P13423 · PAG_BACAN
- ProteinProtective antigen
- GenepagA
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids764 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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).
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).
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).
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:15326297, PubMed:20221438).
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:32521227, PubMed:32810181).
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:15326297, PubMed:20221438).
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:32521227, PubMed:32810181).
Features
Showing features for site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 196-197 | Cleavage; by FURIN | ||||
Sequence: RS | ||||||
Binding site | 206 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Site | 207 | Alpha-clamp | ||||
Sequence: R | ||||||
Binding site | 208 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 208 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 210 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 210 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 212 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Site | 216 | Alpha-clamp | ||||
Sequence: L | ||||||
Binding site | 217 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 217 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 251 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 254 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 264 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Site | 265 | Alpha-clamp | ||||
Sequence: F | ||||||
Site | 343-344 | Cleavage; by chymotrypsin; required for translocation of LF and EF | ||||
Sequence: FD | ||||||
Site | 456 | Phi-clamp | ||||
Sequence: F | ||||||
Site | 493 | Alpha-clamp | ||||
Sequence: F | ||||||
Site | 712 | Essential for binding to cell receptor | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | host cell cytosol | |
Cellular Component | host cell endosome membrane | |
Cellular Component | host cell plasma membrane | |
Cellular Component | membrane | |
Molecular Function | identical protein binding | |
Molecular Function | metal ion binding | |
Molecular Function | toxin activity | |
Biological Process | negative regulation of MAPK cascade | |
Biological Process | positive regulation of apoptotic process in another organism | |
Biological Process | protein homooligomerization |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameProtective antigen
- Short namesPA
- Alternative names
- Cleaved into 2 chains
Gene names
Encoded on
- Plasmid pXO1
Organism names
- Organism
- Strains
- Taxonomic lineageBacteria > Bacillota > Bacilli > Bacillales > Bacillaceae > Bacillus > Bacillus cereus group
Accessions
- Primary accessionP13423
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Protective antigen
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).
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).
Protective antigen PA-63
Host cell membrane ; Multi-pass membrane protein
Host endosome membrane ; Multi-pass membrane protein
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).
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).
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 331-342 | Beta stranded | ||||
Sequence: EVHGNAEVHASF | ||||||
Transmembrane | 345-354 | Beta stranded | ||||
Sequence: IGGSVSAGFS |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 193 | Reduced cleavage by FURIN and reduced toxin activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 193-196 | Abolished cleavage by FURIN and abolished toxin activity. | ||||
Sequence: RKKR → SNSS or SNKE | ||||||
Mutagenesis | 194-195 | Does not affect cleavage by FURIN and does not affect toxin activity. | ||||
Sequence: KK → AA | ||||||
