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 578822469   1 MPFYAEECASMLAVTFSGGDKM-LRSIVTTDWdlQKGTGCTEGHTGTSAAAPLAAGMIALMLQVRPCLTWRDVQHIIVFT 79
Cdd:cd04059  218 RASYSEVGSSVLASAPSGGSGNpEASIVTTDL--GGNCNCTSSHNGTSAAAPLAAGVIALMLEANPNLTWRDVQHILALT 295

                 ..
gi 578822469  80 AT 81
Cdd:cd04059  296 AR 297

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 578822469   1 MPFYAEECASMLAVTFSGGDKM-LRSIVTTDWdlQKGTGCTEGHTGTSAAAPLAAGMIALMLQVRPCLTWRDVQHIIVFT 79
Cdd:cd04059  218 RASYSEVGSSVLASAPSGGSGNpEASIVTTDL--GGNCNCTSSHNGTSAAAPLAAGVIALMLEANPNLTWRDVQHILALT 295

                 ..
gi 578822469  80 AT 81
Cdd:cd04059  296 AR 297

Regulatory P domain of the subtilisin-like proprotein convertases and other proteases [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822469 137 NKAIPQSPRSlevlwNVSRmDLEMSGLKTLEHVAVTVSITHPRRGSLELKLFCPSGMMSLIGAPRSMDSDpngfN-DWTF 215
Cdd:COG4935  534 DVAIPDNGPA-----GVTS-TITVSGGGAVEDVTVTVDITHTYRGDLVITLISPDGTTVVLKNRSGGSAD----NiNATF 603

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 578822469 216 STVRCWGERARGTYRLVIRDVGdeSFQVGILRQWQLTLYG 255
Cdd:COG4935  604 DVANFSGESANGTWTLRVVDTA--GGDTGTLNSWSLTFTG 641

Serine protease, subtilisin family [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 578822469  44 TGTSAAAPLAAGMIALMLQVRPCLTWRDVQHIIVFTATRYED 85
Cdd:COG1404  305 SGTSMAAPHVAGAAALLLSANPDLTPAQVRAILLNTATPLGA 346

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 578822469   1 MPFYAEECASMLAVTFSGGDKM-LRSIVTTDWdlQKGTGCTEGHTGTSAAAPLAAGMIALMLQVRPCLTWRDVQHIIVFT 79
Cdd:cd04059  218 RASYSEVGSSVLASAPSGGSGNpEASIVTTDL--GGNCNCTSSHNGTSAAAPLAAGVIALMLEANPNLTWRDVQHILALT 295

                 ..
gi 578822469  80 AT 81
Cdd:cd04059  296 AR 297

Regulatory P domain of the subtilisin-like proprotein convertases and other proteases [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578822469 137 NKAIPQSPRSlevlwNVSRmDLEMSGLKTLEHVAVTVSITHPRRGSLELKLFCPSGMMSLIGAPRSMDSDpngfN-DWTF 215
Cdd:COG4935  534 DVAIPDNGPA-----GVTS-TITVSGGGAVEDVTVTVDITHTYRGDLVITLISPDGTTVVLKNRSGGSAD----NiNATF 603

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 578822469 216 STVRCWGERARGTYRLVIRDVGdeSFQVGILRQWQLTLYG 255
Cdd:COG4935  604 DVANFSGESANGTWTLRVVDTA--GGDTGTLNSWSLTFTG 641

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
                 ....*....|....*....|....*....|....*....|....
gi 578822469  36 GTGCTEGHTGTSAAAPLAAGMIALMLQVRPCLTWRDVQHIIVFT 79
Cdd:cd00306  198 GGGGYATLSGTSMAAPIVAGVAALLLSANPDLTPAQVKAALLST 241

Peptidase S8 family domain, uncharacterized subfamily 1; 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
                 ....*....|....*....|....*....|....*...
gi 578822469  44 TGTSAAAPLAAGMIALMLQVRPCLTWRDVQHIIVFTAT 81
Cdd:cd07487  227 SGTSMATPHVSGAIALLLQANPILTPDEVKCILRDTAT 264

