Table 1.
Proteases of S. pneumoniae.
| Protease/Peptidase Identification (Other Names) | Genome Locus Tag:* D39 (new) D39 (old) D39V TIGR4 (new) TIGR4 (old) |
Function | Comments | References |
|---|---|---|---|---|
| ATP-dependent Zinc Protease, putative^ | SPD_RS01695 SPD_0310 SPV_0310 SP_RS01660 SP_0341 |
Unknown | Possesses domains of unknown function | |
| CbpD | SPD_RS10730 SPD_2028 SPV_2028 SP_RS11240 SP_2201 |
Peptidoglycan hydrolysis | CHAP domain | 31, 32 |
| CbpG | SPD_RS01935 SPD_0356 SPV_0356 SP_RS01925 SP_0390 |
Serine protease; cleaves casein and fibronectin | Frameshifted in D39; intact in TIGR4; S1 family peptidase [His-Asp-Ser catalytic triad] | 32, 34 |
| ClpP | SPD_RS03495 SPD_0650 SPV_0650 SP_RS03655 SP_0746 |
Cleaves proteins tagged for degradation (complex with ClpA or ClpX] | S14 peptidase family [Ser-His-Asp catalytic triad) | 36; 37, 38, 41–43, 45, 48–52 |
| ComA | SPD_RS00235 SPD_0049 SPV_0049 SP_RS00255 SP_0042 |
Cleavage of competence-stimulating peptide at Gly-Gly | Peptidase C39 family, ABC transporter peptidase subunit | 47 |
| CppA^ | SPD_RS06830 SPD_1278 SPV_1278 SP_RS07120 SP_1449 |
Cleavage of complement C3 | Glyoxalase/Bleomycin Resistance Protein/Dihydroxybiphenyl Dioxygenase homologous superfamily of metalloenzymes | 53–57, 98 |
| DacA (D-Alanyl-D-Alanine Carboxypeptidase; Penicillin-binding Protein 3) | SPD_RS04110 SPD_0767 SPV_0767 SP_RS04300 SP_0872 |
Cleavage of D-alanine residues during peptidoglycan synthesis | Peptidase S11 famly; gene names and synonyms according to D39V annotation: pbp3, dacA, dacC | 86–88 |
| DacB (LdcB) | SPD_RS02940 SPD_0549 SPV_0549 SP_RS03085 SP_0629 |
L,D-carboxypeptidase; peptidoglycan hydrolysis | Peptidase M15B family; Hedgehog signaling/DD-peptidase zinc-binding domain superfamily | 86, 89–91 |
| FtsH/Yme1/Tma family protein | SPD_RS00060 SPD_0013 SPV_0013 SP_RS00065 SP_0013 |
ATP-dependent metallopeptidase; Cleaves proteins tagged for degradation | Peptidase M41 carboxyl-terminal domain | |
| HtpX | SPD_RS06075 SPD_1138 SPV_1138 SP_RS06290 SP_1283 |
Putative stress response protein; zinc metalloprotease | Peptidase M48 family; contains a conserved zinc-binding HExxH motif found in zinc metalloproteases | |
| HtrA (DegP) | SPD_RS10945 SPD_2068 SPV_2068 SP_RS11450 SP_2239 |
Serine protease; chaperone | Peptidase S1C family, protease Do subfamily; PDZ domain [His-Asp-Ser catalytic triad) | 59, 60, 62–72 |
| IgA1 Protease (ZmpA) | SPD_RS05470 SPD_1018 SPV_1018 SP_RS05695 SP_1154 |
Zinc metalloprotease | Contains a conserved zinc-binding HExxH motif found in zinc metalloproteases | 19, 20, 73–85 |
| L,D-Carboxypeptidase (Muramoyltetrapeptide Carboxypeptidase) | SPD_RS00960 SPD_0173 SPV_0173 SP_RS00905 SP_0182 |
Cleavage of the peptidoglycan tetrapeptide | Peptidase family S66 | |
| LepB (Signal peptidase I) | SPD_RS01985 SPD_0367 SPV_0367 SP_RS01995 SP_0402 |
Serine peptidase; cleaves leader peptide from pro-proteins | Serine-lysine catalytic dyad | 107 |
