Arg-gingipain RgpA [Porphyromonas gingivalis]
Protein Classification
List of domain hits
| Name | Accession | Description | Interval | E-value | ||||||
| Peptidase_C25_N_gingipain | cd10913 | gingipain subgroup of the Peptidase C25 family N-terminal domain; Gingipain, produced by ... |
229-573 | 8.70e-138 | ||||||
gingipain subgroup of the Peptidase C25 family N-terminal domain; Gingipain, produced by Porphyromonas gingivalis, exemplifies the Peptidase family C25, a unique class of cysteine proteases. P. gingivalis is one of the primary gram-negative pathogens that causes periodontitis, a disease also associated with other diseases such as diabetes and cardiovascular disease. The gingipain subgroup contains extracellular Arg- and Lys-specific proteinases called Arg-gingipain (Rgp) and Lys-gingipain (Kgp); RgpA and RgpB are homologous Arg-specific gingipains encoded by two closely related genes, rgpA and rgpB, while Lys-specific gingipain is encoded by the single kgp gene. Mutant studies have shown that, among the large quantities of proteolytic enzymes produced by P. gingivalis, these three proteases are major virulence factors of this bacterium. All three genes encode an N-terminal pre-pro fragment, followed by the protease domain; however, rgpA and kgp also encode additional C-terminal HA (hemaglutinin/adhesion) subunits which consist of several sequence-related adhesion domains. Although unique, their cysteine protease active site residues (His and Cys) forming the catalytic dyad, are well-conserved, cleaving the C-terminal peptide bond with Arg or Lys residues. Gingipains are evolutionarily related to other highly specific proteases including caspases, clostripain, legumains, and separase. Gingipains function by dysregulating host defense and inflammatory responses, and degrading host proteins, e.g. tissue, cells, matrix, plasma and immunological proteins. It has been suggested that they enhance gingival crevicular fluid (GCF) production through activation of the kallikrein/kinin pathways, thus increasing vascular permeability and causing gingival inflammation, a distinctive feature of periodontitis. RgpA and RgpB are also able to cleave and activate coagulation factors IX and X in order to activate prothrombin to produce thrombin, which in turn increases production of GCF. The gingipains also play a pivotal role in the survival of P. gingivalis in the host by attacking the host defense system through cleavage of several immunological molecules, while at the same time evading the host-immune response by dysregulating the cytokine network. : Pssm-ID: 199211 Cd Length: 348 Bit Score: 430.67 E-value: 8.70e-138
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| Propeptide_C25 | pfam08126 | Propeptide_C25; This is found at the N terminal end of some of the members of the C25 ... |
24-220 | 7.40e-107 | ||||||
Propeptide_C25; This is found at the N terminal end of some of the members of the C25 peptidase family (PF01364). Little is known about the function of this motif. : Pssm-ID: 285357 Cd Length: 205 Bit Score: 338.83 E-value: 7.40e-107
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| DUF2436 | pfam10365 | Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has ... |
1408-1569 | 3.79e-90 | ||||||
Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has no known function. : Pssm-ID: 287351 Cd Length: 164 Bit Score: 289.53 E-value: 3.79e-90
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| DUF2436 | pfam10365 | Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has ... |
698-856 | 1.24e-89 | ||||||
Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has no known function. : Pssm-ID: 287351 Cd Length: 164 Bit Score: 287.99 E-value: 1.24e-89
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| Cleaved_Adhesin | pfam07675 | Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in ... |
1140-1309 | 3.41e-87 | ||||||
Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in various roles including cell adhesion, cell lysis and carbohydrate binding. A tandem repeat of these modules (either two or three repeats) constitute the haemagglutinin/adhesin (HA) regions of the gingipains, RgpA and Kgp, expressed by Porphyromonas gingivalis (Bacteroides gingivalis). They form components of the major extracellular virulence complex RgpA-Kgp - a mixture of proteinases and adhesin domains. The adhesin domains in this complex are found in proteinase-cleaved forms when isolated from the cell surface. Haemagglutinin genes of P. gingivalis (hagA1 HAGA1_PORGI - and hagA2 HAGA2_PORGI) suggest that such proteins are composed of eight to ten tandem repeats of these adhesin modules. Genomic data predicts that homologous protein modules are also expressed by a number of other bacteria and form part of putative multi-domain proteins, eg. Swiss:Q26BR9 and Swiss:B0VGL6. These domains may be acting in concert with other adhesion modules thought to be part of these multi-domain proteins such as fibronectin type III, pfam00041, and Meprin, A5, mu (MAM), pfam00629, domains. : Pssm-ID: 284979 Cd Length: 166 Bit Score: 281.41 E-value: 3.41e-87
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| Cleaved_Adhesin super family | cl06636 | Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in ... |
965-1128 | 1.02e-50 | ||||||
Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in various roles including cell adhesion, cell lysis and carbohydrate binding. A tandem repeat of these modules (either two or three repeats) constitute the haemagglutinin/adhesin (HA) regions of the gingipains, RgpA and Kgp, expressed by Porphyromonas gingivalis (Bacteroides gingivalis). They form components of the major extracellular virulence complex RgpA-Kgp - a mixture of proteinases and adhesin domains. The adhesin domains in this complex are found in proteinase-cleaved forms when isolated from the cell surface. Haemagglutinin genes of P. gingivalis (hagA1 HAGA1_PORGI - and hagA2 HAGA2_PORGI) suggest that such proteins are composed of eight to ten tandem repeats of these adhesin modules. Genomic data predicts that homologous protein modules are also expressed by a number of other bacteria and form part of putative multi-domain proteins, eg. Swiss:Q26BR9 and Swiss:B0VGL6. These domains may be acting in concert with other adhesion modules thought to be part of these multi-domain proteins such as fibronectin type III, pfam00041, and Meprin, A5, mu (MAM), pfam00629, domains. The actual alignment was detected with superfamily member pfam07675: Pssm-ID: 284979 Cd Length: 166 Bit Score: 177.02 E-value: 1.02e-50
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| Peptidase_C25_C | pfam03785 | Peptidase family C25, C terminal ig-like domain; |
578-651 | 9.45e-30 | ||||||
Peptidase family C25, C terminal ig-like domain; : Pssm-ID: 367657 Cd Length: 74 Bit Score: 113.30 E-value: 9.45e-30
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| Peptidase_M60_C super family | cl39949 | Peptidase M60 C-terminal domain; This is C-terminal domain (CTD) of M60-peptidases pfam13402. ... |
1642-1697 | 1.33e-05 | ||||||
Peptidase M60 C-terminal domain; This is C-terminal domain (CTD) of M60-peptidases pfam13402. It Can also be found at the C-terminal region of gingipain B (RgpB) from P. gingivalis. It was found to possess a typical Ig-like fold encompassing seven antiparallel beta-strands organized in two beta-sheets, packed into a beta-sandwich structure that can spontaneously dimerize through C-terminal strand swapping. Translocation of gingipains from the periplasm across the OM is dependent on the conserved CTD, which appears to be important for secretion of the proteins and in particular, truncation of the last few C-terminal residues of this domain leads to accumulation of gingipains in the periplasm. Subsequently, the T9SS targeting signal was demonstrated to reside within the last 22 residues at the C-terminus of the CTD. During gingipain translocation across the OM, the CTD is cleaved off by PorU. The actual alignment was detected with superfamily member pfam18630: Pssm-ID: 408412 Cd Length: 65 Bit Score: 44.36 E-value: 1.33e-05
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| Name | Accession | Description | Interval | E-value | ||||||
| Peptidase_C25_N_gingipain | cd10913 | gingipain subgroup of the Peptidase C25 family N-terminal domain; Gingipain, produced by ... |
229-573 | 8.70e-138 | ||||||