Mutagenesis | 194-196 | Abolished cleavage by FURIN and abolished toxin activity. | ||||
Sequence: KKR → EGG | ||||||
Mutagenesis | 207 | Abolished interaction with LF. | ||||
Sequence: R → A | ||||||
Mutagenesis | 213 | Decrease in the ability to bind to LF and partially toxic at high concentrations. | ||||
Sequence: P → A | ||||||
Mutagenesis | 216 | Decrease in the ability to bind to LF and partially toxic at high concentrations. | ||||
Sequence: L → A | ||||||
Mutagenesis | 229 | Abolished interaction with LF. | ||||
Sequence: R → S | ||||||
Mutagenesis | 231 | Loss of ability to bind to LF and completely non-toxic. | ||||
Sequence: F → A | ||||||
Mutagenesis | 231 | Does not affect significantly interaction with LF, while it impairs tranlocation of LF. | ||||
Sequence: F → S | ||||||
Mutagenesis | 232 | Loss of ability to bind to LF and completely non-toxic. | ||||
Sequence: L → A | ||||||
Mutagenesis | 234 | Loss of ability to bind to LF and completely non-toxic. | ||||
Sequence: P → A | ||||||
Mutagenesis | 234 | Does not affect significantly interaction with LF. | ||||
Sequence: P → S | ||||||
Mutagenesis | 236 | Loss of ability to bind to LF and completely non-toxic. | ||||
Sequence: I → A | ||||||
Mutagenesis | 236 | Abolished interaction with LF. | ||||
Sequence: I → S | ||||||
Mutagenesis | 239 | Decrease in the ability to bind to LF and partially toxic at high concentrations. | ||||
Sequence: I → A | ||||||
Mutagenesis | 240 | Abolished interaction with LF. | ||||
Sequence: H → A | ||||||
Mutagenesis | 255 | No effect on LF-binding ability and as toxic as the wild-type. | ||||
Sequence: W → A | ||||||
Mutagenesis | 265 | No effect on LF-binding ability and as toxic as the wild-type. | ||||
Sequence: F → A | ||||||
Mutagenesis | 265 | Impaired translocation of LF. | ||||
Sequence: F → S | ||||||
Mutagenesis | 289 | Reduced toxicity in combination with lethal factor. Decreased membrane insertion and translocation of LF. | ||||
Sequence: P → A | ||||||
Natural variant | 295 | in strain: PAI | ||||
Sequence: M → I | ||||||
Mutagenesis | 342 | Loss of toxicity probably due to loss of capability to translocate LF. | ||||
Sequence: F → C | ||||||
Mutagenesis | 342-343 | Loss of toxicity probably due to loss of capability to translocate LF. | ||||
Sequence: Missing | ||||||
Mutagenesis | 342-344 | Decrease in toxicity probably due to slow translocation of LF. | ||||
Sequence: FFD → AAA | ||||||
Mutagenesis | 344 | Decrease in toxicity probably due to slow translocation of LF. | ||||
Sequence: D → A | ||||||
Mutagenesis | 375 | Loss of toxicity probably due to faulty membrane insertion or translocation of LF/EF into the cytosol. | ||||
Sequence: W → A | ||||||
Mutagenesis | 379 | No effect. | ||||
Sequence: M → A | ||||||
Mutagenesis | 381 | Loss of toxicity probably due to faulty membrane insertion or translocation of LF/EF into the cytosol. | ||||
Sequence: L → A | ||||||
Natural variant | 392 | in strain: PAI | ||||
Sequence: N → D | ||||||
Mutagenesis | 393 | Loss of capability to undergo conformational changes that lead to pore formation and translocation. | ||||
Sequence: I → C | ||||||
Mutagenesis | 409 | Loss of capability to undergo conformational changes that lead to pore formation and translocation. | ||||
Sequence: T → C | ||||||
Mutagenesis | 411 | Loss of capability to undergo conformational changes that lead to pore formation and translocation. | ||||
Sequence: S → C | ||||||
Mutagenesis | 422 | Loss of capability to undergo conformational changes that lead to pore formation and translocation. | ||||
Sequence: T → C | ||||||
Mutagenesis | 426 | Loss of capability to undergo conformational changes that lead to pore formation and translocation. | ||||
Sequence: K → A or D | ||||||
Mutagenesis | 428 | Loss of capability to undergo conformational changes that lead to pore formation and translocation. | ||||
