Peptidase S8 family domain in Protein convertases; Protein convertases, whose members include furins and kexins, are members of the peptidase S8 or Subtilase clan of proteases. They have an Asp/His/Ser catalytic triad that is not homologous to trypsin. Kexins are involved in the activation of peptide hormones, growth factors, and viral proteins. Furin cleaves cell surface vasoactive peptides and proteins involved in cardiovascular tissue remodeling in the TGN, at cell surface, or in endosomes but rarely in the ER. Furin also plays a key role in blood pressure regulation though the activation of transforming growth factor (TGF)-beta. High specificity is seen for cleavage after dibasic (Lys-Arg or Arg-Arg) or multiple basic residues in protein convertases. There is also strong sequence conservation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 375 FPDPLFKEQWYLNG----GAKDGLDMNVGPAWQKGYTGKGVVVSILDDGIQTNHPDLAQNYDPEASFDINGNDSDPTPQD 450
Cdd:cd04059    1 PNDPLFPYQWYLKNtgqaGGTPGLDLNVTPAWEQGITGKGVTVAVVDDGLEITHPDLKDNYDPEASYDFNDNDPDPTPRY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 451 NGDNKHGTRCAGEVAAVAFNNFCGVGVAYNASIGGVRMLDGKVNDVVEAQALSLNPSHIDIYSASWGPEDDGSTVDGPGP 530
Cdd:cd04059   81 DDDNSHGTRCAGEIAAVGNNGICGVGVAPGAKLGGIRMLDGDVTDVVEAESLGLNPDYIDIYSNSWGPDDDGKTVDGPGP 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 281360985 531 LARRAFIYGVTSGRQGKGSIFVWASGNGGRYTDSCNCDGYTNSIFTLSISSATQAG 586
Cdd:cd04059  161 LAQRALENGVTNGRNGKGSIFVWAAGNGGNLGDNCNCDGYNNSIYTISVSAVTANG 216

Peptidase S8 family domain in Protein convertases; Protein convertases, whose members include furins and kexins, are members of the peptidase S8 or Subtilase clan of proteases. They have an Asp/His/Ser catalytic triad that is not homologous to trypsin. Kexins are involved in the activation of peptide hormones, growth factors, and viral proteins. Furin cleaves cell surface vasoactive peptides and proteins involved in cardiovascular tissue remodeling in the TGN, at cell surface, or in endosomes but rarely in the ER. Furin also plays a key role in blood pressure regulation though the activation of transforming growth factor (TGF)-beta. High specificity is seen for cleavage after dibasic (Lys-Arg or Arg-Arg) or multiple basic residues in protein convertases. There is also strong sequence conservation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 375 FPDPLFKEQWYLNG----GAKDGLDMNVGPAWQKGYTGKGVVVSILDDGIQTNHPDLAQNYDPEASFDINGNDSDPTPQD 450
Cdd:cd04059    1 PNDPLFPYQWYLKNtgqaGGTPGLDLNVTPAWEQGITGKGVTVAVVDDGLEITHPDLKDNYDPEASYDFNDNDPDPTPRY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 451 NGDNKHGTRCAGEVAAVAFNNFCGVGVAYNASIGGVRMLDGKVNDVVEAQALSLNPSHIDIYSASWGPEDDGSTVDGPGP 530
Cdd:cd04059   81 DDDNSHGTRCAGEIAAVGNNGICGVGVAPGAKLGGIRMLDGDVTDVVEAESLGLNPDYIDIYSNSWGPDDDGKTVDGPGP 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 281360985 531 LARRAFIYGVTSGRQGKGSIFVWASGNGGRYTDSCNCDGYTNSIFTLSISSATQAG 586
Cdd:cd04059  161 LAQRALENGVTNGRNGKGSIFVWAAGNGGNLGDNCNCDGYNNSIYTISVSAVTANG 216