| Lon-like Protease, putative^ | SPD_RS09400 SPD_1765 SPV_1765 SP_RS09890 SP_1967 |
Degradation of misfolded proteins | S16 peptidase family; ATP-dependent serine peptidase | |
| LspA (Signal peptidase II) | SPD_RS04400 SPD_0819 SPV_0819 SP_RS04590 SP_0928 |
Cleaves signal sequence from pro-lipoproteins | Peptidase A8, signal peptidase II family; recognizes lipobox sequence | 108, 109 |
| Matrixin Family Metalloprotease; Putative Zinc-dependent Protease | SPD_RS02880 SPD_0537 SPV_0537 SP_RS03030 SP_0617 |
Unknown | Peptidase M10 metallopeptidase family; domain matching the zinc metalloprotease MMP-like subfamily | |
| M42 Family Metallopeptidase | SPD_RS02930 SPD_0547 SPV_0547 SP_RS03075 SP_0627 |
Glutamyl aminopeptidase, PepA type, putative | Peptidase M42 family | |
| M50 Family Metallopeptidase | SPD_RS09330 SPD_1751 SPV_1751 SP_RS09810 SP_1952 |
Regulated intramembrane proteolysis (RIP] metalloprotease, putative | M50 family of putative membrane-associated zinc metalloproteases; contains a conserved zinc-binding HExxH motif; RIP proteases are involved in a two-step process of cleaving transmembrane proteins; site-2 protease class of zinc metalloproteases | |
| Methionyl Aminopeptidase (MAP) | SPD_RS05220 SPD_0970 SPV_0970 SP_RS05360 SP_1084 |
Cleavage of amino-terminal Met residue | Peptidase M24A family of metallopeptidases; cobalt required for activity | |
| PepA | SPD_RS08780 SPD_1647 SPV_1647 SP_RS09255 SP_1865 |
Glutamyl aminopeptidase | Peptidase M42 family | 58 |
| PepC | SPD_RS01425 SPD_0261 SPV_0261 SP_RS01380 SP_0281 |
Aminopeptidase | Peptidase C1 family; homologous superfamily of papain-like cysteine peptidases | |
| PepF (PepB, PepF1)# | SPD_RS04660 SPD_0866 SPV_0866 SP_RS04855 SP_0979 |
Oligoendopeptidase | Peptidase M3B family | |
| PepF (PepF2)# | SPD_RS08365 SPD_1571 SPV_1571 SP_RS08835 SP_1780 |
Oligoendopeptidase | Peptidase M3B family | |
| PepN | SPD_RS03770 SPD_0700 SPV_0700 SP_RS03900 SP_0797 |
Lysyl aminopeptidase | M1 family metallopeptidase | 23–25 |
| PepO | SPD_RS07765 SPD_1460 SPV_1460 SP_RS08130 SP_1647 |
Endopeptidase | M13 peptidase family | 92, 93, 95–97 |
| PepP (YpdF) | SPD_RS00980 SPD_0177 SPV_0177 SP_RS00925 SP_0187 |
Aminopeptidase | Described as MP-,MA-,MS-,AP-,NP-specific aminopeptidase YpdF by D39V annotation | |
| PepQ | SPD_RS07540 SPD_1418 SPV_1418 SP_RS07840 SP_1591 |
Proline dipeptidase | Peptidase M24 family; creatinase/aminopeptidase P amino-terminal domain | |
| PepS | SPD_RS01405 SPD_0258 SPV_0258 SP_RS01355 SP_0278 |
Aminopeptidase | Peptidase M29 family of metallopeptidases | |
| PepT | SPD_RS04810 SPD_0894 SPV_0894 SP_RS05000 SP_1008 |
Tripeptide aminopeptidase | Described as a tripeptide aminopeptidase by D39V annotation | |
| Peptidase C39 | SPD_RS10955 – - – - SP_RS02605 – - |
Bacteriocin processing, putative | Incomplete in D39 | |
| PepV | SPD_RS02905 SPD_0542 SPV_0542 SP_RS03055 SP_0623 |
Dipeptidase | Described as most specific for beta-Ala-Xaa by D39V annotation | |
| PepX (Xaa-Pro Dipeptidyl-Peptidase) | SPD_RS04205 SPD_0787 SPV_0787 SP_RS04410 SP_0894 |