Sequence: N → C | ||||||
Mutagenesis | 440 | Loss of capability to undergo conformational changes that lead to pore formation and translocation. | ||||
Sequence: Y → C | ||||||
Mutagenesis | 451 | Loss of capability to undergo conformational changes that lead to pore formation and translocation. | ||||
Sequence: N → C | ||||||
Mutagenesis | 454 | Loss of capability to undergo conformational changes that lead to pore formation and translocation. | ||||
Sequence: D → A or K | ||||||
Mutagenesis | 456 | Loss of capability to undergo conformational changes that lead to pore formation and translocation. | ||||
Sequence: F → A | ||||||
Mutagenesis | 456 | Abolished ability for mediate LF and EF protein translocation. | ||||
Sequence: F → C | ||||||
Mutagenesis | 512 | Loss of heptamerization capability. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 541 | Loss of heptamerization capability. | ||||
Sequence: D → A | ||||||
Mutagenesis | 543 | Decrease in heptamerization capability. | ||||
Sequence: L → A | ||||||
Natural variant | 560 | in Sverdlovsk sample | ||||
Sequence: F → L | ||||||
Natural variant | 565 | in strain: BA1024 | ||||
Sequence: P → S | ||||||
Mutagenesis | 581 | Loss of toxicity due to defective oligomerization. | ||||
Sequence: F → A | ||||||
Mutagenesis | 583 | Decrease in toxicity due to defective oligomerization. | ||||
Sequence: F → A | ||||||
Mutagenesis | 591 | Loss of toxicity due to defective oligomerization. | ||||
Sequence: I → A | ||||||
Mutagenesis | 595 | Loss of toxicity due to defective oligomerization. | ||||
Sequence: L → A | ||||||
Natural variant | 600 | in strain: BA1024, V770-NP1-R, Carbosap and Ferrara | ||||
Sequence: A → V | ||||||
Mutagenesis | 603 | Loss of toxicity due to defective oligomerization. | ||||
Sequence: I → A | ||||||
Mutagenesis | 621 | No effect. | ||||
Sequence: R → A | ||||||
Mutagenesis | 686 | Decrease in toxicity due to decrease in cell binding. | ||||
Sequence: N → A | ||||||
Mutagenesis | 708 | No effect on toxicity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 709 | Slight decrease in toxicity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 710 | Great decrease in toxicity due to decrease in cell binding. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 711 | Loss of toxicity due to decrease in cell binding. | ||||
Sequence: N → A | ||||||
Mutagenesis | 712 | Loss of toxicity due to decrease in cell binding. | ||||
Sequence: D → A | ||||||
Mutagenesis | 713 | No effect on toxicity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 714 | No effect on toxicity. | ||||
Sequence: L → A | ||||||
Mutagenesis | 715 | Great decrease in toxicity due to decrease in cell binding. | ||||
Sequence: P → A | ||||||
Mutagenesis | 716 | Decrease in toxicity due to decrease in cell binding. | ||||
Sequence: L → A | ||||||
Mutagenesis | 717 | No effect on toxicity. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 718 | Decrease in toxicity due to decrease in cell binding. | ||||
Sequence: I → A | ||||||
Mutagenesis | 719 | No effect on toxicity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 720 | No effect on toxicity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 721 | No effect on toxicity. | ||||
Sequence: P → A | ||||||
Mutagenesis | 722 | No effect on toxicity. | ||||
Sequence: N → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 5 variants from UniProt as well as other sources including ClinVar and dbSNP.
Miscellaneous
Chemistry
PTM/Processing
Features
Showing features for signal, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-29 | |||||
Sequence: MKKRKVLIPLMALSTILVSSTGNLEVIQA | ||||||
Chain | PRO_0000021997 | 30-196 | Protective antigen PA-20 | |||
Sequence: EVKQENRLLNESESSSQGLLGYYFSDLNFQAPMVVTSSTTGDLSIPSSELENIPSENQYFQSAIWSGFIKVKKSDEYTFATSADNHVTMWVDDQEVINKASNSNKIRLEKGRLYQIKIQYQRENPTEKGLDFKLYWTDSQNKKEVISSDNLQLPELKQKSSNSRKKR | ||||||
