Q9L5A4 · ASP_AERSO
- ProteinAeromonas extracellular serine protease
- Geneasp
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids624 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Exhibits serine protease activity (PubMed:11092244, PubMed:12153115, PubMed:16487335, PubMed:18067862, PubMed:18462393, PubMed:19654332).
Preferentially cleaves the peptide bond following two basic residues, one of which is Lys, but does not recognize the bond following a single basic residue (PubMed:16487335).
Probable potent virulence factor that cleaves various host plasma proteins, including prekallikrein, prothrombin and fibrinogen (PubMed:16487335, PubMed:17142774, PubMed:18067862, PubMed:18462393, PubMed:19654332).
ASP induces vascular leakage and reduction in blood pressure by activating the host plasma kallikrein/kinin system (PubMed:12153115, PubMed:16487335, PubMed:17142774).
It affects the host coagulation system during infection through activation of prothrombin to alpha-thrombin and degradation of fibrinogen, which impairs plasma clottability (PubMed:18067862, PubMed:18462393).
It also hydrolyzes the complement component C5, releasing the C5a anaphylatoxin, which causes the formation of pus and edema (PubMed:18714034).
In addition, degrades its external chaperone ORF2 after the secretion of the ASP-ORF2 complex (PubMed:25784551).
Preferentially cleaves the peptide bond following two basic residues, one of which is Lys, but does not recognize the bond following a single basic residue (PubMed:16487335).
Probable potent virulence factor that cleaves various host plasma proteins, including prekallikrein, prothrombin and fibrinogen (PubMed:16487335, PubMed:17142774, PubMed:18067862, PubMed:18462393, PubMed:19654332).
ASP induces vascular leakage and reduction in blood pressure by activating the host plasma kallikrein/kinin system (PubMed:12153115, PubMed:16487335, PubMed:17142774).
It affects the host coagulation system during infection through activation of prothrombin to alpha-thrombin and degradation of fibrinogen, which impairs plasma clottability (PubMed:18067862, PubMed:18462393).
It also hydrolyzes the complement component C5, releasing the C5a anaphylatoxin, which causes the formation of pus and edema (PubMed:18714034).
In addition, degrades its external chaperone ORF2 after the secretion of the ASP-ORF2 complex (PubMed:25784551).
Catalytic activity
Cofactor
Note: Binds 3 calcium ions per subunit.
Activity regulation
Folding, maturation and production of the active form of the protease by the cell requires a protein (ORF2), encoded just downstream of asp, which acts as a chaperone (PubMed:11092244, PubMed:12446656, PubMed:25784551).
Formation of a complex with ORF2 in the periplasm also inactivates the protease activity and likely protects ASP from intrinsic proteases (PubMed:25784551).
In vitro, protease activity is inhibited by human alpha-2-macroglobulin, suggesting that this inhibitor can impede ASP virulence activities in A.sobria infection sites (PubMed:23089609).
However, slow ASP inhibition by alpha-2-macroglobulin in plasma may indicate insufficient ASP control in vivo (PubMed:23089609).
Activity is inhibited by serine protease inhibitors such as 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) and diisopropyl fluorophosphate (DFP) (PubMed:11092244, PubMed:12153115).
Not inhibited by metallo-protease inhibitors and cysteine protease inhibitors (PubMed:12153115).
The treatment with reagents to modify sulfhydryl group do not reduce the activity (PubMed:12153115).
Formation of a complex with ORF2 in the periplasm also inactivates the protease activity and likely protects ASP from intrinsic proteases (PubMed:25784551).
In vitro, protease activity is inhibited by human alpha-2-macroglobulin, suggesting that this inhibitor can impede ASP virulence activities in A.sobria infection sites (PubMed:23089609).
However, slow ASP inhibition by alpha-2-macroglobulin in plasma may indicate insufficient ASP control in vivo (PubMed:23089609).
Activity is inhibited by serine protease inhibitors such as 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) and diisopropyl fluorophosphate (DFP) (PubMed:11092244, PubMed:12153115).
Not inhibited by metallo-protease inhibitors and cysteine protease inhibitors (PubMed:12153115).
The treatment with reagents to modify sulfhydryl group do not reduce the activity (PubMed:12153115).
pH Dependence
Optimum pH is 7.5.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 53 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 102 | Charge relay system | ||||
Sequence: D | ||||||
Binding site | 111 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 139 | Charge relay system | ||||
Sequence: H | ||||||
Binding site | 150 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 152 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 154 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 156 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 321 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 322 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 324 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 327 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 330 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 350 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Active site | 360 | Charge relay system | ||||
Sequence: S | ||||||
Binding site | 478 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 512 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 577 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 579 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 602 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 603 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: N |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | periplasmic space | |
Molecular Function | metal ion binding | |
Molecular Function | serine-type endopeptidase activity | |
Biological Process | proteolysis |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameAeromonas extracellular serine protease
- EC number
- Short namesASP
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageBacteria > Pseudomonadota > Gammaproteobacteria > Aeromonadales > Aeromonadaceae > Aeromonas
Accessions
- Primary accessionQ9L5A4
Phenotypes & Variants
Disruption phenotype
Disruption mutant releases negligible serine protease activity and does not affect plasma clotting.