Peptidase domain in the S53 family; Members of the peptidase S53 (sedolisin) family include endopeptidases and exopeptidases. The S53 family contains a catalytic triad Glu/Asp/Ser with an additional acidic residue Asp in the oxyanion hole, similar to that of Asn in subtilisin. 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. Characterized sedolisins include Kumamolisin, an extracellular calcium-dependent thermostable endopeptidase from Bacillus. The enzyme is synthesized with a 188 amino acid N-terminal preprotein region which is cleaved after the extraction into the extracellular space with low pH. One kumamolysin paralog, kumamolisin-As, is believed to be a collagenase. TPP1 is a serine protease that functions as a tripeptidyl exopeptidase as well as an endopeptidase. Less is known about PSCP from Pseudomonas which is thought to be an aspartic proteinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 578822469  44 TGTSAAAPLAAGMIALMLQVRPCLTWRDVQHIIVFTATryeDRRaewvtnEAGFSHShqHGFGLLNAWRLVNA 116
Cdd:cd05562  214 FGTSAAAPHAAGVAALVLSANPGLTPADIRDALRSTAL---DMG------EPGYDNA--SGSGLVDADRAVAA 275

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
                 ....*....|....*....|....*....|..
gi 578822469  45 GTSAAAPLAAGMIALMLQVRPCLTWRDVQHII 76
Cdd:cd07498  208 GTSFASPVAAGVAALILSANPNLTPAEVEDIL 239

Peptidase S8 family domain, uncharacterized subfamily 10; 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
                 ....*....|....*....|....*....|....*....|....*...
gi 578822469  36 GTGCTEG---HTGTSAAAPLAAGMIALMLQVRPCLTWRDVQHIIVFTA 80
Cdd:cd07494  235 GTPPNDGwgvFSGTSAAAPQVAGVCALMLQANPGLSPERARSLLNKTA 282

Peptidase domain in the S53 family; Members of the peptidases S53 (sedolisin) family include endopeptidases and exopeptidases sedolisin, kumamolysin, and (PSCP) Pepstatin-insensitive Carboxyl Proteinase. The S53 family contains a catalytic triad Glu/Asp/Ser with an additional acidic residue Asp in the oxyanion hole, similar to that of Asn in subtilisin. 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. Characterized sedolisins include Kumamolisin, an extracellular calcium-dependent thermostable endopeptidase from Bacillus. The enzyme is synthesized with a 188 amino acid N-terminal preprotein region which is cleaved after the extraction into the extracellular space with low pH. One kumamolysin paralog, kumamolisin-As, is believed to be a collagenase. TPP1 is a serine protease that functions as a tripeptidyl exopeptidase as well as an endopeptidase. Less is known about PSCP from Pseudomonas which is thought to be an aspartic proteinase.

                         10        20
                 ....*....|....*....|
gi 578822469  45 GTSAAAPLAAGMIALMLQVR 64
Cdd:cd04056  279 GTSAAAPLFAGLIALINQAR 298

Peptidase S8 family domain, uncharacterized subfamily 9; 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
                 ....*....|....*....|....*....|....*.
gi 578822469  45 GTSAAAPLAAGMIALMLQVRPCLTWRDVQHIIVFTA 80
Cdd:cd07493  225 GTSFSCPLIAGLIACLWQAHPNWTNLQIKEAILKSA 260

Peptidase S8 family domain in Subtilisin_Novo-like proteins; Subtilisins are a group of alkaline proteinases originating from different strains of Bacillus subtilis. Novo is one of the strains that produced enzymes belonging to this group. The enzymes obtained from the Novo and BPN' strains are identical. The Carlsburg and Novo subtilisins are thought to have arisen from a common ancestral protein. They have similar peptidase and esterase activities, pH profiles, catalyze transesterification reactions, and are both inhibited by diispropyl fluorophosphate, though they differ in 85 positions in the amino acid sequence. 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 with an additional acidic residue Asp in the oxyanion hole, similar to that of subtilisin.. 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
                 ....*....|....*....|....*....|....*....
gi 578822469  43 HTGTSAAAPLAAGMIALMLQVRPCLTWRDVQHIIVFTAT 81
Cdd:cd07483  253 DSGTSMAAPVVSGVAALIWSYYPNLTAKEVKQIILESGV 291