gingipain subgroup of the Peptidase C25 family N-terminal domain; Gingipain, produced by Porphyromonas gingivalis, exemplifies the Peptidase family C25, a unique class of cysteine proteases. P. gingivalis is one of the primary gram-negative pathogens that causes periodontitis, a disease also associated with other diseases such as diabetes and cardiovascular disease. The gingipain subgroup contains extracellular Arg- and Lys-specific proteinases called Arg-gingipain (Rgp) and Lys-gingipain (Kgp); RgpA and RgpB are homologous Arg-specific gingipains encoded by two closely related genes, rgpA and rgpB, while Lys-specific gingipain is encoded by the single kgp gene. Mutant studies have shown that, among the large quantities of proteolytic enzymes produced by P. gingivalis, these three proteases are major virulence factors of this bacterium. All three genes encode an N-terminal pre-pro fragment, followed by the protease domain; however, rgpA and kgp also encode additional C-terminal HA (hemaglutinin/adhesion) subunits which consist of several sequence-related adhesion domains. Although unique, their cysteine protease active site residues (His and Cys) forming the catalytic dyad, are well-conserved, cleaving the C-terminal peptide bond with Arg or Lys residues. Gingipains are evolutionarily related to other highly specific proteases including caspases, clostripain, legumains, and separase. Gingipains function by dysregulating host defense and inflammatory responses, and degrading host proteins, e.g. tissue, cells, matrix, plasma and immunological proteins. It has been suggested that they enhance gingival crevicular fluid (GCF) production through activation of the kallikrein/kinin pathways, thus increasing vascular permeability and causing gingival inflammation, a distinctive feature of periodontitis. RgpA and RgpB are also able to cleave and activate coagulation factors IX and X in order to activate prothrombin to produce thrombin, which in turn increases production of GCF. The gingipains also play a pivotal role in the survival of P. gingivalis in the host by attacking the host defense system through cleavage of several immunological molecules, while at the same time evading the host-immune response by dysregulating the cytokine network. Pssm-ID: 199211 Cd Length: 348 Bit Score: 430.67 E-value: 8.70e-138
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| Propeptide_C25 | pfam08126 | Propeptide_C25; This is found at the N terminal end of some of the members of the C25 ... |
24-220 | 7.40e-107 | ||||||
Propeptide_C25; This is found at the N terminal end of some of the members of the C25 peptidase family (PF01364). Little is known about the function of this motif. Pssm-ID: 285357 Cd Length: 205 Bit Score: 338.83 E-value: 7.40e-107
|
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| DUF2436 | pfam10365 | Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has ... |
1408-1569 | 3.79e-90 | ||||||
Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has no known function. Pssm-ID: 287351 Cd Length: 164 Bit Score: 289.53 E-value: 3.79e-90
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| DUF2436 | pfam10365 | Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has ... |
698-856 | 1.24e-89 | ||||||
Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has no known function. Pssm-ID: 287351 Cd Length: 164 Bit Score: 287.99 E-value: 1.24e-89
|
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| Cleaved_Adhesin | pfam07675 | Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in ... |
1140-1309 | 3.41e-87 | ||||||
Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in various roles including cell adhesion, cell lysis and carbohydrate binding. A tandem repeat of these modules (either two or three repeats) constitute the haemagglutinin/adhesin (HA) regions of the gingipains, RgpA and Kgp, expressed by Porphyromonas gingivalis (Bacteroides gingivalis). They form components of the major extracellular virulence complex RgpA-Kgp - a mixture of proteinases and adhesin domains. The adhesin domains in this complex are found in proteinase-cleaved forms when isolated from the cell surface. Haemagglutinin genes of P. gingivalis (hagA1 HAGA1_PORGI - and hagA2 HAGA2_PORGI) suggest that such proteins are composed of eight to ten tandem repeats of these adhesin modules. Genomic data predicts that homologous protein modules are also expressed by a number of other bacteria and form part of putative multi-domain proteins, eg. Swiss:Q26BR9 and Swiss:B0VGL6. These domains may be acting in concert with other adhesion modules thought to be part of these multi-domain proteins such as fibronectin type III, pfam00041, and Meprin, A5, mu (MAM), pfam00629, domains. Pssm-ID: 284979 Cd Length: 166 Bit Score: 281.41 E-value: 3.41e-87
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| Peptidase_C25 | pfam01364 | Peptidase family C25; |
239-571 | 2.53e-65 | ||||||
Peptidase family C25; Pssm-ID: 396092 Cd Length: 343 Bit Score: 225.71 E-value: 2.53e-65