Cleavage of Xaa-Pro dipeptides (Xaa = a hydrophobic amino acid) | Peptidase S15 family of serine peptidases | |
| PhtA (PhpA) | SPD_RS05575 SPD_1038 SPV_1038 SP_RS05790 SP_1175 |
Cleavage of complement C3 | Histidine triad HxxHxH motif | 53, 98–102 |
| Prp | SPD_RS05320 SPD_0990 SPV_0990 SP_RS05480 SP_1106 |
Cleavage of bacterial ribosomal protein L27 | PrP family of cysteine proteases; putative His-Cys catalytic dyad | |
| PrsW | SPD_RS00150 SPD_0031 SPV_2079 SP_RS00170 SP_0026 |
Intramembrane metalloprotease | PrsW family possibly involved in cell membrane stress response; frameshifted in D39 | |
| PrtA | SPD_RS03010 SPD_0558 SPV_0558 SP_RS03145 SP_0641 |
Serine peptidase; cleavage of leader peptides from lantibiotics | S8 family of lantibiotic leader peptide-processing serine proteases; [Asp-His-Ser catalytic triad sequence] | 60, 103–106 |
| PtrB (Protease II) | SPD_RS06300 SPD_1178 SPV_1178 SP_RS06590 SP_1343 |
Serine peptidase | S9 family peptidase (Ser-Asp-His catalytic triad sequence), usually cleaves oligopeptides | |
| Pyroglutamyl Peptidase I (Pcp1) | SPD_RS04040 SPD_0753 SPV_0753 SP_RS04215 SP_0860 |
Cleavage of pyroglutamic acid from peptides or proteins | Peptidase family C15 | |
| Pyroglutamyl Peptidase I (Pcp2) | SPD_RS09930 SPD_1870 SPV_1870 SP_RS10415 SP_2060 |
Cleavage of pyroglutamic acid from peptides or proteins | Peptidase family C15; frameshifted in D39 | |
| Rhomboid Family Intramembrane Serine Protease | SPD_RS10170 SPD_1920 SPV_1920 SP_RS10665 SP_2094 |
Intramembrane cleavage of proteins or peptides | Peptidase S54 domain; (Ser-His catalytic dyad) | |
| RseP (Eep, RasP, RseP, YluC) | SPD_RS01335 SPD_0245 SPV_0245 SP_RS01290 SP_0263 |
Regulated intramembrane proteolysis [RIP) metalloprotease | M50 family of putative membrane-associated zinc metalloproteases; contains a conserved zinc-binding HExxH motif; PDZ domain; RIP proteases are involved in a two-step process of cleaving transmembrane proteins | 33 |
| S8 Family Serine Peptidase | SPD_RS09340 SPD_1753 SPV_1753 SP_RS09820 SP_1954 |
Serine peptidase; cleavage of leader peptides from lantibiotics | S8 family of lantibiotic leader peptide-processing serine proteases; (Asp-His-Ser catalytic triad sequence]; described as epidermin leader peptide processing serine protease EPIP precursor by D39V annotation; frameshifted in TIGR4 |
|
| Sapep Family Mn2+-dependent Dipeptidase/Xaa-His Dipeptidase | SPD_RS10475 SPD_1979 SPV_1979 SP_RS10975 SP_2153 |
Cleavage of Xaa-His dipeptides (Xaa = a hydrophobic amino acid) | Peptidase M20 family, subfamily M20C; exopeptidase dimerization domain; zinc peptidase domain | |
| Site-2 Protease Family Protein; Putative Peptidase M50 | SPD_RS08385 SPD_1575 SPV_1575 SP_RS08855 SP_1784 |
Metalloprotease; cleavage of protein transmembrane domains; RIP protease | M50 family of putative membrane-associated zinc metalloproteases; contains a conserved zinc-binding HExxH motif; RIP proteases are involved in a two-step process of cleaving transmembrane proteins | |