Chain | PRO_0000021996 | 30-764 | Protective antigen | |||
Sequence: EVKQENRLLNESESSSQGLLGYYFSDLNFQAPMVVTSSTTGDLSIPSSELENIPSENQYFQSAIWSGFIKVKKSDEYTFATSADNHVTMWVDDQEVINKASNSNKIRLEKGRLYQIKIQYQRENPTEKGLDFKLYWTDSQNKKEVISSDNLQLPELKQKSSNSRKKRSTSAGPTVPDRDNDGIPDSLEVEGYTVDVKNKRTFLSPWISNIHEKKGLTKYKSSPEKWSTASDPYSDFEKVTGRIDKNVSPEARHPLVAAYPIVHVDMENIILSKNEDQSTQNTDSQTRTISKNTSTSRTHTSEVHGNAEVHASFFDIGGSVSAGFSNSNSSTVAIDHSLSLAGERTWAETMGLNTADTARLNANIRYVNTGTAPIYNVLPTTSLVLGKNQTLATIKAKENQLSQILAPNNYYPSKNLAPIALNAQDDFSSTPITMNYNQFLELEKTKQLRLDTDQVYGNIATYNFENGRVRVDTGSNWSEVLPQIQETTARIIFNGKDLNLVERRIAAVNPSDPLETTKPDMTLKEALKIAFGFNEPNGNLQYQGKDITEFDFNFDQQTSQNIKNQLAELNATNIYTVLDKIKLNAKMNILIRDKRFHYDRNNIAVGADESVVKEAHREVINSSTEGLLLNIDKDIRKILSGYIVEIEDTEGLKEVINDRYDMLNISSLRQDGKTFIDFKKYNDKLPLYISNPNYKVNVYAVTKENTIINPSENGDTSTNGIKKILIFSKKGYEIG | ||||||
Chain | PRO_0000021998 | 197-764 | Protective antigen PA-63 | |||
Sequence: STSAGPTVPDRDNDGIPDSLEVEGYTVDVKNKRTFLSPWISNIHEKKGLTKYKSSPEKWSTASDPYSDFEKVTGRIDKNVSPEARHPLVAAYPIVHVDMENIILSKNEDQSTQNTDSQTRTISKNTSTSRTHTSEVHGNAEVHASFFDIGGSVSAGFSNSNSSTVAIDHSLSLAGERTWAETMGLNTADTARLNANIRYVNTGTAPIYNVLPTTSLVLGKNQTLATIKAKENQLSQILAPNNYYPSKNLAPIALNAQDDFSSTPITMNYNQFLELEKTKQLRLDTDQVYGNIATYNFENGRVRVDTGSNWSEVLPQIQETTARIIFNGKDLNLVERRIAAVNPSDPLETTKPDMTLKEALKIAFGFNEPNGNLQYQGKDITEFDFNFDQQTSQNIKNQLAELNATNIYTVLDKIKLNAKMNILIRDKRFHYDRNNIAVGADESVVKEAHREVINSSTEGLLLNIDKDIRKILSGYIVEIEDTEGLKEVINDRYDMLNISSLRQDGKTFIDFKKYNDKLPLYISNPNYKVNVYAVTKENTIINPSENGDTSTNGIKKILIFSKKGYEIG |
Post-translational modification
Proteolytic activation by FURIN cleaves the protein in two parts, PA-20 and PA-63; the latter is the mature protein (PubMed:11207581, PubMed:1438214, PubMed:1644824, PubMed:8051159).
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:11207581, PubMed:8051159).
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:11207581, PubMed:8051159).
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:11207581, PubMed:8051159).
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:11207581, PubMed:8051159).
Keywords
- PTM
Interaction
Subunit
Protective antigen
Interacts with host ANTXR1 and ANTXR2.
Protective antigen PA-63
Homooligomer; homooligomerizes to form homoheptamers (PA-637) or homooctamers (PA-638) (PubMed:10085027, PubMed:16051798, PubMed:19627991, PubMed:20433851, PubMed:25778700, PubMed:32810181).
PA-637 or PA-638 form ring-shaped oligomers that are in a pre-pore conformation, which do not penetrate the host membrane (PubMed:19627991, PubMed:20433851, PubMed:32810181).
PA-638 displays an enhanced stability, suggesting that this form circulates in the blood to reach and exert toxicity even in distant tissues (PubMed:20433851).
Interacts with lethal factor (LF) and edema factor (EF); can bind LF and EF simultaneously and interaction takes place following homooligomerization on the host cell membrane (PubMed:10085027, PubMed:12117959, PubMed:15313199, PubMed:21037566, PubMed:32047164, PubMed:32521227, PubMed:32810181).
PA-637 homoheptamer interacts with three molecules of LF to form the PA7LF3 complex, in which the relative position of the N-terminal alpha-helices in the three LFs determines which factor is translocated first (PubMed:32810181).
PA-637 or PA-638 form ring-shaped oligomers that are in a pre-pore conformation, which do not penetrate the host membrane (PubMed:19627991, PubMed:20433851, PubMed:32810181).
PA-638 displays an enhanced stability, suggesting that this form circulates in the blood to reach and exert toxicity even in distant tissues (PubMed:20433851).
Interacts with lethal factor (LF) and edema factor (EF); can bind LF and EF simultaneously and interaction takes place following homooligomerization on the host cell membrane (PubMed:10085027, PubMed:12117959, PubMed:15313199, PubMed:21037566, PubMed:32047164, PubMed:32521227, PubMed:32810181).