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| Cleaved_Adhesin | pfam07675 | Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in ... |
965-1128 | 1.02e-50 | ||||||
Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in various roles including cell adhesion, cell lysis and carbohydrate binding. A tandem repeat of these modules (either two or three repeats) constitute the haemagglutinin/adhesin (HA) regions of the gingipains, RgpA and Kgp, expressed by Porphyromonas gingivalis (Bacteroides gingivalis). They form components of the major extracellular virulence complex RgpA-Kgp - a mixture of proteinases and adhesin domains. The adhesin domains in this complex are found in proteinase-cleaved forms when isolated from the cell surface. Haemagglutinin genes of P. gingivalis (hagA1 HAGA1_PORGI - and hagA2 HAGA2_PORGI) suggest that such proteins are composed of eight to ten tandem repeats of these adhesin modules. Genomic data predicts that homologous protein modules are also expressed by a number of other bacteria and form part of putative multi-domain proteins, eg. Swiss:Q26BR9 and Swiss:B0VGL6. These domains may be acting in concert with other adhesion modules thought to be part of these multi-domain proteins such as fibronectin type III, pfam00041, and Meprin, A5, mu (MAM), pfam00629, domains. Pssm-ID: 284979 Cd Length: 166 Bit Score: 177.02 E-value: 1.02e-50
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| choice_anch_J | NF038128 | choice-of-anchor J domain; The choice-of-anchor J domain, about 160 amino acids long, occurs ... |
965-1130 | 8.92e-35 | ||||||
choice-of-anchor J domain; The choice-of-anchor J domain, about 160 amino acids long, occurs as many as times in a protein, although most often only once. Proteins with the domain include proteins with serine hydrolase, metallohydrolase, or adhesin-associated domains. Notably, many members are also found with either the PEP-CTERM term domain, or the type IX secretion system type A domain, both associated with protein-sorting system expected to leave target proteins covalently attached to the bacterial outer membrane. Pssm-ID: 468371 [Multi-domain] Cd Length: 161 Bit Score: 130.90 E-value: 8.92e-35
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| Peptidase_C25_C | pfam03785 | Peptidase family C25, C terminal ig-like domain; |
578-651 | 9.45e-30 | ||||||
Peptidase family C25, C terminal ig-like domain; Pssm-ID: 367657 Cd Length: 74 Bit Score: 113.30 E-value: 9.45e-30
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| choice_anch_J | NF038128 | choice-of-anchor J domain; The choice-of-anchor J domain, about 160 amino acids long, occurs ... |
1139-1308 | 2.83e-22 | ||||||
choice-of-anchor J domain; The choice-of-anchor J domain, about 160 amino acids long, occurs as many as times in a protein, although most often only once. Proteins with the domain include proteins with serine hydrolase, metallohydrolase, or adhesin-associated domains. Notably, many members are also found with either the PEP-CTERM term domain, or the type IX secretion system type A domain, both associated with protein-sorting system expected to leave target proteins covalently attached to the bacterial outer membrane. Pssm-ID: 468371 [Multi-domain] Cd Length: 161 Bit Score: 95.08 E-value: 2.83e-22
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| Peptidase_M60_C | pfam18630 | Peptidase M60 C-terminal domain; This is C-terminal domain (CTD) of M60-peptidases pfam13402. ... |
1642-1697 | 1.33e-05 | ||||||
Peptidase M60 C-terminal domain; This is C-terminal domain (CTD) of M60-peptidases pfam13402. It Can also be found at the C-terminal region of gingipain B (RgpB) from P. gingivalis. It was found to possess a typical Ig-like fold encompassing seven antiparallel beta-strands organized in two beta-sheets, packed into a beta-sandwich structure that can spontaneously dimerize through C-terminal strand swapping. Translocation of gingipains from the periplasm across the OM is dependent on the conserved CTD, which appears to be important for secretion of the proteins and in particular, truncation of the last few C-terminal residues of this domain leads to accumulation of gingipains in the periplasm. Subsequently, the T9SS targeting signal was demonstrated to reside within the last 22 residues at the C-terminus of the CTD. During gingipain translocation across the OM, the CTD is cleaved off by PorU. Pssm-ID: 408412 Cd Length: 65 Bit Score: 44.36 E-value: 1.33e-05
