The S26 Type I signal peptidase (SPase; LepB; leader peptidase B; leader peptidase I; EC 3.4.21.89) family members are essential membrane-bound serine proteases that function to cleave the amino-terminal signal peptide extension from proteins that are translocated across biological membranes. The bacterial signal peptidase I, which is the most intensively studied, has two N-terminal transmembrane segments inserted in the plasma membrane and a hydrophilic, C-terminal catalytic region that is located in the periplasmic space. Although the bacterial signal peptidase I is monomeric, signal peptidases of eukaryotic cells commonly function as oligomeric complexes containing two divergent copies of the catalytic monomer. These are the IMP1 and IMP2 signal peptidases of the mitochondrial inner membrane that remove leader peptides from nuclear- and mitochondrial-encoded proteins. Also, two components of the endoplasmic reticulum signal peptidase in mammals (18-kDa and 21-kDa) belong to this family and they process many proteins that enter the ER for retention or for export to the Golgi apparatus, secretory vesicles, plasma membranes or vacuole. An atypical member of the S26 SPase type I family is the TraF peptidase which has the remarkable activity of producing a cyclic protein of the Pseudomonas pilin system. The type I signal peptidases are unique serine proteases that utilize a serine/lysine catalytic dyad mechanism in place of the classical serine/histidine/aspartic acid catalytic triad mechanism.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 496094023  77 QIYEVKTGSMVPTIPVKSLIL-SRIPKDAAKLAVGDIVTF---QDNGVTITHRIveviqekgaIGYRTKGDNPANSVD 150
Cdd:cd06530    1 EPVVVPGGSMEPTLQPGDLVLvNKLSYGFREPKRGDVVVFkspGDPGKPIIKRV---------IGYFVLGDNRNNSLD 69

The S26 Type I signal peptidase (SPase; LepB; leader peptidase B; leader peptidase I; EC 3.4.21.89) family members are essential membrane-bound serine proteases that function to cleave the amino-terminal signal peptide extension from proteins that are translocated across biological membranes. The bacterial signal peptidase I, which is the most intensively studied, has two N-terminal transmembrane segments inserted in the plasma membrane and a hydrophilic, C-terminal catalytic region that is located in the periplasmic space. Although the bacterial signal peptidase I is monomeric, signal peptidases of eukaryotic cells commonly function as oligomeric complexes containing two divergent copies of the catalytic monomer. These are the IMP1 and IMP2 signal peptidases of the mitochondrial inner membrane that remove leader peptides from nuclear- and mitochondrial-encoded proteins. Also, two components of the endoplasmic reticulum signal peptidase in mammals (18-kDa and 21-kDa) belong to this family and they process many proteins that enter the ER for retention or for export to the Golgi apparatus, secretory vesicles, plasma membranes or vacuole. An atypical member of the S26 SPase type I family is the TraF peptidase which has the remarkable activity of producing a cyclic protein of the Pseudomonas pilin system. The type I signal peptidases are unique serine proteases that utilize a serine/lysine catalytic dyad mechanism in place of the classical serine/histidine/aspartic acid catalytic triad mechanism.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 496094023  77 QIYEVKTGSMVPTIPVKSLIL-SRIPKDAAKLAVGDIVTF---QDNGVTITHRIveviqekgaIGYRTKGDNPANSVD 150
Cdd:cd06530    1 EPVVVPGGSMEPTLQPGDLVLvNKLSYGFREPKRGDVVVFkspGDPGKPIIKRV---------IGYFVLGDNRNNSLD 69

Signal peptidase I [Intracellular trafficking, secretion, and vesicular transport];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496094023  35 RRKLFKLIGNLAGVLIIAFLFITWLqvedarsrgevptvcgYQIYEVKTGSMVPTIPVKSLIL-SRIPKDAAKLAVGDIV 113
Cdd:COG0681    8 KRELREWLKSIVIALLLALLIRTFV----------------FEPFVIPSGSMEPTLLVGDRLLvNKLSYGFGEPKRGDIV 71