PTM/Processing
Features
Showing features for signal, chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-24 | |||||
Sequence: MKQTSLALAITALLSTLPSALVQA | ||||||
Chain | PRO_5004329932 | 25-624 | Aeromonas extracellular serine protease | |||
Sequence: NEGCAPLTGKESGMDIGRSSTERCLPGANPLQDQQWYLLNSGQDGFSARGGIAGNDLNLWWAHRTGVLGQGVNVAVVDDGLAIAHPDLADNVRPGSKNVVTGSDDPTPTDPDTAHGTSVSGIIAAVDNAIGTKGIAPRAQLQGFNLLDDNSQQLQKDWLYALGDSNASRDNRVFNQSYGMSVVDPRSANSLDQSQLDRLFEQQTLKAQGAAYIKAAGNGFNKIAAGGYVLNRTGNGPKLPFENSNLDPSNSNFWNLVVSALNADGVRSSYSSVGSNIFLSATGGEYGTDTPAMVTTDLPGCDMGYNRTDDPSTNRLHGNSQLDASCDYNGVMNGTSSATPSTSGAMALLMSAYPDLSVRDLRDLLARSATRVDAKHQPVMVSYTSSTGKVRDVKGLEGWERNAAGMWFSPTYGFGLIDVNKALELAANHQPLPPLVQLPWQKINVTGSAAAIADVGNSPTSSTTRIATPLTVEAVQVMVSLDHQRLPDLLIELVSPAGTRSILLSPFNSLVGQSLDQQQLGFVRTKGLRDMRMLSNKFYGESAQGTWRLEVTDVANGTRQVSLLNRETRERTTLTERNNRQPGKLISWSLRVLGHDANRS | ||||||
Disulfide bond | 28↔48 | |||||
Sequence: CAPLTGKESGMDIGRSSTERC | ||||||
Disulfide bond | 325↔350 | |||||
Sequence: CDMGYNRTDDPSTNRLHGNSQLDASC |
Keywords
- PTM
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 59-421 | Peptidase S8 | ||||
Sequence: QWYLLNSGQDGFSARGGIAGNDLNLWWAHRTGVLGQGVNVAVVDDGLAIAHPDLADNVRPGSKNVVTGSDDPTPTDPDTAHGTSVSGIIAAVDNAIGTKGIAPRAQLQGFNLLDDNSQQLQKDWLYALGDSNASRDNRVFNQSYGMSVVDPRSANSLDQSQLDRLFEQQTLKAQGAAYIKAAGNGFNKIAAGGYVLNRTGNGPKLPFENSNLDPSNSNFWNLVVSALNADGVRSSYSSVGSNIFLSATGGEYGTDTPAMVTTDLPGCDMGYNRTDDPSTNRLHGNSQLDASCDYNGVMNGTSSATPSTSGAMALLMSAYPDLSVRDLRDLLARSATRVDAKHQPVMVSYTSSTGKVRDVKGLE | ||||||
Region | 116-140 | Disordered | ||||
Sequence: VRPGSKNVVTGSDDPTPTDPDTAHG | ||||||
Compositional bias | 120-140 | Polar residues | ||||
Sequence: SKNVVTGSDDPTPTDPDTAHG | ||||||
Domain | 456-622 | P/Homo B | ||||
Sequence: LPPLVQLPWQKINVTGSAAAIADVGNSPTSSTTRIATPLTVEAVQVMVSLDHQRLPDLLIELVSPAGTRSILLSPFNSLVGQSLDQQQLGFVRTKGLRDMRMLSNKFYGESAQGTWRLEVTDVANGTRQVSLLNRETRERTTLTERNNRQPGKLISWSLRVLGHDAN |
Domain
Contains an N-terminal subtilisin domain and a C-terminal P-domain.
Sequence similarities
Belongs to the peptidase S8 family. Furin subfamily.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length624
- Mass (Da)66,635
- Last updated2009-09-01 v2
- Checksum6B6F2DC8DE639531
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 120-140 | Polar residues | ||||
Sequence: SKNVVTGSDDPTPTDPDTAHG |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF253471 EMBL· GenBank· DDBJ | AAF64521.2 EMBL· GenBank· DDBJ | Genomic DNA |