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| Name | Accession | Description | Interval | E-value | ||||||
| Peptidase_C25_N_gingipain | cd10913 | gingipain subgroup of the Peptidase C25 family N-terminal domain; Gingipain, produced by ... |
229-573 | 8.70e-138 | ||||||
gingipain subgroup of the Peptidase C25 family N-terminal domain; Gingipain, produced by Porphyromonas gingivalis, exemplifies the Peptidase family C25, a unique class of cysteine proteases. P. gingivalis is one of the primary gram-negative pathogens that causes periodontitis, a disease also associated with other diseases such as diabetes and cardiovascular disease. The gingipain subgroup contains extracellular Arg- and Lys-specific proteinases called Arg-gingipain (Rgp) and Lys-gingipain (Kgp); RgpA and RgpB are homologous Arg-specific gingipains encoded by two closely related genes, rgpA and rgpB, while Lys-specific gingipain is encoded by the single kgp gene. Mutant studies have shown that, among the large quantities of proteolytic enzymes produced by P. gingivalis, these three proteases are major virulence factors of this bacterium. All three genes encode an N-terminal pre-pro fragment, followed by the protease domain; however, rgpA and kgp also encode additional C-terminal HA (hemaglutinin/adhesion) subunits which consist of several sequence-related adhesion domains. Although unique, their cysteine protease active site residues (His and Cys) forming the catalytic dyad, are well-conserved, cleaving the C-terminal peptide bond with Arg or Lys residues. Gingipains are evolutionarily related to other highly specific proteases including caspases, clostripain, legumains, and separase. Gingipains function by dysregulating host defense and inflammatory responses, and degrading host proteins, e.g. tissue, cells, matrix, plasma and immunological proteins. It has been suggested that they enhance gingival crevicular fluid (GCF) production through activation of the kallikrein/kinin pathways, thus increasing vascular permeability and causing gingival inflammation, a distinctive feature of periodontitis. RgpA and RgpB are also able to cleave and activate coagulation factors IX and X in order to activate prothrombin to produce thrombin, which in turn increases production of GCF. The gingipains also play a pivotal role in the survival of P. gingivalis in the host by attacking the host defense system through cleavage of several immunological molecules, while at the same time evading the host-immune response by dysregulating the cytokine network. Pssm-ID: 199211 Cd Length: 348 Bit Score: 430.67 E-value: 8.70e-138
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| Propeptide_C25 | pfam08126 | Propeptide_C25; This is found at the N terminal end of some of the members of the C25 ... |
24-220 | 7.40e-107 | ||||||
Propeptide_C25; This is found at the N terminal end of some of the members of the C25 peptidase family (PF01364). Little is known about the function of this motif. Pssm-ID: 285357 Cd Length: 205 Bit Score: 338.83 E-value: 7.40e-107
|
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| DUF2436 | pfam10365 | Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has ... |
1408-1569 | 3.79e-90 | ||||||
Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has no known function. Pssm-ID: 287351 Cd Length: 164 Bit Score: 289.53 E-value: 3.79e-90
|
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| DUF2436 | pfam10365 | Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has ... |
698-856 | 1.24e-89 | ||||||
Domain of unknown function (DUF2436); This domain is found on peptidase C25 proteins and has no known function. Pssm-ID: 287351 Cd Length: 164 Bit Score: 287.99 E-value: 1.24e-89
|
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| Cleaved_Adhesin | pfam07675 | Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in ... |
1140-1309 | 3.41e-87 | ||||||
Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in various roles including cell adhesion, cell lysis and carbohydrate binding. A tandem repeat of these modules (either two or three repeats) constitute the haemagglutinin/adhesin (HA) regions of the gingipains, RgpA and Kgp, expressed by Porphyromonas gingivalis (Bacteroides gingivalis). They form components of the major extracellular virulence complex RgpA-Kgp - a mixture of proteinases and adhesin domains. The adhesin domains in this complex are found in proteinase-cleaved forms when isolated from the cell surface. Haemagglutinin genes of P. gingivalis (hagA1 HAGA1_PORGI - and hagA2 HAGA2_PORGI) suggest that such proteins are composed of eight to ten tandem repeats of these adhesin modules. Genomic data predicts that homologous protein modules are also expressed by a number of other bacteria and form part of putative multi-domain proteins, eg. Swiss:Q26BR9 and Swiss:B0VGL6. These domains may be acting in concert with other adhesion modules thought to be part of these multi-domain proteins such as fibronectin type III, pfam00041, and Meprin, A5, mu (MAM), pfam00629, domains. Pssm-ID: 284979 Cd Length: 166 Bit Score: 281.41 E-value: 3.41e-87
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| Peptidase_C25 | pfam01364 | Peptidase family C25; |
239-571 | 2.53e-65 | ||||||
Peptidase family C25; Pssm-ID: 396092 Cd Length: 343 Bit Score: 225.71 E-value: 2.53e-65
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| Peptidase_C25_N | cd02258 | Peptidase C25 family N-terminal domain, found in Arg-gingipain (Rgp), Lys-gingipain (Kgp) and ... |
236-573 | 9.21e-65 | ||||||
Peptidase C25 family N-terminal domain, found in Arg-gingipain (Rgp), Lys-gingipain (Kgp) and related proteins; Peptidase family C25 is a unique class of cysteine proteases, exemplified by gingipain, which is produced by Porphyromonas gingivalis. P. gingivalis is one of the primary gram-negative pathogens that causes periodontitis, a disease that is also associated with other diseases such as diabetes and cardiovascular disease. Gingipains are a group of extracellular Arg- and Lys-specific proteinases called Arg-gingipain (Rgp) and Lys-gingipain (Kgp); RgpA and RgpB are homologous Arg-specific gingipains encoded by two closely related genes, rgpA and rgpB, while Lys-specific gingipain is encoded by the single kgp gene. Mutant studies have shown that, among the large quantities of proteolytic enzymes produced by P. gingivalis, these three proteases are major virulence factors of this bacterium. All three genes encode an N-terminal pre-pro fragment, followed by the protease domain; however, rgpA and kgp also encode additional C-terminal HA (hemaglutinin/adhesion) subunits which consist of several sequence-related adhesion domains. Although unique, their cysteine protease active site residues (His and Cys) forming the catalytic dyad are well-conserved, cleaving the C-terminal peptide bond with Arg or Lys residues. Gingipains are evolutionarily related to other highly specific proteases including caspases, clostripain, legumains, and separase. Gingipains function by dysregulating host defense and inflammatory responses, and degrading host proteins, e.g. tissue, cells, matrix, plasma and immunological proteins. They are proposed to enhance gingival crevicular fluid (GCF) production through activation of the kallikrein/kinin pathways, thus increasing vascular permeability and causing gingival inflammation, a distinctive feature of periodontitis. RgpA and RgpB are also able to cleave and activate coagulation factors IX and X in order to activate prothrombin to produce thrombin, which in turn increases production of GCF. The gingipains also play a pivotal role in the survival of P. gingivalis in the host by attacking the host defense system through cleavage of several immunological molecules, while at the same time evading the host-immune response by dysregulating the cytokine network. Pssm-ID: 199210 Cd Length: 382 Bit Score: 225.29 E-value: 9.21e-65
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| Cleaved_Adhesin | pfam07675 | Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in ... |
965-1128 | 1.02e-50 | ||||||
Cleaved Adhesin Domain; This is a family of bacterial protein modules thought to function in various roles including cell adhesion, cell lysis and carbohydrate binding. A tandem repeat of these modules (either two or three repeats) constitute the haemagglutinin/adhesin (HA) regions of the gingipains, RgpA and Kgp, expressed by Porphyromonas gingivalis (Bacteroides gingivalis). They form components of the major extracellular virulence complex RgpA-Kgp - a mixture of proteinases and adhesin domains. The adhesin domains in this complex are found in proteinase-cleaved forms when isolated from the cell surface. Haemagglutinin genes of P. gingivalis (hagA1 HAGA1_PORGI - and hagA2 HAGA2_PORGI) suggest that such proteins are composed of eight to ten tandem repeats of these adhesin modules. Genomic data predicts that homologous protein modules are also expressed by a number of other bacteria and form part of putative multi-domain proteins, eg. Swiss:Q26BR9 and Swiss:B0VGL6. These domains may be acting in concert with other adhesion modules thought to be part of these multi-domain proteins such as fibronectin type III, pfam00041, and Meprin, A5, mu (MAM), pfam00629, domains. Pssm-ID: 284979 Cd Length: 166 Bit Score: 177.02 E-value: 1.02e-50
