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 1566159171   1 IEKNHPDLAGNYDPGASFDVNDQDPDPQPRYTqmNDNRHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRMLDGEVTDAV 80
Cdd:cd04059    50 LEITHPDLKDNYDPEASYDFNDNDPDPTPRYD--DDNSHGTRCAGEIAAVGNNGICGVGVAPGAKLGGIRMLDGDVTDVV 127

                  .
gi 1566159171  81 E 81
Cdd:cd04059   128 E 128

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 1566159171   1 IEKNHPDLAGNYDPGASFDVNDQDPDPQPRYTqmNDNRHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRMLDGEVTDAV 80
Cdd:cd04059    50 LEITHPDLKDNYDPEASYDFNDNDPDPTPRYD--DDNSHGTRCAGEIAAVGNNGICGVGVAPGAKLGGIRMLDGDVTDVV 127

                  .
gi 1566159171  81 E 81
Cdd:cd04059   128 E 128

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1566159171   1 IEKNHPDLAGNYDPGASFDVNDQDPDpqprytqmNDNRHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRMLDGE 75
Cdd:COG1404   120 VDADHPDLAGRVVGGYDFVDGDGDPS--------DDNGHGTHVAGIIAANGNNGGGVAGVAPGAKLLPVRVLDDN 186

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 1566159171   1 IEKNHPDLAGNYDPGASFDVNDQDPDPQPRYTqmNDNRHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRMLDGEVTDAV 80
Cdd:cd04059    50 LEITHPDLKDNYDPEASYDFNDNDPDPTPRYD--DDNSHGTRCAGEIAAVGNNGICGVGVAPGAKLGGIRMLDGDVTDVV 127

                  .
gi 1566159171  81 E 81
Cdd:cd04059   128 E 128

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1566159171   1 IEKNHPDLAGNYDPGASFDVNDQDPDpqprytqmNDNRHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRMLDGE 75
Cdd:COG1404   120 VDADHPDLAGRVVGGYDFVDGDGDPS--------DDNGHGTHVAGIIAANGNNGGGVAGVAPGAKLLPVRVLDDN 186

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1566159171   4 NHPDLAGNYDPGASFDVNDQDPDPQPRYTqmndnrHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRMLDGE 75
Cdd:cd07498    13 NHPDLSGKPKLVPGWNFVSNNDPTSDIDG------HGTACAGVAAAVGNNGLGVAGVAPGAKLMPVRIADSL 78

Peptidase S8 family domain in Subtilisin-like proteins; 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 1566159171   1 IEKNHPDLAGN------YDPGASFDvNDQ---------------DPDPqprytqMNDNRHGTRCAGEVAAVANNGVCGVG 59
Cdd:cd07473    13 VDYNHPDLKDNmwvnpgEIPGNGID-DDGngyvddiygwnfvnnDNDP------MDDNGHGTHVAGIIGAVGNNGIGIAG 85

                          90       100
                  ....*....|....*....|....*.
gi 1566159171  60 VAYNARIGGVRMLD----GEVTDAVE 81
Cdd:cd07473    86 VAWNVKIMPLKFLGadgsGTTSDAIK 111

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1566159171  13 DPGASFDVNDQDPDPQPRYTQMNDNRHGTRCAGEVAAVANNGVCGVGVAYNARIGGVRML 72
Cdd:cd07496    47 DPGDWVTGDDVPPGGFCGSGVSPSSWHGTHVAGTIAAVTNNGVGVAGVAWGARILPVRVL 106

Peptidase S8 family domain in Fervidolysin; Fervidolysin found in Fervidobacterium pennivorans is an extracellular subtilisin-like keratinase. It is contains a signal peptide, a propeptide, and a catalytic region. The tertiary structure of fervidolysin is similar to that of subtilisin. It contains a Asp/His/Ser catalytic triad and is a member of the peptidase S8 (subtilisin and kexin) family. The catalytic triad is similar to that found in trypsin-like proteases, but it does 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 1566159171   5 HPDLAGNYD-PGASFDVNDQDPDPQ---PRYTQMNDNRHGTRCAGEVAAVANN--GVCGV----GVAYNARIGGVRMLDG 74
Cdd:cd07485    25 HPDLQGNGDgDGYDPAVNGYNFVPNvgdIDNDVSVGGGHGTHVAGTIAAVNNNggGVGGIagagGVAPGVKIMSIQIFAG 104

                  .
gi 1566159171  75 E 75
Cdd:cd07485   105 R 105

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1566159171   1 IEKNHPDLAGNYDPGASFDVNDQDPDPqprytqmndNRHGTRCAGEVAAVAnngvcgVGVAYNARIGGVRMLDGE 75
Cdd:cd04077    36 IRTTHVEFGGRAIWGADFVGGDPDSDC---------NGHGTHVAGTVGGKT------YGVAKKANLVAVKVLDCN 95

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        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1566159171   1 IEKNHPDLAGNYDPGASFdVNDQDPDPQPRytqmNDNRHGTRCAGEVAA--VANNGVcGVGVAYNARIGGVRMLD 73
Cdd:cd07487    13 IDAPHPDFDGRIIRFADF-VNTVNGRTTPY----DDNGHGTHVAGIIAGsgRASNGK-YKGVAPGANLVGVKVLD 81

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 1566159171   1 IEKNHPDLAGNYDPGASF----DVNDQdpdpqprytqmndNRHGTRCAGEVAAVANNGVcGVGVAYNARI--GGVRMLDG 74
Cdd:cd07480    19 IDLTHPAFAGRDITTKSFvggeDVQDG-------------HGHGTHCAGTIFGRDVPGP-RYGVARGAEIalIGKVLGDG 84

                  ....
gi 1566159171  75 EVTD 78
Cdd:cd07480    85 GGGD 88