Peptidase S8 pro-domain; This domain is the pro-domain of several peptidases belonging to family S8.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 281360985  242 EFAVNIPAGKQMADVIATKHGFINRGQIGSLDNYYLFQHHHVSKRSLRSSRKHQGALKSENEVKWMQQQHEKVRRKR 318
Cdd:pfam16470   1 EWAVHLEGGPEEADRIAEKHGFINLGQIGGLEDYYHFRHRRVSKRSKRSLRHKHSRLKKDPKVKWAEQQRGKKRVKR 77

subtilisin-like protease; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 413 VSILDDGIQTNHPDLAQNYDPEASF---------DINGN----------DSDPTPQDngDNKHGTRCAGEVAAVAFNNFC 473
Cdd:PTZ00262 320 ICVIDSGIDYNHPDLHDNIDVNVKElhgrkgiddDNNGNvddeyganfvNNDGGPMD--DNYHGTHVSGIISAIGNNNIG 397

                         90       100
                 ....*....|....*....|....*..
gi 281360985 474 GVGVAYNASIGGVRMLD----GKVNDV 496
Cdd:PTZ00262 398 IVGVDKRSKLIICKALDshklGRLGDM 424

Peptidase S8 family domain in Protein convertases; Protein convertases, whose members include furins and kexins, are members of the peptidase S8 or Subtilase clan of proteases. They have an Asp/His/Ser catalytic triad that is not homologous to trypsin. Kexins are involved in the activation of peptide hormones, growth factors, and viral proteins. Furin cleaves cell surface vasoactive peptides and proteins involved in cardiovascular tissue remodeling in the TGN, at cell surface, or in endosomes but rarely in the ER. Furin also plays a key role in blood pressure regulation though the activation of transforming growth factor (TGF)-beta. High specificity is seen for cleavage after dibasic (Lys-Arg or Arg-Arg) or multiple basic residues in protein convertases. There is also strong sequence conservation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 375 FPDPLFKEQWYLNG----GAKDGLDMNVGPAWQKGYTGKGVVVSILDDGIQTNHPDLAQNYDPEASFDINGNDSDPTPQD 450
Cdd:cd04059    1 PNDPLFPYQWYLKNtgqaGGTPGLDLNVTPAWEQGITGKGVTVAVVDDGLEITHPDLKDNYDPEASYDFNDNDPDPTPRY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 451 NGDNKHGTRCAGEVAAVAFNNFCGVGVAYNASIGGVRMLDGKVNDVVEAQALSLNPSHIDIYSASWGPEDDGSTVDGPGP 530
Cdd:cd04059   81 DDDNSHGTRCAGEIAAVGNNGICGVGVAPGAKLGGIRMLDGDVTDVVEAESLGLNPDYIDIYSNSWGPDDDGKTVDGPGP 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 281360985 531 LARRAFIYGVTSGRQGKGSIFVWASGNGGRYTDSCNCDGYTNSIFTLSISSATQAG 586
Cdd:cd04059  161 LAQRALENGVTNGRNGKGSIFVWAAGNGGNLGDNCNCDGYNNSIYTISVSAVTANG 216

Peptidase S8 pro-domain; This domain is the pro-domain of several peptidases belonging to family S8.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 281360985  242 EFAVNIPAGKQMADVIATKHGFINRGQIGSLDNYYLFQHHHVSKRSLRSSRKHQGALKSENEVKWMQQQHEKVRRKR 318
Cdd:pfam16470   1 EWAVHLEGGPEEADRIAEKHGFINLGQIGGLEDYYHFRHRRVSKRSKRSLRHKHSRLKKDPKVKWAEQQRGKKRVKR 77

