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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568966980  70 VTTDLH--HQCTDKHTGTSASAPLAAGMIALALEANPLLTWRDLQHLVVRASR 120
Cdd:cd04059  245 VTTDLGgnCNCTSSHNGTSAAAPLAAGVIALMLEANPNLTWRDVQHILALTAR 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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568966980  70 VTTDLH--HQCTDKHTGTSASAPLAAGMIALALEANPLLTWRDLQHLVVRASR 120
Cdd:cd04059  245 VTTDLGgnCNCTSSHNGTSAAAPLAAGVIALMLEANPNLTWRDVQHILALTAR 297

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568966980 229 EHVQVQLSLSYSRRGDLEIFLTSPMGTRSTLvaIRPLDISGQGYnNWIFMSTHYWDEDPQGLWTL 293
Cdd:COG4935  558 EDVTVTVDITHTYRGDLVITLISPDGTTVVL--KNRSGGSADNI-NATFDVANFSGESANGTWTL 619

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568966980  70 VTTDLH--HQCTDKHTGTSASAPLAAGMIALALEANPLLTWRDLQHLVVRASR 120
Cdd:cd04059  245 VTTDLGgnCNCTSSHNGTSAAAPLAAGVIALMLEANPNLTWRDVQHILALTAR 297

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568966980 229 EHVQVQLSLSYSRRGDLEIFLTSPMGTRSTLvaIRPLDISGQGYnNWIFMSTHYWDEDPQGLWTL 293
Cdd:COG4935  558 EDVTVTVDITHTYRGDLVITLISPDGTTVVL--KNRSGGSADNI-NATFDVANFSGESANGTWTL 619

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
                 ....*....|....*....|....*....|....*.
gi 568966980  82 HTGTSASAPLAAGMIALALEANPLLTWRDLQHLVVR 117
Cdd:cd00306  205 LSGTSMAAPIVAGVAALLLSANPDLTPAQVKAALLS 240

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
                 ....*....|....*....|....*....|....*...
gi 568966980  83 TGTSASAPLAAGMIALALEANPLLTWRDLQHLVVRASR 120
Cdd:cd07494  246 SGTSAAAPQVAGVCALMLQANPGLSPERARSLLNKTAR 283

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        30
                 ....*....|....*....|....*....|....*
gi 568966980  84 GTSASAPLAAGMIALALEA------------NPLL 106
Cdd:cd04056  279 GTSAAAPLFAGLIALINQArlaagkpplgflNPLL 313

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
                 ....*....|....*....|....*
gi 568966980  83 TGTSASAPLAAGMIALALEANPLLT 107
Cdd:cd07487  227 SGTSMATPHVSGAIALLLQANPILT 251

Peptidase S8 family domain in Vpr-like proteins; The maturation of the peptide antibiotic (lantibiotic) subtilin in Bacillus subtilis ATCC 6633 includes posttranslational modifications of the propeptide and proteolytic cleavage of the leader peptide. Vpr was identified as one of the proteases, along with WprA, that are capable of processing subtilin. Asp, Ser, His triadPeptidases 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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 568966980  82 HTGTSASAPLAAGMIALALEANPLLTWRDLQHLVVRASrpAQLQAEDWRINGVGRQGA 139
Cdd:cd07474  232 MSGTSMAAPHVAGAAALLKQAHPDWSPAQIKAALMNTA--KPLYDSDGVVYPVSRQGA 287