                         90
                 ....*....|....*..
gi 496094023 114 TF---QDNGVTITHRIV 127
Cdd:COG0681   72 VFkypEDPSKDYIKRVI 88

The S26 Type I signal peptidase (SPase; LepB; leader peptidase B; leader peptidase I; EC 3.4.21.89) family members are essential membrane-bound serine proteases that function to cleave the amino-terminal signal peptide extension from proteins that are translocated across biological membranes. The bacterial signal peptidase I, which is the most intensively studied, has two N-terminal transmembrane segments inserted in the plasma membrane and a hydrophilic, C-terminal catalytic region that is located in the periplasmic space. Although the bacterial signal peptidase I is monomeric, signal peptidases of eukaryotic cells commonly function as oligomeric complexes containing two divergent copies of the catalytic monomer. These are the IMP1 and IMP2 signal peptidases of the mitochondrial inner membrane that remove leader peptides from nuclear- and mitochondrial-encoded proteins. Also, two components of the endoplasmic reticulum signal peptidase in mammals (18-kDa and 21-kDa) belong to this family and they process many proteins that enter the ER for retention or for export to the Golgi apparatus, secretory vesicles, plasma membranes or vacuole. An atypical member of the S26 SPase type I family is the TraF peptidase which has the remarkable activity of producing a cyclic protein of the Pseudomonas pilin system. The type I signal peptidases are unique serine proteases that utilize a serine/lysine catalytic dyad mechanism in place of the classical serine/histidine/aspartic acid catalytic triad mechanism.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 496094023  77 QIYEVKTGSMVPTIPVKSLIL-SRIPKDAAKLAVGDIVTF---QDNGVTITHRIveviqekgaIGYRTKGDNPANSVD 150
Cdd:cd06530    1 EPVVVPGGSMEPTLQPGDLVLvNKLSYGFREPKRGDVVVFkspGDPGKPIIKRV---------IGYFVLGDNRNNSLD 69

The S24, S26 LexA/signal peptidase superfamily contains LexA-related and type I signal peptidase families. The S24 LexA protein domains include: the lambda repressor CI/C2 family and related bacterial prophage repressor proteins; LexA (EC 3.4.21.88), the repressor of genes in the cellular SOS response to DNA damage; MucA and the related UmuD proteins, which are lesion-bypass DNA polymerases, induced in response to mitogenic DNA damage; RulA, a component of the rulAB locus that confers resistance to UV, and RuvA, which is a component of the RuvABC resolvasome that catalyzes the resolution of Holliday junctions that arise during genetic recombination and DNA repair. The S26 type I signal peptidase (SPase) family also includes mitochondrial inner membrane protease (IMP)-like members. SPases are essential membrane-bound proteases which function to cleave away the amino-terminal signal peptide from the translocated pre-protein, thus playing a crucial role in the transport of proteins across membranes in all living organisms. All members in this superfamily are unique serine proteases that carry out catalysis using a serine/lysine dyad instead of the prototypical serine/histidine/aspartic acid triad found in most serine proteases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496094023  77 QIYEVKTGSMVPTIPVKSLILsrIPKDAAKLAVGDIVTFQ-DNGVTITHRiveVIQEKGAIGYRTKGDNPaNSVDPNILT 155
Cdd:cd06462    1 FALRVEGDSMEPTIPDGDLVL--VDKSSYEPKRGDIVVFRlPGGELTVKR---VIGLPGEGHYFLLGDNP-NSPDSRIDG 74

                 ....*....
gi 496094023 156 PDRIQAVYV 164
Cdd:cd06462   75 PPELDIVGV 83

Signal peptidase, peptidase S26; This is a family of membrane signal serine endopeptidases which function in the processing of newly-synthesized secreted proteins. Peptidase S26 removes the hydrophobic, N-terminal, signal peptides as proteins are translocated across membranes. The active site residues take the form of a catalytic dyad that is Ser, Lys in subfamily S26A; the Ser is the nucleophile in catalysis, and the Lys is the general base.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496094023   35 RRKLFKLIGNLAGVLIIAFLFItwlqvedarsrgevptvcgYQIYEVKTGSMVPTIPVKSLIL-SRIPKDAAKLAVGDIV 113
Cdd:pfam10502   1 LLEWVKAIVIALLLALLIRTFL-------------------FEPYVVPGGSMSPTLPIGDYLIvNKFSYGLGEPKRGDIV 61

                          90
                  ....*....|....*..
gi 496094023  114 TFQ---DNGVTITHRIV 127
Cdd:pfam10502  62 VFRppeGPGVPLIKRVI 78