Peptidase S8 family domain, uncharacterized subfamily 15; This family is a member of the Peptidases S8 or Subtilases serine endo- and exo-peptidase clan. They have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular, some function at extreme temperatures and pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 411 VVVSILDDGIQTNHPDLAQNYDPEASFDINGNDSDPTPQDNgdnkHGTRCAGEVAAVAFNNFCGVGVAYNASIGGVRMLD 490
Cdd:cd07498    1 VVVAIIDTGVDLNHPDLSGKPKLVPGWNFVSNNDPTSDIDG----HGTACAGVAAAVGNNGLGVAGVAPGAKLMPVRIAD 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 281360985 491 GKVNDVVEAQALSLN---PSHIDIYSASWGPEDDGSTVdgpgplaRRAFIYGVTSGRQGKGSIFVWASGNGGRYTDS 564
Cdd:cd07498   77 SLGYAYWSDIAQAITwaaDNGADVISNSWGGSDSTESI-------SSAIDNAATYGRNGKGGVVLFAAGNSGRSVSS 146

Peptidase S8 family domain in Thermitase-like proteins; Thermitase is a non-specific, trypsin-related serine protease with a very high specific activity. It contains a subtilisin like domain. The tertiary structure of thermitase is similar to that of subtilisin BPN'. It contains a Asp/His/Ser catalytic triad. Members of the peptidases S8 (subtilisin and kexin) and S53 (sedolisin) clan include endopeptidases and exopeptidases. The S8 family has an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. Serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base. The S53 family contains a catalytic triad Glu/Asp/Ser with an additional acidic residue Asp in the oxyanion hole, similar to that of subtilisin. The serine residue here is the nucleophilic equivalent of the serine residue in the S8 family, while glutamic acid has the same role here as the histidine base. However, the aspartic acid residue that acts as an electrophile is quite different. In S53 the it follows glutamic acid, while in S8 it precedes histidine. The stability of these enzymes may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. There is a great diversity in the characteristics of their members: some contain disulfide bonds, some are intracellular while others are extracellular, some function at extreme temperatures, and others at high or low pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 377 DPLFKEQWYLNggakdglDMNVGPAWQKGyTGKGVVVSILDDGIQTNHPDLAQ-NYDPeaSFDINGNDSDPTPqdngDNK 455
Cdd:cd07484    4 DPYYSYQWNLD-------QIGAPKAWDIT-GGSGVTVAVVDTGVDPTHPDLLKvKFVL--GYDFVDNDSDAMD----DNG 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 456 HGTRCAGEVAAVAFNNFCGVGVAYNASIGGVRMLD----GKVNDVVEAqalslnpshIdIYSAswgpeDDGSTV-----D 526
Cdd:cd07484   70 HGTHVAGIIAAATNNGTGVAGVAPKAKIMPVKVLDangsGSLADIANG---------I-RYAA-----DKGAKVinlslG 134

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 281360985 527 GPGP--LARRAFIYGvtsgrQGKGSIFVWASGNGGRYTDS 564
Cdd:cd07484  135 GGLGstALQEAINYA-----WNKGVVVVAAAGNEGVSSVS 169

Peptidase domain in the S8 and S53 families; Members of the peptidases S8 (subtilisin and kexin) and S53 (sedolisin) family include endopeptidases and exopeptidases. The S8 family has an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. Serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base. The S53 family contains a catalytic triad Glu/Asp/Ser with an additional acidic residue Asp in the oxyanion hole, similar to that of subtilisin. The serine residue here is the nucleophilic equivalent of the serine residue in the S8 family, while glutamic acid has the same role here as the histidine base. However, the aspartic acid residue that acts as an electrophile is quite different. In S53, it follows glutamic acid, while in S8 it precedes histidine. The stability of these enzymes may be enhanced by calcium; some members have been shown to bind up to 4 ions via binding sites with different affinity. There is a great diversity in the characteristics of their members: some contain disulfide bonds, some are intracellular while others are extracellular, some function at extreme temperatures, and others at high or low pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 411 VVVSILDDGIQTNHPDLAQNYDPEASFDINGNDSDPTPQDNGDNKHGTRCAGEVAAVAfNNFCGVGVAYNASIGGVRMLD 490
Cdd:cd00306    1 VTVAVIDTGVDPDHPDLDGLFGGGDGGNDDDDNENGPTDPDDGNGHGTHVAGIIAASA-NNGGGVGVAPGAKLIPVKVLD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 491 GKVN----DVVEAQALSLNPSHIDIYSASWgpeddGSTVDGPGPLARRAFIYGVTSgrqgKGSIFVWASGNGGRYTDScN 566
Cdd:cd00306   80 GDGSgsssDIAAAIDYAAADQGADVINLSL-----GGPGSPPSSALSEAIDYALAK----LGVLVVAAAGNDGPDGGT-N 149