| SprT Family Metalloprotease, putative^ | SPD_RS04300 – – SPV_2244 SP_RS04490 SP_0909 |
Zinc metalloprotease | Contains a conserved zinc-binding HExxH motif found in zinc metalloproteases; locus tag not present in D39 accession number CP000410.2 | |
| Type IV Prepilin Peptidase, putative | SPD_RS08500 SPD_1593 SPV_1593 SP_RS08975 SP_1808 |
Cleavage of leader peptide from type IV prepilin-like proteins | Gene names and synonyms according to D39V annotation: cclA, cilC, pilD | |
| U32 Family Peptidase | SPD_RS03790 SPD_0704 SPV_0704 SP_RS03920 SP_0801 |
Unknown | Diverse family with unknown catalytic mechanisms | |
| U32 Family Peptidase | SPD_RS06710 SPD_1256 SPV_1256 SP_RS07000 SP_1427 |
Unknown | Diverse family with unknown catalytic mechanisms; noted as incomplete sequence in D39 but not in D39V; incomplete sequence in TIGR4; D39V annotation indicates SPV_1256 to encode a large C1 subunit | |
| U32 Family Peptidase | SPD_RS06720 SPD_1258 SPV_1258 SP_RS07010 SP_1429 |
Unknown | Diverse family with unknown catalytic mechanisms; D39V annotation indicates SPV_1258 to encode a large C1 subunit | |
| YdiL | SPD_RS01935 – - SPV_2157 SP_RS02120 SP_0430 |
Putative membrane peptidase, hypothetical protein | TIGR4 protein sequence does not indicate homology to any protease or peptidase families; frameshifted in D39 | |
| YhfC Family Intramembrane Metalloprotease | SPD_RS06540 SPD_1223 SPV_1223 SP_RS06820 SP_1391 |
Metalloprotease | Intramembrane metalloprotease YhfC Family; possess a consensus signature and two additional conserved motifs |
|
| Zinc Protease (Insulinase Family Protein)^ | SPD_RS10855 SPD_2052 SPV_2052 SP_RS11360 SP_2225 |
Metallopeptidase | M16 family peptidase (requires a divalent cation such as zinc) | |
| ZmpB | SPD_RS03120 SPD_0577 SPV_0577 SP_RS03260 SP_0664 |
Zinc metalloprotease | Contains a conserved zinc-binding HExxH motif found in zinc metalloproteases | 28, 84, 105, 110, 112, 113, 114; 111, |
| ZmpC | – - – - – - SP_RS00380 SP_0071 |
Zinc metalloprotease | Not present in D39; Contains a conserved zinc-binding HExxH motif found in zinc metalloproteases | 110, 115–117, 119, 120, 118 |
| ZmpD | – - – - – - – - – - |
Zinc metalloprotease | Not present in D39 or TIGR4; Contains a conserved zinc-binding HExxH motif found in zinc metalloproteases | 27, 110 |
* National Center for Biotechnology Information (NCBI] gene/nucleotide accession numbers for strains D39 [122] with new locus tags, D39 with old locus tags, D39V [124], TIGR4 [123] with new locus tags, and TIGR4 with old locus tags are NC_008533.2, CP000410.2, CP027540.1, NC_003028.3, and AE005672.3, respectively.
#The D39 and TIGR4 annotations list two genes as pepF. The D39V annotation distinguishes these genes as pepF1 and pepF2. Both gene products are approximately 600 amino acids but only share 24% identity in the D39 background.
^These locus tags were identified as encoding proteins with putative protease activity by the deep annotation method employed for D39V [124].