Protective antigen PA-63) form, which constitutes the mature form of the protein that oligomerizes and forms a pore to translocate the enzymatic toxin components edema factor (EF) and lethal factor (LF) into the host cytosol (PubMed:11700562, PubMed:15243628, PubMed:15326297). {ECO:0000269|PubMed:11700562, ECO:0000269|PubMed:14507921, ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297}.; FUNCTION: [Protective antigen PA-63]: Mature form that oligomerizes and forms a pore to translocate the enzymatic toxin components edema factor (EF) and lethal factor (LF) into the host cytosol (PubMed:15243628, PubMed:15326297). Following attachment to host cell receptors and cleavage by FURIN, homooligomerizes to form ring-shaped oligomers that are in a pre-pore conformation, and associates with EF and LF (PubMed:10085027, PubMed:12117959, PubMed:15313199). Toxin-leaded complexes are then endocytosed in a clathrin-dependent process, followed by a conformational change of oligomerized PA-63 from the pre-pore to pore state, which is triggered by the low pH in the endosome (PubMed:10085027, PubMed:12551953, PubMed:20221438, PubMed:15326297). Once active, the pore mediates unfolding of EF and LF, which pass through the pore and translocate into the host cytosol (PubMed:16051798, PubMed:21037566, PubMed:32047164, PubMed:32810181, PubMed:32521227). {ECO:0000269|PubMed:10085027, ECO:0000269|PubMed:12117959, ECO:0000269|PubMed:12551953, ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15313199, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:16051798, ECO:0000269|PubMed:20221438, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:32047164, ECO:0000269|PubMed:32521227, ECO:0000269|PubMed:32810181}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (61); Chain (3); Compositional bias (1); Domain (1); Helix (23); Metal binding (11); Mutagenesis (64); Natural variant (5); Region (7); Sequence conflict (1); Signal peptide (1); Site (8); Transmembrane (2); Turn (8) |
| Keywords | 3D-structure;Calcium;Cleavage on pair of basic residues;Host cell membrane;Host endosome;Host membrane;Membrane;Metal-binding;Plasmid;Reference proteome;Secreted;Signal;Toxin;Transmembrane;Transmembrane beta strand;Virulence |
| Interact With | P15917; Itself; Q9H6X2-2; P58335; P0A6F5 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Protective antigen]: Secreted {ECO:0000269|PubMed:11207581, ECO:0000269|PubMed:12606539}. Host cell membrane {ECO:0000269|PubMed:11700562, ECO:0000269|PubMed:14507921}. Note=Secreted through the Sec-dependent secretion pathway (PubMed:12606539). Therefore, PA is translocated across the membrane in an unfolded state and then it is folded into its native configuration on the trans side of the membrane, prior to its release to the environment (PubMed:12606539). PA requires the extracellular chaperone PrsA for efficient folding (PubMed:12606539). It circulates in the host blood and binds host cell receptors at the cell surface (PubMed:11700562, PubMed:14507921). {ECO:0000269|PubMed:11700562, ECO:0000269|PubMed:12606539, ECO:0000269|PubMed:14507921}.; SUBCELLULAR LOCATION: [Protective antigen PA-63]: Host cell membrane {ECO:0000305|PubMed:16051798, ECO:0000305|PubMed:25778700}; Multi-pass membrane protein {ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164}. Host endosome membrane {ECO:0000305|PubMed:10085027}; Multi-pass membrane protein {ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164}. Note=Following attachment to host cell receptors at the cell surface and cleavage by FURIN, homooligomerizes to form ring-shaped oligomers that are in a pre-pore conformation, and associates with EF and LF (PubMed:15313199). Loaded complexes are then endocytosed in a clathrin-dependent process, followed by a conformational change of oligomerized PA-63 from the pre-pore to pore state, which is triggered by the low pH in the endosome (PubMed:10085027, PubMed:15326297). {ECO:0000269|PubMed:10085027, ECO:0000269|PubMed:15313199, ECO:0000269|PubMed:15326297}. |
| Modified Residue | |
| Post Translational Modification | PTM: Proteolytic activation by FURIN cleaves the protein in two parts, PA-20 and PA-63; the latter is the mature protein (PubMed:1644824, PubMed:1438214, PubMed:8051159, PubMed:11207581). The cleavage occurs at the cell surface and probably in the serum of infected animals as well; both native and cleaved PA are able to bind to the cell receptor (PubMed:8051159, PubMed:11207581). The release of PA-20 from the remaining receptor-bound PA-63 exposes the binding site for EF and LF, and promotes oligomerization and internalization of the protein (PubMed:8051159, PubMed:11207581). {ECO:0000269|PubMed:11207581, ECO:0000269|PubMed:1438214, ECO:0000269|PubMed:1644824, ECO:0000269|PubMed:8051159}. |
| Signal Peptide | SIGNAL 1..29; /evidence=ECO:0000305|PubMed:9039918 |
| Structure 3D | Electron microscopy (12); X-ray crystallography (22) |
| Cross Reference PDB | 1ACC; 1T6B; 1TZN; 1TZO; 3ETB; 3INO; 3J9C; 3KWV; 3MHZ; 3Q8A; 3Q8B; 3Q8C; 3Q8E; 3Q8F; 3TEW; 3TEX; 3TEY; 3TEZ; 4EE2; 4H2A; 4NAM; 5FR3; 6PSN; 6UJI; 6UZB; 6UZD; 6UZE; 6VRA; 6WJJ; 6ZXJ; 6ZXK; 6ZXL; 7KXR; 7O85; |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | Plasmid pXO1 |
| Mass | 85,811 |
| Kinetics | |
| Metal Binding | METAL 206; /note="Calcium 1"; /evidence="ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE"; METAL 208; /note="Calcium 1"; /evidence="ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE"; METAL 208; /note="Calcium 2"; /evidence="ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE"; METAL 210; /note="Calcium 1"; /evidence="ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE"; METAL 210; /note="Calcium 2"; /evidence="ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE"; METAL 212; /note="Calcium 1; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE"; METAL 217; /note="Calcium 1"; /evidence="ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, ECO:0000269|PubMed:9039918, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE"; METAL 217; /note="Calcium 2"; /evidence="ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE"; METAL 251; /note="Calcium 2; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE"; METAL 254; /note="Calcium 2; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:25778700, ECO:0000269|PubMed:32047164, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3J9C, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE"; METAL 264; /note="Calcium 2"; /evidence="ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:21037566, ECO:0000269|PubMed:32047164, ECO:0007744|PDB:1ACC, ECO:0007744|PDB:1T6B, ECO:0007744|PDB:1TZN, ECO:0007744|PDB:1TZO, ECO:0007744|PDB:3KWV, ECO:0007744|PDB:6PSN, ECO:0007744|PDB:6UZB, ECO:0007744|PDB:6UZD, ECO:0007744|PDB:6UZE" |
| Rhea ID | |
| Cross Reference Brenda |