                        170       180
                 ....*....|....*....|
gi 281360985 567 CDGYTNSIFTLSISSATQAG 586
Cdd:cd00306  150 IGYPAASPNVIAVGAVDRDG 169

Peptidase S8 family domain in Subtilisin proteins; This group is composed of many different subtilisins: Pro-TK-subtilisin, subtilisin Carlsberg, serine protease Pb92 subtilisin, and BPN subtilisins just to name a few. Pro-TK-subtilisin is a serine protease from the hyperthermophilic archaeon Thermococcus kodakaraensis and consists of a signal peptide, a propeptide, and a mature domain. TK-subtilisin is matured from pro-TK-subtilisin upon autoprocessing and degradation of the propeptide. Unlike other subtilisins though, the folding of the unprocessed form of pro-TK-subtilisin is induced by Ca2+ binding which is almost completed prior to autoprocessing. Ca2+ is required for activity unlike the bacterial subtilisins. The propeptide is not required for folding of the mature domain unlike the bacterial subtilases because of the stability produced from Ca2+ binding. Subtilisin Carlsberg is extremely similar in structure to subtilisin BPN'/Novo thought it has a 30% difference in amino acid sequence. The substrate binding regions are also similar and 2 possible Ca2+ binding sites have been identified recently. Subtilisin Carlsberg possesses the highest commercial importance as a proteolytic additive for detergents. Serine protease Pb92, the serine protease from the alkalophilic Bacillus strain PB92, also contains two calcium ions and the overall folding of the polypeptide chain closely resembles that of the subtilisins. Members of the peptidases S8 and S35 clan include endopeptidases, exopeptidases and also a tripeptidyl-peptidase. The S8 family has an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The S53 family contains a catalytic triad Glu/Asp/Ser. The stability of these enzymes may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular, some function at extreme temperatures and pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 410 GVVVSILDDGIQTNHPDLAQNYDPEASFdINGNDSDPTPqDNGdnkHGTRCAGEVAAVAfNNFCGVGVAYNASIGGVRML 489
Cdd:cd07477    1 GVKVAVIDTGIDSSHPDLKLNIVGGANF-TGDDNNDYQD-GNG---HGTHVAGIIAALD-NGVGVVGVAPEADLYAVKVL 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 281360985 490 D----GKVNDVVEAQALSLNpSHIDIYSASWGPEDDGSTVdgpgplaRRAFIYGVtsgrqGKGSIFVWASGNGG 559
Cdd:cd07477   75 NddgsGTYSDIIAGIEWAIE-NGMDIINMSLGGPSDSPAL-------REAIKKAY-----AAGILVVAAAGNSG 135

Peptidase S8 family domain, uncharacterized subfamily 13; This family is a member of the Peptidases S8 or Subtilases serine endo- and exo-peptidase clan. They have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular, some function at extreme temperatures and pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 410 GVVVSILDDGIQTNHPDLA----QNYD----PEASFDINGNDSDPTPQDNGDNK------------------HGTRCAGE 463
Cdd:cd07496    1 GVVVAVLDTGVLFHHPDLAgvllPGYDfisdPAIANDGDGRDSDPTDPGDWVTGddvppggfcgsgvspsswHGTHVAGT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 464 VAAVAfNNFCGV-GVAYNASIGGVRML---DGKVNDVVEAqalslnpshidIYSASwgpeddGSTVDGPGPLARRAFIYG 539
Cdd:cd07496   81 IAAVT-NNGVGVaGVAWGARILPVRVLgkcGGTLSDIVDG-----------MRWAA------GLPVPGVPVNPNPAKVIN 142