PA-637 homoheptamer interacts with three molecules of LF to form the PA7LF3 complex, in which the relative position of the N-terminal alpha-helices in the three LFs determines which factor is translocated first (PubMed:32810181).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P13423 | ANTXR1 Q9H6X2-2 | 3 | EBI-456868, EBI-905659 | |
XENO | P13423 | ANTXR2 P58335 | 7 | EBI-456868, EBI-456840 | |
XENO | P13423 | groEL P0A6F5 | 2 | EBI-456868, EBI-543750 | |
BINARY | P13423 | lef P15917 | 28 | EBI-456868, EBI-456923 | |
BINARY | P13423 | pagA P13423 | 16 | EBI-456868, EBI-456868 |
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 30-287 | Domain 1, calcium-binding; LF and EF binding sites | ||||
Sequence: EVKQENRLLNESESSSQGLLGYYFSDLNFQAPMVVTSSTTGDLSIPSSELENIPSENQYFQSAIWSGFIKVKKSDEYTFATSADNHVTMWVDDQEVINKASNSNKIRLEKGRLYQIKIQYQRENPTEKGLDFKLYWTDSQNKKEVISSDNLQLPELKQKSSNSRKKRSTSAGPTVPDRDNDGIPDSLEVEGYTVDVKNKRTFLSPWISNIHEKKGLTKYKSSPEKWSTASDPYSDFEKVTGRIDKNVSPEARHPLVAA | ||||||
Domain | 43-179 | PA14 | ||||
Sequence: SSSQGLLGYYFSDLNFQAPMVVTSSTTGDLSIPSSELENIPSENQYFQSAIWSGFIKVKKSDEYTFATSADNHVTMWVDDQEVINKASNSNKIRLEKGRLYQIKIQYQRENPTEKGLDFKLYWTDSQNKKEVISSDN | ||||||
Region | 176-214 | Disordered | ||||
Sequence: SSDNLQLPELKQKSSNSRKKRSTSAGPTVPDRDNDGIPD | ||||||
Region | 231-239 | Alpha-clamp | ||||
Sequence: FLSPWISNI | ||||||
Region | 288-516 | Domain 2, membrane insertion and heptamerization | ||||
Sequence: YPIVHVDMENIILSKNEDQSTQNTDSQTRTISKNTSTSRTHTSEVHGNAEVHASFFDIGGSVSAGFSNSNSSTVAIDHSLSLAGERTWAETMGLNTADTARLNANIRYVNTGTAPIYNVLPTTSLVLGKNQTLATIKAKENQLSQILAPNNYYPSKNLAPIALNAQDDFSSTPITMNYNQFLELEKTKQLRLDTDQVYGNIATYNFENGRVRVDTGSNWSEVLPQIQET | ||||||
Compositional bias | 302-331 | Polar residues | ||||
Sequence: KNEDQSTQNTDSQTRTISKNTSTSRTHTSE | ||||||
Region | 302-333 | Disordered | ||||
Sequence: KNEDQSTQNTDSQTRTISKNTSTSRTHTSEVH | ||||||
Region | 517-624 | Domain 3, heptamerization | ||||
Sequence: TARIIFNGKDLNLVERRIAAVNPSDPLETTKPDMTLKEALKIAFGFNEPNGNLQYQGKDITEFDFNFDQQTSQNIKNQLAELNATNIYTVLDKIKLNAKMNILIRDKR | ||||||
Region | 625-764 | Domain 4, binding to the receptor | ||||
Sequence: FHYDRNNIAVGADESVVKEAHREVINSSTEGLLLNIDKDIRKILSGYIVEIEDTEGLKEVINDRYDMLNISSLRQDGKTFIDFKKYNDKLPLYISNPNYKVNVYAVTKENTIINPSENGDTSTNGIKKILIFSKKGYEIG |
Domain
The molecule is folded into four functional domains (PubMed:1651334, PubMed:9039918).
Each domain is required for a particular step in the toxicity process (PubMed:1651334).
Domain 1 contains two calcium ions and the proteolytic activation site (PubMed:1651334).
Cleavage of the PA monomer releases the subdomain 1a, which is the N-terminal fragment of 20-kDa (PA-20) (PubMed:11207581, PubMed:8051159, PubMed:9039918).
The subdomain 1b is part of the remaining 63-kDa fragment (PA-63) and contains the binding sites for LP and EF (PubMed:11207581, PubMed:8051159, PubMed:9039918).
Domain 2 is a beta-barrel core containing a large flexible loop that has been implicated in membrane insertion and pore formation (PubMed:11356563, PubMed:1651334, PubMed:9039918).
There is a chymotrypsin cleavage site in this loop that is required for toxicity (PubMed:1512256, PubMed:7961869, PubMed:9039918).
Domain 3 has a hydrophobic patch thought to be involved in protein-protein interactions (PubMed:11222612, PubMed:1651334, PubMed:9039918).
Domain 4 appears to be a separate domain and shows limited contact with the other three domains: it would swing out of the way during membrane insertion (PubMed:10085028, PubMed:12771151, PubMed:1651334, PubMed:9039918).