|
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| choice_anch_J | NF038128 | choice-of-anchor J domain; The choice-of-anchor J domain, about 160 amino acids long, occurs ... |
965-1130 | 8.92e-35 | ||||||
choice-of-anchor J domain; The choice-of-anchor J domain, about 160 amino acids long, occurs as many as times in a protein, although most often only once. Proteins with the domain include proteins with serine hydrolase, metallohydrolase, or adhesin-associated domains. Notably, many members are also found with either the PEP-CTERM term domain, or the type IX secretion system type A domain, both associated with protein-sorting system expected to leave target proteins covalently attached to the bacterial outer membrane. Pssm-ID: 468371 [Multi-domain] Cd Length: 161 Bit Score: 130.90 E-value: 8.92e-35
|
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| Peptidase_C25_C | pfam03785 | Peptidase family C25, C terminal ig-like domain; |
578-651 | 9.45e-30 | ||||||
Peptidase family C25, C terminal ig-like domain; Pssm-ID: 367657 Cd Length: 74 Bit Score: 113.30 E-value: 9.45e-30
|
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| choice_anch_J | NF038128 | choice-of-anchor J domain; The choice-of-anchor J domain, about 160 amino acids long, occurs ... |
1139-1308 | 2.83e-22 | ||||||
choice-of-anchor J domain; The choice-of-anchor J domain, about 160 amino acids long, occurs as many as times in a protein, although most often only once. Proteins with the domain include proteins with serine hydrolase, metallohydrolase, or adhesin-associated domains. Notably, many members are also found with either the PEP-CTERM term domain, or the type IX secretion system type A domain, both associated with protein-sorting system expected to leave target proteins covalently attached to the bacterial outer membrane. Pssm-ID: 468371 [Multi-domain] Cd Length: 161 Bit Score: 95.08 E-value: 2.83e-22
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| Peptidase_C25_N_1 | cd10914 | uncharacterized subgroup of the Peptidase C25 family N-terminal domain; Domains in this ... |
238-573 | 3.41e-22 | ||||||
uncharacterized subgroup of the Peptidase C25 family N-terminal domain; Domains in this subgroup are uncharacterized members of the Peptidase family C25 N-terminal domain family. Peptidase family C25 is a unique class of cysteine proteases, exemplified by gingipain, which is produced by Porphyromonas gingivalis. P. gingivalis is one of the primary gram-negative pathogens that causes periodontitis, a disease that is also associated with other diseases such as diabetes and cardiovascular disease. Gingipains are a group of extracellular Arg- and Lys-specific proteinases called Arg-gingipain (Rgp) and Lys-gingipain (Kgp); RgpA and RgpB are homologous Arg-specific gingipains encoded by two closely related genes, rgpA and rgpB, while Lys-specific gingipain is encoded by the single kgp gene (also called prtK, prkP). Mutant studies have shown that, among the large quantities of proteolytic enzymes produced by P. gingivalis, these three proteases are major virulence factors of this bacterium. All three genes encode an N-terminal pre-pro fragment, followed by the protease domain; however, rgpA and kgp also encode additional C-terminal HA (hemaglutinin/adhesion) subunits which consist of several sequence-related adhesion domains. Although unique, their cysteine protease active site residues (His and Cys) forming the catalytic dyad are well-conserved, cleaving the C-terminal peptide bond with Arg or Lys residues. Gingipains are evolutionarily related to other highly specific proteases including caspases, clostripain, legumains, and separase. Gingipains function by dysregulating host defense and inflammatory responses, and degrading host proteins, e.g. tissue, cells, matrix, plasma and immunological proteins. They are proposed to enhance gingival crevicular fluid (GCF) production through activation of the kallikrein/kinin pathways, thus increasing vascular permeability and causing gingival inflammation, a distinctive feature of periodontitis. RgpA and RgpB are also able to cleave and activate coagulation factors IX and X in order to activate prothrombin to produce thrombin, which in turn increases production of GCF. The gingipains also play a pivotal role in the survival of P. gingivalis in the host by attacking the host defense system through cleavage of several immunological molecules, while at the same time evading the host-immune response by dysregulating the cytokine network. Pssm-ID: 199212 Cd Length: 365 Bit Score: 100.63 E-value: 3.41e-22