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 281360985 540 VTSGRQG---------------KGSIFVWASGNGGRYTD---SCNCDGytnsifTLSISSATQAG 586
Cdd:cd07496  143 LSLGGDGacsatmqnaindvraRGVLVVVAAGNEGSSASvdaPANCRG------VIAVGATDLRG 201

Peptidase S8 family domain in ProteinaseK-like proteins; The peptidase S8 or Subtilase clan of proteases have a Asp/His/Ser catalytic triad that is not homologous to trypsin. This CD contains several members of this clan including: PCSK9 (Proprotein convertase subtilisin/kexin type 9), Proteinase_K, Proteinase_T, and other subtilisin-like serine proteases. PCSK9 posttranslationally regulates hepatic low-density lipoprotein receptors (LDLRs) by binding to LDLRs on the cell surface, leading to their degradation. The binding site of PCSK9 has been localized to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. Characterized Proteinases K are secreted endopeptidases with a high degree of sequence conservation. Proteinases K are not substrate-specific and function in a wide variety of species in different pathways. It can hydrolyze keratin and other proteins with subtilisin-like specificity. The number of calcium-binding motifs found in these differ. Proteinase T is a novel proteinase from the fungus Tritirachium album Limber. The amino acid sequence of proteinase T as deduced from the nucleotide sequence is about 56% identical to that of proteinase K.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 406 YTGKGVVVSILDDGIQTNHPDLAQNydpeASFDINGNDSDPTPQDNGdnkHGTRCAGEVAAVAFnnfcgvGVAYNASIGG 485
Cdd:cd04077   22 STGSGVDVYVLDTGIRTTHVEFGGR----AIWGADFVGGDPDSDCNG---HGTHVAGTVGGKTY------GVAKKANLVA 88

                         90
                 ....*....|....*...
gi 281360985 486 VRMLD----GKVNDVVEA 499
Cdd:cd04077   89 VKVLDcngsGTLSGIIAG 106

Peptidase S8 family domain, uncharacterized subfamily 12; This family is a member of the Peptidases S8 or Subtilases serine endo- and exo-peptidase clan. They have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular, some function at extreme temperatures and pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 406 YTGKGVVVSILDDGIQTNHPDLAQNYDPEASFDINGNDSDptpqdngDNKHGTRCAGEVAAvAFNNFCGVGVAYNASIgg 485
Cdd:cd07480    5 FTGAGVRVAVLDTGIDLTHPAFAGRDITTKSFVGGEDVQD-------GHGHGTHCAGTIFG-RDVPGPRYGVARGAEI-- 74

                         90
                 ....*....|
gi 281360985 486 vrMLDGKVND 495
Cdd:cd07480   75 --ALIGKVLG 82

Peptidase S8 family domain, uncharacterized subfamily 6; This family is a member of the Peptidases S8 or Subtilases serine endo- and exo-peptidase clan. They have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular, some function at extreme temperatures and pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 410 GVVVSILDDGIQTNHPDLAQNYDPEASFDINGNDSDPTPQDNgdNKHGTRCAGEVaAVAFNNFCGVGVAynasiGGVRML 489
Cdd:cd07490    1 GVTVAVLDTGVDADHPDLAGRVAQWADFDENRRISATEVFDA--GGHGTHVSGTI-GGGGAKGVYIGVA-----PEADLL 72

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 281360985 490 DGKVNDVVEAQALSLnpshidIYSASWGPEDD--------GSTVDGPGPLARRafiygVTSGRQGKGSIFVWASGNGG 559
Cdd:cd07490   73 HGKVLDDGGGSLSQI------IAGMEWAVEKDadvvsmslGGTYYSEDPLEEA-----VEALSNQTGALFVVSAGNEG 139