It is required for binding to the receptor; the small loop is involved in receptor recognition (PubMed:10085028, PubMed:12771151, PubMed:1651334, PubMed:9039918).
Each domain is required for a particular step in the toxicity process (PubMed:1651334).
Domain 1 contains two calcium ions and the proteolytic activation site (PubMed:1651334).
Cleavage of the PA monomer releases the subdomain 1a, which is the N-terminal fragment of 20-kDa (PA-20) (PubMed:11207581, PubMed:8051159, PubMed:9039918).
The subdomain 1b is part of the remaining 63-kDa fragment (PA-63) and contains the binding sites for LP and EF (PubMed:11207581, PubMed:8051159, PubMed:9039918).
Domain 2 is a beta-barrel core containing a large flexible loop that has been implicated in membrane insertion and pore formation (PubMed:11356563, PubMed:1651334, PubMed:9039918).
There is a chymotrypsin cleavage site in this loop that is required for toxicity (PubMed:1512256, PubMed:7961869, PubMed:9039918).
Domain 3 has a hydrophobic patch thought to be involved in protein-protein interactions (PubMed:11222612, PubMed:1651334, PubMed:9039918).
Domain 4 appears to be a separate domain and shows limited contact with the other three domains: it would swing out of the way during membrane insertion (PubMed:10085028, PubMed:12771151, PubMed:1651334, PubMed:9039918).
It is required for binding to the receptor; the small loop is involved in receptor recognition (PubMed:10085028, PubMed:12771151, PubMed:1651334, PubMed:9039918).
Protective antigen PA-63
Phe-456 residue forms the phi-clamp in the pore and catalyzes protein translocation via a charge-state-dependent Brownian ratchet (PubMed:16051798, PubMed:25778700).
During conversion of the heptameric pre-pore precursor to the pore, the seven Phe-427 residues converge within the lumen to generate the narrowest point in the channel lumen (6 Angstroms in width) (PubMed:16051798, PubMed:25778700).
To pass through this hydrophobic restriction, substrate proteins LF and EF need to be unfolded prior to translocation (PubMed:25778700).
During conversion of the heptameric pre-pore precursor to the pore, the seven Phe-427 residues converge within the lumen to generate the narrowest point in the channel lumen (6 Angstroms in width) (PubMed:16051798, PubMed:25778700).
To pass through this hydrophobic restriction, substrate proteins LF and EF need to be unfolded prior to translocation (PubMed:25778700).
Protective antigen PA-63
The alpha-clamp consists in an amphipathic cleft between two adjacent PA protomers, which assists the unfolding of substrate proteins LF and EF (PubMed:21037566, PubMed:32047164, PubMed:32521227).
The alpha-clamp binds non-specifically to alpha-helices of substrate proteins LF and EF (PubMed:21037566, PubMed:32047164, PubMed:32521227).
The alpha-clamp binds non-specifically to alpha-helices of substrate proteins LF and EF (PubMed:21037566, PubMed:32047164, PubMed:32521227).
Sequence similarities
Belongs to the bacterial binary toxin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length764
- Mass (Da)85,811
- Last updated2001-10-18 v2
- Checksum3AE1EFBF48FAA03F
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 302-331 | Polar residues | ||||
Sequence: KNEDQSTQNTDSQTRTISKNTSTSRTHTSE | ||||||
Sequence conflict | 314 | in Ref. 1; AAA22637 | ||||
Sequence: Q → E |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M22589 EMBL· GenBank· DDBJ | AAA22637.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF306778 EMBL· GenBank· DDBJ | AAG24446.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF306779 EMBL· GenBank· DDBJ | AAG24447.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF306780 EMBL· GenBank· DDBJ | AAG24448.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF306781 EMBL· GenBank· DDBJ | AAG24449.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF306782 EMBL· GenBank· DDBJ | AAG24450.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF306783 EMBL· GenBank· DDBJ | AAG24451.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF268967 EMBL· GenBank· DDBJ | AAF86457.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF065404 EMBL· GenBank· DDBJ | AAD32414.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AE011190 EMBL· GenBank· DDBJ | AAM26109.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AE017336 EMBL· GenBank· DDBJ | AAT28905.2 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ413936 EMBL· GenBank· DDBJ | CAC93934.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ413937 EMBL· GenBank· DDBJ | CAC93935.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB125961 EMBL· GenBank· DDBJ | BAD14937.1 EMBL· GenBank· DDBJ | Genomic DNA |