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| Peptidase_C25_N_2 | cd10915 | uncharacterized subgroup of the Peptidase C25 family N-terminal domain; Domains in this ... |
230-529 | 4.53e-16 | ||||||
uncharacterized subgroup of the Peptidase C25 family N-terminal domain; Domains in this subgroup are uncharacterized members of the Peptidase family C25 N-terminal domain family. Peptidases family C25 are a unique class of cysteine proteases, exemplified by gingipain, which is produced by Porphyromonas gingivalis. P. gingivalis is one of the primary gram-negative pathogens that causes periodontitis, a disease that is also associated with other diseases such as diabetes and cardiovascular disease. Gingipains are a group of extracellular Arg- and Lys-specific proteinases called Arg-gingipain (Rgp) and Lys-gingipain (Kgp); RgpA and RgpB are homologous Arg-specific gingipains encoded by two closely related genes, rgpA and rgpB, while Lys-specific gingipain is encoded by the single kgp gene. Mutant studies have shown that, among the large quantities of proteolytic enzymes produced by P. gingivalis, these three proteases are major virulence factors of this bacterium. All three genes encode an N-terminal pre-pro fragment, followed by the protease domain; however, rgpA and kgp also encode additional C-terminal HA (hemaglutinin/adhesion) subunits which consist of several sequence-related adhesion domains. Although unique, their cysteine protease active site residues (His and Cys) forming the catalytic dyad are well-conserved, cleaving the C-terminal peptide bond with Arg or Lys residues. Gingipains are evolutionarily related to other highly specific proteases including caspases, clostripain, legumains, and separase. Gingipains function by dysregulating host defense and inflammatory responses, and degrading host proteins, e.g. tissue, cells, matrix, plasma and immunological proteins. They are proposed to enhance gingival crevicular fluid (GCF) production through activation of the kallikrein/kinin pathways, thus increasing vascular permeability and causing gingival inflammation, a distinctive feature of periodontitis. RgpA and RgpB are also able to cleave and activate coagulation factors IX and X in order to activate prothrombin to produce thrombin, which in turn increases production of GCF. The gingipains also play a pivotal role in the survival of P. gingivalis in the host by attacking the host defense system through cleavage of several immunological molecules, while at the same time evading the host-immune response by dysregulating the cytokine network. Pssm-ID: 199213 Cd Length: 403 Bit Score: 82.30 E-value: 4.53e-16
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| Peptidase_M60_C | pfam18630 | Peptidase M60 C-terminal domain; This is C-terminal domain (CTD) of M60-peptidases pfam13402. ... |
1642-1697 | 1.33e-05 | ||||||
Peptidase M60 C-terminal domain; This is C-terminal domain (CTD) of M60-peptidases pfam13402. It Can also be found at the C-terminal region of gingipain B (RgpB) from P. gingivalis. It was found to possess a typical Ig-like fold encompassing seven antiparallel beta-strands organized in two beta-sheets, packed into a beta-sandwich structure that can spontaneously dimerize through C-terminal strand swapping. Translocation of gingipains from the periplasm across the OM is dependent on the conserved CTD, which appears to be important for secretion of the proteins and in particular, truncation of the last few C-terminal residues of this domain leads to accumulation of gingipains in the periplasm. Subsequently, the T9SS targeting signal was demonstrated to reside within the last 22 residues at the C-terminus of the CTD. During gingipain translocation across the OM, the CTD is cleaved off by PorU. Pssm-ID: 408412 Cd Length: 65 Bit Score: 44.36 E-value: 1.33e-05
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