Peptidase S8 family domain in Lantiobiotic (lanthionine-containing antibiotics) specific proteases; Lantiobiotic (lanthionine-containing antibiotics) specific proteases are very similar in structure to serine proteases. Lantibiotics are ribosomally synthesised antimicrobial agents derived from ribosomally synthesised peptides with antimicrobial activities against Gram-positive bacteria. The proteases that cleave the N-terminal leader peptides from lantiobiotics include: epiP, nsuP, mutP, and nisP. EpiP, from Staphylococcus, is thought to cleave matured epidermin. NsuP, a dehydratase from Streptococcus and NisP, a membrane-anchored subtilisin-like serine protease from Lactococcus cleave nisin. MutP is highly similar to epiP and nisP and is thought to process the prepeptide mutacin III of S. mutans. Members of the peptidases S8 (subtilisin and kexin) and S53 (sedolisin) clan include endopeptidases and exopeptidases. The S8 family has an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. Serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base. The S53 family contains a catalytic triad Glu/Asp/Ser with an additional acidic residue Asp in the oxyanion hole, similar to that of subtilisin. The serine residue here is the nucleophilic equivalent of the serine residue in the S8 family, while glutamic acid has the same role here as the histidine base. However, the aspartic acid residue that acts as an electrophile is quite different. In S53 the it follows glutamic acid, while in S8 it precedes histidine. The stability of these enzymes may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. There is a great diversity in the characteristics of their members: some contain disulfide bonds, some are intracellular while others are extracellular, some function at extreme temperatures, and others at high or low pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 411 VVVSILDDGIQTNHPDLA-------QNYDPEASFDINGNDSDPTPQDNGD-NKHGTRCAGEVAAVAFNNfcgvGVAYNAS 482
Cdd:cd07482    2 VTVAVIDSGIDPDHPDLKnsissysKNLVPKGGYDGKEAGETGDINDIVDkLGHGTAVAGQIAANGNIK----GVAPGIG 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 483 IGGVRMLD----GKVNDVVEAQALSLNpSHIDIYSASWGP---EDDGSTVDGPGPLA-RRAFIYGvtsgrQGKGSIFVWA 554
Cdd:cd07482   78 IVSYRVFGscgsAESSWIIKAIIDAAD-DGVDVINLSLGGyliIGGEYEDDDVEYNAyKKAINYA-----KSKGSIVVAA 151

                 ....*.
gi 281360985 555 SGNGGR 560
Cdd:cd07482  152 AGNDGL 157

Peptidase S8 family domain in BacillopeptidaseF-like proteins; Bacillus subtilis produces and secretes proteases and other types of exoenzymes at the end of the exponential phase of growth. The ones that make up this group is known as bacillopeptidase F, encoded by bpr, a serine protease with high esterolytic activity which is inhibited by PMSF. Like other members of the peptidases S8 family these have a Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of these enzymes may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 408 GKGVVVSILDDGIQTNHPDLAQNYDPE--ASFDINGNDSDP---TPQDNGDNKHGTRCAGevAAVAFN-NFCGVGVAYNA 481
Cdd:cd07481    1 GTGIVVANIDTGVDWTHPALKNKYRGWggGSADHDYNWFDPvgnTPLPYDDNGHGTHTMG--TMVGNDgDGQQIGVAPGA 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 482 SIGGVRMLD---GKVNDVVEAQALSLNPSHI-----------DIYSASWGPEDDGSTVDGPGPLARRAfiygvtsgrqgK 547
Cdd:cd07481   79 RWIACRALDrngGNDADYLRCAQWMLAPTDSagnpadpdlapDVINNSWGGPSGDNEWLQPAVAAWRA-----------A 147

                        170
                 ....*....|....*....
gi 281360985 548 GSIFVWASGNGGRYTDSCN 566
Cdd:cd07481  148 GIFPVFAAGNDGPRCSTLN 166

Peptidase S8 family domain in Streptococcal C5a peptidases; Streptococcal C5a peptidase (SCP), is a highly specific protease and adhesin/invasin. The subtilisin-like protease domain is located at the N-terminus and contains a protease-associated domain inserted into a loop. There are three fibronectin type III (Fn) domains at the C-terminus. SCP binds to integrins with the help of Arg-Gly-Asp motifs which are thought to stabilize conformational changes required for substrate binding. Peptidases S8 or Subtilases are a serine endo- and exo-peptidase clan. They have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular, some function at extreme temperatures and pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 400 PAWQKG-YTGKGVVVSILDDGIQTNHPDLAQNYDPEA---------------------------SFDINGNDSDPTPQDN 451
Cdd:cd07475    1 PLWDKGgYKGEGMVVAVIDSGVDPTHDAFRLDDDSKAkyseefeakkkkagigygkyynekvpfAYNYADNNDDILDEDD 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 281360985 452 GDNkHGTRCAGEVAAVAFNNFCG---VGVAYNASI 483
Cdd:cd07475   81 GSS-HGMHVAGIVAGNGDEEDNGegiKGVAPEAQL 114

Peptidase S8 family domain in CspA-like proteins; GSP (germination-specific protease) converts the spore peptidoglycan hydrolase (SleC) precursor to an active enzyme during germination of Clostridium perfringens S40 spores. Analysis of an enzyme fraction of GSP showed that it was composed of a gene cluster containing the processed forms of products of cspA, cspB, and cspC which are positioned in a tandem array just upstream of the 5' end of sleC. The amino acid sequences deduced from the nucleotide sequences of the csp genes showed significant similarity and showed a high degree of homology with those of the catalytic domain and the oxyanion binding region of subtilisin-like serine proteases. Members of the peptidases S8 and S35 clan include endopeptidases, exopeptidases and also a tripeptidyl-peptidase. The S8 family has an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The S53 family contains a catalytic triad Glu/Asp/Ser. The stability of these enzymes may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular, some function at extreme temperatures and pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 406 YTGKGVVVSILDDGIQTNHP---------------DLAQNYDPEASFDING-----------------NDSDPTPQDNGd 453
Cdd:cd07478    1 LTGKGVLVGIIDTGIDYLHPefrnedgttrilyiwDQTIPGGPPPGGYYGGgeyteeiinaalasdnpYDIVPSRDENG- 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 281360985 454 nkHGTRCAGEVAAVAFNNFCGVGVAYNASI 483
Cdd:cd07478   80 --HGTHVAGIAAGNGDNNPDFKGVAPEAEL 107

Peptidase S8 family domain, uncharacterized subfamily 14; This family is a member of the Peptidases S8 or Subtilases serine endo- and exo-peptidase clan. They have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium, some members have been shown to bind up to 4 ions via binding sites with different affinity. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular, some function at extreme temperatures and pH values.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 408 GKGVVVSILDDGIQTNHPDLAQ--NYDPEASFDINGN---DSDPTPQ----DNGDNKHGTRCAGEVAAVAFNNFCG---- 474
Cdd:cd07497    1 GEGVVIAIVDTGVDYSHPDLDIygNFSWKLKFDYKAYllpGMDKWGGfyviMYDFFSHGTSCASVAAGRGKMEYNLygyt 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281360985 475 -----VGVAYNASIGGVRML------------DGKVNDVVEAQALSLNPSHIDIYSASWGPEDDGSTVDGPGPLARRAFI 537
Cdd:cd07497   81 gkfliRGIAPDAKIAAVKALwfgdviyawlwtAGFDPVDRKLSWIYTGGPRVDVISNSWGISNFAYTGYAPGLDISSLVI 160

                        170       180
                 ....*....|....*....|..
gi 281360985 538 YGVTSgrqGKGSIFVWASGNGG 559
Cdd:cd07497  161 DALVT---YTGVPIVSAAGNGG 179